Shared Gene Expression Alterations in Schizophrenia and Bipolar Disorder

Schizophrenia (SZ) and bipolar disorder (BPD) have traditionally been diagnosed by clinical examination of psychotic symptoms and affective dysregulation. The clinical impressions along these two dimensions coupled with historical separation into current diagnostic classifications have led to these illnesses being viewed and treated in research as independent classes (1,2). Categorization into separate classes has led to efforts for identification of separate pathophysiologies for each disorder (3). However, it has not escaped attention that the classifications share some pathophysiology, vulnerability and risk factors, genetic loci, clinical manifestations, and approximate ages of onset. Classifications have arisen that are based upon meeting clinical characteristics, and multiple criteria can be combined into discrete subgroups, which might be different in terms of pathophysiology. Recent discussions have centered on the idea that schizophrenia and bipolar are not separate illnesses (1-5), but share many criteria and differ along a dimension related to psychosis and affective symptom clusters. Medication response can be effective in one or both disorders or equally ineffective in both. Furthermore, patients clinically present with both affective and psychotic symptoms. This study was motivated by the idea of identifying common gene-expression profiles akin to recent reports of shared candidate genes that overlap in linkage and association genetic studies of BPD and SZ, although clearly not in all studies (1). Most reports of SZ or BPD microarray studies have not compared both disorders with a common reference control group with a few exceptions (6,7). We now present a common molecular profile of both SZ and BPD as one potential indicator of a partially shared molecular phenotype.