Classification and neurobiological concepts of mania, bipolar disorder and major depression.

Abstract

of a G72 susceptibility haplotype on fiber tract integrity in young healthy probands. They found clusters of increased fractional anisotropy in homozygous risk haplotype carriers in the right periinsular and inferior parietal region. Both regions have been hypothesized to be involved in the pathophysiology of bipolar disorder and schizophrenia, and alterations in fractional anisotropy may reflect changes in neuropil such as morphology of dendrites. In a functional magnetic resonance imaging (fMRI) study using a working memory task, Stegmayer et al. [4] found reduced functional interactions of the right amygdala with cortical regions supporting verbal working memory in 18 bipolar patients compared with 18 healthy controls. The results point to a disturbed right-hemispheric cognitive–emotional interaction between the amygdala and cortical regions, leading to deficits in working memory. In bipolar disorder, poorer prognosis is related to weight gain and obesity. Lackner et al. [5] investigated body mass index, obesity measures, lipometry, metabolic parameters and monoamines in a large sample of bipolar patients compared with healthy controls. In the patient group, they found increased abdominal fat accumulation and measures of the metabolic syndrome along with correlation with epinephrine levels. The glutamate system has been reported to be involved in the pathophysiology of both bipolar disorder and major depression. Quinolinic acid is produced by activated microglia and is an agonist at the glutamatergic N-methyl-d-aspartate (NMDA) receptor. In a postmortem study, Busse et al. [6] investigated immunohistochemistry of quinolinic acid in hippocampal subregions of 12 patients with depression, among them 6 unipolar and 6 bipolar, and 10 healthy controls. Quinolinic-positive microglia was reduced in unipolar and bipolar patients in the right CA1 subregion. A degradation of quinolinic acid may be involved in the In the new DSM-5 and ICD-11 classification systems, pure mania and mania with mild depression are subsumed under bipolar disorder. In a comprehensive review, Angst and Grobler [1] vote for improved differential diagnoses of unipolar mania. This is clinically relevant since the disorder has a prevalence of approximately 1.8 %, and clinical follow-up studies demonstrated good diagnostic stability. Moreover, mania is associated with a hyperthymic temperament, more psychotic symptoms and higher heritability compared with depression. In contrast, the concept of bipolar disorder has been widely investigated in neurogenetic studies. For example, the dopaminergic system has been suggested to be affected in bipolar disorder, but the impact of the genetic variants of the human dopamine transporter DAT1 (SLC6A3) is inconsistent. Huang et al. [2] investigated the association of 18 polymorphisms of the DAT1 gene with bipolar disorder and explored its influence on specific personality traits such as novelty seeking and harm avoidance. Several polymorphisms had a weak association with bipolar disorder, and the promotor G-A-C-G haplotype was overrepresented in their sample of 492 patients compared with 436 healthy controls. Bipolar II patients had the highest harm avoidance score and a significant association between rs40184 of DAT1 and this personality trait in patients with bipolar disorder. G72 (D-amino acid oxidase activator, DAOA) is a susceptibility gene for bipolar disorder and schizophrenia. In a diffusion tensor imaging (DTI) study, Nickl-Jockschat et al. [3] investigated the influence