raclopride and Bipolar-Disorder

Neurochemical mechanisms underlying stress induced relapse of mood episodes in Bipolar I Disorder (BD) remain unknown. This study investigated whether euthymic BD patients have a greater dopamine release in ventral striatum, caudate and putamen in response to psychological stress using Positron Emission Tomography (PET) scanning with the radiotracer [. Euthymic patients with BD (n = 10) and 10 matched healthy controls underwent two [. There was a significant effect of stress in reducing the [. Small sample size and recruitment of euthymic patients who may be less vulnerable to stress may limit the generalizability of findings.. Our findings showed that psychological stress led to dopamine release in the basal ganglia for all participants but the magnitude of dopamine release during a stress task was not different between euthymic BD patients and healthy controls.

Topics: Bipolar Disorder; Dopamine; Humans; Positron-Emission Tomography; Raclopride; Stress, Psychological

The Sp4 transcription factor plays a critical role for both development and function of mouse hippocampus. Reduced expression of the mouse Sp4 gene results in a variety of behavioral abnormalities relevant to human psychiatric disorders. The human SP4 gene is therefore examined for its association with both bipolar disorder and schizophrenia in European Caucasian and Chinese populations respectively. Out of ten SNPs selected from human SP4 genomic locus, four displayed significant association with bipolar disorder in European Caucasian families (rs12668354, p = 0.022; rs12673091, p = 0.0005; rs3735440, p = 0.019; rs11974306, p = 0.018). To replicate the genetic association, the same set of SNPs was examined in a Chinese bipolar case control sample. Four SNPs displayed significant association (rs40245, p = 0.009; rs12673091, p = 0.002; rs1018954, p = 0.001; rs3735440, p = 0.029), and two of them (rs12673091, rs3735440) were shared with positive SNPs from European Caucasian families. Considering the genetic overlap between bipolar disorder and schizophrenia, we extended our studies in Chinese trios families for schizophrenia. The SNP7 (rs12673091, p = 0.012) also displayed a significant association. The SNP7 (rs12673091) was therefore significantly associated in all three samples, and shared the same susceptibility allele (A) across all three samples. On the other hand, we found a gene dosage effect for mouse Sp4 gene in the modulation of sensorimotor gating, a putative endophenotype for both schizophrenia and bipolar disorder. The deficient sensorimotor gating in Sp4 hypomorphic mice was partially reversed by the administration of dopamine D2 antagonist or mood stabilizers. Both human genetic and mouse pharmacogenetic studies support Sp4 gene as a susceptibility gene for bipolar disorder or schizophrenia. The studies on the role of Sp4 gene in hippocampal development may provide novel insights for the contribution of hippocampal abnormalities in these psychiatric disorders.

Topics: Adolescent; Adult; Animals; Antimanic Agents; Asian People; Bipolar Disorder; Carbamazepine; Case-Control Studies; Dopamine Antagonists; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Haplotypes; Hippocampus; Humans; Linkage Disequilibrium; Male; Mice; Mice, Mutant Strains; Middle Aged; Polymorphism, Single Nucleotide; Raclopride; Schizophrenia; Sensory Gating; Sp4 Transcription Factor; White People; Young Adult

A previous study reported a higher than normal density of dopamine D(2) receptors in psychotic mania but not in nonpsychotic mania. The purpose of this study was to further examine D(2) receptor density in a larger sample of nonpsychotic manic patients by using positron emission tomography (PET) and [(11)C]raclopride.. Thirteen neuroleptic- and mood- stabilizer-naive patients with DSM-IV mania without psychotic features and 14 healthy comparison subjects underwent [(11)C]raclopride PET scans. Of the 13 patients, 10 were treated with divalproex sodium monotherapy. PET scans were repeated 2-6 weeks after commencement of divalproex sodium. D(2) receptor binding potential was calculated by using a ratio method with the cerebellum as the reference region.. The [(11)C]raclopride D(2) binding potential was not significantly different in manic patients than in the comparison subjects in the striatum. Treatment with divalproex sodium had no significant effect on the [(11)C]raclopride D(2) binding potential in manic patients. There was no correlation between the D(2) binding potential and manic symptoms before or after treatment.. These results suggest that D(2) receptor density is not altered in nonpsychotic mania and that divalproex sodium treatment does not affect D(2) receptor availability.

Topics: Adolescent; Adult; Anticonvulsants; Bipolar Disorder; Brain; Cerebellum; Corpus Striatum; Female; Humans; Male; Middle Aged; Raclopride; Receptors, Dopamine D2; Tomography, Emission-Computed; Valproic Acid