vasoactive-intestinal-peptide and Bipolar-Disorder

Schizophrenia and bipolar disorder are often viewed as distinct clinical disorders, however there is substantial overlap in their neuropathologies. While compromised cortical interneurons are implicated in both diseases, few studies have examined the relative contribution of the distinct interneuron populations to each psychotic disorder. We report reductions in somatostatin and vasoactive intestinal peptide mRNAs in prefrontal and orbitofrontal cortices in bipolar disorder (n=31) and schizophrenia (n=35) compared to controls (n=34) and increased calbindin mRNA in schizophrenia. We show, at the molecular level, shared deficits in interneuron markers in schizophrenia and bipolar disorder, and a unique interneuron marker increase in schizophrenia.

Topics: Adult; Biomarkers; Bipolar Disorder; Calbindins; Cerebral Cortex; Female; Humans; Interneurons; Male; Middle Aged; RNA, Messenger; Schizophrenia; Somatostatin; Vasoactive Intestinal Peptide; Young Adult

The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic nucleus (SCN). This feedback is mediated by the melatonin receptors, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). The circadian system may play a role in the pathophysiology of mood disorders, and indeed, melatonin-receptor agonists are considered a potential therapy for depression.. In order to investigate melatonin receptors in the SCN during depression, and their relationship to the major neuropeptides in the SCN, vasopressin (AVP) and vasoactive intestinal peptide (VIP), we studied the SCN in 14 depressed patients (five major depression and nine bipolar disorder) and 14 matched controls by immunocytochemistry.. We show here that hypothalamic MT2 receptor immunoreactivity was limited to SCN, the supraoptic nucleus and paraventricular nucleus. We found that numbers of MT1-immunoreactive (MT1-ir) cells and AVP and/or VIP-ir cells were increased in the central SCN in depression, but numbers of MT2-ir cells were not altered. Moreover, the number of MT1-ir cells, but not MT2-ir cells was negatively correlated with age at onset of depression, while positively correlated with disease duration. CONCLUSION AND LIMITATIONS: Although every post-mortem study has limitations, MT1 receptors appeared specifically increased in the SCN of depressed patients, and may increase during the course of the disease. These changes may be involved in the circadian disorders and contribute to the efficacy of MT agonists or melatonin in depression. Moreover, we suggest that melatonin receptor agonists for depression should be targeted towards the MT1 receptor selectively.

Topics: Aged; Aged, 80 and over; Bipolar Disorder; Case-Control Studies; Circadian Rhythm; Depressive Disorder, Major; Female; Humans; Immunohistochemistry; Male; Melatonin; Middle Aged; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins

Disruptions in circadian rhythms have been described in mood disorders (MD), but the involvement of genetic variation in genes pertaining to the molecular circadian machinery in the susceptibility to MD has not been conclusively determined. We examined 209 single-nucleotide polymorphisms (SNPs) covering 19 circadian genes (ADCYAP1, ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1E, DBP, NPAS2, NR1D1, PER1, PER2, PER3, RORA, TIMELESS, VIP, and VIPR2) in a sample of 534 MD patients (335 with unipolar major mood depression (MDD) and 199 with bipolar disorder (BD)) and 440 community-based screened controls. Nominally, statistically significant associations were found in 15 circadian genes. The gene-wide test, corrected for the number of SNPs analyzed in each gene, identified significant associations in CRY1 (rs2287161), NPAS2 (rs11123857), and VIPR2 (rs885861) genes with the combined MD sample. In the MDD subsample, the same SNPs in CRY1 and NPAS2 of the combined sample remained associated, whereas in the BD subsample CLOCK (rs10462028) and VIP (rs17083008) were specifically associated. The association with an SNP located 3' near CRY1 gene in MDD remained statistically significant after permutation correction at experiment level (p=0.007). Significant additive effects were found between the SNPs that were statistically significant at the gene-wide level. We also found evidence of associations between two-marker haplotypes in CRY1 and NPAS2 genes and MD. Our data support the contribution of the circadian system to the genetic susceptibility to MD and suggest that different circadian genes may have specific effects on MD polarity.

Topics: Adult; Aged; Basic Helix-Loop-Helix Transcription Factors; Bipolar Disorder; Chronobiology Disorders; CLOCK Proteins; Cryptochromes; Depressive Disorder, Major; DNA Mutational Analysis; Female; Genetic Predisposition to Disease; Genetic Testing; Genome-Wide Association Study; Genotype; Humans; Male; Middle Aged; Mutation; Nerve Tissue Proteins; Polymorphism, Single Nucleotide; Vasoactive Intestinal Peptide

Levels of vasopressin, somatostatin, neurotensin, vasoactive intestinal peptide, corticotrophin-releasing factor and adrenocorticotrophin in CSF were determined in lithium-treated and unmedicated euthymic bipolar patients and controls, in a search for a trait marker in affective disorder. No group differences in levels of these peptides were found. Highly significant positive correlations were found among these peptides (with the exception of neurotensin), suggesting that their presence in CSF is functionally significant, as opposed to the result of random diffusion from the interstitial space of the brain.

Topics: Adrenocorticotropic Hormone; Bipolar Disorder; Corticotropin-Releasing Hormone; Humans; Lithium; Neuropeptides; Neurotensin; Somatostatin; Vasoactive Intestinal Peptide; Vasopressins

Vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and gastrin in the cerebrospinal fluid (CSF) were studied in patients with endogenous depression, non-endogenous depression, mania, schizophrenia and a control group. All patients were classified according to ICD-9 and the group of depressions was further classified according to the Newcastle Rating Scales for depression (Carney et al. 1965) (N-I). In the group of non-endogenously depressed patients, CSF-VIP levels (median 16 pmol/l) were found to be significantly lower than those of controls (median = 32 pmol/l) and endogenous depressives (36 pmol/l). In the non-endogenous group, it appeared that the low CSF-VIP was due to a group of patients who, during a past or present depressive episode, had been diagnosed as suffering from endogenous depression. Moreover, this group was clinically characterized by 'dysphoric/hysterical features', 'reversed diurnal variation' (i.e. worse in the evening), and 'lack of clearly circumscribed episodes'. In many aspects this group seems similar to the atypical depressives described as monoamine oxidase inhibitor responders. Concerning CSF-CCK and CSF-gastrin, no significant differences between the examined groups were demonstrated.

Topics: Adult; Aged; Bipolar Disorder; Cholecystokinin; Depressive Disorder; Female; Gastrins; Humans; Male; Middle Aged; Psychological Tests; Psychotic Disorders; Schizophrenia; Vasoactive Intestinal Peptide