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A high-risk study of bipolar disorder. Childhood clinical phenotypes as precursors of major mood disorders.

ABSTRACT: The childhood precursors of adult bipolar disorder (BP) are still a matter of controversy.To report the lifetime prevalence and early clinical predictors of psychiatric disorders in offspring from families of probands with DSM-IV BP compared with offspring of control subjects.A longitudinal, prospective study of individuals at risk for BP and related disorders. We report initial (cross-sectional and retrospective) diagnostic and clinical characteristics following best-estimate procedures.Assessment was performed at 4 university medical centers in the United States between June 1, 2006, and September 30, 2009.Offspring aged 12 to 21 years in families with a proband with BP (n = 141, designated as cases) and similarly aged offspring of control parents (n = 91).Lifetime DSM-IV diagnosis of a major affective disorder (BP type I; schizoaffective disorder, bipolar type; BP type II; or major depression).At a mean age of 17 years, cases showed a 23.4% lifetime prevalence of major affective disorders compared with 4.4% in controls (P = .002, adjusting for age, sex, ethnicity, and correlation between siblings). The prevalence of BP in cases was 8.5% vs 0% in controls (adjusted P = .007). No significant difference was seen in the prevalence of other affective, anxiety, disruptive behavior, or substance use disorders. Among case subjects manifesting major affective disorders (n = 33), there was an increased risk of anxiety and externalizing disorders compared with cases without mood disorder. In cases but not controls, a childhood diagnosis of an anxiety disorder (relative risk = 2.6; 95% CI, 1.1-6.3; P = .04) or an externalizing disorder (3.6; 1.4-9.0; P = .007) was predictive of later onset of major affective disorders.Childhood anxiety and externalizing diagnoses predict major affective illness in adolescent offspring in families with probands with BP.

SUBMITTER: Nurnberger JI

PROVIDER: S-EPMC4552246 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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A high-risk study of bipolar disorder. Childhood clinical phenotypes as precursors of major mood disorders.

Nurnberger John I JI McInnis Melvin M Reich Wendy W Kastelic Elizabeth E Wilcox Holly C HC Glowinski Anne A Mitchell Philip P Fisher Carrie C Erpe Mariano M Gershon Elliot S ES Berrettini Wade W Laite Gina G Schweitzer Robert R Rhoadarmer Kelly K Coleman Vegas V VV Cai Xueya X Azzouz Faouzi F Liu Hai H Kamali Masoud M Brucksch Christine C Monahan Patrick O PO

Archives of general psychiatry 20111001 10

<h4>Context</h4>The childhood precursors of adult bipolar disorder (BP) are still a matter of controversy.<h4>Objective</h4>To report the lifetime prevalence and early clinical predictors of psychiatric disorders in offspring from families of probands with DSM-IV BP compared with offspring of control subjects.<h4>Design</h4>A longitudinal, prospective study of individuals at risk for BP and related disorders. We report initial (cross-sectional and retrospective) diagnostic and clinical character ...[more]

PMID: 21969459

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Project description:Bipolar disorder and schizophrenia are serious psychiatric conditions that cause a significant reduction in quality of life and shortened life expectancy. Treatments including medications and psychosocial support exist, but many people with these disorders still struggle to participate in society and some are resistant to current therapies. Although the exact pathophysiology of bipolar disorder and schizophrenia remains unclear, increasing evidence supports the role of oxidative stress and redox dysregulation as underlying mechanisms. Oxidative stress is an imbalance between the production of reactive oxygen species generated by metabolic processes and antioxidant systems that can cause damage to lipids, proteins, and DNA. Sleep is a critical regulator of metabolic homeostasis and oxidative stress. Disruption of sleep and circadian rhythms contribute to the onset and progression of bipolar disorder and schizophrenia and these disorders often coexist with sleep disorders. Furthermore, sleep deprivation has been associated with increased oxidative stress and worsening mood symptoms. Dysfunctional brain metabolism can be improved by fatty acid derived ketones as the brain readily uses both ketones and glucose as fuel. Ketones have been helpful in many neurological disorders including epilepsy and Alzheimer's disease. Recent clinical trials using the ketogenic diet suggest positive improvement in symptoms for bipolar disorder and schizophrenia as well. The improvement in psychiatric symptoms from the ketogenic diet is thought to be linked, in part, to restoration of mitochondrial function. These findings encourage further randomized controlled clinical trials, as well as biochemical and mechanistic investigation into the role of metabolism and sleep in psychiatric disorders. This narrative review seeks to clarify the intricate relationship between brain metabolism, sleep, and psychiatric disorders. The review will delve into the initial promising effects of the ketogenic diet on mood stability, examining evidence from both human and animal models of bipolar disorder and schizophrenia. The article concludes with a summary of the current state of affairs and encouragement for future research focused on the role of metabolism and sleep in mood disorders.

Project description:OBJECTIVE:The authors sought to identify diagnostic risk factors of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder ("high-risk offspring"). METHOD:High-risk offspring 6-18 years old (N=391) and demographically matched offspring (N=248) of community parents without bipolar disorder were assessed longitudinally with standardized diagnostic instruments by staff blind to parental diagnoses. Follow-up assessments were completed in 91% of the offspring (mean follow-up interval, 2.5 years; mean follow-up duration, 6.8 years). RESULTS:Compared with community offspring, high-risk offspring had significantly higher rates of subthreshold mania or hypomania (13.3% compared with 1.2%), manic, mixed, or hypomanic episodes (9.2% compared with 0.8%), and major depressive episodes (32.0% compared with 14.9%). They also had higher rates of attention deficit hyperactivity disorder (30.7% compared with 18.1%), disruptive behavior disorders (27.4% compared with 15.3%), anxiety disorders (39.9% compared with 21.8%), and substance use disorders (19.9% compared with 10.1%), but not unipolar major depressive disorder (major depression with no bipolarity; 18.9% compared with 13.7%). Multivariate Cox regressions showed that in the high-risk offspring, subthreshold manic or hypomanic episodes (hazard ratio=2.29), major depressive episodes (hazard ratio=1.99), and disruptive behavior disorders (hazard ratio=2.12) were associated with subsequent manic, mixed, or hypomanic episodes. Only subthreshold manic or hypomanic episodes (hazard ratio=7.57) were associated when analyses were restricted to prospective data. CONCLUSIONS:Subthreshold manic or hypomanic episodes were a diagnostic risk factor for the development of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder and should be a target for clinical assessment and treatment research. Major depressive episodes and disruptive behavior disorders are also indications for close clinical monitoring of emergent bipolarity in high-risk offspring.

Dataset Information

A high-risk study of bipolar disorder. Childhood clinical phenotypes as precursors of major mood disorders.

Publications

A high-risk study of bipolar disorder. Childhood clinical phenotypes as precursors of major mood disorders.

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