The Care of Patients With Complex Mood Disorders.

This article focuses on some common dilemmas facing clinicians, patients, and families in managing the treatment of complicated mood disorders. Specifically, this article reviews the interaction of depressive states, including unipolar, bipolar, and mixed, with other adversities, including comorbid physical and psychological disorders, personality vulnerabilities, misuse of drugs and alcohol, and social and family problems. These issues are not always clearly differentiated from the depressive illness.

A collaborative approach to teaching medical students how to screen, intervene, and treat substance use disorders.

Few medical schools require a stand-alone course to develop knowledge and skills relevant to substance use disorders (SUDs). The authors successfully initiated a new course for second-year medical students that used screening, brief intervention, and referral to treatment (SBIRT) as the course foundation. The 15-hour course (39 faculty teaching hours) arose from collaboration between faculty in Departments of Medicine and Psychiatry and included 5 hours of direct patient interaction during clinical demonstrations and in small-group skills development.

Genome-wide linkage and follow-up association study of postpartum mood symptoms.

Objective: Family studies have suggested that postpartum mood symptoms might have a partly genetic etiology. The authors used a genome-wide linkage analysis to search for chromosomal regions that harbor genetic variants conferring susceptibility for such symptoms. The authors then fine-mapped their best linkage regions, assessing single nucleotide polymorphisms (SNPs) for genetic association with postpartum symptoms.

Premenstrual mood symptoms: study of familiality and personality correlates in mood disorder pedigrees.

We sought to determine whether premenstrual mood symptoms exhibit familial aggregation in bipolar disorder or major depression pedigrees. Two thousand eight hundred seventy-six women were interviewed with the Diagnostic Interview for Genetic Studies as part of either the NIMH Genetics Initiative Bipolar Disorder Collaborative study or the Genetics of Early Onset Major Depression (GenRED) study and asked whether they had experienced severe mood symptoms premenstrually. In families with two or more female siblings with bipolar disorder (BP) or major depressive disorder (MDD), we examined the odds of having premenstrual mood symptoms given one or more siblings with these symptoms.

Family-based association study of Neuregulin 1 with psychotic bipolar disorder.

The Neuregulin 1 gene (NRG1) has been associated with schizophrenia, and, to a lesser extent, with bipolar disorder (BP). We investigated the association of NRG1 with BP in a large family sample, and then performed analyses according to the presence of psychotic features or mood-incongruent psychotic features. We genotyped 116 tagSNPs and four Icelandic "core" SNPs in 1,199 subjects from 314 nuclear families.

Evidence of association between brain-derived neurotrophic factor gene and bipolar disorder.

Objective: Brain-derived neurotrophic factor (BDNF) plays an important role in the survival, differentiation, and outgrowth of select peripheral and central neurons throughout adulthood. Growing evidence suggests that BDNF is involved in the pathophysiology of mood disorders.

Methods: Ten single nucleotide polymorphisms (SNPs) across the BDNF gene were genotyped in a sample of 1749 Caucasian Americans from 250 multiplex bipolar families.

Bipolar disorder as maladaptive arousal: a behavioral model and evidence.

Bipolar disorder can be understood as a disorder of behavioral regulation. Manic and depressed individuals are impaired in the titration of appetitive arousal, possibly at the level of neuronal plasticity. An experiment in which fixed 5% CO2 stimulates respiration and blocks satiety tests the regulation of appetitive arousal.

Carbon dioxide induces erratic respiratory responses in bipolar disorder.

Background: CO(2) respiration stimulates both anxiety and dyspnea ("air hunger") and has long been used to study panic vulnerability and respiratory control. High comorbidity with panic attacks suggests individuals with bipolar disorder may also mount a heightened anxiety response to CO(2). Moreover, problems in the arousal and modulation of appetites are central to the clinical syndromes of mania and depression; hence CO(2) may arouse an abnormal respiratory response to "air hunger".

Familial aggregation of postpartum mood symptoms in bipolar disorder pedigrees.

Objectives: We sought to determine if postpartum mood symptoms and depressive episodes exhibit familial aggregation in bipolar I pedigrees.

Methods: A total of 1,130 women were interviewed with the Diagnostic Interview for Genetic Studies as part of the National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative Study and were asked whether they had ever experienced mood symptoms within four weeks postpartum. Women were also asked whether either of two major depressive episodes described in detail occurred postpartum.

Psychotic features in bipolar and unipolar depression.

Background: While some prior studies have found higher rates of psychotic depression in those with bipolar disorder or a bipolar relative, others have failed to confirm these observations. We examined the relationship of psychotic depression to polarity in several large familial samples of mood disorder.

Methods: A total of 4,724 subjects with major mood disorder in three family studies on the genetics of bipolar I disorder (BPI) or recurrent major depressive disorder (MDDR) were administered semi-structured interviews by clinicians.

Genome-wide scan of bipolar II disorder.

Objective: Bipolar disorder (BD) II is characterized by recurrent hypomanic and depressive episodes and has been somewhat of a controversial diagnosis since its description in the 1970s. Clinical opinions notwithstanding, the biological validity of BD II was supported in a genetic study of 58 multiplex bipolar families wherein the statistical evidence for linkage derived from BD II sibling-pairs sharing marker alleles on chromosome 18q. The BD II phenotype alone has never been studied in a genome-wide scan analysis in the current or other bipolar family samples.

The bipolar disorder phenome database: a resource for genetic studies.

Objective: The purpose of this study was to assemble and validate a database of phenotypic variables that were collected from families with bipolar disorder as a resource for genetic and other biological studies.

Method: Participants were ascertained for two bipolar disorder genetic linkage studies: the University of Chicago, Johns Hopkins, and National Institute of Mental Health (NIMH) Intramural Program (CHIP) Collaboration and the NIMH Genetics Initiative project. All participants underwent detailed, phenotypic assessment with either the Schedule for Affective Disorders and Schizophrenia-Lifetime Version or one of four versions of the Diagnostic Interview for Genetic Studies.

SNP fine mapping of chromosome 8q24 in bipolar disorder.

We previously reported linkage to chromosome 8q24 in bipolar disorder (BP) with a LOD of 3.32. We fine mapped the locus with SNPs and tested for association with BP in families with evidence of linkage to the region.

Genetics of recurrent early-onset major depression (GenRED): final genome scan report.

Objective: The authors carried out a genomewide linkage scan to identify chromosomal regions likely to contain genes that contribute to susceptibility to recurrent early-onset major depressive disorder, the form of the disorder with the greatest reported risk to relatives of index cases.

Method: Microsatellite DNA markers were studied in 656 families with two or more such cases (onset before age 31 in probands and age 41 in other relatives), including 1,494 informative "all possible" affected relative pairs (there were 894 independent affected sibling pairs). Analyses included a primary multipoint allele-sharing analysis (with ALLEGRO) and a secondary logistic regression analysis taking the sex of each relative pair into account (male-male, male-female, female-female).

Mood-incongruent psychotic features in bipolar disorder: familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33.

Objective: Mood-incongruent psychotic features in bipolar disorder may signify a more severe form of the illness and might represent phenotypic manifestations of susceptibility genes shared with schizophrenia. This study attempts to characterize clinical correlates, familial aggregation, and genetic linkage in subjects with these features.

Method: Subjects were drawn from The National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Disorder Collaborative cohort, consisting of 708 families recruited at 10 academic medical centers.

Panic comorbidity with bipolar disorder: what is the manic-panic connection?

Context: Bipolar/panic comorbidity has been observed in clinical, community and familial samples. As both are episodic disorders of affect regulation, the common pathophysiological mechanism is likely to involve deficits in amygdala-mediated, plasticity-dependent emotional conditioning.

Evidence: Neuronal genesis and synaptic remodeling occur in the amygdala; bipolar and panic disorders have both been associated with abnormality in the amygdala and related structures, as well as in molecules that modulate plasticity, such as serotonin, norepinephrine, brain-derived neurotrophic factor (BDNF) and corticotrophin releasing factor (CRF).