Multiple Sclerosis and Depression.

A MEDLINE Search by, Ivan Goldberg, M.D.

1: Am J Psychiatry  2002 Nov;159(11):1862-8 

Depressive symptoms and severity of illness in multiple sclerosis: epidemiologic
study of a large community sample.

Chwastiak L, Ehde DM, Gibbons LE, Sullivan M, Bowen JD, Kraft GH.

Department of Psychiaty and Behavioral Sciences, Harborview Medical Center, Box
359911, Seattle, WA 98104, USA.

OBJECTIVE: Previous research has shown high prevalence rates of depression in
multiple sclerosis patients seen in specialty clinics. The relationships among
depressive symptoms and severity, duration, and course of multiple sclerosis are
controversial. METHOD: A survey was mailed to members of the Multiple Sclerosis
Association of King County (Wash.). Of the 1,374 eligible participants, 739
returned the survey, a response rate of 53.8%. Data about demographic
characteristics, employment, and duration and course of multiple sclerosis were
collected. Severity of multiple sclerosis was determined by the Expanded
Disability Status Scale, self-report version. Severity of depressive symptoms
was evaluated with the Center for Epidemiologic Studies Depression Scale (CES-D
Scale). Analysis of covariance was used to compare mean CES-D Scale scores
across categories of multiple sclerosis, and logistic regression was used to
identify variables associated with clinically significant depression. RESULTS:
Clinically significant depressive symptoms (CES-D Scale score > or =16) were
found in 41.8% of the subjects, and 29.1% of the subjects had moderate to severe
depression (score > or =21). Subjects with advanced multiple sclerosis were much
more likely to experience clinically significant depressive symptoms than
subjects with minimal disease. Shorter duration of multiple sclerosis was
associated with a greater likelihood of significant depressive symptoms, but the
pattern of illness progression was not. CONCLUSIONS: In this large community
sample, the severity of multiple sclerosis was more strongly associated with
depressive symptoms than was pattern of illness. Clinicians should evaluate
depression in patients with recent diagnoses of multiple sclerosis, major
changes in functioning, or limited social support.

PMID: 12411220 [PubMed - indexed for MEDLINE]

2: Int J Psychiatry Med  2002;32(2):167-78 

Major depressive disorder and health care costs in multiple sclerosis.

Patten SB, Jacobs P, Petcu R, Reimer MA, Metz LM.

Department of Community Health Sciences, The University of Calgary, Alberta,

OBJECTIVE: Multiple Sclerosis (MS) is associated with elevated levels of
depressive symptoms and an elevated frequency of depressive disorders.
Depressive disorders, in general, are associated with substantial direct and
indirect economic costs, and have been shown to increase the costs associated
with the management of medical conditions in a variety of clinical settings.
However, the impact of depressive disorders on costs associated with MS have not
been evaluated. The objective of this study was to evaluate this association.
METHODS: The Composite International Diagnostic Interview (CIDI) was used to
identify subjects with major depressive disorder in a sample who had earlier
been selected for a broader economic evaluation of the costs associated with MS.
Costs were measured in two ways: retrospectively (by questionnaire covering a
2-year period) and prospectively (using a 6-month diary). The proportion of
subjects reporting any costs and the proportion exceeding various cost
thresholds were calculated in subjects with and without lifetime major
depression. These proportions were compared using exact statistical tests and
confidence intervals. Non-parametric (rank sum) tests were used to compare
median costs. RESULTS: Of 136 subjects, 31 had a lifetime history of major
depression. MS-related expenses evaluated retrospectively (e.g., house and
vehicle alterations and purchases) did not differ depending on major depression
status. In the prospective analysis, subjects with lifetime major depression
were more likely to purchase vitamins, herbs, and naturopathic remedies (p <
0.01) and more likely to incur costs associated with utilization of services
provided by alternative practitioners (p = 0.04). Other differences (e.g., in
mental health care, medical specialists, general practitioner visits) were not
observed. CONCLUSIONS: Contrary to expectation, this study did not find
increased direct medical costs in persons with comorbid major depressive
disorder and multiple sclerosis. Persons with comorbid MS and (lifetime) major
depression did not incur greater costs or utilize more services. The Canadian
health care system is guided by principles of universality and is publicly
funded and administered, however, the lack of an impact of major depression on
utilization may reflect limited access to services. The lack of an association
between costs and major depression may or may not be generalizable to health
care systems in other countries.

PMID: 12269597 [PubMed - indexed for MEDLINE]

3: Int J Psychiatry Med  2002;32(2):155-65 

Hopelessness ratings in relapsing-remitting and secondary progressive multiple

Patten SB, Metz LM.

Department of Community Health Sciences, University of Calgary MS Clinic,
Alberta, Canada.

OBJECTIVE: Two recent randomized double-blind placebo controlled clinical trials
of interferon beta-1a in multiple sclerosis have obtained hopelessness ratings
using the Beck Hopelessness Scale (BHS). One of these studies, the PRISMS trial,
evaluated interferon beta-1a in relapsing remitting multiple sclerosis (RRMS).
Another, the SPECTRIMS trial, evaluated the same medication in secondary
progressive (SP) MS. The objective of this analysis was to compare levels of
hopelessness in persons with RRMS and SPMS, and to describe changes over time in
the clinical trial participants. METHOD: Raw data from each clinical trial was
obtained from the sponsor of the trials (Serono). Median BHS ratings, and the
proportions at or above the BHS cut-point of 10 were calculated over a two
(PRISMS) or three (SPECTRIMS) year period. RESULTS: The analysis included n =
532 clinical trial participants. Ratings of hopelessness were higher in SPMS
clinical trial participants (SPECTRIMS) than in the RRMS group (PRISMS) at
baseline (Fisher's exact test, p = 0.0035). Furthermore, ratings of hopelessness
were higher during follow-up than at baseline, in the SPMS group (McNemar's
exact probability,p = 0.0015), but not in the RRMS group (McNemar's exact
probability,p = 0.65). Depression was strongly associated with hopelessness in
both RRMS (z = 4.13, p < 0.001) and SPMS (z = 5.24, p < 0.001). CONCLUSIONS:
Hopelessness is associated with SPMS, and may increase over time in this group.
Hopelessness may influence suicide risk in people with MS and may potentially
have an impact on coping and quality of life. Additional research is necessary
to define the clinical implications of hopelessness in persons with this

Publication Types:
    Clinical Trial

PMID: 12269596 [PubMed - indexed for MEDLINE]

4: Eur J Neurol  2002 Sep;9(5):497-502 

Health-related quality of life and its relationship to cognitive and emotional
functioning in multiple sclerosis patients.

Benito-Leon J, Morales JM, Rivera-Navarro J.

Department of Neurology, Mostoles General Hospital, Madrid, Spain.

The existing knowledge about the health-related quality of life (HRQoL) and its
relationship to cognitive and/or emotional functioning in multiple sclerosis
(MS) is scarce. We assessed differences between subgroups of MS outpatients (n =
209) on one HRQoL instrument: a version of the Functional Assessment of Multiple
Sclerosis quality of life instrument; on two cognitive functioning tests: the
Mini-Mental State Examination and the clock drawing test; and on two emotional
functioning tests: the Hamilton Rating Scale for Depression and the Hamilton
Rating Scale for Anxiety. Three disease-related characteristics were assessed:
physical disability, duration of the illness, and clinical course. The results
showed that each of these has an effect on at least one dimension of HRQoL and
on one mental functioning test. Thus, the more severe, the more progressive, and
the longer the illness duration, the lower the HRQoL. Likewise, cognitive mean
scores decreased and emotional mean scores increased with greater illness
severity and progressive the MS. Furthermore, we also found significant
correlations between cognitive and emotional functioning tests and HRQoL
dimensions. Thus, the worse cognitive functioning and the higher depressive and
anxiety symptoms score the lower the HRQoL.

PMID: 12220381 [PubMed - indexed for MEDLINE]

5: Eur J Neurol  2002 Sep;9(5):491-6 

Depressive symptoms and MRI changes in multiple sclerosis.

Zorzon M, Zivadinov R, Nasuelli D, Ukmar M, Bratina A, Tommasi MA, Mucelli RP,
Brnabic-Razmilic O, Grop A, Bonfigli L, Cazzato G.

Department of Clinical Medicine and Neurology, University of Trieste, Italy.

To determine whether changes in specific regions of the brain can contribute to
the development of depression in patients with multiple sclerosis (MS). We
prospectively studied 90 patients with clinically definite MS. Disability,
independence, cognitive performances, and depressive and anxiety symptoms have
been assessed at baseline and 2 years later. At these two time-points, patients
underwent a 1.5-T magnetic resonance examination of the brain including T1- and
T2-weighted images. Calculation of regional and total lesion loads (LL) have
been performed by a semiautomatic technique; total and regional brain volumes
have been calculated by a fully automatic highly reproducible computerized
interactive program. Measurements of LL did not show any significant difference
between depressed and non-depressed patients. Brain atrophy was significantly
more conspicuous in the left frontal lobe (P=0.039), in both frontal lobes
(P=0.046) and showed a trend towards a difference in the right frontal lobe
(P=0.056), in the right temporal lobe (P=0.057) and in both temporal lobes
(P=0.072) of depressed patients. Disability, independence and cognitive
performances were similar in depressed and non-depressed patients (P=NS).
Spearman correlation analysis and multiple-regression analysis demonstrated that
the severity of the depressive symptoms score was associated both with the
disability score and the right temporal brain volume. Destructive lesions in the
right temporal lobe can contribute to the severity of depression in patients
with MS but the influence of the severity of neurological impairment should be
taken into account.

PMID: 12220380 [PubMed - indexed for MEDLINE]

6: J Obstet Gynecol Neonatal Nurs  2002 Jul-Aug;31(4):444-53 

Disability, social support, and concern for children: depression in mothers with
multiple sclerosis.

Harrison T, Stuifbergen A.

School of Nursing, The University of Texas at Austin, USA.

OBJECTIVE: To investigate the relationship between disability, concern for
children, social support, and depressive symptoms in a group of mothers with
multiple sclerosis (MS). DESIGN: An exploratory secondary analysis using
correlation and multiple regression techniques. SETTING AND PARTICIPANTS: Two
hundred one women with MS responded to a survey as part of a cohort
participating in a longitudinal study of health promotion and quality of life.
OUTCOME MEASURES: Depressive symptoms were measured using the CESD-10. RESULTS:
The results indicate that disability and concern for children are independent
predictors of depressive symptoms, and social support can partially mediate the
effect of concern for children on depressive symptoms. CONCLUSION: Appropriate
support should be identified and provided by nurses caring for mothers with
disabilities such as MS to decrease the depressive symptoms related to the
concern they have for their children.

PMID: 12146934 [PubMed - indexed for MEDLINE]

7: J Neurol  2002 Jul;249(7):815-20 

Multiple sclerosis, interferon beta-1b and depression A prospective

Feinstein A, O'Connor P, Feinstein K.

Department of Psychiatry, University of Toronto and Sunnybrook and Women's
College Health Sciences Centre, Room FG38, 2075 Bayview Avenue, Ontario M4N 3M5,

The objectives were twofold: a) to explore a possible association between major
depression and treatment with interferon beta-1b in patients with multiple
sclerosis; and b) to investigate whether putative antecedent risk factors such
as a previous psychiatric history and a family history of affective illness
influence the prevalence of major depression post-treatment with interferon
beta-1b. Forty-two patients with relapsing-remitting MS underwent neurological
examination and were interviewed with the Structured Clinical Interview for Axis
1 DSM-IV Disorders prior to starting interferon beta-1b and thereafter at 3, 6
and 12 months. Ethical considerations dictated that patients diagnosed with
major depression received anti-depressant medication. At index assessment, 21.4
% of the sample were diagnosed with a major depression, the figures falling to
17.5 %, 11.4 % and 6.3 % at 3, 6 and 12 months respectively. The majority of
subjects with a major depression had a history of psychiatric illness prior to
treatment with interferon beta-1b. A family history of affective disorder was
not associated with a significantly increased rate of major depression either
before or after treatment with interferon beta-1b. While the study's methodology
did not address causality, the data demonstrate that major depression
post-treatment with interferon beta-1b is linked to a history of psychiatric
illness prior to starting treatment. The threefold decline in prevalence rates
for major depression over the course of a year demonstrates a good response to
anti-depressant medication and possible beneficial effects of interferon beta-1b
on mood.

PMID: 12140662 [PubMed - indexed for MEDLINE]

8: Przegl Lek  2001;58(9):873-6 

[Emotional disorders in patients with multiple sclerosis]

[Article in Polish]

Kulakowska A, Drozdowski W, Halicka D.

Klinika Neurologii AMB/SPSK ul. Sklodowskiej 24a, 15-276 Bialystok.

Multiple sclerosis (MS) is the most common demyelinating disease of the central
nervous system, especially young adults. Although MS is usually looked on as a
disorder of the sensory and motor systems it can also be associated with
emotional dysfunctions and changes in personality. The depression, bipolar
disorders, euphoria, and pathological laughing and crying are most frequently
associated with the disease. Authors present a review of current opinions on
pathogenesis, diagnostic criteria and treatment of emotional problems in MS

Publication Types:
    Review, Tutorial

PMID: 11868251 [PubMed - indexed for MEDLINE]

9: Rev Neurol (Paris)  2001 Sep;157(8-9 Pt 2):1128-34 

[Neuropsychological evaluation and psychopathology of multiple sclerosis]

[Article in French]

Defer G.

Service de Neurologie Dejerine, CHU Cote de Nacre, 14033 Caen.

Cognitive and psychiatric disorders have long been described in MS. However,
these symptoms were only well evaluated starting about fifteen years ago. More
recently, there has been renewed interest in cognitive and psychiatric
assessment in MS, especially due to the emergence of new therapies for the
disease. Psychiatric symptoms mainly include depression and anxiety. Depression
is generally moderate, but there is a risk of suicide that is clearly higher
than in the general population. Depression is not correlated with the duration
of symptoms, type of disease or level of disability. Mild elation and
pathological laughing and crying can be associated and are more frequent in case
of severe disease. Bipolar affective disorders and alexithymia are more rare.
The question of premorbid personality has been questioned for depression but not
confirmed. It has been suspected for bipolar affective disorders. Cognitive
disorders are observed in 40 to 65% of the cases at any period of the disease.
They mainly include an impairment of working and long-term memory, executive
functions and attention whereas global intellectual efficiency is impaired
later. While cognitive disorders can be observed early in the course of the
disease, there is no correlation with the level of disability or duration of the
disease. Progressive MS and especially secondary progressive then primary
progressive forms are more subject to cognitive deficits than relapsing
remitting MS. For a similar cognitive impairment, progression could be a
negative factor for the disease course. Cognitive and psychiatric assessment of
patients can be discussed on the basis of why, how and when. Psychiatric
assessment is not particularly difficult when there are psychiatric complaints,
but cognitive assessment should be explained to the patients and justified when
there is no complaint. However, detection of cognitive deficits would lead to
better patient management. Psychiatric assessment will mainly use controlled or
open interviews and assessment scales to evaluate the level of depression and/or
anxiety. For cognitive assessment, short-term batteries focusing on the main
dysfunctions are recommended. Psychometric evaluation should not be performed
during a period of relapse, hospitalization or immediately after starting drug
therapy for depression or anxiety. The cognitive evaluation should be explained
to the patient and should include a parallel assessment by a psychologist well
trained in MS. The evaluations will be adapted to the situation and the goals.
Early interviews evaluate the psychopathological profile that can then be
reevaluated during each consultation. Cognitive assessment is mainly proposed in
case of interferon therapy, spontaneous complaints of the patient or abnormal
difficulties in daily life or occupational activities. In all cases, patient
management requires a multidisciplinary approach.

PMID: 11787345 [PubMed - indexed for MEDLINE]

10: Rev Neurol (Paris)  2001 Sep;157(8-9 Pt 2):1085-90 

[Therapeutic indications in symptomatic cognitive and psychopathological
disorders in multiple sclerosis]

[Article in French]

Lebrun C.

Service de Neurologie, Hopital Pasteur, 30, Voie Romaine, BP69, 06002 Nice.

Cognitive impairment and psychiatric disorders occur in about 60 p. cent of
multiple sclerosis patients. In general, impairment develops in established
cases, although it can present early in the disease course. The pattern of
neuropsychological deficits is characterized by deficits in attention, memory
and executive functions; No specific treatment seems to be effective in
cognitive impairment but appropriate strategies could limit the negative impact
on this disease. Depressive states are twice frequent and usual antidepressant
drugs seems to demonstrate some efficacy.

PMID: 11787341 [PubMed - indexed for MEDLINE]

11: J Consult Clin Psychol  2001 Dec;69(6):942-9 

Comparative outcomes for individual cognitive-behavior therapy,
supportive-expressive group psychotherapy, and sertraline for the treatment of
depression in multiple sclerosis.

Mohr DC, Boudewyn AC, Goodkin DE, Bostrom A, Epstein L.

Department of Neurology, University of California, San Fancisco, USA.

This study compared the efficacy of 3 16-week treatments for depression in 63
patients with multiple sclerosis (MS) and major depressive disorder (MDD):
individual cognitive-behavioral therapy (CBT), supportive-expressive group
therapy (SEG). and the antidepressant sertraline. Significant reductions were
seen from pre- to posttreatment in all measures of depression. Intent-to-treat
and completers analyses using the Beck Depression Inventory (BDI; A. T. Beck, C.
H. Ward. M. Medelson. J. Mock, & J. Erbaugh, 1961) and MDD diagnosis found that
CBT and sertraline were more effective than SEG at reducing depression. These
results were largely supported by the BDI-18, which eliminates BDI items
confounded with MS. However, the Hamilton Rating Scale for Depression (M.
Hamilton, 1960) did not show consistent differences between treatments. Reasons
for this inconsistency are discussed. These findings suggest that CBT or
sertraline is more likely to be effective in treating MDD in MS compared with
supportive group treatments.

Publication Types:
    Clinical Trial
    Randomized Controlled Trial

PMID: 11777121 [PubMed - indexed for MEDLINE]

12: Clin Rehabil  2001 Dec;15(6):657-68 

Assessment of emotional problems in people with multiple sclerosis.

Nicholl CR, Lincoln NB, Francis VM, Stephan TF.

Department of Clinical Psychology, Central Notts Healthcare NHS Trust
Headquarters and School of Psychology, University of Nottingham, UK.

OBJECTIVE: To investigate the occurrence of emotional problems in multiple
sclerosis (MS) patients. The utility of rating scales used to measure such
problems was studied to make recommendations for clinical practice. DESIGN:
Questionnaires were both sent by post and completed with an assistant
psychologist at a home visit. SUBJECTS: Ninety-six MS patients in contact with a
rehabilitation consultant. MEASURES: Patients were assessed using the Guy's
Neurological Disability Scale (GNDS), Extended Activities of Daily Living Scale
(EADL), Hospital Anxiety and Depression Scale (HAD), Beck Anxiety and Depression
Scales (BAI, BDI), Clinical Outcomes in Routine Evaluation Measure (CORE) and
the Brief Symptom Inventory (BSI). RESULTS: Rates of anxiety and depression
ranged from 16% to 48% according to the measures used. All mood scales were
highly significantly correlated with each other. Disability as measured by the
GNDS, but not the EADL, was significantly correlated with all mood measures.
Kappa values showed poor correspondence in the classification of cases. Receiver
operating characteristic curves indicated an optimum cut-off point of 7/8 on the
HAD and 2/3 on the General Health Questionnaire (GHQ-12). CONCLUSIONS: Rates of
emotional problems were low given the highly disabled population studied. The
HAD was relatively insensitive in comparison with the BAI and BDI. The GHQ-12
was sensitive and therefore recommended as a short screening measure. An
alternative short screen, 'Emotional GNDS', was proposed.

PMID: 11777096 [PubMed - indexed for MEDLINE]

13: Acta Neurol Scand  2001 Nov;104(5):257-61 

Depression and quality of life in multiple sclerosis.

Fruehwald S, Loeffler-Stastka H, Eher R, Saletu B, Baumhackl U.

Clinical Department of Social Psychiatry, Vienna University Medical School,
Vienna, Austria.

OBJECTIVES: Health related quality of life (QoL) has gained increasing influence
as a relevant evaluation criterion in multiple sclerosis. The high prevalence of
psychiatric comorbidity in MS is, however, hardly ever considered in studies
concerning QoL. MATERIALS AND METHODS: In 60 patients of a MS outpatient clinic,
symptoms of anxiety (Zung Anxiety Scale) and depression (Zung Depression Scale),
as well as the health-related quality of life were rated and set into relation
to the EDSS and to the duration of illness, respectively. RESULTS: There was a
highly significant correlation between depression as well as anxiety and the
self-assessed quality of life. Depression was the by far strongest predictor for
reduced QoL. CONCLUSION: Clinical studies, which seek to register the
increasingly important evaluation criterion of health-related quality of life in
MS, should consider the prevalence of depressive disorders and the decisive
effect of depression on the self-assessed quality of life of affected patients.

PMID: 11696017 [PubMed - indexed for MEDLINE]

14: Neuroepidemiology  2001 Oct;20(4):262-7 

Psychometric properties of the Center for Epidemiologic Studies-Depression scale
in multiple sclerosis.

Verdier-Taillefer MH, Gourlet V, Fuhrer R, Alperovitch A.

INSERM U360, Hopital la Salpetriere, F-75651 Paris Cedex 13, France.

The factorial structure of the Center for Epidemiologic Studies-Depression
(CES-D) scale has been examined on a large sample of multiple sclerosis (MS)
subjects (n = 696), general practice patients (n = 1,308) and healthy workers (n
= 342). The aim of this study was to verify if the CES-D is a valid and reliable
scale to assess depressive symptomatology in MS. As previously reported in the
literature, we found four factors that measure depressed affect, positive
affect, somatic complaints or retarded activity and interpersonal relationships.
The percent of total variance explained by the four factors was greater than 50%
in each group. Cronbach's alpha coefficients were 0.90 in the MS sample and 0.93
in the general practice sample, indicative of high reliability in both samples.
From these results, we conclude that the CES-D can be used to screen for
depression in epidemiological studies of this psychiatric disorder among MS
patients. Copyright 2001 S. Karger AG, Basel

Publication Types:
    Validation Studies

PMID: 11684903 [PubMed - indexed for MEDLINE]

15: Mult Scler  2001 Aug;7(4):243-8 

Interferon beta-1 a and depression in relapsing-remitting multiple sclerosis: an
analysis of depression data from the PRISMS clinical trial.

Patten SB, Metz LM.

Department of Community Health Sciences, University of Calgary, Alberta, Canada.

Depression is a suspected side effect of multiple sclerosis (MS) treatment with
interferon beta-1a. However, this has not been confirmed by rigorous studies.
Several psychological symptom rating scales were completed during the PRISMS
clinical trial of subcutaneous interferon beta-1a (Rebif) for
relapsing-remitting MS. We conducted an analysis of these data in order to
determine whether symptom elevations were associated with treatment. The PRISMS
clinical trial included 560 subjects from 22 centres in nine countries. There
were two active treatment arms (44 mcg x 3 and 22 mcg x 3 subcutaneously three
times per week) and a placebo group. Two hundred and sixty-seven of these
subjects were enrolled at English speaking study centres, where psychiatric
symptom ratings were obtained at baseline, 6, 12, 18 and 24 months using the
Center for Epidemiological Studies Depression Rating Scale (CES-D), the General
Health Questionnaire (GHQ) and the Beck Hopelessness Scale (BHS). After
randomization, the groups completing these scales were similar in terms of age,
gender, EDSS, duration of illness and employment status. Median CES-D scores in
the high dose, low dose and placebo groups at baseline were also similar: 8.0,
7.0 and 8.0, respectively. After 6 months of treatment the median change in
CES-D score was zero in all three groups. The proportion of subjects exceeding
the traditional CES-D cut-point for clinically significant depression (> 15)
after 6 months of treatment was strongly associated with pre-treatment
depression (RR 2.9, 95% C.I.: 1.8-4.7), but not with treatment group
(chi-square=1.64, d.f.=2, P=0.44). The results were comparable at 12, 18 and 24
months and when ratings from the other scales were evaluated. This analysis
confirms that depression is common in persons with MS: the incidence of CES-D
depression in the first 6 months of follow-up was 15.6%. However, no evidence of
increased depressive symptomatology was observed in association with interferon
beta-1a (Rebif).

Publication Types:
    Clinical Trial
    Controlled Clinical Trial
    Multicenter Study

PMID: 11548984 [PubMed - indexed for MEDLINE]

16: Arch Neurol  2001 Jul;58(7):1081-6 

Treatment of depression is associated with suppression of nonspecific and
antigen-specific T(H)1 responses in multiple sclerosis.

Mohr DC, Goodkin DE, Islar J, Hauser SL, Genain CP.

Department of Psychiatry, University of California, San Francisco, USA.

OBJECTIVE: To examine the relationship between depression, treatment of
depression, and interferon gamma (IFN-gamma) production by peripheral blood
mononuclear cells in patients with comorbid diagnoses of relapsing-remitting
multiple sclerosis (MS) and major depressive disorder. DESIGN: A randomized
comparative outcome trial of three 16-week treatments for depression.
Assessments were conducted at baseline, week 8, and treatment cessation.
SETTING: An academic outpatient treatment and clinical research center.
PATIENTS: Fourteen patients who met the criteria for relapsing-remitting MS and
major depressive disorder. INTERVENTIONS: Individual cognitive behavioral
therapy, group psychotherapy, or sertraline therapy. MAIN OUTCOME MEASURES:
Depression was assessed using the Beck Depression Inventory. Interferon gamma
production by peripheral blood mononuclear cells was measured following
stimulation with OKT3 or recombinant human myelin oligodendrocyte glycoprotein
(MOG). Variability in immune assays was controlled using 8 nondepressed healthy
subjects who were enrolled at times corresponding with the enrollment of MS
patients. RESULTS: Results of the Beck Depression Inventory were significantly
related to IFN-gamma production stimulated with OKT3 or MOG at baseline (P< or =
.03 for all). Level of depression, OKT3-stimulated IFN-gamma production, and
MOG-stimulated IFN-gamma production all declined significantly over the 16-week
treatment period (P< or = .03 for all). Among controls, there were no
significant changes over time in OKT3- or MOG-stimulated IFN-gamma, or in
depression (P> or = .25 for all). CONCLUSIONS: These findings suggest that the
production of the proinflammatory cytokine IFN-gamma by autoaggressive T cells
in relapsing-remitting MS is related to depression and that treatment of
depression may decrease IFN-gamma production. Thus, treatment of depression may
provide a novel disease-modifying therapeutic strategy as well as a symptomatic
treatment for patients with MS.

Publication Types:
    Clinical Trial
    Randomized Controlled Trial

PMID: 11448297 [PubMed - indexed for MEDLINE]

17: J Neurol  2001 May;248(5):416-21 

Depression and anxiety in multiple sclerosis. A clinical and MRI study in 95

Zorzon M, de Masi R, Nasuelli D, Ukmar M, Mucelli RP, Cazzato G, Bratina A,
Zivadinov R.

Department of Radiology, University of Trieste, Italy.

The aim of the present study was to investigate the relationship between
involvement of specific areas of the brain and the occurrence of depression and
anxiety in patients with multiple sclerosis. We studied 95 patients (62 women
and 33 men, mean age 39.5 years, SD 11.2) with definite MS, 97 patients (65
women and 32 men, mean age 40.7, SD 11.9) suffering from chronic rheumatoid
diseases and 110 healthy subjects (71 women and 39 men, mean age 40.1, SD 12.7).
The disability, the independence, the cognitive performances, the depressive and
anxiety symptoms were assessed. The diagnosis of major depression was made
according to the DSM-IV. The patients with multiple sclerosis underwent a 1.5
Tesla magnetic resonance examination including T1 and T2 weighted images.
Calculation of regional and total lesion loads and brain volumes were performed.
The number (%) of subjects with a diagnosis of major depression was 18 (18.9)
among MS cases, 16 (16.5) among controls with chronic disease (p=NS), and 4
(3.6) among healthy volunteers (p < 0.0001). The Hamilton Depression and Anxiety
rating scales median scores were 5 and 18, respectively in the MS patients, 5
(p= NS) and 14 (p= NS) in the chronic rheumatoid diseases controls, and 3 (p= <
0.0001) and 6 (p= < 0.0001) in the healthy controls. Both severity of depressive
symptoms and diagnosis of major depression correlated, albeit weakly, with right
frontal lesion load (r=0.22, p=0.035, and r=0.23, p=0.026, respectively) and
right temporal brain volume (r=0.22, p=0.005 and r=0.22, p=0.036, respectively).
The severity of depression was related significantly also with total temporal
brain volume (r=0.26, p=0.012), right hemisphere brain volume (r=0.25, p=0.015),
disability (r=0.30, p=0.003) and independence of MS cases (r=-0.26, p=0.01). The
anxiety did not correlate significantly with any of the measures of regional and
total lesion loads and brain volume or with any of the considered clinical
variables. The similar frequency of depression and severity of depressive
symptoms in MS patients and in chronic disease patients, the significant
difference in this respect with the normal controls, and the significant
correlation between depression and the disability measures would suggest a
psychological reaction to the impact of the disease but the relationship between
depression and the alterations in the frontal and temporal lobes of the right
hemisphere supports, on the contrary, the causative role of organic brain
damage. The lack of any significant association between symptoms of anxiety and
either MRI abnormalities or clinical variables led us to the opinion that
anxiety is a reactive response to the psychosocial pressure put on the patients.

PMID: 11437165 [PubMed - indexed for MEDLINE]

18: Mult Scler  2001 Apr;7(2):131-5 

The relation between objective and subjective impairment in cognitive function
among multiple sclerosis patients--the role of depression.

Maor Y, Olmer L, Mozes B.

Center for the Study of Clinical Reasoning, Gertner Institute for Epidemiology
and Health Policy Research, Sackler School of Medicine, Tel Aviv University,
Sheba Medical Center, Tel Hashomer, Israel.

OBJECTIVE: To evaluate the relations between perceived cognitive function and
objective cognitive deficit and to assess variables affecting perceived
cognitive function among multiple sclerosis (MS) patients. METHODS: A cross
sectional study of patients with MS. All patients were interviewed and the
Expanded Disability Status Scale (EDSS) score was determined. The dependent
variables were four items assessing perceived concentration and thinking,
attention, memory, and whether others have noticed memory or concentration
problems. The explanatory variables were age, sex, duration of disease, number
of relapses in the last 2 years, EDSS score, depressive symptoms score (CES-D)
and the domains of the Neurobehavioral Cognitive Status Examination (NCSE)
assessing cognitive performance. Bivariate and then multivariate analysis were
performed. RESULTS: One hundred and sixty-one MS patients were included. Mean
age was 44.2 years (s.d. 11.3 years), mean EDSS score was 4.86 (s.d. 1.93).
Seventy-two per cent of the patients had objective cognitive impairment and 51%
reported decreased perceived cognitive function. In all models assessing
perceived cognitive function we could explain only a small part of the variance
(R2 ranged between 18-26%). In all these models depressive symptoms explained
the highest portion of the variance (partial R2 ranging between 13-26%). The
only domain of the NCSE that entered some of the models was calculation (partial
R2 ranging between 3-7%). CONCLUSIONS: These findings emphasize the gap between
objective and subjective assessment of cognitive function and the high
correlation between perceived cognitive deficit and depressive symptoms.

PMID: 11424633 [PubMed - indexed for MEDLINE]

19: Psychiatry Res  2000 Oct 30;99(3):151-9 

Beck Depression Inventory factors related to demyelinating lesions of the left
arcuate fasciculus region.

Pujol J, Bello J, Deus J, Cardoner N, Marti-Vilalta JL, Capdevila A.

Magnetic Resonance Center of Pedralbes, Monestir, 3, 08034, Barcelona, Spain.

This study was conducted to further establish the significance of the previously
reported association between depressive symptoms and demyelinating lesions in
the region of the left arcuate fasciculus in multiple sclerosis patients. The
Beck Depression Inventory (BDI) was broken down into its main symptom categories
on the basis of well-established factor analyses from the literature, and the
correlation pattern between the resulting BDI subscores and lesion measurements
was analyzed. We found that lesions of the left arcuate fasciculus region were
selectively associated with BDI items expressing patients' Affective Symptoms
and Somatic Complaints. Specifically, lesion measurements from this brain
location accounted for 26% of symptom score variance of the BDI part that
includes only these two factors. Performance Difficulties and Cognitive
Distortions were not consistently associated with the lesion measurement.
Performance Difficulties, however, showed a high correlation with the neurologic
deficit detected in the physical examination. These results show that lesions in
the left arcuate fasciculus region are associated with the core of the
depressive syndrome rather than marginal symptoms and, thus, further suggest
that this left suprainsular brain region involves white matter tracts relevant
to mood regulation.

PMID: 11068196 [PubMed - indexed for MEDLINE]

20: Mult Scler  2000 Oct;6(5):343-8 

Multiple sclerosis, disease modifying treatments and depression: a critical
methodological review.

Feinstein A.

Department of Psychiatry, Sunnybrook and Women's College Health Science Centre,
Room FG38, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5.

BACKGROUND: Major depression affects one in two patients with multiple sclerosis
(MS) during the course of their lifetime. This adds to the morbidity associated
with the disorder and may contribute to an increased mortality rate because of
suicide. Over the past few years, with the advent of disease modifying
treatments for MS, a new concern with respect to mood has arisen, namely the
possibility that some of these drugs may have depression as a clinically
significant side effect. OBJECTIVE: To ascertain whether disease modifying
treatments in MS are associated with the development of depression or the
worsening of a depressive illness. METHODOLOGY: A MEDLINE and PSYCHLIT search
focusing on depression and disease modifying treatments going back to 1993 (the
publication date of the results of the first randomised, placebo controlled
trial). The methodology pertaining to the assessment of depression is critically
reviewed. Furthermore, a critical summary is provided of treatment modalities
for the depressed MS patient. RESULTS: There are conflicting data that
depression may occur with some disease modifying drugs, particularly interferon
beta-1b. However, all studies reveal limitations with respect to the assessment
of mood. Some reports, despite omitting details of how mentation was assessed,
still comment on the presence or absence of depression. Others suffer from one
or more of the following shortcomings: a failure to assess premorbid risk
factors for mood disorder; a reliance on one question to assess depression; the
utilisation of self report mood rating scales of questionable validity;
neglecting to distinguish depression as a symptom from depression as a syndrome
(i.e. major depression as defined by the DMS-1V). CONCLUSIONS: Given the many
methodological pitfalls inherent in all studies to date, it is premature to
conclude that disease modifying drugs are associated with depression. Evidence
suggests that treatment of depression, irrespective of a putative association
with a disease modifying agent, is frequently effective. This applies to
pharmacotherapy or psychotherapy, although the former may be preferred should
depression arise during a course of treatment with a disease modifying agent.
Multiple Sclerosis (2000) 6 343 - 348

Publication Types:
    Review Literature

PMID: 11064445 [PubMed - indexed for MEDLINE]

21: Mult Scler  2000 Jun;6(3):156-62 

Lesion pattern in patients with multiple sclerosis and depression.

Berg D, Supprian T, Thomae J, Warmuth-Metz M, Horowski A, Zeiler B, Magnus T,
Rieckmann P, Becker G.

Department of Neurology, Bayerische Julius-Maximilians-Universitat Wurzburg,

To assess if a specific lesion pattern or changes of the basal limbic system as
seen in primary depression and depression associated with neurodegenerative
disorders might be identified in depressive multiple sclerosis (MS) patients, we
submitted 78 MS patients to a MRI examination consisting of a quantitative
measurement of lesions and of hyperintense signals from the pontomesencephalic
midline (raphe). Furthermore relaxometry of the pontomesencephalic midline, a
transcranial ultrasound examination rating its echogenicity semiquantitatively
and a standardized neurological, neuropsychiatric and neuropsychological
assessment were obtained. Thirty-one patients fulfilled the DSM-IV criteria for
depression. Depressed MS patients had a significantly larger temporal lesion
load than non-depressed MS patients, especially on the right side. A trend of
difference was detected for lesions of the right parietal lobe, the right
frontal lobe, the cerebellum and the total lesion load. Neither hyperintense
signals or relaxometry nor echogenicity of the region at the level of the
pontomesencephalic midline were significantly different between the groups. We
conclude that depression in MS patients is not associated with an alteration of
the basal limbic system at the brainstem as seen in Parkinson's disease or
unipolar depression but with an increased lesion load of the projection areas of
the basal limbic system.

PMID: 10871826 [PubMed - indexed for MEDLINE]

22: J Neurovirol  2000 May;6 Suppl 2:S160-7 

Mood disorders in multiple sclerosis: diagnosis and treatment.

Minden SL.

Brigham and Women's Hospital, Division of Psychiatry, 75 Francis Street, Boston,
Massachusetts, MA 02115, USA.

Emotional disturbances are common in MS and consist of disturbances of mood and
disturbances of affect. The important mood disorders are major depressive
disorder, dysthymic disorder, bipolar disorder, panic disorder, and generalized
anxiety disorder. Their relationship to MS is multi-factorial and complex, and
the extent to which they are direct consequences of the disease process or
psychological reactions to it remains unclear. Whatever their cause, however,
the symptoms of mood disorders in people with MS are no different from the
symptoms of mood disorders in people without MS, and respond just as well to
standard treatments. The disorders of affect are euphoria, pathological laughing
and weeping, and other frontal lobe syndromes. These disorders result from
demyelination, are some of the most characteristic symptoms of MS, and have the
same implications for treatment as do other aspects of the disease. Mood and
affective disturbances can cause enormous pain and suffering and lead to
significant disruption of family, work, and social life. Physicians who can
identify, diagnose, treat, and manage mood and affective disturbances
effectively and who can help their patients and family members acknowledge these
difficulties, talk about them, and accept psychiatric consultation and treatment
can have a dramatic impact on the quality of their lives. This paper outlines
the symptoms and diagnostic criteria for mood disorders and affective
disturbances, reviews current treatment options, summarizes data from
epidemiologic and pathophysiological studies, and suggests areas for future

Publication Types:
    Review Literature

PMID: 10871806 [PubMed - indexed for MEDLINE]

23: J Consult Clin Psychol  2000 Apr;68(2):356-61 

Telephone-administered cognitive-behavioral therapy for the treatment of
depressive symptoms in multiple sclerosis.

Mohr DC, Likosky W, Bertagnolli A, Goodkin DE, Van Der Wende J, Dwyer P, Dick

Department of Neurology, University of California, San Francisco (UCSF)
94115-1642, USA.

This study examined the efficacy of an 8-week telephone-administered
cognitive-behavioral therapy (CBT) for the treatment of depressive
symptomatology in multiple sclerosis (MS) patients. The treatment, Coping with
MS (CMS), included a patient workbook designed to structure the treatment,
provide visual aids, and help with homework assignments. Thirty-two patients
with MS, who scored at least 15 on the Profile of Mood States
Depression-Dejection scale, were randomly assigned to either the telephone CMS
or to a usual-care control (UCC) condition. Depressive symptomatology decreased
significantly in the CMS condition compared with the UCC condition. Furthermore,
adherence to interferon beta-1a, a disease-modifying medication for the
treatment of MS, was significantly better at the 4-month follow-up among
patients who received CMS as compared with those in the UCC condition.

Publication Types:
    Clinical Trial
    Randomized Controlled Trial

PMID: 10780138 [PubMed - indexed for MEDLINE]

24: Mult Scler  2000 Apr;6(2):115-20 

Biopsychosocial correlates of lifetime major depression in a multiple sclerosis

Patten SB, Metz LM, Reimer MA.

Department of Community Health Sciences, Faculty of Medicine, University of
Calgary, 3330 Hospital Drive NW Calgary, Alberta T2N 4N1, Canada.

The objective of this paper was to evaluate the lifetime and point prevalence of
major depression in a population-based Multiple Sclerosis (MS) clinic sample,
and to describe associations between selected biopsychosocial variables and the
prevalence of lifetime major depression in this sample. Subjects who had
participated in an earlier study were re-contacted for additional data
collection. Eighty-three per cent (n=136) of those eligible consented to
participate. Each subject completed the Composite International Diagnostic
Interview (CIDI) and an interviewer-administered questionnaire evaluating a
series of biopsychosocial variables. The lifetime prevalence of major depression
in this sample was 22.8%, somewhat lower than previous estimates in MS clinic
populations. Women, those under 35, and those with a family history of major
depression had a higher prevalence. Also, subjects reporting high levels of
stress and heavy ingestion of caffeine (>400 mg) had a higher prevalence of
major depression. As this was a cross-sectional analysis, the direction of
causal effect for the observed associations could not be determined. By
identifying variables that are associated with lifetime major depression, these
data generate hypotheses for future prospective studies. Such studies will be
needed to further understand the etiology of depressive disorders in MS.

PMID: 10773857 [PubMed - indexed for MEDLINE]

25: Clin Rehabil  2000 Feb;14(1):50-4 

The role of affect on the perception of disability in multiple sclerosis.

Smith SJ, Young CA.

Department of Neuroscience, University of Liverpool, UK.

OBJECTIVE: To determine the prevalence of depression in multiple sclerosis in
the community and to assess how the presence of depression affects patients'
perception of their disability. DESIGN: Consecutive case series. SETTING: The
study was carried out at a regional multiple sclerosis (MS) clinic. SUBJECTS:
Eighty-eight patients with MS. MAIN OUTCOME MEASURES: Patients were asked to
complete the following questionnaires: Hospital Anxiety and Depression Scale
(HADS), Beck Depression Inventory (BDI), Rankin Scale of Disability/Handicap
(completed by patient and physician to assess relative perceived disability) and
two visual analogue scales (coping ability and perceived service adequacy).
RESULTS: Thirty-nine per cent were case level for depression using the BDI
criteria of Sullivan; 17% were case level for depression (34% borderline case)
and 34% case level for anxiety on HADS. Depressed patients using both BDI and
HADS criteria were three times more likely than nondepressed patients to
perceive their disability as being greater than the physicians' perception (p <
0.001). CONCLUSION: Depression is common in MS and adversely affects patients'
perception of their disability.

PMID: 10688344 [PubMed - indexed for MEDLINE]

26: J Clin Exp Neuropsychol  2000 Feb;22(1):125-31 

Autobiographical memory, depression and quality of life in multiple sclerosis.

Kenealy PM, Beaumont GJ, Lintern T, Murrell R.

School of Psychology, Roehampton Institute London, Putney, London, United

The relationship between autobiographical memory, depression and quality of life
(QoL) was investigated in a study of 30 persons with severe neurodisability
resulting from multiple sclerosis. Sixty percent (n = 18) of patients were found
to have deficits in autobiographical memory (AMI) for incidents in their earlier
life; these deficits were associated with significant impairments in personal
semantic memory of facts from their past life. Patients with impaired
autobiographical memory who had been diagnosed for longer than 21 years reported
significantly better QoL (SF-36: Role Physical) than those diagnosed more
recently, or those with normal autobiographical memory; patients who had been
diagnosed for longer were also significantly less depressed than patients
diagnosed more recently. Patients with normal autobiographical memory reported
the highest levels of depression (HADS) and the lowest levels of QoL (Role
Physical). It is concluded that impairment of autobiographical memory affects
perception of QoL; patients with deficits in autobiographical memory had
impaired knowledge about their past QoL and may therefore be unable to make
valid comparative judgements about the quality of their present life.

PMID: 10649551 [PubMed - indexed for MEDLINE]

27: Neuropsychology  1999 Jul;13(3):434-46 

Depressed mood in multiple sclerosis: relationship to capacity-demanding memory
and attentional functioning.

Arnett PA, Higginson CI, Voss WD, Wright B, Bender WI, Wurst JM, Tippin JM.

Department of Psychology, Washington State University, Pullman 99164-4820, USA.

Because it is theorized that depression results in reduced available attentional
capacity that, in turn, can explain the impaired performance on
capacity-demanding tasks in depressed individuals, the authors predicted that
multiple sclerosis (MS) patients with depressed mood would have difficulty with
these types of tasks. Twenty depressed mood MS participants were compared with
41 nondepressed mood MS participants and 8 nondepressed mood controls on 5
attentional capacity-demanding clinical memory and attentional tasks and 3 tasks
with minimal capacity demands. Depressed mood MS patients performed
significantly worse than both nondepressed mood groups on the 3 speeded
capacity-demanding attentional measures but not on any of the tasks requiring
few capacity demands, supporting the authors' predictions. The possibility that
the impaired performance of depressed mood MS patients on speeded attentional
tasks was mediated by reduced verbal working memory capacity, impaired
deployment of executive strategies that access working memory capacity, or
psychomotor slowing is explored.

PMID: 10447304 [PubMed - indexed for MEDLINE]

28: Lik Sprava  1999 Mar;(2):91-3 

[The characteristics of the psychoemotional disorders in multiple sclerosis
patients studied by using the method of the multiphasic personality inventory]

[Article in Ukrainian]

Mialovyts'ka OA, Gulkevych OV, Lembers'ka OP.

A total of 57 patients with multiple sclerosis (MS) who ranged from 15 to 58
years old (18 male patients, 39 female patients) were studied together with 10
essentially healthy persons (control group). Psychoemotional disorders in MS
patients were described with the aid of the Minnesota Multiphasic Personality
Inventory (MMPI). All MS patients revealed changes in MMPI profile of
personality. There were higher T-scores on the first, second, as well as sixth,
seventh, and eighth scales. During the initial stages of the illness there
prevail neurosis-like symptomatology presenting as depressive-hypochondriac
syndrome. The degree of the pathological process in MS makes for aggravation of
disorders in the psychoemotional sphere. During the advanced stages of the
malady there occur autism, attempts at isolating oneself, disruption of
interpersonal connections.

PMID: 10424053 [PubMed - indexed for MEDLINE]

29: J Behav Med  1999 Apr;22(2):127-42 

Assessing depressive symptoms in multiple sclerosis: is it necessary to omit
items from the original Beck Depression Inventory?

Aikens JE, Reinecke MA, Pliskin NH, Fischer JS, Wiebe JS, McCracken LM, Taylor

Department of Psychiatry, University of Chicago Medical Center, Illinois 60637,

Overlap between depression scale item content and medical symptoms may
exaggerate depression estimates for patients with multiple sclerosis (MS). We
reconsider Mohr and co-workers' (1997) recommendation to omit Beck Depression
Inventory (BDI) items assessing work ability (item 15), fatigue (17), and health
concerns (20) for MS patients. Subjects were medical patients with either MS (n
= 105) or a medical disorder for which the BDI is empirically supported
[diabetes mellitus (DM), n = 71; chronic pain (CP), n = 80], psychiatric
patients with depressive disorder (MDD; n = 37), and healthy controls (HC; n =
80). Relative scores for the eight "somatic" BDI items were analyzed by
multivariate analysis of variance with demographic variables and BDI total as
covariates. The only significant difference was MS > HC (item 15). On raw
scores, MS patients exceeded HCs on items 15 and 21 (sexual disinterest), but
this was attributable to the low HC item endorsement. There were no other
differences on somatic items or item-total correlations. Scale consistency was
good across groups, regardless of item omission. Somatic items were unassociated
with major MS parameters. We thus encourage continued application of the full
BDI for assessing depressive symptoms in patients with MS.

Publication Types:
    Clinical Trial
    Controlled Clinical Trial

PMID: 10374139 [PubMed - indexed for MEDLINE]

30: J Neuropsychiatry Clin Neurosci  1999 Spring;11(2):271-3 

Moclobemide treatment in multiple sclerosis patients with comorbid depression:
an open-label safety trial.

Barak Y, Ur E, Achiron A.

Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Israel.

Depression is common in multiple sclerosis (MS) patients, but tricyclic
compounds are not well tolerated and newer antidepressants have not been
studied. Effects of 150-400 mg/day of moclobemide, a reversible monoamine
oxidase A inhibitor, were studied in a 3-month open design in 10 MS patient with
DSM-IV-diagnosed depression. Nine patients reached complete remission. No
adverse effects were noted. Four patients reported side effects including nausea
and insomnia. The authors conclude that moclobemide is a well tolerated and
efficient treatment for depression comorbid with MS.

Publication Types:
    Clinical Trial

PMID: 10334000 [PubMed - indexed for MEDLINE]

31: Pharmacopsychiatry  1999 Mar;32(2):47-55 

Possible use of amantadine in depression.

Huber TJ, Dietrich DE, Emrich HM.

Department of Clinical Psychiatry, Medical School of Hanover, Germany.

Amantadine, originally used in the treatment and prophylaxis of influenza
infection, has also proved beneficial in drug-induced Parkinsonism, Parkinson's
disease, traumatic head injury, dementia, multiple sclerosis and cocaine
withdrawal. Amantadine appears to act through several pharmacological
mechanisms, none of which has been identified as the one chief mode of action.
It is a dopaminergic, noradrenergic and serotonergic substance, blocks
monoaminoxidase A and NMDA receptors, and seems to raise
beta-endorphin/beta-lipotropin levels. However, it is still uncertain which of
these actions are relevant in therapeutic doses. One new aspect is the antiviral
effect of amantadine on Borna disease virus, which it is suspected may possibly
play a role in affective disorders. All of these actions could constitute an
antidepressant property, and it is suggested that amantadine might work as an
antidepressant not through one, but through several mechanisms thought to be
related to antidepressant activity. Effects of amantadine on symptoms of
affective disorders have been demonstrated in several trials administering it
for varying purposes. Additionally, animal studies as well as clinical trials in
humans have hinted at an antidepressant activity of amantadine. We present here
an overview of the current data. However, only a limited body of evidence is
available, and further studies are needed to investigate the efficacy of
amantadine as well as its modes of action in depression.

Publication Types:
    Review, Academic

PMID: 10333162 [PubMed - indexed for MEDLINE]

32: Encephale  1999 Jan-Feb;25(1):78-85 

[determining factors of depression in multiple sclerosis: review of the

[Article in French]

Even C, Lafitte C, Etain B, Dardennes R.

Clinique des Maladies Mentales et de l'Encephale, CH Sainte-Anne, Paris.

Depression is considered to occur more frequently in multiple sclerosis than in
other chronic organic disorders. The determining factors of this specific
association have been appraised by most authors in a dichotomic manner,
confronting organic to psychogenic hypotheses. To assess these hypotheses two
investigational methods have been used in the literature: either the search for
correlations between depression and other parameters linked to the neurologic
process, or the comparison of the course of neurologic and thymic symptoms.
Systematically scrutinizing this literature enabled us to discuss its findings
as well as its methodologic and conceptual limitations.

Publication Types:
    Review, Tutorial

PMID: 10205738 [PubMed - indexed for MEDLINE]

33: J Neuropsychiatry Clin Neurosci  1999 Winter;11(1):51-7 

Neuropsychiatric manifestations of multiple sclerosis.

Diaz-Olavarrieta C, Cummings JL, Velazquez J, Garcia de la Cadena C.

Laboratory of Experimental Psychology, National Institute of Neurology and
Neurosurgery of Mexico, Mexico City, Mexico.

The range of neuropsychiatric symptoms in multiple sclerosis (MS) has not been
prospectively assessed. The authors, working at a tertiary medical center in
Mexico City, used the Neuropsychiatric Inventory (NPI) to evaluate
neuropsychiatric symptoms prospectively in 44 MS patients who were stable
between relapses and 25 control subjects of similar age, education, and
cognitive function. Neuropsychiatric symptoms were present in 95% of patients
and 16% of control subjects. Changes present were depressive symptoms (79%),
agitation (40%), anxiety (37%), irritability (35%), apathy (20%), euphoria
(13%), disinhibition (13%), hallucinations (10%), aberrant motor behavior (9%),
and delusions (7%). The only relationships with MRI were between euphoria and
hallucinations and moderately severe MRI abnormalities. The authors conclude
that diverse types of neuropsychiatric symptoms are common in MS; symptoms are
present between exacerbations; and there are variable correlations with MRI

PMID: 9990556 [PubMed - indexed for MEDLINE]

34: Can J Neurol Sci  1998 Aug;25(3):230-5 

Hospital-based psychiatric service utilization and morbidity in multiple

FisK JD, Morehouse SA, Brown MG, Skedgel C, Murray TJ.

Department of Psychology, Queen Elizabeth II Health Sciences Centre, Halifax,
Nova Scotia, Canada.

BACKGROUND: Despite the common association of psychiatric morbidity and multiple
sclerosis (MS), population-based prevalence estimates of these disorders are
limited. Such estimates are of particular importance to those conducting trials
of interventions for the treatment of MS. This study examined the prevalence of
bipolar disorder, depression, and attempted suicide among hospital service
utilizers in Nova Scotia and compared these measures for the MS and non-MS
population. METHODS: Data regarding diagnosis and utilization were extracted
from two linked databases which included all hospital separation records for
Nova Scotia over a 3 year period (1992/93-1994/95). RESULTS: The prevalence of
bipolar disorder in hospitalized MS patients was 1.97% and depression was 4.27%.
These rates were significantly higher than the 0.92% and 2.04%, respectively,
for the non-MS hospital utilizers. These diagnoses also accounted for more than
half of the primary diagnostic codes for psychiatric service separations by MS
patients. The proportion of total hospital utilization which was accounted for
by psychiatric services did not differ between MS and non-MS utilizers. While
suicide attempts were rare, the estimated frequency of suicide attempts in the
total MS population was more than three times that of the general population.
CONCLUSIONS: Bipolar disorder and depression were twice as prevalent in
hospitalized MS patients as in the general population of hospital utilizers
while the estimated frequency of suicide attempts was at least three times
greater. These results illustrate that psychiatric morbidity and service
utilization are important considerations in the care of MS patients.

PMID: 9706725 [PubMed - indexed for MEDLINE]

35: J Behav Med  1997 Oct;20(5):433-45 

A replicated prospective investigation of life stress, coping, and depressive
symptoms in multiple sclerosis.

Aikens JE, Fischer JS, Namey M, Rudick RA.

Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic
Foundation, USA.

Life stress and coping responses jointly contribute to psychological adjustment
in many chronic illness populations, but their significance in multiple
sclerosis (MS) has not been extensively investigated. Physical disability,
cognitive status, negative life stress, coping strategies, and depressive
symptoms were prospectively assessed in 27 adults with definite or probable MS.
Of the original subjects, 22 provided two additional assessments at 6-month
intervals. After accounting for cognitive status and physical disability, life
stress was positively correlated with current as well as future depressive
symptoms; the prospective relationship was replicated within the second pair of
prospective data waves. Escape avoidance was the only coping strategy that added
to the prediction of future mood symptoms, but this was not replicated. Results
suggest that MS-related depressive symptoms are a function of prior
disease-related impairment, life stress, and possibly escape avoidance coping.

PMID: 9415854 [PubMed - indexed for MEDLINE]

36: Psychother Psychosom  1997;66(6):286-92 

Depression in multiple sclerosis.

Patten SB, Metz LM.

Alberta Heritage Foundation for Medical Research, Department of Community Health
Sciences, Canada.

BACKGROUND: An association between multiple sclerosis (MS) and depression has
been recognized for several decades and has attracted considerable attention in
research. However, there are considerable gaps in the current state of
knowledge. In this review, the literature concerned with: (1) the burden of
depression in MS; (2) the etiology of depression in MS, and (3) the treatment of
depression in MS are critically examined. METHOD: The literature review utilized
Medline (1966-1996), and was supplemented by citations extracted from the papers
originally uncovered. RESULTS: Numerous studies have identified elevated
depressive symptom scores in MS patients relative to nonclinical and (some)
clinical control groups. Furthermore, studies of depressive disorders have
clearly documented elevated prevalence rates in MS samples. The literature does
not identify any specific pattern of neurological involvement as being
consistently associated with depressive symptoms or disorders. Psychosocial risk
factors contribute to the etiology of depression in MS, but the relative
importance of various risk factors is yet to be determined. A single randomized
controlled clinical trial, and additional anecdotal evidence, suggests that
antidepressant pharmacotherapy is effective for depressive disorders in MS.
CONCLUSIONS: Future epidemiological studies should not restrict their evaluation
of risk factors to those specific factors that are closely related to the
disease process. In particular, future researchers should resist the temptation
to focus too exclusively on neuropathology. Biological, psychological and social
risk factors are all potentially important. Additional empirical efforts to
refine the various treatment approaches would be a welcome addition to this

Publication Types:
    Review, Tutorial

PMID: 9403917 [PubMed - indexed for MEDLINE]

37: Mult Scler  1995 Jun;1(2):104-8 

Depression before and after diagnosis of multiple sclerosis.

Sullivan MJ, Weinshenker B, Mikail S, Edgley K.

Department of Psychology, Dalhousie University, Nova Scotia, Canada.

Depression was examined in 45 patients evaluated within 2 months of diagnosis of
MS. At the time of testing, 40% of the MS sample met the diagnostic criteria for
major depression, 22% had adjustment disorder with depressed mood and 37% showed
no evidence of mood disorder. Personal and family history of depression in
patients with MS was also examined and compared with a sample of patients with
chronic low back pain (CLBP) who were matched for age, gender, marital and
employment status and current level of depression. Fifty-two per cent of
patients with MS reported experiencing a depressive episode before the onset of
MS compared with 17% of patients with CLBP (P < 0.001). Sixteen patients with MS
(35%) reported family history (parent or sibling) of treatment for depression
compared with seven (15%) of patients with CLBP (P < 0.05). MS patients with a
history of depression reported more initial symptoms than MS patients without a
history of depression. Clinical and theoretical implications of the findings are

PMID: 9345460 [PubMed - indexed for MEDLINE]

38: Neurology  1997 Oct;49(4):1105-10 

Lesions in the left arcuate fasciculus region and depressive symptoms in
multiple sclerosis.

Pujol J, Bello J, Deus J, Marti-Vilalta JL, Capdevila A.

Magnetic Resonance Center of Pedralbes, Creu Roja Hospital, Hospitalet de
Llobregat, Barcelona, Spain.

Depression is a common mood disturbance in multiple sclerosis (MS) patients.
Epidemiologic data suggest a causative relationship between depressive symptoms
and cerebral demyelination, although a specific lesion site responsible for
depressed mood has not been identified. Given that depression in neurologic
disease is closely related to frontal and temporal lobe damage, we focused our
study on investigating the extent to which lesions in the white matter
connecting both cerebral lobes may account for depressive symptoms in MS.
Forty-five patients were assessed using the Beck Depression Inventory and an MRI
protocol conceived to quantify lesions separately in the basal, medial, and
lateral frontotemporal white matter. The presence of lesions in the left
suprainsular white matter, the region that mainly includes the arcuate
fasciculus, was specifically associated with depressive symptoms, accounting for
a significant 17% of the depression score variance. Although a multifactorial
origin is suspected for depression in MS, this finding gives support to the
existence of a direct negative effect of demyelination on mood.

PMID: 9339697 [PubMed - indexed for MEDLINE]

39: J Behav Med  1997 Aug;20(4):407-14 

Identification of Beck Depression Inventory items related to multiple sclerosis.

Mohr DC, Goodkin DE, Likosky W, Beutler L, Gatto N, Langan MK.

UCSF/Mt. Zion MS Center 94115-1642, USA.

The percentage contribution of each item on the Beck Depression Inventory (BDI)
to the total BDI score was compared across patients with multiple sclerosis
(MS), patients diagnosed with major depressive disorder, and normal college
students. We considered an item to be confounded by MS-related symptoms if its
percentage contribution to the total BDI score was significantly greater in the
MS group than the major depression and control groups. Items measuring work
difficulty, fatigue, and concerns about health met this criterion. These items
accounted for 34, 17, and 19% of the total BDI score in the MS, major
depression, and control groups, respectively. Using the 18-item BDI (BDI-18)
which resulted from excluding the 3 confounded items, MS patients found to be
were more depressed than controls but less depressed than the major depression
group. The identification of signs of depression not confounded with MS which
could be substituted for confounded signs was also discussed.

PMID: 9298438 [PubMed - indexed for MEDLINE]

40: Can J Psychiatry  1996 Sep;41(7):441-5 

Comment in:
     Can J Psychiatry. 1997 Apr;42(3):324-5.

Psychiatric manifestations of multiple sclerosis: a review.

Rodgers J, Bland R.

Department of Psychiatry, University of Alberta, Edmonton.

OBJECTIVE: To report the occurrence, type, causes, and management of psychiatric
manifestations in multiple sclerosis (MS). METHOD: Review of recent, relevant
literature. RESULTS: Psychiatric illness, especially depression, occurs much
more frequently than expected in patients with MS, is frequently unrecognized or
ignored, and is treatable using standard methods, although patients with MS may
be unusually sensitive to side effects of tricyclic antidepressants.
CONCLUSIONS: Research is needed to better define the causes of psychiatric
syndromes in patients with MS. Those treating MS should increase their awareness
of and sensitivity to the likelihood of psychiatric disorder in these patients.

Publication Types:
    Review, Tutorial

PMID: 8884033 [PubMed - indexed for MEDLINE]

41: J Affect Disord  1996 Jun 20;39(1):21-30 

Depression in fatiguing illness: comparing patients with chronic fatigue
syndrome, multiple sclerosis and depression.

Johnson SK, DeLuca J, Natelson BH.

Chronic Fatigue Syndrome Center, University of Medicine and Dentistry of New
Jersey--New Jersey Medical School, West Orange, USA.

Because depression is commonly observed in the chronic fatigue syndrome (CFS),
the present study sought to determine whether the symptom pattern is similar to
that seen in clinically depressed subjects (DEP). Individuals with multiple
sclerosis (MS) were chosen as an additional comparison group because MS is a
fatiguing illness of known organic etiology. The Beck Depression Inventory (BDI)
was used to compare categories of depressive symptomatology. Absolute scores on
the BDI were higher for the depressed group on mood and self-reproach symptoms,
but were not higher than the CFS group on somatic and vegetative items. Analysis
of symptoms as a percentage of total BDI score revealed no significant
differences in mood or vegetative items among the three groups. The CFS and MS
groups exhibited a significantly lower percentage of self-reproach symptoms than
DEP, whereas the DEP group showed a lower percentage of somatic symptoms than
the CFS and MS groups.

PMID: 8835650 [PubMed - indexed for MEDLINE]

42: Biol Psychiatry  1996 Jun 1;39(11):970-5 

Involvement of the limbic system in multiple sclerosis patients with depressive

Sabatini U, Pozzilli C, Pantano P, Koudriavtseva T, Padovani A, Millefiorini E,
Di Biasi C, Gualdi GF, Salvetti M, Lenzi GL.

First Neuroradiology Unit, University La Sapienza, Rome, Italy.

This study investigates the relationship between depression and both anatomic
and cerebral blood flow abnormalities in multiple sclerosis (MS) patients. Ten
nondepressed MS patients were compared with 10 depressed MS patients matched for
age, sex, and functional disability. Both groups were evaluated by means of
neuropsychological tests, magnetic resonance imaging, and single-photon emission
tomography imaging. There was no difference between the two groups with regard
to the global cognitive score. Magnetic resonance imaging data showed no
significant differences in the number, side, location, and area of the
demyelinating lesions between the two groups; however, regional cerebral blood
flow asymmetries in the limbic cortex did distinguish the two groups. Analysis
of variance showed a significant effect of depression on the perfusion
asymmetries in the limbic cortex. Finally, perfusion asymmetries in limbic
cortex significantly correlated with depression test scores. Our findings
suggest that depression in MS patients could be induced by a disconnection
between subcortical and cortical areas involved in the function of the limbic

Publication Types:
    Clinical Trial

PMID: 9162210 [PubMed - indexed for MEDLINE]

43: Ital J Neurol Sci  1996 Jun;17(3):189-91 

Multiple sclerosis and psychiatric disturbances: clinical aspects and a review
of the literature.

Giberti L, Croce R, Neri S.

Associazione Italiana Sclerosi Multipla (A.I.S.M.), Centro Servizi Nazionale,
Genova, Italy.

Psychiatric disturbances during the course of multiple sclerosis (MS) may derive
from the particular emotional situation induced by a more or less manifest
awareness of the disease, or be directly attributable to the pathological
process itself. In this latter case, the range of clinical manifestations is
somewhat characteristic, as there is often a concomitant impairment of the
superior nervous functions, particularly those relating to memory and attention.
Interpretation of the role played by affective disorders is particularly
controversial, as it is not possible to establish with precision (and the result
would in any case be a simplistic interpretation of the problem) a direct
relationship between the sites of cerebral lesions and the psychiatric
manifestations observed in MS.

Publication Types:
    Review, Tutorial

PMID: 8856408 [PubMed - indexed for MEDLINE]

44: Psychother Psychosom  1996 Mar-Apr;65(2):86-90 

Risk factors for suicide in multiple sclerosis.

Stenager EN, Koch-Henriksen N, Stenager E.

Clinical Neuropsychiatric Research Unit, Odense University Hospital, Denmark.

BACKGROUND: The purpose of the present study was to identify risk factors for
suicide in patients with multiple sclerosis (MS). METHODS: The study is based on
available information about MS patients identified in the Danish MS Registry
(DMSR) with onset in the period 1950-1985. We compared the MS suicides with the
1950-1985 onset cohort patients in the DSMR as to distribution of age at onset,
presenting symptoms, and time from onset to diagnosis. We reviewed
sociodemographic data, age of onset, the course of the disease, recent
deterioration, type of deterioration, Kurtzke Disability Status Scale (DSS)
score, previous mental disorder, type of mental disorder, previous suicide
attempts, expression of suicidal intentions, circumstances at suicide, and
suicide method for all MS patients who had committed suicide. In order to
characterize MS suicides with respect to risk factors, comparisons were made for
male and female suicides and for various groups of MS suicides according to
disability status. RESULTS: The male suicide patients were characterized by a
tendency to commit suicide in the age interval 40-49 years, by the use of a
violent suicide method, by previous suicidal behaviour, by a previous mental
disorder, by recent deterioration of MS, and by a moderate disability. For women
the characteristics were less distinct. Patients with a severe course of MS had
been subjected to more risk factors before the suicide than patients with a
moderate course of the disease. CONCLUSION: Careful counselling and good
information on all aspects of the disease, especially in the first stages and at
time of progression, could be an instrument of prevention of suicides in MS
patients. Furthermore, recognition and treatment of depression and pain is

PMID: 8711087 [PubMed - indexed for MEDLINE]

45: J Neuropsychiatry Clin Neurosci  1996 Spring;8(2):206-8 

Multiple sclerosis and bipolar disorder: a case report with autopsy findings.

Casanova MF, Kruesi M, Mannheim G.

Medical College of Georgia, Augusta USA.

An 81-year-old woman with postmenopausal onset of a bipolar disorder had
multiple individual manic and depressive episodes over the span of 31 years.
Autopsy disclosed widespread periventricular demyelinated plaques. Although the
late age at onset of bipolar symptoms suggested an underlying organic disorder,
the multiple affective episodes and lack of additional neurological
manifestations make the case atypical. The authors stress the use of modern
imaging modalities such as MRI in investigating secondary mood disorders.

PMID: 9081558 [PubMed - indexed for MEDLINE]

46: J Neuropsychiatry Clin Neurosci  1996 Summer;8(3):318-23 

Characterization of major depression symptoms in multiple sclerosis patients.

Scott TF, Allen D, Price TR, McConnell H, Lang D.

Department of Neurology, Medical College of Pennsylvania, USA.

Retrospective review of affective disturbances in 238 patients with multiple
sclerosis (MS) seen over a 6-month period revealed: 1) 51 patients (22%)
received pharmacologic treatment for depressive symptoms during or within 4
years of the study period, and 17 (7%) received treatment for rapid mood swings;
2) among the 51 depressed patients, response rate to medication was extremely
high; 3) relapse of depressive symptomatology after discontinuation of
medication was also high (17/29); 4) first episodes of major depression
frequently occurred during periods of MS progression or exacerbation, but first
episodes also occurred during periods of relative clinical stability; 5)
suicidal ideation was common (12 patients), but only 1 patient had a history of
attempted suicide; and 6) side effects were tolerable in most patients.

Publication Types:
    Clinical Trial

PMID: 8854304 [PubMed - indexed for MEDLINE]

47: Can J Psychiatry  1995 Dec;40(10):573-6 

Depression associated with multiple sclerosis: an etiological conundrum.

Feinstein A.

Department of Psychiatry, University of Toronto, Ontario.

OBJECTIVE: Although depression frequently occurs in multiple sclerosis (MS), an
association with cerebral pathology is unclear. This sets MS apart from other
common neurological disorders. The reasons for this are explored. METHOD: The
literature on depression and magnetic resonance imaging (MRI) is reviewed and
methodological issues are critically evaluated. RESULTS: Failure to demonstrate
cerebral correlates of depression is in part a function of poor study design.
However, the diffuse nature of cerebral demyelination creates difficulties in
image analysis peculiar to MS. CONCLUSIONS: More research using valid
psychiatric assessment procedures, high field strength MRI and automated lesion
detection is needed to resolve the issue. It is premature to reject psychosocial
causes at this stage.

Publication Types:
    Review, Tutorial

PMID: 8681253 [PubMed - indexed for MEDLINE]

48: Neurol Res  1995 Dec;17(6):421-2 

Measurement of treatment response to sertraline in depressed multiple sclerosis
patients using the Carroll scale.

Scott TF, Nussbaum P, McConnell H, Brill P.

Medical College of Pennsylvania, Allegheny General Hospital Pittsburgh, USA.

We studied 11 patients with stable multiple sclerosis (MS) with major depression
in terms of response to Sertraline at 100 mg q.d. in an open label trial.
Patients were evaluated with self assessment measurements (Carroll scale) prior
to and during treatment. Only one patient discontinued the drug during the three
month treatment trial, and this was due to perceived lack of efficacy by the
patient. The remainder of the patients completed at least three months of
treatment and had significant improvement in depressive symptoms by self
assessment measurements. No patients experienced side effects. Sertraline
appears to be well tolerated and effective in treatment of major depression in
MS. The Carroll scale is an easily administered means of assessing treatment
response, and correlated highly with our clinical impressions.

Publication Types:
    Clinical Trial

PMID: 8622794 [PubMed - indexed for MEDLINE]

49: J Am Acad Child Adolesc Psychiatry  1995 Dec;34(12):1591-5 

Case study: mania associated with multiple sclerosis.

Heila H, Turpeinen P, Erkinjuntti T.

Department of Psychiatry, University of Helsinki, Finland.

Mania occurs sometimes in association with an organic condition affecting the
brain. A case of a 15-year-old girl with secondary mania related to multiple
sclerosis is described, along with a selective review of the subject. The
English-language literature published from 1986 to 1994 was reviewed, but
geriatric and mentally retarded cases were excluded. This case points out that
organic causes, often multifactorial, have to be kept in mind when treating
patients who have mania.

Publication Types:
    Review, Tutorial

PMID: 8543530 [PubMed - indexed for MEDLINE]

50: Ital J Neurol Sci  1995 Nov;16(8):551-3 

Parallel fluctuations of psychiatric and neurological symptoms in a patient with
multiple sclerosis and bipolar affective disorder.

Salmaggi A, Eoli M, La Mantia L, Erbetta A.

Istituto Nationale Neurologico C. Besta, Divisione di Neurologia, Milano, Italy.

The case of a female patient affected by simultaneously onsetting multiple
sclerosis and bipolar affective disorder at age 33 is reported. Over the
following years, the patient displayed minor mood fluctuations but, at the ages
of 41 and 42 years, respectively, she suffered from a major depressive and a
manic episode, both of which were concomitant with a marked worsening in her
neurological condition.

PMID: 8613416 [PubMed - indexed for MEDLINE]

51: Can J Neurol Sci  1995 Aug;22(3):228-31 

Screening for major depression in the early stages of multiple sclerosis.

Sullivan MJ, Weinshenker B, Mikail S, Bishop SR.

Department of Psychology, Dalhousie University, Halifax, Nova Scotia, Canada.

BACKGROUND: Multiple Sclerosis (MS) is associated with a high risk of developing
major depression, but depression in MS patients frequently goes undetected and
untreated. The current study examined the clinical utility of the Beck
Depression Inventory (BDI) as a screening measure for major depression in newly
diagnosed MS patients. METHODS: Forty-six new referrals to an MS clinic
completed the BDI and participated in a structured interview for major
depression, within 2 months of the diagnosis of MS. RESULTS: According to
DSM-III-R criteria, 40% of patients were diagnosed with major depression, 22%
had adjustment disorder with depressed mood, and 37% showed no evidence of mood
disorder. Sensitivity and specificity values, and positive and negative
predictive values are reported for every BDI cut-off score between 9 and 21.
CONCLUSIONS: A BDI cut-off score of 13 (sensitivity = .71, specificity = .79) is
recommended as optimal for use in screening for major depression in newly
diagnosed MS patients. The use of the BDI as a screening measure for major
depression must proceed with caution given that a cut-off score of 13 still
yielded a false-negative rate of 30%.

PMID: 8529176 [PubMed - indexed for MEDLINE]

52: Fortschr Neurol Psychiatr  1995 Aug;63(8):310-9 

[Psychoses in multiple sclerosis--a reevaluation]

[Article in German]

Schifferdecker M, Krahl A, Krekel NO.

Klinik und Poliklinik fur Neurologie und Psychiatrie, Universtitat zu Koln.

With the aim of reaching a new classification of psychoses with multiple
sclerosis we reviewed the twentieth century literature for observations with
regard to the subject, as well as 688 medical records of our patients, looking
for the occurrence of paranoid and hallucinatory psychoses in the course of
multiple sclerosis. Special attention was paid to the occurrence of cycloid
psychoses. With multiple sclerosis, psychoses on the whole--but cycloid
psychoses in particular--occur more frequently than in the general population.
Women are affected just as frequently as men. Cycloid psychoses occur earlier in
the course of the multiple sclerosis than the other psychoses; here,
hallucinations occur with a higher frequency. Similar as in the case of
HIV-infection, multiple sclerosis can act as a trigger of a cycloid psychosis.
The results of our study indicate that men and women experience this disease as
similarly threatening. A shortcoming of critical faculties based on the organic
disease is an additional factor that favours the outbreak of such a psychosis.

Publication Types:
    Review, Tutorial

PMID: 7557814 [PubMed - indexed for MEDLINE]

53: J Clin Psychiatry  1995 Jul;56(7):297-306; discussion 307-8 

Comment in:
     J Clin Psychiatry. 1997 Mar;58(3):123.

Patients with multiple sclerosis presenting to psychiatric hospitals.

Pine DS, Douglas CJ, Charles E, Davies M, Kahn D.

Department of Psychiatry, Columbia University, College of Physicians and
Surgeons, New York, N.Y., USA.

BACKGROUND: Although many neuropsychiatric syndromes are associated with
multiple sclerosis, few recent studies have examined the clinical features of
psychiatric illness in inpatients with multiple sclerosis. Florid
psychopathology can obscure neurologic symptoms in multiple sclerosis. It is
therefore important to consider the range of severe psychiatric states that can
occur in multiple sclerosis and the frequency with which multiple sclerosis
patients are seen in inpatient facilities. METHOD: We examined records for 2720
consecutive admissions to three psychiatric units and conducted a chart review
comparing the DSM-III psychiatric diagnoses of patients with multiple sclerosis
with those of the inpatient population as a whole. RESULTS: The 10 patients with
multiple sclerosis were significantly more likely to present with histories of
mania and manic psychosis than the inpatient population as a whole. Further, 7
of the 10 patients had psychiatric hospitalizations before the multiple
sclerosis diagnosis. In 4 of these 7 patients, a review of the medical record
documented neurologic symptoms that were not recognized as typical of multiple
sclerosis. Three of these 4 patients were psychotic and the fourth was catatonic
at the time of their admissions. CONCLUSION: While multiple sclerosis patients
account for a small proportion of all psychiatric admissions, clinicians should
consider the diagnosis of multiple sclerosis in patients exhibiting manic
symptoms in tandem with unexplained neurologic findings.

PMID: 7615483 [PubMed - indexed for MEDLINE]

54: Clin Ter  1995 Jun-Jul;146(6-7):449-52 

[Multiple sclerosis and major depression resistant to treatment. Case of a
patient with antidepressive therapy-induced mood disorder, associated with manic

[Article in Italian]

Pariante CM, Orru MG, Carpiniello B, Rudas N.

Istituto di Clinica Psichiatrica, Universita degli Studi di Cagliari.

Patients with multiple sclerosis show higher prevalence of psychiatric disorders
compared to general population, that are hardly managed by pharmacotherapy. In
the present report a female patient, 44 years old, with diagnosis (according to
DSM-IV) of 340 multiple sclerosis, 296.32 major depressive disorder, recurrent,
moderate, 292.84 antidepressant-induced mood disorder, with manic features, is
described. In this patient depressive symptoms did not respond to a number of
drugs, including tricyclic antidepressants, selective serotonine re-uptake
inhibitors hand lithium. Moreover, she had hypomanic and manic episodes induced
by two different antidepressant, hydroxy-tryptophan and clorimipramine. Until
today, only amisulpride (50 mg/die for four months, then 50 mg every two days
for two months) has shown a significant effect on depressive symptomatology,
moreover, this drug has not induced the occurrence of manic symptoms.

PMID: 7586996 [PubMed - indexed for MEDLINE]

55: Int J Psychiatry Med  1995;25(2):123-30 

The neuropsychiatry of multiple sclerosis.

Mendez MF.

Neurobehavior Unit, VA Medical Center West, Los Angeles, USA.

OBJECTIVE: This article examines the cognitive and psychiatric features of
multiple sclerosis. MS can manifest as a neuropsychiatric disturbance even in
the absence of physical disabilities. METHOD: Two MS patients with predominant
behavioral symptoms are described, and the literature is reviewed. RESULTS: The
first patient had an interhemispheric disconnection syndrome, and the second
patient had cognitive fatigue and depression. Other patients have slowed
information processing speed, memory retrieval difficulty, frontal-executive
dysfunction, and visuospatial difficulty. CONCLUSIONS: MS results in specific
cognitive deficits and mood disorders. These two patients had organic mental
disorders from cerebral demyelination particularly affecting the corpus
callosum. Our patients have neuropsychiatric symptoms from extensive
demyelination of prefrontal-subcortical circuits. Evaluation and management
strategies are discussed.

PMID: 7591490 [PubMed - indexed for MEDLINE]

56: Arch Neurol  1994 Jul;51(7):705-10 

Cognitive functioning and depression in patients with chronic fatigue syndrome
and multiple sclerosis.

Krupp LB, Sliwinski M, Masur DM, Friedberg F, Coyle PK.

Department of Neurology, State University of New York-Stony Brook.

OBJECTIVE: To assess cognitive function in patients with chronic fatigue
syndrome (CFS) and multiple sclerosis (MS) and to evaluate the role of
depressive symptoms in cognitive performance. DESIGN: Case-control. All subjects
were given a neuropsychological battery, self-report measures of depression and
fatigue, and a global cognitive impairment rating by a neuropsychologist
"blinded" to clinical diagnosis. Patients with MS and CFS were additionally
evaluated with a Structured Clinical Interview for DSM-III-R (Diagnostic and
Statistical Manual of Mental Disorders, Revised Third Edition) disorders.
SETTING: Institutional and private neurological practices and the community at
large. PATIENTS: Twenty patients with CFS diagnosed in accord with the Centers
for Disease Control and Prevention-revised criteria who had cognitive
complaints; 20 patients with clinically definite MS who were ambulatory and were
matched for fatigue severity, age, and education to CFS subjects; and 20 age-
and education-matched healthy controls. RESULTS: Patients with CFS had
significantly elevated depression symptoms compared with patients with MS and
healthy controls (P < .001) and had a greater lifetime prevalence of depression
and dysthymia compared with MS subjects. Patients with CFS, relative to
controls, performed more poorly on the Digit Symbol subtest (P = .023) and
showed a trend for poorer performance on logical memory (P = .087). Patients
with MS compared with controls had more widespread differences of greater
magnitude on the Digit Span (P < .004) and Digit Symbol (P < .001), Trail Making
parts A (P = .022) and B (P = .037), and Controlled Oral Word Association (P =
.043) tests. Patients with MS also showed a trend of poorer performance on the
Booklet Category Test (P = .089). When patients with CFS and MS were directly
compared, MS subjects had lower scores on all measures, but the differences
reached significance only for the Digit Span measure of attention (P = .035).
CONCLUSIONS: Patients with CFS compared with MS have more depressive symptoms
but less cognitive impairment. Relative to controls, a subset of CFS subjects
did poorly on tests of visuomotor search and on the logical memory measure of
the Wechsler Memory Scale-revised. Poor performance of logical memory in CFS
appears to be related to depression, while visuomotor deficits in CFS are
unrelated. Cognitive deficits in patients with MS are more widespread compared
with those in patients with CFS and are independent of depressive symptoms.

PMID: 8018045 [PubMed - indexed for MEDLINE]

57: J Psychosom Res  1994 Apr;38(3):193-201 

Depression, cognitive impairment and social stress in multiple sclerosis.

Gilchrist AC, Creed FH.

Department of Psychiatry, Manchester University, U.K.

Twenty-four out-patients with established multiple sclerosis (MS) who had been
neurologically assessed underwent detailed psychiatric, cognitive and social
assessments. Depression was associated with significant cognitive impairment and
with social stress but not with degree of neurological impairment, specific
neurological symptoms, disability or handicap. It is suggested that depression
in relapsing-remitting MS may arise when cognitive deficits cause problems in
occupational performance and impinge on close personal relationships.

Publication Types:
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 8027959 [PubMed - indexed for MEDLINE]

58: Acta Psychiatr Scand  1994 Feb;89(2):117-21 

Correlates of cognitive impairment and depressive mood disorder in multiple

Moller A, Wiedemann G, Rohde U, Backmund H, Sonntag A.

Clinical Institute, Max Planck Institute of Psychiatry, Munich, Germany.

The psychopathological status of 25 inpatients suffering from clinically
definite multiple sclerosis (MS) according to Poser criteria was assessed by
using standardized methods (Structured Clinical Interview for DSM-III-R,
Inpatient Multidimensional Psychiatric Scale, Hamilton and Montgomery-Asberg
Depression Rating Scales and the Structured Interview for the Diagnosis of
Alzheimer Dementia and Dementias of other Aetiology (SIDAM). Magnetic resonance
(MRT) (0.5 T; T2-weighted sequence) of the brain was analysed by measuring the
ventricular brain ration (VBR), the area of the corpus callosum (CC) and the
extension of hyperintense lesions of the brainstem, the temporal lobes and the
brain at all. Six of 25 (24%) of these moderately disabled patients (mean
Extended Disability Score (EDSS) 3.3) were diagnosed to suffer from depressive
mood disorder (major depression or dysthymia); 2 were demented. In correlation
analysis, depression was unrelated to age, gender, duration of illness, status
of disability (EDSS) or the results of cognitive assessment. No relationship
between the depression scores and the different MRT measures could be
identified. The presence or absence of gadolinium enhancement was also
uncorrelated to depressive symptoms. Fatigue as measured by the Fatigue Severity
Scale was unrelated to depression or subcortical brain atrophy (increased VBR)
but significantly correlated to the area of hyperintense MRT changes in
brainstem and midbrain. Cognitive impairment (decreased SIDAM scores) was
correlated to the total area of hyperintense MRT changes of the brain
parenchyma. The type of clinical course (relapsing-remitting vs chronic
progredient) was not found to influence the affective or cognitive state in our
MS patient's sample.

PMID: 8178661 [PubMed - indexed for MEDLINE]

59: Eur Neurol  1994;34(6):324-8 

Influence of clinical variables on neuropsychological performance in multiple

Filippi M, Alberoni M, Martinelli V, Sirabian G, Bressi S, Canal N, Comi G.

Department of Neurology, Scientific Institute Ospedale San Raffaele, University
of Milan, Italy.

The effects of age, educational level, duration and course of the disease,
physical disability and mood status on several cognitive functions (short- and
long-term memory, frontal functions, attention, language and visuospatial
skills) have been evaluated in 42 multiple sclerosis (MS) patients. The Hamilton
Depression Rating Scale (HDRS) scores and a secondary progressive disease course
significantly influenced neuropsychological performance. Factorial analysis
revealed that indexes of (1) frontal function impairment, (2) long-term verbal
memory and language function impairment, and (3) visuospatial short- and
long-term memory and visuoperceptive function impairment accounted for 85% of
the variance in neuropsychological performance. Only the first factor was
significantly related to the presence of depressive symptomatology, as assessed
by the HDRS. These results indicate that both the course of the disease and the
presence of affective disorders must be taken into account when evaluating the
natural history of cognitive impairment in MS and suggest that depressive
symptomatology and cognitive dysfunction in MS are related to the involvement of
at least partially overlapping anatomofunctional circuits.

PMID: 7851453 [PubMed - indexed for MEDLINE]

60: Acta Neurol Scand  1993 Dec;88(6):388-93 

Bipolar affective disorder prior to the onset of multiple sclerosis.

Hutchinson M, Stack J, Buckley P.

Department of Neurology, St. Vincent's Hospital, Dublin, Ireland.

The frequent association of affective disorder and multiple sclerosis raises
important aetiological and clinical considerations. Reported here are seven
patients who presented with symptoms of multiple sclerosis and who had a
preceding history of bipolar affective disorder. The hypothesis that bipolar
illness may be the initial manifestation of multiple sclerosis is discussed with
reference to relevant clinical and epidemiological research on the topic.

PMID: 8116337 [PubMed - indexed for MEDLINE]

61: Psychosomatics  1993 Mar-Apr;34(2):124-30 

Increased depression in multiple sclerosis patients. A meta-analysis.

Schubert DS, Foliart RH.

Case Western Reserve University School of Medicine, Cleveland, OH.

Clinical reports and experimental studies have conflicted on depression in
multiple sclerosis (MS) patients. Recent reviews show that few controlled
studies have been done. A comprehensive search of the literature revealed six
studies that compared depression in MS patients with depression in comparison
groups. The meta-analytic combination of these studies indicates that MS
patients are significantly more depressed than comparison groups.

Publication Types:

PMID: 8456154 [PubMed - indexed for MEDLINE]

62: J Psychosom Res  1993;37(2):163-70 

Restless sleep, illness intrusiveness, and depressive symptoms in three chronic
illness conditions: rheumatoid arthritis, end-stage renal disease, and multiple

Devins GM, Edworthy SM, Paul LC, Mandin H, Seland TP, Klein G, Costello CG,
Shapiro CM.

Clarke Institute of Psychiatry, Toronto, Ontario, Canada.

Restless sleep was compared across 110 out-patients with rheumatoid arthritis
(RA), 101 with end-stage renal disease (ESRD), 94 with multiple sclerosis (MS),
and an unselected control group of 176 individuals attending their family
practitioners (FP). It was also investigated in the three chronic illness groups
as a contributor to illness intrusiveness--the extent to which one's illness
and/or its treatment interfere with continued involvements in valued activities
and interests--a determinant of depression and emotional distress in chronic
conditions. Reported frequencies of restless sleep were highest in RA, lower in
ESRD, and lowest in MS; FP patients reported frequencies that were similar,
overall, to those observed in MS. These differences were evident among
nondepressed, (chi 2 9, N = 309, p < 0.0001), but not depressed, individuals.
The occurrence of restless sleep correlated significantly with increased illness
intrusiveness, r (279) = 0.31, p < 0.001, in RA, ESRD, and MS. Results supported
the hypothesis that the relation between restless sleep and emotional distress
is mediated by illness intrusiveness. Treatment of restless sleep may offer the
added benefit of diminishing illness intrusiveness and may, thereby, enhance
quality of life in chronic physical illness.

PMID: 8463992 [PubMed - indexed for MEDLINE]

63: J Neurol Neurosurg Psychiatry  1992 Jul;55(7):542-5 

Suicide and multiple sclerosis: an epidemiological investigation.

Stenager EN, Stenager E, Koch-Henriksen N, Bronnum-Hansen H, Hyllested K, Jensen
K, Bille-Brahe U.

Department of Psychiatry, Odense University.

In a nationwide investigation the risk of death by suicide for patients with
multiple sclerosis (MS) was assessed using records kept at the Danish Multiple
Sclerosis Registry (DMSR) and the Danish National Register of Cause of Death.
The investigation covers all MS patients registered with DSMR with an onset of
the disease within the period 1953-85, or for whom MS was diagnosed in the same
period. Fifty three of the 5525 cases in the onset cohort group committed
suicide. Using the figures from the population death statistics by adjustment to
number of subjects, duration of observation, sex, age, and calendar year at the
start of observation, the expected number of suicides was calculated to be
nearly 29. The cumulative lifetime risk of suicide from onset of MS, using an
actuarial method of calculation, was 1.95%. The standard mortality ratio (SMR)
of suicide in MS was 1.83. It was highest for males and for patients with onset
of MS before the age of 30 years and those diagnosed before the age of 40. The
SMR was highest within the first five years after diagnosis.

PMID: 1640228 [PubMed - indexed for MEDLINE]

64: Psychiatr Clin North Am  1992 Jun;15(2):427-38 

Behavioral manifestations associated with multiple sclerosis.

Mahler ME.

Neurobehavior Program, Brentwood Division, West Los Angeles Department of
Veterans Affairs Medical Center, California.

The behavioral manifestations associated with MS include both cognitive and
emotional disturbances. Overall intellect is slightly affected in about half of
patients, and 20% to 33% demonstrate more severe impairments. Memory
disturbances are particularly common, and retrieval function is especially
affected. Difficulties with concept formation and other executive functions can
be subtle yet have significant impact on daily living. Depression is frequent in
MS, sometimes despite an outward euphoria that is more prevalent with advancing
disease. Psychosis occurs rarely, but bipolar disorder is more frequent than in
the general population. MS may be associated with a variety of personality
changes, but it is impossible to generalize about this or to identify an "MS
personality." Disturbances of emotional control are relatively frequent.
Comprehensive management of these problems uses multiple modalities including
good neurologic care, cognitive rehabilitation, counseling and support groups,
and pharmacotherapy.

Publication Types:
    Review, Tutorial

PMID: 1603734 [PubMed - indexed for MEDLINE]

65: Actas Luso Esp Neurol Psiquiatr Cienc Afines  1992 May-Jun;20(3):97-103 

[Depressive states in multiple sclerosis. Critical bibliographic review]

[Article in Spanish]

Arias Bal MA, Vazquez Barquero JL, Miro J, Pena C, Berciano J.

Departamento de Psiquiatria, Hospital Universitario, Marques de Valdecilla,
Universidad de Cantabria, Santander, Espana.

The aim of this paper is to review the question of depression in patients with
multiple sclerosis (MS). Morbidity and methodological difficulties in the
investigation of depressive states in MS are analyzed. Prevalence of depression
in MS in previous series is critically compared. The role of chronic invalidity
and topography of demyelinating lesions in the development of depression are
considered. We also review the treatment of depressive states and future
guidelines for investigation of this topic.

Publication Types:
    Review, Academic

PMID: 1496912 [PubMed - indexed for MEDLINE]

66: Gen Hosp Psychiatry  1992 May;14(3):177-85 

Depression and neurological disease. Their distinction and association.

Caplan LR, Ahmed I.

Department of Neurology, Tufts University School of Medicine, Boston,

Depression and neurological disease often coexist but sometimes are difficult to
distinguish. By analyzing eight patients, all seen by psychiatrists and the same
neurologist, and by reviewing the pertinent literature, we will explore the
complex differential features, coexistence, and interaction between depression
and neurological disease. Neurological disease may lead to changes in mood and
behavior, and these patients may present to psychiatrists with depression. In
addition, depression may present with or exaggerate neurological signs and
symptoms. Awareness of these interactions can lead to appropriate evaluation and
treatment of both these disorders.

PMID: 1318243 [PubMed - indexed for MEDLINE]

67: J Neuropsychiatry Clin Neurosci  1992 Spring;4(2):145-51 

Multiple sclerosis and ECT: possible value of gadolinium-enhanced magnetic
resonance scans for identifying high-risk patients.

Mattingly G, Baker K, Zorumski CF, Figiel GS.

Department of Psychiatry, Washington University School of Medicine, St. Louis,

Electroconvulsive therapy (ECT) has been used effectively in treating depressed
patients with multiple sclerosis (MS). However, several reports have observed
that some patients with MS may suffer neurological deterioration during ECT. The
authors describe the outcomes of 3 depressed patients with MS who were treated
with ECT. Consistent with previous works, ECT effectively treated the
psychiatric symptoms; however, 1 patient deteriorated neurologically during ECT.
The brain MRI findings and clinical courses of all 3 patients are discussed,
along with the possible value of gadolinium-contrast MRI scans for identifying
high-risk patients.

PMID: 1627975 [PubMed - indexed for MEDLINE]

68: Clin Neurol Neurosurg  1992;94 Suppl:S144-6 

Psychiatric symptoms and mental changes as major features of multiple sclerosis.

Sanders EA, van Lieshout HB.

Ignatius Hospital, Department of Neurology, Breda, The Netherlands.

A patient is presented with clinically and laboratory supported definite
multiple sclerosis who developed severe depression followed by mental
deterioration. Magnetic resonance imaging MRI demonstrated multiple
hemispherical lesions. It is suggested that the psychiatric and cognitive signs
and symptoms observed in this patient are due to severe cerebral demyelination.

PMID: 1320493 [PubMed - indexed for MEDLINE]

69: Acta Psychiatr Scand  1991 Apr;83(4):292-6 

Comment in:
     Acta Psychiatr Scand. 1991 Oct;84(4):398.

Psychiatric aspects of multiple sclerosis.

Arias Bal MA, Vazquez-Barquero JL, Pena C, Miro J, Berciano JA.

Department of Psychiatry, University Hospital Valdecilla Medical School,
University of Cantabria, Santander, Spain.

A consecutive sample of 50 patients with a diagnosis of definite multiple
sclerosis was evaluated by means of the Clinical Interview Schedule (CIS) and
other psychopathological instruments. A global prevalence of psychopathology of
54% was found, with the prevalence of depression being 22%. Moreover, 46% of the
sample presented signs indicative of neuropsychological deterioration in the
Benton Visual Retention Test. The association between the presence of
psychopathology and the social and neurological characteristics of the sample
was also investigated, with results of low significance.

PMID: 2028805 [PubMed - indexed for MEDLINE]

70: Can J Psychiatry  1991 Mar;36(2):112-7 

Multiple sclerosis and affective disorders.

Garland EJ, Zis AP.

Department of Psychiatry, University of British Columbia, University
Hospital--UBC Site, Vancouver.

Affective disorders occurring in association with multiple sclerosis have been
attributed both to the psychosocial impact of a chronic disabling illness and to
the structural lesions of cerebral demyelination. A review of research evidence
suggests that while there is a correlation between chronic depressive symptoms
and both progressive disability and lack of social support, acute major
depressive and manic episodes may be psychiatric manifestations of demyelinating
lesions and may be the initial presenting symptoms of multiple sclerosis.
Anti-inflammatory agents may be required in the management of acute psychiatric
symptoms despite the fact that these agents have a propensity to precipitate
psychotic episodes. Two case reports are presented to illustrate the clinical
challenge of distinguishing between organic and functional affective illness in
patients with multiple sclerosis. The interplay between biological and
psychological aspects of multiple sclerosis in precipitating affective disorders
is discussed, with implications for patient assessment and management.

PMID: 2044028 [PubMed - indexed for MEDLINE]

71: Psychosomatics  1991 Summer;32(3):255-67 

Psychological factors affecting neurological conditions. Depression and stroke,
multiple sclerosis, Parkinson's disease, and epilepsy.

McNamara ME.

Department of Psychiatry, Rhode Island Hospital, Brown University, Providence

As a contribution to the proposed revision of the DSM-III-R category
"Psychological Factors Affecting Physical Condition" for DSM-IV, this article
reviews the history of how the relationship of psychiatric illness to
neurological illness has been understood with respect to depression. Since both
psychiatric and neurological illness are aspects of brain functioning, any
statement of the relationship of these categories entails certain
epistemological assumptions, some of which have undergone considerable change
and rapid evolution in the course of the last century.

Publication Types:
    Review, Tutorial

PMID: 1882016 [PubMed - indexed for MEDLINE]

72: Am J Psychiatry  1990 Nov;147(11):1493-7 

Antidepressant pharmacotherapy of depression associated with multiple sclerosis.

Schiffer RB, Wineman NM.

Department of Psychiatry, University of Rochester Medical Center.

In a double-blind clinical trial involving 28 patients with multiple sclerosis
and major depressive disorder, 14 patients were randomly assigned to a 5-week
trial of desipramine and individual psychotherapy and 14 to placebo plus
psychotherapy. Clinical judgments indicated that patients treated with
desipramine improved significantly more than the placebo group. This was
confirmed by scores on the Hamilton Rating Scale for Depression but not by Beck
Depression Inventory scores. Side effects limited desipramine dosage in half of
the treated patients. The authors conclude that desipramine has a modest
beneficial effect in serious depression associated with multiple sclerosis but
that side effects may be more of a limiting factor than in patients without
medical or neurologic disease.

Publication Types:
    Clinical Trial
    Randomized Controlled Trial

PMID: 2221162 [PubMed - indexed for MEDLINE]

73: J Neurosci Nurs  1990 Aug;22(4):209-14 

Depression in multiple sclerosis: critique of the research literature.

Acorn S, Andersen S.

University of British Columbia, School of Nursing, Vancouver, Canada.

Depression has been found to be increased in individuals with multiple sclerosis
(MS). Depression is currently being studied as either a reactive response, a
part of the symptomatology or a precipitating factor of the disease. The purpose
of this article is to provide a review of the research literature on depression
in multiple sclerosis. In addition, implications for neuroscience nurse who work
with MS individuals are identified.

Publication Types:
    Review, Tutorial

PMID: 2144554 [PubMed - indexed for MEDLINE]

74: Br J Psychiatry  1990 Jan;156:10-6 

Depressive illness in multiple sclerosis. Clinical and theoretical aspects of
the association.

Berrios GE, Quemada JI.

Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital.

The present state of knowledge of the possible relationship between depressive
illness and multiple sclerosis is described. Problems of the research
methodology are identified and suggestions made for useful areas of inquiry.

Publication Types:
    Review, Tutorial

PMID: 2404535 [PubMed - indexed for MEDLINE]

75: Arch Neurol  1990 Jan;47(1):98-104 

Affective disorders in multiple sclerosis. Review and recommendations for
clinical research.

Minden SL, Schiffer RB.

Division of Psychiatry, Brigham and Women's Hospital, Harvard Medical School,
Boston, Mass.

This review of research on affective disorders in multiple sclerosis was
prepared by members of the Cognitive Function Study Group of the National
Multiple Sclerosis Society (New York, NY) to call attention to the prevalence
and seriousness of emotional disturbances in multiple sclerosis, and to
encourage further investigation of these syndromes. We present English-language
studies of euphoria, pathological laughing and weeping, depression, and bipolar
disorder, describe methodological limitations, and suggest areas for future
clinical research.

Publication Types:
    Review, Tutorial

PMID: 2403790 [PubMed - indexed for MEDLINE]

76: Mayo Clin Proc  1989 Jun;64(6):657-63 

Cognitive and psychiatric abnormalities in multiple sclerosis.

Petersen RC, Kokmen E.

Department of Neurology, Mayo Clinic, Rochester, MD 55905.

In multiple sclerosis, behavioral changes, including alterations in cognitive
functions and psychiatric abnormalities, have been recognized with increasing
frequency in recent years. Multiple sclerosis formerly was thought to be
primarily a disorder of the brain stem and spinal cord; however, functional
changes that can be attributed, at least in part, to cerebral dysfunction are
being recognized. Certain cognitive functions such as memory and conceptual
processes seem to be preferentially impaired. The degrees of impairment of other
functions such as attention and visuospatial skills are now being evaluated.
Psychiatrically, affective disorders seem to be the most common diagnoses, and
debate exists about whether these abnormalities are a function of the
demyelinating process itself or are a reaction to the disability produced by the

Publication Types:
    Review, Tutorial

PMID: 2664362 [PubMed - indexed for MEDLINE]

77: Ital J Neurol Sci  1988 Dec;9(6):551-7 

Depression and neuroticism in multiple sclerosis.

Colombo G, Armani M, Ferruzza E, Zuliani C.

Istituto di Clinica Psichiatrica, Universita di Padova.

88 subjects (36 males and 52 females) affected by multiple sclerosis (MS), were
studied with the CES-D and SRT tests for the evaluation of depressive reactions
and neuroticism. Comparing the results with those of the control group, we found
a significant score for depression and somatization in the MS patients, whereas
the scores for anxiety and inadequacy were normal.

PMID: 3225165 [PubMed - indexed for MEDLINE]

78: Arch Neurol  1988 Dec;45(12):1345-8 

Multiple sclerosis and affective disorder. Family history, sex, and HLA-DR

Schiffer RB, Weitkamp LR, Wineman NM, Guttormsen S.

Department of Psychiatry, University of Rochester Medical Center, NY 14642.

To investigate a possible genetic cause underlying the clinical association
between multiple sclerosis (MS) and affective disorder, we studied 56 patients
with MS for psychiatric and genetic (family history, sex, and HLA-DR)
characteristics. The 2:1 ratio of females to males expected for patients with MS
was observed in this sample (40:16), but the excess of females occurred entirely
among the 31 MS patients with major affective disorder (27 females and four
males). Bipolar probands with MS had significantly more relatives with affective
disorder or MS than did unipolar probands with MS. The HLA-DR antigen
frequencies in patients with MS categorized by type and family history of
affective disorder suggest that it may be possible to validate such clustering
of patients. We concluded that sex and other genetic factors are related to the
affective symptoms in MS and emphasize the importance of psychiatric evaluation
of these patients.

PMID: 3196194 [PubMed - indexed for MEDLINE]

79: J Clin Psychiatry  1988 Sep;49(9):364-6 

Multiple sclerosis presenting as major depression: a diagnosis suggested by MRI
scan but not CT scan.

Salloway S, Price LH, Charney DS, Shapiro M.

Department of Psychiatry, Yale University School of Medicine, New Haven, Conn.

A 43-year-old woman had melancholic major depression and mild incoordination. A
magnetic resonance imaging (MRI) scan showed extensive lesions of the cerebral
white matter that were not detected on a computed tomography (CT) scan. Since
multiple sclerosis may initially present as depression, the differential
sensitivities of MRI and CT scanning should be considered in deciding which
neurodiagnostic studies should be conducted in depressed patients.

PMID: 3417622 [PubMed - indexed for MEDLINE]

80: Gen Hosp Psychiatry  1987 Nov;9(6):426-34 

Depression in multiple sclerosis.

Minden SL, Orav J, Reich P.

Division of Psychiatry, Brigham and Women's Hospital, Harvard Medical School.

Standardized interview techniques, diagnostic criteria, and rating scales were
used to assess 50 moderately disabled multiple sclerosis (MS) patients.
Fifty-four percent met lifetime Research Diagnostic Criteria for major
depression, with a significant increase in the rate from before to after the
onset of MS symptoms. The MS patients were significantly more depressed than
other medical patients described in the literature. Major depressions were
associated with steroid-treated exacerbations and a history of major depression.
Symptoms of depression may be easily confused with those of MS, resulting in
inadequate diagnosis and treatment.

PMID: 3692149 [PubMed - indexed for MEDLINE]

81: Gen Hosp Psychiatry  1987 Jul;9(4):294-301 

Psychiatric aspects of multiple sclerosis.

Tomsyck RR, Jenkins PL.

A patient who presented with depressive and hysterical symptoms of several
years' duration and who proved to have multiple sclerosis is presented. Two
further cases whose initial symptoms of dissociation and major depression were
prodromes of multiple sclerosis are also presented. A discussion of the factors
leading to the correct diagnosis in these cases and reference to relevant
literature on psychiatric presentations of multiple sclerosis are presented to
illustrate the need for psychiatrists' awareness of multiple sclerosis as a
causative factor in patients with a wide variety of psychiatric syndromes.

PMID: 3609736 [PubMed - indexed for MEDLINE]

82: Arch Neurol  1987 Jun;44(6):596-9 

The spectrum of depression in multiple sclerosis. An approach for clinical

Schiffer RB.

Twenty patients with clinically definite multiple sclerosis who experienced
major depressive episodes according to Research Diagnostic Criteria are
described. The heterogeneous quality of these depressive episodes is presented
by categorizing the episodes according to ten Research Diagnostic Criteria
depressive subtypes. Four interpersonal management strategies for such patients
that are applicable within a neurologic practice setting are described. The most
important feature concerning prognosis for these depressive episodes appears to
be the relationship between the depressive episode and the underlying
demyelinating disease. When depression occurred in the setting of clinically
significant disease activity, the outcome was usually favorable.

PMID: 3579677 [PubMed - indexed for MEDLINE]

83: Arch Neurol  1987 Apr;44(4):376-8 

Mood disorder and multiple sclerosis.

Joffe RT, Lippert GP, Gray TA, Sawa G, Horvath Z.

A systematic psychiatric evaluation was performed on 100 consecutive patients
attending a multiple sclerosis clinic. Forty-two percent of the patients had
lifetime history of depression, and 13% fulfilled criteria for manic-depressive
illness. Only 28% of the patients had no psychiatric diagnosis. The relationship
of psychiatric disorder to neurologic dysfunction and other aspects of multiple
sclerosis are presented. Clinical and theoretical implications of these findings
are discussed.

PMID: 3827692 [PubMed - indexed for MEDLINE]

84: Rev Neurol (Paris)  1987;143(8-9):595-601 

[Intellectual and mood disorders in multiple sclerosis]

[Article in French]

Truelle JL, Palisson E, Le Gall D, Stip E, Derouesne C.

Service de neurologie, C.H.U., Angers.

Reports of frequency and interpretation of intellectual and mood disorders
differ in multiple sclerosis (MS). Forty-one patients with MS defined according
to MacAlpine's criteria were evaluated by psychometric tests (WAIS) and
neuropsychologic examinations (study of language, gnosic and praxic activities,
dynamic gestural organization, memory and learning) together with, in 24 of
them, the AMDP psychopathologic rating scale. Intellectual disorders were noted
in 65 p. 100 of patients. Although more frequent in severe and chronic forms
they were nevertheless of early onset since more than a half of the patients
with onset of disease less than 5 years ago were affected. Their semiology was
fairly homogeneous, combining disturbances of dynamic gestural organization
(decomposition or simplification) and memory and learning deficiencies without
anomalies of instrumental functions or usual psychometric mental deterioration.
Application of the AMDP scale failed to reveal any psychotic type of disorders.
Mood disturbances were predominant, affecting 60 p. 100 of the subpopulation
studied (24 cases) and combining, in an unexpected manner: dysphoria, euphoria
and depression. Only euphoria appeared to be correlated with intellectual
disorders. Frequency of both intellectual and mood disorders was similar to that
reported in other series published. The relative homogeneity of semiology, seen
by the correlation between the different disturbances (decomposition and
simplification, plateau learning curve and euphoria) and the unusual grouping of
these effects, is suggestive of their organic basis. In addition, signs and
symptoms resemble the neuropsychological expression of frontal lobe lesions and
certain lesions of central grey nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 3671962 [PubMed - indexed for MEDLINE]

85: Am J Psychiatry  1986 Jan;143(1):94-5 

Association between bipolar affective disorder and multiple sclerosis.

Schiffer RB, Wineman NM, Weitkamp LR.

Ten patients from Monroe County, N.Y., had both multiple sclerosis and bipolar
affective disorder. Epidemiologic data indicate that the expected number would
be 5.4. This difference may indicate an association between these disorders.

PMID: 3942295 [PubMed - indexed for MEDLINE]

86: Psychother Psychosom  1985;44(1):25-33 

Multiple sclerosis and affective disorder: 2 case reports of mania with

Garfield DA.

Multiple sclerosis and affective disorder are both diseases that wax and wane as
well as have variable clinical symptomatology. Their common co-occurrence has
given rise to intense speculation about their etiological and clinical
connection. In this paper, 2 case reports and discussions are presented, and a
pertinent review of the literature is included concerning the question whether
affective symptomatology is the direct result of, a reaction to, or coexistent
with, the neurological disease process. The specific cataloguing of affective
symptoms with multiple sclerosis is suggested as possibly being helpful in
warning clinicians as to the presence of multiple sclerosis. The rhythmicity of
both illnesses is briefly discussed in the light of recent literature on
circadian rhythms.

PMID: 4080926 [PubMed - indexed for MEDLINE]

87: Br J Psychiatry  1984 Oct;145:366-71 

An evaluation of cognitive-behaviour therapy for depression in patients with
multiple sclerosis.

Larcombe NA, Wilson PH.

Twenty depressed multiple sclerotic patients were randomly allocated either to
cognitive-behaviour therapy or to a waiting list control condition. Assessment
of depressive symptoms was conducted at pre-treatment, post-treatment, and a
four-week follow-up. In comparison to the waiting list condition,
cognitive-behaviour therapy was found to result in clinically and statistically
significant improvement on most measures. Although the mechanism by which such
treatment achieves its effects is unclear, these results clearly support the use
of cognitive-behavioural treatments for depression in this population.

Publication Types:
    Clinical Trial
    Randomized Controlled Trial

PMID: 6487909 [PubMed - indexed for MEDLINE]

88: Am J Psychiatry  1984 Jan;141(1):112-3 

Rapidly cycling bipolar disorder and multiple sclerosis.

Kellner CH, Davenport Y, Post RM, Ross RJ.

The authors describe two patients with rapidly cycling bipolar disorder who were
found to have multiple sclerosis. They suggest that multiple sclerosis be
considered in the differential diagnosis of patients who have affective
disorders and minor neurological complaints.

PMID: 6691425 [PubMed - indexed for MEDLINE]

89: Am J Psychiatry  1983 Nov;140(11):1498-1500 

Depressive episodes in patients with multiple sclerosis.

Schiffer RB, Caine ED, Bamford KA, Levy S.

Thirty multiple sclerosis patients were assessed: 15 with predominantly cerebral
involvement of their demyelinating disease and 15 with predominantly spinal cord
and cerebellar involvement. The groups were matched with regard to age, duration
of illness, and Kurtzke disability scores. Assessment included
neuropsychological testing, the Beck Depression Inventory, and a psychiatric
interview patterned after the Schedule for Affective Disorders and
Schizophrenia. A group of normal volunteers served as controls for the
neuropsychological testing. There were significantly more major depressive
episodes in the cerebral group, as assessed by the patients' histories and by
interview, and there was a trend toward more depressive symptoms in this group,
as measured by the Beck inventory.

PMID: 6625001 [PubMed - indexed for MEDLINE]

90: Zh Nevropatol Psikhiatr Im S S Korsakova  1983;83(5):732-7 

[Mental disorders in multiple sclerosis]

[Article in Russian]

Korkina MV, Malkov GF, Zavalishin IA, Vavilov SB, Adarcheva LS.

On the basis of clinical and follow up study of 106 patients with multiple
sclerosis, including psychological tests and computerized tomography (34
observations), the authors specify the major types of psychic disorders related
to this disease and represented in the form of the asthenic, hysteroformative,
obsessive, and depressive syndromes, as well as in the form of an initial state
with the clinical picture of organic dementia. Correlation of the examination
data to computerized tomography findings usually reveals a direct relationship
between the degree of psychic disorders and the severity of a cerebral injury.
The authors point both to the necessity of controlling the psychic disturbances
described and to their importance as a telltale sign in making the differential
diagnosis of multiple sclerosis.

PMID: 6880504 [PubMed - indexed for MEDLINE]

91: Acta Psychiatr Belg  1981 Jul-Aug;81(4):337-49 

Manic syndrome associated with multiple sclerosis: secondary mania?

Mapelli G, Ramelli E.

Mania is generally assumed to be a "primary" affective disorder and is usually
regarded as part of bipolar manic-depressive disease or as unipolar mania.
Suggestions that manic states can be causally related to organic
dysfunction--medical and pharmacological--are found in the most recent
literature. These manic states are best considered "secondary" manias. We
present a patient in whom mania occurred in association with multiple sclerosis.
We assumed that, in this patient, the temporal coincidence of neurological and
manic manifestations was not accidental, but that the manic state was caused by
the demyelinating process. Multiple sclerosis is absent from the list of
possible physical causes of secondary mania reported in literature, and we
suggest that even multiple sclerosis merits consideration as a possible
antecedent to secondary mania.

PMID: 7331840 [PubMed - indexed for MEDLINE]

92: Z Psychosom Med Psychoanal  1981 Apr-Jun;27(2):168-79 

[Multiple sclerosis - a depressive syndrome? Report on the course of

[Article in German]

Caliezi JM.

The findings concerning the basic psychic condition preceding the onset of a
so-called multiple sclerosis seem to correspond to the basic structure and
disorders of a narcissistic neurosis, especially that of the phobic type of this
illness. The same psychic structure may also be referred to as faulty identify
establishment or, in terms of depression, described as a somatically masked
depression. Because of the deep-rooted psychic damage lasting results can only
be obtained by long-term uncovering analytic psychotherapy. In general patients
afflicted with a neurosis of this type violently oppose to psychic training and

PMID: 7234151 [PubMed - indexed for MEDLINE]

93: J Neurol Neurosurg Psychiatry  1980 Oct;43(10):861-5 

Depression as a major symptom of multiple sclerosis.

Whitlock FA, Siskind MM.

Thirty patients suffering from multiple sclerosis have been compared with 30
patients suffering from other chronic neurological diseases. The degree of
disability was similar in these two groups. The patients with multiple sclerosis
had experienced more episodes of severe depression both before and after the
onset of neurological symptoms. The possible reasons for these episodes are
discussed and it is concluded that in some patients serious affective disorder
may be a presenting or complicating feature of multiple sclerosis.

PMID: 7441263 [PubMed - indexed for MEDLINE]

94: Dis Nerv Syst  1977 Feb;38(2):127-31 

Multiple sclerosis--presenting as depressive illness.

Goodstein RK, Ferrell RB.

A diagnostic dilemma exists when clinicians face patients with atypical
recurrent symptoms involving both physical and psychologic elements. Multiple
sclerosis (MS) represents such a dilemma. Few authors address themselves to the
significance of depressive illness as the initial presentation in MS. Three
patients hospitalized solely due to recurrent emotional disorders are described.
Depressive symptoms predominated. In each case no precipitant for depression was
identified, no previous neurologic diagnosis was entertained by clinician or
patient, and multiple prior psychotherapeutic interventions were unsuccessful.
The episodic nature of the symptoms and poor response to usually effective
treatments created a high index of suspicion for central nervous system disease.
A diagnosis of MS was made based on subtle neurologic signs, spinal fluid gamma
globulin elevations, and abnormalities in neuropsychological testing. Treatment
involved integrated psychiatric and medical measures.

PMID: 837811 [PubMed - indexed for MEDLINE]


Revised 3/30/03