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Subsyndromal Mood Disorders. By, Ivan Goldberg, M.D.
1: J Affect Disord 2003 Jan;73(1-2):123-31
The prevalence and disability of bipolar spectrum disorders in the US
population: re-analysis of the ECA database taking into account subthreshold
cases.
Judd LL, Akiskal HS.
Department of Psychiatry, University of California, San Diego (UCSD), 9500
Gilman Drive, 92093-0603, La Jolla, CA, USA
BACKGROUND: Despite emerging international consensus on the high prevalence of
the bipolar spectrum in both clinical and community samples, many skeptics
contend that narrowly defined bipolar disorder with a lifetime rate of about 1%
represents a more accurate estimate of prevalence. This may in part be due to
the fact that higher figures proposed for the bipolar spectrum (5-8%) have not
been based on national data and have not included all levels of manic symptom
severity. In the present secondary analyses of the US National Epidemiological
Catchment Area (ECA) database, we provide further clarification on this
fundamental public health issue. METHODS: All respondents in the first wave
(first interview) of the ECA household five site sample (n=18,252) were
classified on the basis of DSM-III criteria into lifetime manic and hypomanic
episodes, as well as those with at least two lifetime manic/hypomanic symptoms
below the threshold for at least 1 week duration (subsyndromal manic symptoms
[SSM] group). Odds ratios were calculated on lifetime service utilization for
mental health problems, measures of adverse psychosocial outcome, and suicidal
behavior compared to subjects with no mental disorders or manic symptoms.
RESULTS: As originally reported nearly two decades ago by the primary
investigators of the ECA, the lifetime prevalence for manic episode was 0.8%,
and for hypomania, 0.5%. What is new here is the inclusion of subthreshold SSM
subjects, which accounted for 5.1%, yielding a total of 6.4% lifetime prevalence
for the bipolar spectrum. All three (manic, hypomanic and SSM) groups had
greater marital disruption. There were significant increases in lifetime health
service utilization, need for welfare and disability benefits and suicidal
behavior when the SSM, hypomanic and manic subjects were compared to the no
mental disorder group. Suicidal behavior was non-significantly highest in the
hypomanic (bipolar II) group. Otherwise, hypomanic and manic groups had
comparable level of service utilization and social disruption. LIMITATIONS:
Comorbid disorders, which might influence functioning, were not included in the
present analyses. CONCLUSION: These secondary analyses of the US National ECA
database provide convincing evidence for the high prevalence of a spectrum of
bipolarity in the community at 6.4%, and indicate that subthreshold cases are at
least five times more prevalent than DSM-based core syndromal diagnoses at about
1%. These SSM subjects, who met the criteria of "caseness" from the point of
view of harmful dysfunction, are of great theoretical and public health
significance.
2: Bipolar Disord 2002 Oct;4(5):328-34
Olanzapine in diverse syndromal and subsyndromal exacerbations of bipolar
disorders.
Janenawasin S, Wang PW, Lembke A, Schumacher M, Das B, Santosa CM, Mongkolcheep
J, Ketter TA.
Department of Psychiatry and Behavioral Sciences, Stanford University School of
Medicine, Stanford, CA 94305-5723, USA.
OBJECTIVE: To evaluate effects of olanzapine in diverse exacerbations of bipolar
disorders. METHODS: Twenty-five evaluable bipolar disorder [14 bipolar I (BPI),
10 bipolar II (BPII) and one bipolar disorder not otherwise specified (BP NOS)]
outpatients received open olanzapine (15 adjunctive, 10 monotherapy). Thirteen
had elevated (11 syndromal, two subsyndromal) and 12 depressed (four syndromal,
eight subsyndromal) mood symptoms of at least mild severity, with Clinical
Global Impression-Severity (CGI-S) scores of at least 3. Only one had psychotic
symptoms. RESULTS: With open olanzapine (15 adjunctive, 10 monotherapy), overall
symptom severity (CGI-S) as well as mood elevation (Young Mania Rating Scale),
depression (Hamilton and Montgomery-Asberg Depression Rating Scales), and
anxiety (Hamilton Anxiety Rating Scale), rapidly decreased (significantly by
days 2-3). Patients with the greatest baseline severity (CGI-S) had the greatest
improvement. Fifteen of 25 (60%) patients responded. Time to consistent response
was bimodal, with five early (by 0.5 +/- 0.3 weeks) and 10 late (by 7.0 +/- 1.9
weeks) responders. Early compared with late responders had 51% lower final
olanzapine doses. Olanzapine was generally well tolerated, with sedation and
weight gain the most common adverse effects. CONCLUSIONS: Olanzapine was
effective in diverse exacerbations of bipolar disorders. The bimodal
distribution of time to response and different final doses are consistent with
differential mechanisms mediating early compared with late responses. Controlled
studies are warranted to further explore these preliminary observations.
3: Psychiatr Clin North Am 2002 Dec;25(4):685-98
The prevalence, clinical relevance, and public health significance of
subthreshold depressions.
Judd LL, Schettler PJ, Akiskal HS.
Department of Psychiatry, University of California, San Diego, 9500 Gilman
Drive, La Jolla, CA 92093-0603, USA. ljudd@ucsd.edu
Scientific evidence has accumulated during the last 15 years establishing that
SD symptoms have a high prevalence in the general population and in clinically
depressed patient cohorts studied cross-sectionally or followed longitudinally.
The clinical relevance and public health importance of SD symptoms were
confirmed when various investigators, including the authors' group at University
of California, San Diego, found that SD symptoms are associated with a
significant and pervasive impairment of psychosocial function when compared to
no depressive symptoms. There is strong evidence that all levels of depressive
symptom severity of unipolar MDD are associated with significant psychosocial
impairment, which increases significantly and linearly with each increment in
level of symptom severity. It is only when MDD patients are completely symptom
free that psychosocial function returns to good or very good levels. The
disability associated with depression is state dependent, and disability returns
to good or normal levels only when all of the depressed patients' symptoms
abate, because disability is present when even a few symptoms (i.e., SD
symptoms) are detected. There is strong evidence during the long-term course of
illness that major, minor, dysthymic, and subsyndromal symptoms wax and wane
within the same patient and that these symptomatic periods are interspersed in
the overall course with times when patients are remitted and symptom free. The
modal longitudinal symptom status of MDD patients involves primarily
subthreshold depressive symptoms, which are much more common than symptoms at
the syndromal MDE level. The longitudinal systematic examination of the clinical
relevance and high prevalence of SD symptoms helped establish the fact that the
long-term symptomatic expression of MDD is dimensional, not categorical, in
nature. Abatement of SD symptoms is of fundamental importance in defining full
remission or recovery of MDEs. Ongoing residual SD symptoms during the recovery
periods after an MDE are associated with psychosocial disability, more rapid MDE
relapse, and a more severe chronic future course of illness, all of which
indicate that when residual SD symptoms are present the MDE has not fully
remitted and the disease is still active. When all depressive symptoms of an MDE
abate for a minimum of 8 weeks, then full remission has been achieved. MDE
remission defined in this way is associated with significant delay or even
prevention of future episode relapse and a less severe, relapsing, and chronic
future course. The authors submit that the research reviewed in this article
heralds a new paradigm in understanding the progression of clinical depression
through various overlapping stages of severity, which begin at the seemingly
"subclinical" level of depressive symptoms. This conceptualization in turn
dictates a public health approach, which emphasizes that treatment of MDD even
at the deceptively mild levels of symptoms should be initiated or maintained.
4: J Clin Psychiatry 2002 Sep;63(9):807-11
Subsyndromal depression is associated with functional impairment in patients
with bipolar disorder.
Altshuler LL, Gitlin MJ, Mintz J, Leight KL, Frye MA.
Department of Psychiatry and Biobehavioral Sciences, University of California,
Los Angeles, USA. altshuler.lori@west-la.va.gov
BACKGROUND: The purpose of this study was to assess whether a relationship
exists between mild depressive symptoms and overall functioning in subjects with
bipolar disorder. METHOD: Twenty-five male subjects with bipolar I disorder
(DSM-III-R criteria), who had not experienced a DSM-III-R episode of mania,
hypomania, or major depression for 3 months as determined using the Structured
Clinical Interview for DSM-III-R, were evaluated for degree of depressive
symptoms using the Hamilton Rating Scale for Depression (HAM-D) and for overall
functional status using the Global Assessment of Functioning (GAF, DSM-IV Axis
V). RESULTS: GAF scores were significantly negatively correlated with HAM-D
scores (r = -0.61, df = 23, p = .001), despite the fact that no patient had a
HAM-D score high enough to be considered clinically depressed. CONCLUSION: The
results of this study support a relationship between subsyndromal depressive
symptoms and functional impairment in bipolar subjects, despite their not
meeting threshold criteria for a major depressive episode. These findings raise
the possibility that in some patients with bipolar disorder subsyndromal
depressive symptoms might contribute to ongoing functional impairment.
5: Psychother Psychosom 2001 Sep-Oct;70(5):232-8
Prevalence and clinical correlates of residual depressive symptoms in bipolar II
disorder.
Benazzi F.
Department of Psychiatry, National Health Service (AUSL), Forli, Italy.
f.benazzi@fo.nettuno.it
BACKGROUND: Most patients with unipolar and bipolar I disorder have residual
symptoms, despite successful treatment. The appraisal of subsyndromal
symptomatology has important implications for pathophysiological models of
disease and relapse prevention. Residual symptoms in bipolar II disorder were
studied insufficiently. The study of residual symptoms in bipolar II disorder is
important, because many depressed outpatients may suffer from it and because
bipolar II disorder may be distinct from type I. The study aims were to assess
the prevalence and clinical correlates of persistent residual depressive
symptoms in bipolar II disorder. METHODS: 138 consecutive patients with bipolar
II disorder and 83 unipolar disorder outpatients, presenting for major
depressive episode treatment in private practice, were interviewed with the
Structured Clinical Interview for DSM-IV Axis I Disorders - Clinician's Version.
Study variables were persistent (more than 2 years) residual depressive
symptoms, age, gender, age at onset, illness duration, recurrences, axis I
comorbidity, severity, psychotic, melancholic and atypical features. RESULTS:
The prevalence of residual depressive symptoms was 44.9% in bipolar II disorder
and 43.3% in unipolar disorder. Residual depressive symptoms in bipolar II and
unipolar disorders were significantly and positively associated with illness
duration and recurrences. CONCLUSIONS: Persistent residual depressive symptoms
were common in bipolar II disorder. Residual unipolar and bipolar II depressive
symptoms were related to duration of illness and number of recurrences. Reducing
these variables could reduce and prevent residual symptoms. A mechanism of
kindling (more mood episodes leading to worse outcome) could be that of leaving
a larger and larger amount of residual symptoms after the acute episode has
subsided. Copyright 2001 S. Karger AG, Basel.
6: Am J Orthopsychiatry 2001 Jan;71(1):87-97
Subsyndromal depressive symptoms and major depression in postpartum women.
Weinberg MK, Tronick EZ, Beeghly M, Olson KL, Kernan H, Riley JM.
Department of Pediatrics, Harvard Medical School, Boston, USA.
weinberg@hub.tch.harvard.edu
This study documents differences in the psychosocial functioning of women three
months postpartum with subclinical depression, major depression prior to the
birth of the baby, major depression both pre- and post-birth, and no depression.
An understanding of these differences may have implications for intervention
insofar as maternal depression places at risk not only the mother's functioning
but her infant's development, as well.
7: J Affect Disord 2001 Mar;63(1-3):51-8
Subsyndromal depression in adolescents after a brief psychotherapy trial: course
and outcome.
Brent DA, Birmaher B, Kolko D, Baugher M, Bridge J.
Division of Child and Adolescent Psychiatry, Western Psychiatric Institute and
Clinic, 3811 O'Hara Street, Pittsburgh, PA 15213, USA. brentda@msx.upmc.edu
INTRODUCTION: Subsyndromal depression has been associated with an increased risk
of the development of major depressive disorder (MDD). Since treatment trials of
adolescent MDD often result in subsyndromal depression as the outcome, the
long-term course of these youth would be useful to understand. METHODS: 107
adolescents with MDD participated in a clinical psychotherapy trial, of whom 99
were followed up for two years after acute treatment. Those with subsyndromal
depression (2-3 symptoms) at the end of acute treatment were compared to those
who were well (< or =1 symptom) and those who were still depressed (> or =4
symptoms) on presentation at intake, the end of treatment, and over the two-year
follow-up. RESULTS: Of the 99 youth, at the end of acute treatment 26 were well,
18 were subsyndromal, and 55 were still depressed. A substantial proportion of
the subsyndromally depressed youth were functionally impaired (38%), and showed
a protracted time to recovery. The risk of recurrence was similar to those who
were without depression at the end of acute treatment (46% vs. 44%). Recurrence
was predicted by depressive symptom severity and family difficulties at the end
of acute treatment. LIMITATIONS: A large proportion of the subsyndromal groups
received open treatment that may have altered their course. Also, this was a
referred sample, rather than an epidemiological one. CONCLUSIONS: In clinical
samples treated with psychotherapy, subsyndromal depression poses a significant
risk for functional impairment and protracted recovery. Depressive recurrence
may be prevented by targeting reduction of symptom severity and of family
difficulties.
8: Depress Anxiety 2000;12(1):30-9
Subsyndromal symptomatic depression: a new concept.
Sadek N, Bona J.
Department of Psychiatry and Behavioral Sciences, Emory University School of
Medicine, Atlanta, Georgia, USA.
Although DSM-IV acknowledged the clinical significance of some subthreshold
forms of unipolar depression, such as minor depression (MinD) and recurrent
brief depression (RBD), clinicians continued to struggle with the concept of
"subthreshold" depression. A substantial number of patients continued to present
with depressive symptoms that still did not satisfy any DSM-IV diagnosis.
Generally, these patients failed to complain of anhedonia and depressed mood, a
criterion that DSM-IV mandates for any diagnosis of depression. Therefore,
researchers reexamined the question of whether this cluster of depressive
symptoms, in the absence of anhedonia and depressed mood, was clinically
significant. Some researchers labeled this cluster of symptoms, "subsyndromal
symptomatic depression" (SSD). Specifically, SSD is defined as a depressive
state having two or more symptoms of depression of the same quality as in major
depression (MD), excluding depressed mood and anhedonia. The symptoms must be
present for more than 2 weeks and be associated with social dysfunction. Using
Medline Search, the authors reviewed the literature on the epidemiology,
demographics, clinical characteristics, and psychosocial impairment of SSD. SSD
is found to be comparable in demographics and clinical characteristics to MD,
MinD, and dysthymia. SSD is also associated with significant psychosocial
dysfunction as compared with healthy subjects. Further; it has significant risk
for suicide and future MD. Few studies have been conducted on the treatment of
SSD. The high prevalence of SSD, the significant psychosocial impairment
associated with it, and the chronicity of its course make subsyndromal
symptomatic depression a matter for serious consideration by clinicians and
researchers.
9: Subthreshold depression in the elderly: qualitative or quantitative distinction?
Geiselmann B, Bauer M.
Department of Behavioral Therapy and Psychosomatic Medicine, Klinik Seehof BfA,
Teltow, Germany.
Recent studies revealed that subthreshold depression (or "subclinical" or
"subsyndromal" depression) can have clinical validity because it is related to
dysfunction and disability and is a risk factor for major depression. However,
none of these studies focused on old age. Therefore, one aim of the psychiatric
part of the multidisciplinary Berlin Aging Study (BASE) was also to detect
milder forms of psychopathological syndromes, especially subthreshold
depression, compared with specified forms such as major depression and dysthymia
according to the DSM-III-R. The present evaluation shows that subthreshold
depression can be characterized in 2 ways: firstly, as a quantitatively minor
variant of depression or a depression-like state with fewer symptoms or with
less continuity; and secondly, as qualitatively different from major depression
with fewer suicidal thoughts or feelings of guilt or worthlessness, while
worries about health and weariness of living occur with a similar frequency.
10: Epidemiol Psichiatr Soc 1999 Oct-Dec;8(4):255-61
Subthreshold affective disorders: a useful concept in psychiatric epidemiology?
Schotte K, Cooper B.
Section of Old Age Psychiatry, Institute of Psychiatry, London, UK.
OBJECTIVE: In recent years an extensive literature has grown up around the
concepts of subthreshold, subsyndromal, minor and brief recurrent affective
disorder and their applications in population-based research. The aim of this
short review is to examine the definitions and current status of these proposed
categories with special reference to depression, and to assess their potential
contribution to psychiatric epidemiology. METHOD: A Medline search was carried
out for the period 1965-1999, based on the above four terms. Relevant references
found in all identified publications were also followed up. RESULTS: In great
measure these constructs have been developed as a response to deficiencies in
the DSM classification system and to a lesser extent in the ICD. The groups are
all defined by having fewer criterial symptoms, or a shorter duration of
symptoms, than the 'official' diagnostic categories. Use of these definitions
has resulted in widely varying prevalence estimates. CONCLUSION: Improved
methods are badly needed for classifying all those persons in the wider
community who are in need of medical treatment and help for psychological
disorder, but do not satisfy operational criteria laid down in the official
guidelines. This cannot, however, be achieved simply by lowering operational
thresholds in these systems. Further research on clinical and psycho-social
characteristics of the common mental disorders is called for, and in many
societies a favourable setting is that of primary health care, where a move
towards pragmatic, comprehensive classification of community health problems is
already under way.
11: Addict Behav 1999 Nov-Dec;24(6):781-94
History of depression and subsyndromal depression in women smokers.
Borrelli B, Marcus BH, Clark MM, Bock BC, King TK, Roberts M.
Brown University School of Medicine & The Miriam Hospital, Division of
Behavioral and Preventive Medicine, Providence, RI 02906, USA.
Belinda_Borrelli@Brown.edu
While Major Depressive Disorder (MDD) is associated with difficulty quitting
smoking, few studies have examined the role of subsyndromal depression (SubD).
We examined pretreatment differences in smoking, weight concerns, and negative
affect among three groups of women (N = 281) enrolling in a smoking cessation
program who responded to a self-report questionnaire about the lifetime presence
of MDD symptoms: self-report positive for MDD, self-report positive for SubD,
and self-report negative for depression (fulfilling either DSM-III-R symptom or
duration criteria, but not both). Compared to MDD Subjects (Ss), SubD Ss were
more likely to report eating disordered behaviors. Compared to Non-Depressed
(Non-Dep) Ss, SubD Ss initiated smoking earlier, and reported greater previous
withdrawal symptoms, more eating disordered behaviors, and higher anxiety,
depression, and stress. Compared to Non-Dep Ss, MDD Ss reported a greater
smoking rate during their heaviest usage period, greater previous withdrawal
symptoms, lower self-efficacy to manage food intake (especially during negative
affect situations), and greater depression and anxiety. Many of these
significant differences disappeared when SubD Ss were combined with Non-Dep Ss
and compared with MDD Ss as is done traditionally. SubD does not appear to be on
a continuum with Non-Dep and MDD groups, but rather warrants further
investigation as a discrete subset of smokers. The implications for assessment
and treatment are discussed.
12: Actas Esp Psiquiatr 1999 Jul-Aug;27(4):223-7
[Subsyndromal depressive semiology in severe alcoholism]
[Article in Spanish]
Huertas D, Bautista S, Sanjoaquin A, Chamorro L, Gilaberte I.
Servicio de Psiquiatria, Hospital Universitario de Guadalajara, Guadalajara,
19002, Espana.
INTRODUCTION: Several investigations have communicated frequent association
between alcohol dependence and depression. METHOD: 21 subjects with DSM-IV
criteria for alcohol dependence were included in an open label trial for alcohol
withdrawal. At inclusion and along the follow-up none of the probands met DSM-IV
criteria for mood disorder. Follow-up included a 15-day detoxification period
and 195 days of withdrawal program, including treatment with 20 mg/d of
fluoxetine. Occurrence of depressive semiology was measured using the Beck
Depression Inventory (BDI) on day 15 (after detoxification), day 75 and day 210
(after withdrawal from ethanol of 195 days). RESULTS: 67% of the sample showed a
positive basal BDI (after-detoxification-BDI> 9). Global retention rate after
210 days of follow-up was 57%. All patients who dropped out the investigation
before completing the protocol showed a basal BDI in the depressive rank (BDI=
10-63), and maintained depressive scores in this instrument until their
abandonment. CONCLUSIONS: Prevalence of <
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