Comorbid Bipolar and Alcohol Use Disorder-A Therapeutic Challenge.

Comorbidity rates in Bipolar disorder rank highest among major mental disorders, especially comorbid substance use. Besides cannabis, alcohol is the most frequent substance of abuse as it is societally accepted and can be purchased and consumed legally. Estimates for lifetime comorbidity of bipolar disorder and alcohol use disorder are substantial and in the range of 40-70%, both for Bipolar I and II disorder, and with male preponderance. Alcohol use disorder and bipolarity significantly influence each other's severity and prognosis with a more complicated course of both disorders. Modern treatment concepts acknowledge the interplay between these disorders using an integrated therapy approach where both disorders are tackled in the same setting by a multi-professional team. Motivational interviewing, cognitive behavioral and socio- therapies incorporating the family and social environment are cornerstones in psychotherapy whereas the accompanying pharmacological treatment aims to reduce craving and to optimize mood stability. Adding valproate to lithium may reduce alcohol consumption whereas studies with antipsychotics or naltrexone and acamprosate did not affect mood fluctuations or drinking patterns. In summary, there is a continuous need for more research in order to develop evidence-based approaches for integrated treatment of this frequent comorbidity.

Dopamine transporter genotype influences N-acetyl-aspartate in the left putamen.

INTRODUCTION: Dopaminergic activity in the brain is modulated by the dopamine transporter (DAT). Several lines of evidence suggest that a variable number of tandem repeats (VNTR) polymorphism of the DAT1 gene (SLC6A3) influences its gene expression. The aim of this study was to determine whether the DAT1VNTR polymorphism alters the metabolic ratios NAA/Cho, NAA/Cr, Cho/Cr and Ins/Cr in the left dorsolateral prefrontal cortex, anterior cingulate cortex, and putamen in healthy subjects and psychiatric patients irrespective of clinical diagnosis. MATERIAL AND METHODS: Sixty-four individuals (30 patients with bipolar disorder, 18 patients with obsessive-compulsive disorder, and 16 healthy subjects) participated in the study. The 3'-UTR VNTR polymorphism of DAT1 (SLC6A3) gene was genotyped in all individuals. (1)H-MRS was performed in the above-mentioned brain regions. RESULTS: The individuals with the homozygous DAT1 10-repeat genotype presented significantly higher ratios of NAA/Cho and NAA/Cr in the left putamen compared to the group of individuals with the 9/9-repeat or 9/10-repeat genotype. CONCLUSION: The VNTR polymorphism of the DAT1-gene modulates NAA/Cho and NAA/Cr in the left putamen independent of psychiatric diagnosis status. These results suggest an association of DAT1 VNTR polymorphism, dopaminergic activity, and neuronal function in putamen.

Proton magnetic resonance spectroscopy in subjects at risk for schizophrenia.

We used proton magnetic resonance spectroscopy (1H MRS) to examine biochemical characteristics of the brain tissue in subjects at risk for schizophrenia. Nineteen participants fulfilling research criteria for an early (n=10) or a late (n=9) at-risk syndrome, 21 patients with full disease according to DSM IV and 31 healthy control subjects were included in the study. Single-voxel 1H MRS was performed in the left frontal lobe, the anterior cingulate gyrus and the left superior temporal lobe. Subjects were followed longitudinally to detect conversion to schizophrenia. We observed a significant reduction of the metabolic ratios NAA/Cr and NAA/Cho in the left frontal lobe and of NAA/Cr in the anterior cingulate gyrus in both at-risk groups and in the schizophrenic patients compared with healthy controls. Those at-risk subjects, who converted to schizophrenia within the observation period, had a higher Cho/Cr and a lower NAA/Cho ratio in the anterior cingulate gyrus compared with non-converters. NAA/Cr did not differ between converters and non-converters. Six at-risk subjects were taking antidepressants, two were taking antipsychotics. There was no difference in any metabolic ratio in any region between at-risk subjects with and without medication. We conclude that the reduction of the neuronal marker NAA in the left prefrontal lobe and the anterior cingulate gyrus may represent a vulnerability indicator for schizophrenia in at-risk subjects, while elevated Cho in the anterior cingulate gyrus may be a predictor for conversion from the prodromal state to the full disease.

Effects of antipsychotics on brain structure.

PURPOSE OF REVIEW: This review highlights the recent findings of different effects of typical and atypical antipsychotics on brain structure. RECENT FINDINGS: Studies examining the effect of treatment with typical antipsychotics on brain structure revealed a significant increase in basal ganglia volumes and decreased grey matter volume in different cortical regions. These volume changes were detectable even after a 12-week treatment. In contrast to these results, treatment with atypical antipsychotics does not seem to change basal ganglia volumes in neuroleptic-naïve patients. Moreover, switching from typical to atypical antipsychotic treatment reduces the increased basal ganglia volume to normal values compared with healthy controls. Only the volumes of thalamus and cortical grey matter increased after atypical antipsychotic treatment. SUMMARY: Currently, there is growing evidence that atypical antipsychotics might ameliorate structural changes caused by the disease process underlying schizophrenia and effects of typical antipsychotics. Further studies have to investigate the mechanism leading to these varying effects on brain structure.