The Relationship Between Bipolar Disorder and A.D.D.

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

J Child Adolesc Psychopharmacol. 2003 Winter;13(4):531-43. 
 
Temperament and character factors in a prepubertal and early adolescent bipolar
disorder phenotype compared to attention deficit hyperactive and normal
controls.
 
Tillman R, Geller B, Craney JL, Bolhofner K, Williams M, Zimerman B, Frazier J,
Beringer L.
 
Department of Psychiatry, Washington University School of Medicine, St. Louis,
Missouri 63110, USA.
 
OBJECTIVE: To compare temperament and character (T/C) factors in a prepubertal
and early adolescent bipolar disorder phenotype (PEA-BP), attention deficit
hyperactivity disorder (ADHD), and normal community controls (NC). METHODS:
Subjects in PEA-BP (n = 101), ADHD (n = 68), and NC (n = 94) groups were
diagnostically assessed with the Washington University in St. Louis Kiddie
Schedule for Affective Disorders and Schizophrenia given separately to mothers
about their children and to children about themselves. Diagnosis of PEA-BP was
defined as Diagnostic and Statistical Manual of Mental Disorders, fourth
edition, bipolar disorder (manic or mixed phase) with at least one cardinal
symptom of mania (i.e., elation and/or grandiosity) to avoid diagnosing mania by
symptoms that overlapped with those for ADHD. The Junior Temperament and
Character Inventory (JTCI) was used to measure T/C factors. Separate JTCI data
were obtained from mothers about their children and from children about
themselves. RESULTS: Parent- and child-reported novelty seeking were
significantly higher in PEA-BP than in NC subjects. Novelty seeking was
significantly higher in the ADHD group than in the NC group only by parent
report. Parent and/or child report showed PEA-BP and ADHD subjects to be
significantly less reward-dependent, persistent, self-directed, and cooperative
than NC subjects. Parent-reported cooperativeness was significantly lower in
PEA-BP than in ADHD subjects. CONCLUSION: These findings are consistent with
studies of novelty seeking in adults who had either BP or ADHD and are discussed
in relationship to genetic studies of dopamine receptors and novelty seeking.
 
PMID: 14977466 [PubMed - indexed for MEDLINE]
<HR>
J Child Adolesc Psychopharmacol. 2003 Winter;13(4):507-14. 
 
Clinical correlates of episodicity in juvenile mania.
 
Bhangoo RK, Dell ML, Towbin K, Myers FS, Lowe CH, Pine DS, Leibenluft E.
 
The Mood and Anxiety Program, National Institute of Mental Health, National
Institutes of Health, Department of Health and Human Services, Bethesda,
Maryland, USA.
 
OBJECTIVE: Researchers debate whether the diagnostic criteria for mania should
differ between children and adults. Specifically, although the Diagnostic and
Statistical Manual of Mental Disorders (fourth edition; DSM-IV) requires
episodic mood changes, children commonly are diagnosed as manic on the basis of
chronic irritability. In this preliminary study, children carrying a diagnosis
of bipolar disorder (BPD) in the community were classified as having either
episodic or chronic symptoms. We hypothesized that the episodic group would be
more likely to have a history of psychosis and a parental history of BPD,
whereas the chronic group would be more likely to have conduct disorder.
METHODS: Parents of children carrying the BPD diagnosis were interviewed on the
telephone to obtain psychiatric and family histories. Children were considered
episodic (n = 34) if they had a history of one or more DSM-IV manic/hypomanic
episodes meeting full duration criteria and chronic (n = 53) if they had no
discernable episodes. RESULTS: The episodic group was more likely to have had
psychosis, parental history of BPD, and to have experienced each manic symptom
except for irritability and psychomotor agitation. Children in the episodic
group were also more likely to have had a depressive episode meeting full DSM-IV
criteria and were more likely to have made a suicide attempt. Children in the
chronic group were not more likely to meet criteria for conduct disorder but
were more likely to exhibit violence toward others. CONCLUSIONS: These
preliminary data indicate that, among children being treated for BPD in the
community, those with discrete episodes of mania may be more likely to have a
lifetime history of psychosis and a parental history of BPD. The latter
hypothesis should be tested in a sample where relatives are interviewed
directly.
 
PMID: 14977463 [PubMed - indexed for MEDLINE]
<HR>
J Child Adolesc Psychopharmacol. 2003 Winter;13(4):489-94. 
 
Mania in six preschool children.
 
Tumuluru RV, Weller EB, Fristad MA, Weller RA.
 
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania
15213, USA. tumulururv@upmc.edu
 
At least nine cases of apparent preschool manic-depressive illness have been
previously reported in the literature. In each of these children, a strong
family history of affective illness was noted. In this report, the case
histories of six preschool children ages 3 to 5 years with bipolar illness are
summarized. These six were obtained from a sample of 36 consecutively
hospitalized preschool children. Thus 17% of these hospitalized preschool
children had bipolar illness. All had irritable mood, strong family history of
affective illness, and previous presentation with symptoms of attention deficit
hyperactivity disorder. They were diagnosed following a thorough clinical
interview. Five children were treated with lithium; all five improved. Preschool
mania exists as an identifiable entity and may respond to classic pharmacologic
treatments.
 
Publication Types:
 Case Reports
 
PMID: 14977461 [PubMed - indexed for MEDLINE]
<HR>
J Clin Psychiatry. 2003 Oct;64(10):1170-6; quiz, 1274-6. 
 
Occult mood disorders in 104 consecutively presenting children referred for the
treatment of attention-deficit/hyperactivity disorder in a community mental
health clinic.
 
Dilsaver SC, Henderson-Fuller S, Akiskal HS.
 
Rio Grande City Texas Community Mental Health Mental Retardation Clinic, Rio
Grande City, TX, USA. StevenDilsaver@aol.com
 
OBJECTIVE: To ascertain the prevalence of mood disorders among consecutively
evaluated prepubertal children presenting for the treatment of
attention-deficit/hyperactivity disorder (ADHD) in a community mental health
clinic. METHOD: 104 children received systematic assessments designed to
identify individuals meeting the DSM-IV criteria for major depressive disorder
(MDD), mania, and ADHD. "Standard" and "modified" criteria for mania were
employed. Modified criteria, in an effort to minimize false-positive diagnoses
of mania, required the presence of euphoria and/or flight of ideas. A child
meeting the criteria for MDD or either set of criteria for mania was categorized
as having a mood disorder. Mood disorders in first-degree relatives were
assessed using a systematic interview. Data were gathered from 2000 to 2002.
RESULTS: Sixty-two children (59.6%) had a mood disorder. Compared with those who
did not have a mood disorder, they were 3.3 times more likely (54.8% vs. 16.7%)
to have a family history of any affective disorder (p <.0001) and 18.3 times
more likely (43.5% vs. 2.4%) to have a family history of bipolar disorder (p
<.0001). Twenty (32.3%) of the children with and none without a mood disorder
had psychotic features (p <.0001). Compared with those meeting only the standard
criteria for mania, those meeting the modified criteria were 9.1 times more
likely (69.8% vs. 7.7%) to have a family history of an affective disorder (p
<.0001) and 7.3 times more likely (55.8% vs. 7.7%) to have a family history of
bipolar disorder (p =.002). CONCLUSION: Children who presumably have ADHD often
have unrecognized affective illness. Our findings support the view that children
meeting the modified criteria for mania have veritable bipolar disorder. These
findings, which were derived in the course of delivering routine clinical
services in a community mental health clinic, are consistent with those obtained
in research settings suggesting that children presenting with ADHD often have
occult mood disorders, especially unrecognized bipolarity. We suggest that
clinicians encountering children with prominent features of ADHD inquire about
the presence of euphoria and flight of ideas. We submit that the presence of
these "classic" manifestations of mania strongly suggests the presence of occult
bipolarity, even if course of illness otherwise markedly deviates from "classic"
descriptions.
 
PMID: 14658964 [PubMed - indexed for MEDLINE]
<HR>
J Am Acad Child Adolesc Psychiatry. 2003 Dec;42(12):1486-93. 
 
Ages of onset and rates of syndromal and subsyndromal comorbid DSM-IV diagnoses
in a prepubertal and early adolescent bipolar disorder phenotype.
 
Tillman R, Geller B, Bolhofner K, Craney JL, Williams M, Zimerman B.
 
Department of Psychiatry, Washington University School of Medicine, St. Louis,
USA.
 
OBJECTIVE: To study rates and ages of onset of DSM-IV syndromal and subsyndromal
comorbidity in a prepubertal and early adolescent bipolar disorder phenotype
(PEA-BP) (N = 93) compared to attention-deficit/hyperactivity disorder (ADHD) (N
= 81). METHOD: The WASH-U-KSADS was given by raters blinded to subject group
separately to mothers about their children and to children about themselves.
PEA-BP was defined as DSM-IV mania with at least one cardinal symptom of mania
(elation or grandiosity) to avoid diagnosing using only symptoms that overlapped
with those for ADHD. Syndromal diagnoses required a CGAS score of 60 or less to
ensure severity at a level of definite "caseness." RESULTS: PEA-BP subjects were
aged 10.9 (SD = 2.6) at baseline and 6.8 (SD = 3.4) at onset of first mania
episode. Rates of oppositional defiant disorder and total number of
comorbidities were significantly higher in the PEA-BP group than the ADHD group.
In PEA-BP subjects, mean ages of onset of ADHD occurred before the first manic
episode, and obsessive compulsive, oppositional defiant, social phobia,
generalized anxiety, separation anxiety, and conduct disorders occurred after.
CONCLUSIONS: Onsets of ADHD before mania and of oppositional defiant
disorder/conduct disorder after mania have clinical and research implications.
These include the need to examine for mania symptoms in children with ADHD
and/or oppositional defiant disorder/conduct disorder and to develop scales to
differentiate preschool mania from ADHD. Comparison with other studies
demonstrated the importance of DSM system and severity scales in reporting
comorbidity rates.
 
PMID: 14627884 [PubMed - indexed for MEDLINE]
<HR>
Paediatr Drugs. 2003;5(11):741-50. 
 
Psychiatric comorbidities in children with attention deficit hyperactivity
disorder: implications for management.
 
Pliszka SR.
 
Division of Child and Adolescent Psychiatry, Department of Psychiatry, The
University of Texas Health Science Center at San Antonio, San Antonio, Texas,
USA.
 
Attention deficit hyperactivity disorder (ADHD) is frequently comorbid with a
variety of psychiatric disorders. These include oppositional defiant disorder
and conduct disorder (CD), as well as affective, anxiety, and tic disorders.
ADHD and ADHD with comorbid CD appear to be distinct subtypes; children with
ADHD/CD are at higher risk of antisocial personality and substance abuse as
adults. Stimulants are often effective treatments for aggressive or antisocial
behavior in patients with ADHD, but mood stabilizers or atypical antipsychotics
may be used to treat explosive aggressive outbursts. Response to stimulants is
not affected by comorbid anxiety, but children with ADHD/anxiety disorder may
show greater benefit from psychosocial interventions than those with ADHD alone.
The degree of prevalence of major depressive disorder (MDD) and bipolar disorder
among children with ADHD is controversial, but a subgroup of severely
emotionally labile ADHD children who present serious management issues for the
clinician clearly exists. Antidepressants may be used in conjunction with
stimulants to treat MDD, while mood stabilizers and atypical antipsychotics are
often required to treat manic symptoms or aggression. After resolution of the
manic episode, stimulant treatment of the comorbid ADHD may be safely
undertaken. Recent research suggests that stimulants can be safely used in
children with comorbid ADHD and tic disorders, but the addition of anti-tic
agents to stimulants is often necessary. Clinicians who work with patients with
ADHD should be prepared to deal with a wide range of emotional and behavioral
problems beyond the core symptoms of inattention and impulsivity/hyperactivity.
 
PMID: 14580223 [PubMed - in process]
<HR>
7: Curr Opin Pediatr. 2003 Oct;15(5):476-82. 
 
Assessment and treatment of attention deficit hyperactivity disorder in children
with comorbid psychiatric illness.
 
Waxmonsky J.
 
State University of New York at Buffalo, Department of Psychiatry, USA.
jgw@buffalo.edu
 
PURPOSE OF REVIEW: Attention deficit hyperactivity disorder (ADHD) frequently
occurs with a wide variety of comorbid psychiatric disorders such as conduct
disorder, depression, mania, anxiety, and learning disabilities. Because the
vast majority of children with ADHD are treated in primary care settings, it is
important that primary medical doctors be proficient in the diagnosis and
initial treatment of children with ADHD and its commonly occurring comorbid
disorders. ADHD research is beginning to focus on the treatment of these
comorbidly ill children. This review will summarize the recent findings from the
psychiatric literature in an attempt to provide the clinician with some initial
diagnostic and treatment guidelines for ADHD and its comorbidities. RECENT
FINDINGS: The NIMH Multimodal Treatment Study of ADHD found that children with
other disruptive behavior disorders plus ADHD respond well to stimulant
medications, with behavioral interventions reducing academic and social
impairment. Children with anxiety and ADHD are very responsive across multiple
dimensions to behavioral and pharmacological ADHD treatments. Much less is known
about the impact of depression on ADHD, and significant debate exists
surrounding the identification and treatment of bipolar disorder in children
with ADHD. Children with learning disabilities respond well to stimulants but
often require additional educational supports. New findings suggest that
treating ADHD may prevent the development of future psychiatric disorders.
SUMMARY: The presence of comorbid illness is associated with significant
additional morbidity and complicates the diagnosis, treatment, and prognosis of
ADHD. Therefore, it is important to identify and treat any comorbid psychiatric
conditions in a child with ADHD.
 
Publication Types:
 Review
 Review, Tutorial
 
PMID: 14508296 [PubMed - indexed for MEDLINE]
<HR>
Int J Neuropsychopharmacol. 2003 Jun;6(2):139-44. 
 
Bipolar comorbidity: from diagnostic dilemmas to therapeutic challenge.
 
Sasson Y, Chopra M, Harrari E, Amitai K, Zohar J.
 
Chaim Sheba Medical Centre, Division of Psychiatry, Tel Hashomer, Israel.
 
Comorbidity in bipolar disorder is the rule rather than the exception more than
60% of bipolar patients have a comorbid diagnosis and is associated with a mixed
affective or dysphoric state; high rates of suicidality; less favourable
response to lithium and poorer overall outcome. There is convincing evidence
that rates of substance use and anxiety disorders are higher among patients with
bipolar disorder compared to their rates in the general population. The
interaction between anxiety disorders and substance use goes both ways: patients
with bipolar disorder have a higher rate of substance use and anxiety disorder,
and vice versa. Bipolar disorder is also associated with borderline personality
disorder and ADHD, and to a lesser extent with weight gain. As more than 40% of
bipolar patients have anxiety disorder, it is indicated that while diagnosing
bipolar patients, systematic enquiry about different anxiety disorders is called
for. This also presents a therapeutic challenge, since agents that effectively
treat anxiety disorders are associated with the risk of induced mania.
Therefore, the treating psychiatrist needs to carefully evaluate the potential
benefit of treating the anxiety against the potential cost of inducing a manic
episode. A possible solution would be to use, when possible, a
non-pharmacological intervention, such as a cognitivebehavioural approach.
Alternately, it is suggested that the clinician attempts to ensure that the
patient receives adequate treatment with mood stabilizers before slowly and
carefully attempting the addition of anti-anxiety compounds with a relatively
lower risk of mania induction (e.g. SSRIs compared to TCAs).
 
PMID: 12890307 [PubMed - indexed for MEDLINE]
<HR>
J Child Adolesc Psychopharmacol. 2003 Summer;13(2):123-36. 
 
Response to methylphenidate in children with attention deficit hyperactivity
disorder and manic symptoms in the multimodal treatment study of children with
attention deficit hyperactivity disorder titration trial.
 
Galanter CA, Carlson GA, Jensen PS, Greenhill LL, Davies M, Li W, Chuang SZ,
Elliott GR, Arnold LE, March JS, Hechtman L, Pelham WE, Swanson JM.
 
Columbia University/New York State Psychiatric Institute, New York, New York
10032, USA. cg168@columbia.edu
 
OBJECTIVE: Recent reports raise concern that children with attention deficit
hyperactivity disorder (ADHD) and some manic symptoms may worsen with stimulant
treatment. This study examines the response to methylphenidate in such children.
METHODS: Data from children participating in the 1-month methylphenidate
titration trial of the Multimodal Treatment Study of Children with ADHD were
reanalyzed by dividing the sample into children with and without some manic
symptoms. Two "mania proxies" were constructed using items from the Diagnostic
Interview Schedule for Children (DISC) or the Child Behavior Checklist (CBCL).
Treatment response and side effects are compared between participants with and
without proxies. RESULTS: Thirty-two (11%) and 29 (10%) participants fulfilled
criteria for the CBCL mania proxy and DISC mania proxy, respectively. Presence
or absence of either proxy did not predict a greater or lesser response or side
effects. CONCLUSION: Findings suggest that children with ADHD and manic symptoms
respond robustly to methylphenidate during the first month of treatment and that
these children are not more likely to have an adverse response to
methylphenidate. Further research is needed to explore how such children will
respond during long-term treatment. Clinicians should not a priori avoid
stimulants in children with ADHD and some manic symptoms.
 
PMID: 12880507 [PubMed - indexed for MEDLINE]
<HR>
Biol Psychiatry. 2003 Jul 1;54(1):9-16. 
 
An open trial of bupropion for the treatment of adults with
attention-deficit/hyperactivity disorder and bipolar disorder.
 
Wilens TE, Prince JB, Spencer T, Van Patten SL, Doyle R, Girard K, Hammerness P,
Goldman S, Brown S, Biederman J.
 
Clinical Research Program in Pediatric Psychopharmacology, Massachusetts General
Hospital, Harvard Medical School, Boston, Massachusetts, USA.
 
BACKGROUND: Despite the increasing recognition of comorbid
attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) in
adults, there are no prospective trials of pharmacological agents to treat ADHD
in these patients. Given the efficacy of bupropion for ADHD in adults, as well
as its use in the management of bipolar depression, we studied the tolerability
and efficacy of sustained-release (SR) bupropion in adults with ADHD plus BPD.
METHODS: This was an open, prospective, 6-week trial of bupropion SR (up to 200
mg b.i.d.) in adults with DSM-IV ADHD plus historical bipolar I disorder (BPD I)
(10%) or bipolar II disorder (BPD II) (90%). Adults receiving adjunct antimanic
agents (mood stabilizers and antipsychotics) at baseline were included in the
study. We used standardized psychiatric instruments for diagnosis and outcome.
Efficacy was based primarily on the Clinical Global Impression Scale (CGI) for
ADHD and the ADHD symptom checklist. RESULTS: Of 36 patients entered (75% male,
mean age 34 years), 30 patients (83%) completed the protocol. At end point (last
observation carried forward [LOCF]) compared to baseline, treatment with
bupropion SR resulted in significant reductions in the ADHD symptom checklist
(-55%, z = 5.63, p <.001) and CGI severity of ADHD (-40%, z = 6.285, p <.001).
Bupropion was associated with reductions in ratings of mania and depression.
CONCLUSIONS: The results from this open study of adults with ADHD plus BPD
suggest that sustained-release bupropion may be effective in treating ADHD in
the context of a lifetime diagnosis of BPD, without significant activation of
mania. Further controlled trials are warranted.
 
Publication Types:
 Clinical Trial
 
PMID: 12842303 [PubMed - indexed for MEDLINE]
<HR>
Biol Psychiatry. 2003 Jul 1;54(1):1-8. 
 
Can adults with attention-deficit/hyperactivity disorder be distinguished from
those with comorbid bipolar disorder? Findings from a sample of clinically
referred adults.
 
Wilens TE, Biederman J, Wozniak J, Gunawardene S, Wong J, Monuteaux M.
 
Clinical Research Program in Pediatric Psychopharmacology, Massachusetts General
Hospital, Harvard Medical School, Boston, Massachusetts, USA.
 
BACKGROUND: Despite data describing the overlap of attention deficit
hyperactivity disorder (ADHD) and bipolar disorder (BPD) in youth, little is
known about adults with these co-occurring disorders. We now evaluate the
clinical characteristics of referred adults with (n = 24) and without BPD (n =
27). METHODS: Referred adults to clinical trials of ADHD were evaluated by
psychiatric evaluation using DSM-IV criteria. Structured psychiatric interviews
were used to systematically assess adult and childhood disorders. RESULTS: The
vast majority of patients with ADHD plus BPD had bipolar II disorder (88%).
Adults with ADHD plus BPD had higher rates of the combined subtype of ADHD
compared to ADHD without BPD (chi(2) = 8.7, p =.003), a greater number of DSM-IV
ADHD symptoms (14.8 +/- 2.9 and 11.4 +/- 4.0; t = -3.4, p <.01), more
attentional symptoms of ADHD (8.1 +/- 1.4 and 6.8 +/- 2.1; t = -2.5, p <.02;
trend), poorer global functioning (47 +/- 5.9 and 52 +/- 7.4, t = 2.6, p <.02;
trend), and additional comorbid psychiatric disorders (3.7 +/- 2.5 and 2.0 +/-
1.9; t = -2.9, p <.01). CONCLUSIONS: These results suggest that adults with ADHD
plus BPD have prototypic symptoms of both disorders, suggesting that both
disorders are present and are distinguishable clinically.
 
PMID: 12842302 [PubMed - indexed for MEDLINE]
<HR>
J Child Psychol Psychiatry. 2003 May;44(4):612-36. 
 
The validity of analyses testing the etiology of comorbidity between two
disorders: a review of family studies.
 
Rhee SH, Hewitt JK, Corley RP, Stallings MC.
 
Institute for Behavioral Genetics, University of Colorado, Boulder 80309, USA.
soo.rhee@colorado.edu
 
BACKGROUND: Knowledge regarding the causes of comorbidity between two disorders
has a significant impact on research regarding the classification, treatment,
and etiology of the disorders. Two main analytic methods have been used to test
alternative explanations for the causes of comorbidity in family studies:
biometric model fitting and family prevalence analyses. Unfortunately, the
conclusions of family studies using these two methods have been conflicting. In
the present study, we examined the validity of family prevalence analyses in
testing alternative comorbidity models. METHOD: We reviewed 42 family studies
that used family prevalence analyses to test three comorbidity models: the
alternate forms model, the correlated liabilities model, or the three
independent disorders model. We conducted the analyses used in these studies on
datasets simulated under the assumptions of 13 alternative comorbidity models
including the three models tested most often in the literature. RESULTS: Results
suggest that some analyses may be valid tests of the alternate forms model
(i.e., two disorders are alternate manifestations of a single liability), but
that none of the analyses are valid tests of the correlated liabilities model
(i.e., a significant correlation between the risk factors for the two disorders)
or the three independent disorders model (i.e., the comorbid disorder is a
third, independent disorder). CONCLUSION: Family studies using family prevalence
analyses may have made incorrect conclusions regarding the etiology of
comorbidity between disorders.
 
Publication Types:
 Review
 Review, Academic
 Validation Studies
 
PMID: 12751852 [PubMed - indexed for MEDLINE]
<HR>
J Am Acad Child Adolesc Psychiatry. 2003 May;42(5):552-60. 
 
Manic symptoms in young males with ADHD predict functioning but not diagnosis
after 6 years.
 
Hazell PL, Carr V, Lewin TJ, Sly K.
 
Center for Mental Health Studies, University of Newcastle, Newcastle, New South
Wales, Australia. hazell@mail.newcastle.edu.au
 
OBJECTIVE: To compare the outcome in early adulthood of males who met criteria
for attention-deficit/hyperactivity disorder (ADHD) and mania, ADHD alone, or no
psychiatric disorder when aged 9-13 years. METHOD: Males who met criteria at
baseline assessment conducted in the period 1992-1994 for mania+ADHD (n = 15),
ADHD without mania (n = 65), or no psychiatric diagnosis (n = 17) were
reevaluated after 6 years using computer-assisted structured interviews for Axis
I and Axis II disorders, questionnaires about functioning and service
utilization, and a clinician-rated assessment of global functioning. RESULTS:
There were no group differences in the prevalence of Axis I or Axis II
disorders, with the exception of alcohol abuse, which was higher in controls.
Manic symptoms persisted in only one mania+ADHD subject, while three (5%) of the
ADHD subjects had new-onset manic symptoms. There were no clear cases of bipolar
disorder. The groups were not distinguished on levels of service utilization or
criminal behavior, but global functioning was significantly lower at follow-up
in the mania+ADHD group compared with controls. CONCLUSIONS: Although a pilot
study in scope, the findings cast doubt on a link between mania symptoms
associated with ADHD in childhood and later bipolar disorder.
 
PMID: 12707559 [PubMed - indexed for MEDLINE]
<HR>
Am J Psychiatry. 2002 Jun;159(6):927-33. 
 
Comment in:
 Am J Psychiatry. 2002 Jun;159(6):893-4.
 
Two-year prospective follow-up of children with a prepubertal and early
adolescent bipolar disorder phenotype.
 
Geller B, Craney JL, Bolhofner K, Nickelsburg MJ, Williams M, Zimerman B.
 
Department of Psychiatry, Washington University School of Medicine, St. Louis,
MO 63110, USA. gellerb@medicine.wustl.edu
 
OBJECTIVE: Longitudinal outcomes of bipolar disorder with onset in the late
teenage years or in adulthood have been reported, but little is known about the
natural history of childhood-onset mania. This study sought to provide rates and
predictors of recovery and relapse in children with a prepubertal and early
adolescent bipolar disorder phenotype. METHOD: Eighty-nine consecutively
ascertained outpatient subjects (mean age=10.9 years [SD=2.7]) received
comprehensive research assessments, including separate interviews of mothers
about their children and of children about themselves, at baseline and at 6, 12,
18, and 24 months after baseline. The study phenotype required DSM-IV mania with
elation and/or grandiosity as one criterion to distinguish the study phenotype
from a diagnosis of mania based on criteria overlapping with those for attention
deficit hyperactivity disorder and to ensure that subjects had at least one of
the two cardinal features of mania (i.e., elation and/or grandiosity). Subjects
were treated by their own community practitioners. RESULTS: The proportions of
subjects who recovered from mania and who relapsed after recovery were 65.2% and
55.2%, respectively. The mean time to recovery was 36.0 weeks (SD=25.0). Relapse
occurred after a mean of 28.6 weeks (SD=13.2). Living with an intact biological
family significantly predicted rate of recovery, and a low level of maternal
warmth significantly predicted rate of relapse. CONCLUSIONS: The relatively poor
outcomes of these subjects may be related to their phenotypic resemblance to
severely ill adults with bipolar disorder who have mixed mania, continuous rapid
cycling, psychosis, and treatment-resistant psychopathology. A lower level of
effectiveness of mood stabilizers in children cannot be ruled out. Although the
significance of maternal warmth as a predictor is consistent with reports in
adult mania, the significance of intact family as a predictor may be unique to
childhood mania.
 
PMID: 12042179 [PubMed - indexed for MEDLINE]
>HR>
J Child Adolesc Psychopharmacol. 2002 Spring;12(1):63-7. 
 
Can stimulant rebound mimic pediatric bipolar disorder?
 
Sarampote CS, Efron LA, Robb AS, Pearl PL, Stein MA.
 
Department of Psychology, Children's National Medical Center, George Washington
University School of Medicine, Washington, DC 20010, USA.
 
The authors describe the case of a 7-year-old girl diagnosed with attention
deficit hyperactivity disorder (ADHD) who, following an unsuccessful trial of
stimulant medication and subsequent mood symptoms, was diagnosed with bipolar
disorder. Following a comprehensive, multidisciplinary assessment, and
withdrawal of her complex medication regimen, she was rediagnosed with ADHD. She
displayed a positive response to behavioral parent training and pharmacological
treatment with a long-acting stimulant. The case illustrates the benefits of a
comprehensive, multidisciplinary evaluation and multimodal treatment. Her
dramatic response to the long-acting stimulant suggests that many of her
affective symptoms were due to stimulant "rebound" versus bipolar disorder. This
case highlights the complexities of differentiating severe ADHD from bipolar
disorder and suggests that stimulant rebound and other iatrogenic effects should
be considered during the differential diagnostic process as potential mimics of
bipolar disorder.
 
Publication Types:
 Case Reports
 
PMID: 12014597 [PubMed - indexed for MEDLINE]
<HR>
J Child Adolesc Psychopharmacol. 2002 Spring;12(1):11-25. 
 
DSM-IV mania symptoms in a prepubertal and early adolescent bipolar disorder
phenotype compared to attention-deficit hyperactive and normal controls.
 
Geller B, Zimerman B, Williams M, Delbello MP, Bolhofner K, Craney JL, Frazier
J, Beringer L, Nickelsburg MJ.
 
Department of Psychiatry, Washington University School of Medicine, St Louis,
Missouri 63110, USA. gellerb@medicine.wustl.edu
 
OBJECTIVE: To compare the prevalence of Diagnostic and Statistical Manual of
Mental Disorders, 4th edition (DSM-IV) mania symptoms in a prepubertal and early
adolescent bipolar disorder phenotype (PEA-BP) to those with attention deficit
hyperactivity disorder (ADHD) and normal community controls (CC). METHODS: To
optimize generalizeability, subjects with PEA-BP and ADHD were consecutively
ascertained from outpatient pediatric and psychiatric sites, and CC subjects
were obtained from a random survey. All 268 subjects (93 with PEA-BP, 81 with
ADHD, and 94 CC) received comprehensive, blind, baseline research assessments of
mothers about their children and of children about themselves. PEA-BP was
defined by DSM-IV mania with elation and/or grandiosity as one criterion to
ensure that subjects had one of the two cardinal symptoms of mania and to avoid
diagnosing mania only by criteria that overlapped with those for ADHD. RESULTS:
Five symptoms (i.e., elation, grandiosity, flight of ideas/racing thoughts,
decreased need for sleep, and hypersexuality) provided the best discrimination
of PEA-BP subjects from ADHD and CC controls. These five symptoms are also
mania-specific in DSM-IV (i.e., they do not overlap with DSM-IV symptoms for
ADHD). Irritability, hyperactivity, accelerated speech, and distractibility were
very frequent in both PEA-BP and ADHD groups and therefore were not useful for
differential diagnosis. Concurrent elation and irritability occurred in 87.1% of
subjects with PEA-BP. Data on suicidality, psychosis, mixed mania, and
continuous rapid cycling were also provided. CONCLUSION: Unlike late
teenage/adult onset bipolar disorder, even subjects with PEA-BP selected for
DSM-IV mania with cardinal symptoms have high rates of comorbid DSM-IV ADHD.
High rates of concurrent elation and irritability were similar to those in adult
mania.
 
Publication Types:
 Clinical Trial
 Controlled Clinical Trial
 
PMID: 12014591 [PubMed - indexed for MEDLINE]
<HR>
Curr Psychiatry Rep. 2002 Apr;4(2):146-52. 
 
Familial links between attention deficit hyperactivity disorder, conduct
disorder, and bipolar disorder.
 
Doyle AE, Faraone SV.
 
Massachusetts General Hospital, 15 Parkman Street, ACC-725, Boston, MA 02114,
USA. doylea@helix.mgh.harvard.edu
 
Although family, twin, and adoption studies indicate that attention deficit
hyperactivity disorder (ADHD) is a familial condition with a robust genetic
component, molecular genetic studies of candidate genes have produced
inconsistent findings. One of the challenges to elucidating the genetic
architecture of ADHD is its potential genetic heterogeneity. Therefore, efforts
are needed to identify etiologically homogeneous subgroups of subjects with ADHD
for use in genetic studies. The current article reviews evidence suggesting that
parsing ADHD subjects based on comorbidity with conduct and bipolar disorders
may yield familial subtypes that are suitable for genetic analyses.
 
Publication Types:
 Review
 Review, Tutorial
 
PMID: 11914177 [PubMed - indexed for MEDLINE]
<HR>
J Affect Disord. 2001 Dec;67(1-3):159-65. 
 
Measures of attention and hyperactivity symptoms in a high-risk sample of
children of bipolar parents.
 
Duffy A, Grof P, Kutcher S, Robertson C, Alda M.
 
Dalhousie University, Department of Psychiatry, Halifax, Nova Scotia, Canada.
 
BACKGROUND: To determine whether significant symptoms of inattention were
present among the offspring of well-characterized bipolar parents. METHODS: We
included 53 offspring of 30 parents meeting DSM-IV criteria for bipolar disorder
diagnosed by consensus on the basis of a SADS-L interview and a wealth of
longitudinal clinical data. The unaffected parent had no lifetime history of a
major psychiatric illness. Offspring, prospectively followed for up to 5 years,
completed psychometric measures of attention and mood when judged to be at a
good level of functioning (well, remitted or treated). RESULTS: Those offspring
with any lifetime psychiatric diagnosis endorsed more subjective problems with
attention. However, there was no measurable difference on tasks of sustained
attention between those with and those without a lifetime psychiatric illness
including affective disorder. There was a significant association between
self-reported symptoms of depression and inattention, but no association between
either self-report measure and an objective measure of sustained attention.
LIMITATIONS: This study was not intended to be a comprehensive
neuropsychological investigation of at risk offspring. CONCLUSIONS: In this
high-risk population, subjective difficulty with attention appeared to be
state-dependent, associated with the degree of subjective distress related to an
underlying psychiatric illness.
 
PMID: 11869763 [PubMed - indexed for MEDLINE]
<HR>
J Child Adolesc Psychopharmacol. 2001 Fall;11(3):301-9. 
 
Gabapentin and methylphenidate treatment of a preadolescent with attention
deficit hyperactivity disorder and bipolar disorder.
 
Hamrin V, Bailey K.
 
Yale University, School of Nursing, New Haven, Connecticut 06510, USA.
 
Gabapentin is an anticonvulsant drug released in the United States in 1993 for
use as adjunctive therapy in refractory partial epilepsy. The mechanism of
action of gabapentin is unknown, but the drug has very favorable
pharmacokinetics and a good safety profile, which allows its use in high-risk
patients. Several reports have described the successful use of gabapentin for
bipolar disorders in adults, but there are no controlled studies in the use of
gabapentin in children and adolescents. We describe a 12-year-old boy with a
history of attention deficient hyperactivity disorder (ADHD), reading disorder,
mixed receptive and expressive language disorder, encopresis, and bipolar
disorder II who was treated with gabapentin 200 mg/day added to methylphenidate
30 mg/day. Within 3 weeks the improvement and stabilization of mood symptoms was
remarkable, as noted by mother, teacher, and clinician, and remained so for 6
months of follow-up. Comorbid bipolar disorder and ADHD is a hotly debated topic
in the child and adolescent psychiatric literature, with rates of comorbid ADHD
and bipolar disorder ranging from 22% to 90%. Controlled studies are needed to
evaluate the possible antimanic mood stabilizing and/or antidepressant
properties or gabapentin in youths.
 
Publication Types:
 Case Reports
 
PMID: 11642481 [PubMed - indexed for MEDLINE]
<HR>
J Neuropsychiatry Clin Neurosci. 2001 Summer;13(3):385-95. 
 
Impairments of attention and effort among patients with major affective
disorders.
 
Cohen R, Lohr I, Paul R, Boland R.
 
Department of Psychiatry and Human Behavior, Brown University School of
Medicine, Miriam Hospital, Providence, Rhode Island 02906, USA. rac@brown.edu
 
Impairments of attention are common among people with major affective disorders,
yet the influence of effortful task demands on attentional performance in
unipolar and bipolar illness has been little studied. The authors compared
psychiatric inpatients with primary diagnoses of unipolar or bipolar affective
disorder (n=27) and age-matched normal control subjects (n=20) on a battery of
eight neuropsychological tasks designed to measure different attentional
functions. There were low-effort and high-effort versions of each task.
Significant group differences were consistently observed on tasks demanding
sustained and focused attention, but not on tasks requiring visual selective
attention. Although affective disorder patients showed impairments on most tasks
regardless of level of task effort, group differences were greatest on
high-effort conditions. Results indicate that patients with major affective
disorders show significant attentional impairments on most measures of effortful
attention, and the magnitude of these impairments increases as the effortful
demands of the task increase.
 
PMID: 11514646 [PubMed - indexed for MEDLINE]
<HR>
J Clin Psychiatry. 2001;62 Suppl 14:10-5. 
 
Diagnostic and therapeutic dilemmas in the management of pediatric-onset bipolar
disorder.
 
Wozniak J, Biederman J, Richards JA.
 
Pediatric Psychopharmacology Unit of the Child Psychiatry Service, Massachusetts
General Hospital, Harvard Medical School, Boston 02114, USA.
wozniak@helix.mgh.harvard.edu
 
Although the diagnosis of pediatric-onset bipolar disorder is controversial, an
increasing literature of systematic research has challenged the traditional view
that this disorder is a rare condition. This article summarizes research
regarding the atypical presentation of pediatric bipolar disorder and its
overlap with attention-deficit/hyperactivity disorder and other comorbid
conditions, as well as family-genetic and treatment data. When structured
interview data were examined, cases of pediatric mania constituted 16% of
referrals to our outpatient clinic. Presentation is atypical by adult standards
and includes irritability, chronicity, and mixed state. Family-genetic and
treatment data help to establish diagnostic validity. Pediatric bipolar disorder
is not a rare condition. Treatment requires a combined pharmacotherapy approach
to address issues of comorbidity. Atypical antipsychotic medications have
provided promising treatment results, but additional controlled clinical trials
are needed.
 
Publication Types:
 Review
 Review, Tutorial
 
PMID: 11469669 [PubMed - indexed for MEDLINE]
<HR>
J Affect Disord. 2001 Jul;65(2):197-215. 
 
Evolutionary recasting: ADHD, mania and its variants.
 
Brody JF.
 
jbrody@compuserve.com
 
This paper reviews clinical observations and evolutionary theory in relation to
attention deficit hyperactivity disorder (ADHD) on the one hand and mania and
its variants on the other. Both groups of disorders resemble each other in
regard to high levels of motor activity, perhaps occurring together more often
than not, and are confounded in most existing research. Making distinctions
requires isolating the contribution of activity level from other characteristics
such as those of flawed executive functions for ADHD or grandiosity and lapses
in reciprocity for mania. High activity level is an asset throughout nature
except in extreme intensities or when it amplifies the characteristics of
psychopathology. Fitness, social displays, and behavioral adaptations for
survival are clues to some aspects of hypomania and ADHD. While hypomania can be
a competitive advantage in certain niches, it appears there can be few
opportunities for ADHD to do so. Indeed, the impulsiveness seen in ADHD is
probably the outcome of flaws in executive functions rather than being the cause
of them. Neither lapses in executive functions nor in reciprocity are apt to be
domain general but may interact sharply with each person's repertoire of
psychological adaptations. The author submits that a theoretical orientation as
outlined here would not only help in better understanding the disorders under
consideration, but could be useful in providing new directions to treatment
decisions.
 
Publication Types:
 Review
 Review, Tutorial
 
PMID: 11356245 [PubMed - indexed for MEDLINE]
<HR>
Bipolar Disord. 2001 Apr;3(2):58-62. 
 
Persistent attentional dysfunction in remitted bipolar disorder.
 
Wilder-Willis KE, Sax KW, Rosenberg HL, Fleck DE, Shear PK, Strakowski SM.
 
Bipolar and Psychotic Disorders Research Program, Department of Psychiatry,
University of Cincinnati College of Medicine, OH 45267-0559, USA.
 
OBJECTIVES: Although previous research has shown that attentional dysfunction is
common during acute mood episodes in individuals with bipolar disorder (BPD),
few studies have examined whether attentional deficits are evident during
periods of symptom stability. The goal of this study was to determine whether
clinically stable individuals with BPD would have attentional disturbances
relative to healthy subjects. METHODS: Fourteen patients with BPD and 12 healthy
comparison subjects participated in the study, and were administered the
Degraded Stimulus Continuous Performance Test (DSCPT), Digit Span
Distractibility Test (DSDT) and Grooved Pegboard Test (GPT). Psychiatric
symptoms were assessed with the Young Mania Rating Scale and the Scale for the
Assessment of Positive Symptoms. Medication side effects were measured with the
Simpson Rating Scale. RESULTS: The patient group responded significantly more
slowly than the control group on the DSCPT (z = -2.52, p = 0.01) and the GPT (z
= -3.37, p = 0.001). There was a trend towards the BPD patients demonstrating
impaired perceptual sensitivity on the DSCPT (z = 1.68, p = 0.09). The two
groups did not differ on the DSDT (z = -1.06, p = 0.3). Poor performance on the
GPT and DSCPT target reaction time were not associated with symptom ratings or
medications. CONCLUSION: The findings suggest that impairments in fine motor
skills and reaction time may be present in clinically stable patients with BPD,
even after accounting for psychiatric symptoms and medication effects.
Performance decrements on attentional tasks may be in part reflective of motor
impairments in patients with BPD.
 
PMID: 11333063 [PubMed - indexed for MEDLINE]
<HR>
J Affect Disord. 2001 Apr;64(1):19-26. 
 
Attention deficit hyperactivity disorder with bipolar disorder in girls: further
evidence for a familial subtype?
 
Faraone SV, Biederman J, Monuteaux MC.
 
Pediatric Psychopharmacology Unit, Psychiatry Service, ACC 725, Massachusetts
General Hospital, Fruit Street, Boston, MA 02114, USA. faraone@mediaone.net
 
BACKGROUND: To clarify the nosologic status of girls with attention deficit
hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar
disorder (BPD). METHODS: Using blind raters and structured psychiatric
interviews, we examined 140 girls with ADHD, 122 non-ADHD comparisons and their
786 first degree relatives. Analyses tested specific hypotheses about the
familial relationship between ADHD and bipolar disorder in girls. RESULTS: After
stratifying our ADHD sample into those with and without BPD, we found that: (1)
relatives of both ADHD subgroups were at significantly greater risk for ADHD
than relatives of non-ADHD controls, (2) the two subgroups did not significantly
differ in their relatives' risk for ADHD; (3) an elevated risk for bipolar
disorder was observed among relatives when the proband child had BPD but not
ADHD alone; (4) weak evidence of cosegregation between ADHD and BPD, and (5) no
evidence of a trend for random mating between ADHD parents and those with mania.
LIMITATIONS: Limitations of this study include the lack of direct interviewing
of probands and the limited number of ADHD/BPD probands available. CONCLUSIONS:
These findings extend to girls what was previously documented in boys and
suggest that comorbid ADHD with BPD in girls is familially distinct from other
forms of ADHD and may be related to what others have termed childhood onset BPD.
Future work could determine if this subgroup has a characteristic course,
outcome and response to treatment.
 
PMID: 11292516 [PubMed - indexed for MEDLINE]
<HR>
J Am Acad Child Adolesc Psychiatry 2000 Dec;39(12):1543-8

Psychosocial functioning in a prepubertal and early adolescent bipolar disorder phenotype.

Geller B, Bolhofner K, Craney JL, Williams M, DelBello MP, Gundersen K

Department of Psychiatry, Washington University School of Medicine, St. Louis 63110, USA. gellerb@medicine.wustl.edu

OBJECTIVE: To compare psychosocial functioning (PF) in a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP) sample to two comparison groups, i.e., attention-deficit/hyperactivity disorder (ADHD) and community controls (CC). METHOD: There were 93 PEA-BP (with or without comorbid ADHD), 81 ADHD, and 94 CC subjects who were participants in an ongoing study, the Phenomenology and Course of Pediatric Bipolar Disorders. Cases in the PEA-BP and ADHD groups were outpatients obtained by consecutive new case ascertainment, and CC subjects were from a survey conducted by the Research Triangle Institute. To fit the study phenotype, PEA-BP subjects needed to have current DSM-IV mania or hypomania with elation and/or grandiosity as one criterion. Assessments for PF were by experienced research nurses who were blind to group status. Mothers and children were separately interviewed with the Psychosocial Schedule for School Age Children-Revised. RESULTS: Compared with both ADHD and CC subjects, PEA-BP cases had significantly greater impairment on items that assessed maternal-child warmth, maternal-child and paternal-child tension, and peer relationships. CONCLUSIONS: Clinicians need to consider PF deficits when planning interventions. In the PEA-BP group, there was a 43% rate of hypersexuality with a 

<1% rate of sexual abuse, supporting hypersexuality as a manifestation of child mania.>

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J Child Adolesc Psychopharmacol 2000 Fall;10(3):175-84
Stimulant treatment in young boys with symptoms suggesting childhood mania: a report from a longitudinal study. Carlson GA, Loney J, Salisbury H, Kramer JR, Arthur C
Division of Child and Adolescent Psychiatry, State University of New York at Stony Brook, 11794-8790, USA. Gcarlson@mail.psychiatry.sunysb.edu
This study used data from a completed longitudinal study to