Evaluation of tissue collection for postmortem studies of bipolar disorder.

OBJECTIVES: Postmortem human brain is a valuable resource for studying the neuropathology, neurochemistry, and molecular pathways of genes associated with bipolar disorder (BPD), yet available, well-characterized BPD brain tissue appears scarce. We set out to evaluate BPD postmortem brain collections in order to identify both successful methods as well as barriers to collection. METHODS: We conducted a literature review of postmortem studies of BPD over the past 30 years, compared and contrasted characteristics of established BPD collections, and identified possible barriers specific to BPD brain collection based on our experience at the NIMH Brain Collection. RESULTS: Currently, 80% of postmortem BPD studies were derived from just two brain repositories worldwide: the Stanley Brain Collection (69%) and Harvard Brain Tissue Resource Center (HBTRC) (11%) (combined subjects n = 72). The NIMH Brain Collection collected BPD cases four times less frequently than cases with schizophrenia, despite similar prevalence rates for these disorders. Only 53% of cases referred to the NIMH collection as BPD met DSM-IV criteria, with inadequate documentation and comorbid substance abuse as primary confounds for diagnosis in the remaining 47% of cases. CONCLUSIONS: Accurate identification and diagnosis of BPD is a central obstacle to BPD brain collection. Comorbid substance abuse and manner of death are two of many critical factors to consider in BPD postmortem studies. Difficulties in BPD brain collection, coupled with the cessation of brain collection by the Stanley Brain Collection, make the need for alternative BPD brain sources imperative. Recommendations for future BPD tissue collection are offered.

Reliability of psychiatric diagnosis in postmortem research.

BACKGROUND: Postmortem human brain research is an important approach for identifying the cellular, molecular, and genetic pathways involved in the pathophysiology of psychiatric disorders. One critical component in postmortem research is the reliability of psychiatric diagnoses used to define study cohorts. Finding reliable methods for assessing lifetime psychiatric diagnoses in subjects after death is extremely challenging. METHODS: Two commonly used approaches were compared: psychiatric record reviews and postmortem family interviews. We hypothesized that these two methods would lead to more diagnostic agreement for subjects with schizophrenia than those with mood disorders. For 37 cases, psychiatric records were reviewed retrospectively using the Diagnostic Evaluation After Death, and family members were interviewed using the Structured Clinical Interview for DSM-IV. RESULTS: Comparison of diagnoses derived from these two approaches generated an overall kappa coefficient of .67. Kappa coefficients for the schizophrenia cohort were .94, .68 for the major depressive disorder cohort, and .58 for the bipolar disorder cohort. CONCLUSIONS: Thus, although it may be sufficient to establish the postmortem diagnosis of schizophrenia using one of the two methods, the best method for reaching an accurate postmortem diagnosis for mood disorders is more difficult to determine and requires further study.