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: 5.94). 11/2009; 40(7):1079-88. DOI: 10.1017/S0033291709991437
Source: PubMed


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.

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Available from: Michael C Monuteaux, Oct 29, 2014
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    • "As previously described (Wozniak et al., 2010), BP-I probands were ascertained from our clinical service, referrals from local clinicians or self-referral in response to advertisements in the local media. All probands were ascertained blind to the diagnostic status of their relatives. "
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    ABSTRACT: BACKGROUND: Since little is known as to whether sex differences affect the clinical presentation of pediatric BP-I disorder, it is an area of high clinical, scientific and public health relevance. METHODS: Subjects are 239 BP-I probands (65 female probands, 174 male probands) and their 726 first-degree relatives, and 136 non-bipolar, non-ADHD control probands (37 female probands, 99 male probands) and their 411 first-degree relatives matched for age and sex. We modeled the psychiatric and cognitive outcomes as a function of BP-I status, sex, and the BP-I status-gender interaction. RESULTS: BP-I disorder was equally familial in both sexes. With the exception of duration of mania (shorter in females) and number of depressive episodes (more in females), there were no other meaningful differences between the sexes in clinical correlates of BP-I disorder. With the exception of a significant sex effect for panic disorder and a trend for substance use disorders (p=0.05) with female probands being at a higher risk than male probands, patterns of comorbidity were similar between the sexes. Despite the similarities, boys with BP-I disorder received more intensive and costly academic services than girls with the same disorder. LIMITATIONS: Since we studied children referred to a family study of bipolar disorder, our findings may not generalize to clinic settings. CONCLUSIONS: We found more similarities than differences between the sexes in the personal and familial correlates of BP-I disorder. Clinicians should consider bipolar disorder in the differential diagnosis of both boys and girls afflicted with symptoms suggestive of this disorder.
    Journal of Affective Disorders 02/2013; 149(1-3). DOI:10.1016/j.jad.2013.01.040 · 3.38 Impact Factor
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    • "Like other major mental illnesses, the risk to develop child BP-I is multifactorial; influenced by both familial and psychosocial factors (Geller et al., 2008; Geller et al., 2006; Geller et al., 2004b; Wozniak et al., 2009). These include external stressors, such as the presence of bipolar disorder in a family member, and putative protective factors, including level of maternal warmth (Geller et al., 2008; Geller et al., 2006; Wozniak et al., 2009). In particular, low maternal warmth is one of the leading risk factor associated with the risk of mania relapse after recovery in child BP-I subjects (Geller et al., 2008; Geller et al., 2004b). "
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    ABSTRACT: The risk for relapse of child bipolar I disorder (BP-I) is highly correlated with environmental factors. Immediate early genes of the early growth response (EGR) gene family are activated at high levels in the brain in response to environmental events, including stress, and mediate numerous neurobiological processes that have been associated with mental illness risk. The objective of this study is to evaluate whether single nucleotide polymorphisms (SNPs) in EGR genes are associated with the risk to develop child bipolar I disorder. To investigate whether EGR genes may influence susceptibility to child bipolar I disorder (BP-I), we used Family Based Association Tests to examine whether SNPs in each of the EGR genes were associated with illness in 49 families. Two SNPs in EGR3 displayed nominally significant associations with child BP-I (p=0.027 and p=0.028); though neither was statistically significant following correction for multiple comparisons. Haplotype association analysis indicated that these SNPs are in linkage disequilibrium (LD). None of the SNPs tested in EGR1, EGR2, or EGR4 was associated with child BP-I. This study was limited by small sample size, which resulted in it being underpowered to detect a significant association after correction for multiple comparisons. Our study revealed a preliminary finding suggesting that EGR3, a gene that translates environmental stimuli into long-term changes in the brain, warrants further investigation for association with risk for child BP-I disorder in a larger sample. Such studies may help reveal mechanisms by which environment can interact with genetic predisposition to influence this severe mental illness.
    Journal of Affective Disorders 02/2012; 138(3):387-96. DOI:10.1016/j.jad.2012.01.011 · 3.38 Impact Factor
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    ABSTRACT: RESUMEN Antecedentes: la asociación entre alteraciones de la función tiroidea y distintos trastornos psiquiátricos se señala en la bibliografía y se corrobora en la práctica clínica con niños y adolescentes. Los trastornos graves del humor y del comportamiento abarcan una amplia gama de presentaciones clínicas polimorfas y cambiantes, pero con algunas características específicas que permiten identificar un grupo de gravedad dentro de la psicopatología infantil. Una de las escalas más utilizadas para esta identificación es la Child Behavior CheckList, subescala CBCL-DSS (Dysregulation Short Scale). Objetivo: evaluar la asociación entre el hipotiroidismo subclínico y los trastornos graves del humor y del comportamiento como paradigma de la gravedad de la psicopatología infantil. Material y método: estudio descriptivo, retrospectivo, efectuado mediante encuesta de tipo transversal. Se revisaron las historias clínicas de 299 pacientes de entre 6 y 16 años de edad, de medio socioeconómico de medio a alto. Se registró la información de la subescala CBCL 6-18 y los valores de TSH y T4 previos al tratamiento farmacológico. La subescala CBCL-DSS diferencia una muestra clínica problema (T ≥ 65; n:198) y una muestra clínica control (T < 65; n: 101). El punto de corte para alteraciones de la función tiroidea es TSH ≥ 3.5 µU/mL. Resultados: el hipotiroidismo subclínico fue significativamente mayor en los pacientes capturados por la CBCL-DSS. Se subraya la asociación entre gravedad de la psicopatología y el hipotiroidismo subclínico. Conclusiones: en esta población de pacientes es pertinente la pesquisa y el tratamiento sistemático de la patología tiroidea. Se propone continuar esta línea de investigación con estudios prospectivos que permitan evaluar los resultados de estas mediciones. ABSTRACT Background: The association between thyroid function abnormalities and various psychiatric disorders were noted in the literature and is confirmed in clinical practice with children and adolescents. Severe disorders of mood and behavior encompass a wide range of polymorphous and changing clinical presentations, but with some specific characteristics that identify a group of serious psychopathology in children. One of the scales used for this identification is the Child Behavior Checklist, CBCL subscale-DSS (Dysregulation Short Scale). Objectives: To assess the association between subclinical hypothyroidism and severe disorders of mood and behavior as a paradigm of the severity of childhood psychopathology. Material and Methods: A descriptive, retrospective study, conducted by cross-sectional survey. We reviewed the medical records of 299 patients aged 6 to 16 years of age, socio-economic environment from medium to high. Information was recorded 6-18 CBCL subscale and the values of TSH and T4 prior to pharmacologic treatment. The subscale CBCL-DSS differenced a clinical problem (T ≥ 65, n = 198) and a clinical control (T <65, n = 101). The cutoff point for impairment of thyroid function is TSH ≥ 3.5 mU/mL. Results: Subclinical hypothyroidism was significantly higher in patients captured by the CBCL-DSS. It underlines the association between severity of psychopathology and subclinical hypothyroidism. Conclusions: In this patient population is appropriate to search for and the systematic treatment of thyroid disease. We propose to pursue this line of research with prospective studies to evaluate the results of these measurements.
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