Intermediate phenotypes in schizophrenia: a selective review.

Studies aiming to identify susceptibility genes for schizophrenia and other complex psychiatric disorders are faced with the confounds of subjective clinical criteria, commonly occurring phenocopies, significant between-subject variability of candidate traits, and the likelihood of allelic and locus heterogeneity that has been shown to define the genetics of other complex human brain and somatic disorders. Additionally, research aimed at identification of the molecular origins of schizophrenia must also deal with the confounding nature of the human brain. Unlike organs with a few common cellular phenotypes, transcriptomes, and proteomes, individual neurons are often distinct from one another in all of these respects. In this review, we present recent work testing the assumption that studies of genetic susceptibility in complex polygenic disorders such as schizophrenia might be enhanced by the identification of intermediate phenotypes related to more fundamental aspects of brain development and function. Progress in the identification of meaningful intermediate phenotypes in schizophrenia has been made possible by the advent of newer methods in cognitive neuroscience and neuroimaging, and the use of combined multimodal techniques.

Borderline personality disorder in patients with bipolar disorder and response to lamotrigine.

BACKGROUND: Recent reports suggesting lamotrigine as an effective treatment in bipolar disorder, and perhaps borderline personality disorder, a common comorbid personality disorder in bipolar patients, led us to retrospectively examine patients from two bipolar studies to investigate this pattern of comorbidity, and to determine whether lamotrigine effected the dimensions of borderline personality. METHODS: Fifteen months following entry into either study, we retrospectively assessed DSM-IV dimensions of borderline personality disorder pre- and post-treatment with lamotrigine in 35 bipolar patients. RESULTS: Forty percent met criteria for borderline personality disorder; this subgroup had a more frequent history of substance abuse and childhood symptoms of attention deficit hyperactivity disorder (ADHD). Dimensions of borderline personality improved significantly with treatment in both patient groups, and corresponded with response of bipolar symptoms. Six (43%) comorbid bipolar patients endorsed three or fewer criteria of borderline personality during treatment with lamotrigine. There was a trend for comorbid bipolar patients to require a second psychoactive medication in addition to lamotrigine during extended treatment. LIMITATIONS: Criteria for borderline personality and improvement were assessed retrospectively in an open manner. CONCLUSIONS: Dimensions of borderline personality disorder may respond to lamotrigine in comorbid bipolar patients; controlled studies appear warranted. Bipolar studies should assess and specify the number of patients with personality disorders in the trial.