A controlled family study of children with DSM-IV bipolar-I disorder and psychiatric co-morbidity.

Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital, Boston, MA 02114, USA.
Psychological Medicine (Impact Factor: 5.43). 11/2009; 40(7):1079-88. DOI: 10.1017/S0033291709991437
Source: PubMed

ABSTRACT To estimate the spectrum of familial risk for psychopathology in first-degree relatives of children with unabridged DSM-IV bipolar-I disorder (BP-I).
We conducted a blinded, controlled family study using structured diagnostic interviews of 157 children with BP-I probands (n=487 first-degree relatives), 162 attention deficit hyperactivity disorder (ADHD) (without BP-I) probands (n=511 first-degree relatives), and 136 healthy control (without ADHD or BP-I) probands (n=411 first-degree relatives).
The morbid risk (MR) of BP-I disorder in relatives of BP-I probands (MR=0.18) was increased 4-fold [95% confidence interval (CI) 2.3-6.9, p<0.001] over the risk to relatives of control probands (MR=0.05) and 3.5-fold (95% CI 2.1-5.8, p<0.001) over the risk to relatives of ADHD probands (MR=0.06). In addition, relatives of children with BP-I disorder had high rates of psychosis, major depression, multiple anxiety disorders, substance use disorders, ADHD and antisocial disorders compared with relatives of control probands. Only the effect for antisocial disorders lost significance after accounted for by the corresponding diagnosis in the proband. Familial rates of ADHD did not differ between ADHD and BP-I probands.
Our results document an increased familial risk for BP-I disorder in relatives of pediatric probands with DSM-IV BP-I. Relatives of probands with BP-I were also at increased risk for other psychiatric disorders frequently associated with pediatric BP-I. These results support the validity of the diagnosis of BP-I in children as defined by DSM-IV. More work is needed to better understand the nature of the association between these disorders in probands and relatives.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: The existence of bipolar disorder (BP) in youth is controversial. The current evidence regarding the diagnosis of BP in youth was reviewed. BP is a recurrent familial disorder that occurs in 1-3% of youth, particularly in adolescents. Except for subsyndromal BP, the prevalence of BP-I is similar across most countries. Due to the child's immaturity, the presence of comorbid disorders, and divergent interpretations of manic symptomatology it is difficult to diagnose BP in youth. Youth with subsyndromal mania and family history of BP, are at high risk to develop BP-I and BP-II. Both the full and subsyndromal syndromal BP are associated with significant psychosocial difficulties and increased risk for use of substances, suicidality, legal problems, and services utilization. BP disorder exists in youth, but it is difficult to diagnose. The recurrent nature and psychosocial morbidity associated with this illness during critical developmental stages calls for comprehensive longitudinal evaluation and accurate recognition and treatment because delays in treatment are associated with poor outcome.
    Child and Adolescent Mental Health 09/2013; 18(3). · 0.95 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The goal of this study is to investigate the familial transmission of the spectrum of bipolar disorder in a nonclinical sample of probands with a broad range of manifestations of mood disorders. The sample included a total of 447 probands recruited from a clinically enriched community screening and their 2082 adult living and deceased first-degree relatives. A best estimate diagnostic procedure that was based on either direct semistructured interview or structured family history information from multiple informants regarding non-interviewed relatives was employed. Results revealed that there was specificity of familial aggregation of bipolar I (BP I; odds ratio (OR)=8.40; 3.27-20.97; h2=0.83) and major depressive disorder (OR=2.26; 1.58-3.22; h2=0.20), but not BP II. The familial aggregation of BP I was primarily attributable to the familial specificity of manic episodes after adjusting for both proband and relative comorbid anxiety and substance use disorders. There was no significant cross-aggregation between mood disorder subtypes suggesting that the familial transmission of manic and major depressive episodes is independent despite the high magnitude of comorbidity between these mood states. These findings confirm those of earlier studies of the familial aggregation of bipolar disorder and major depression in the first nonclinical sample, and the largest family study of bipolar disorder in the USA using contemporary nonhierarchical diagnostic criteria for mood and anxiety disorders. The results suggest that these major components of bipolar disorder may represent distinct underlying pathways rather than increasingly severe manifestations of a common underlying diathesis. Therefore, dissection of the broad bipolar phenotype in genetic studies could actually generate new findings that could index novel biologic pathways underlying bipolar disorder.Molecular Psychiatry advance online publication, 15 October 2013; doi:10.1038/mp.2013.116.
    Molecular Psychiatry 10/2013; 19(2). · 15.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Previous work shows that children with high scores (2SD, combined score≥210) on the Attention Problems, Aggressive Behavior, and Anxious-Depressed (A-A-A) subscales of the Child Behavior Checklist (CBCL) are more likely than other children to meet criteria for bipolar (BP)-I disorder. However, the utility of this profile as a screening tool has remained unclear. Methods We compared 140 patients with pediatric BP-I disorder, 83 with attention deficit hyperactivity disorder (ADHD), and 114 control subjects. We defined the CBCL-Severe Dysregulation profile as an aggregate cutoff score of≥210 on the A-A-A scales. Patients were assessed with structured diagnostic interviews and functional measures. Results Patients with BP-I disorder were significantly more likely than both control subjects (Odds Ratio [OR]: 173.2; 95% Confidence Interval [CI], 21.2 to 1413.8; P<0.001) and those with ADHD (OR: 14.6; 95% CI, 6.2 to 34.3; P<0.001) to have a positive CBCL-Severe Dysregulation profile. Receiver Operating Characteristics analyses showed that the area under the curve for this profile comparing children with BP-I disorder against control subjects and those with ADHD was 99% and 85%, respectively. The corresponding positive predictive values for this profile were 99% and 92% with false positive rates of<0.2% and 8% for the comparisons with control subjects and patients with ADHD, respectively. Limitations Non-clinician raters administered structured diagnostic interviews, and the sample was referred and largely Caucasian. Conclusions The CBCL-Severe Dysregulation profile can be useful as a screen for BP-I disorder in children in clinical practice.
    Journal of Affective Disorders 08/2014; 165:81–86. · 3.71 Impact Factor

Full-text (2 Sources)

Available from
Oct 29, 2014