cholecystokinin and Mood-Disorders

The satiety-inducing effects of centrally and peripherally administered cholecystokinin (CCK) in experimental animals have been well documented. Recently, studies in humans showed that CCK is released into plasma following food ingestion, a phenomenon postulated to promote meal-related satiety. To explore whether abnormal CCK secretion during feeding may be related to pathophysiological mechanisms in disorders associated with appetite abnormalities, we report here studies of the plasma CCK response to a test meal in patients with bulimia nervosa, as well as seasonal (hyperphagic) and melancholic (anorexic) depression. Compared to controls, bulimic patients had impaired meal-related CCK secretion, correlated with an impaired sense of postprandial satiety. This defect resolved with tricyclic antidepressant-induced amelioration of bulimic behavior, suggesting that deficient CCK secretion may constitute a fundamental pathophysiologic derangement in this disorder. In contrast to patients with bulimia nervosa, hyperphagic patients with seasonal affective disorder failed to show abnormal meal-related CCK secretion. Preliminary evidence shows robust meal-related CCK secretion in melancholic depression with anorexia. We have also begun to explore the dynamics of CCK secretion into cerebrospinal fluid (CSF) utilizing an indwelling lumbar catheter. From studies in humans, we note that this peptide is secreted into the CSF in large (ng/ml) quantities in an episodic fashion that may bear some relationship to food ingestion. Further study of this parameter in volunteers and patients is now underway.

Topics: Cholecystokinin; Eating; Feeding and Eating Disorders; Humans; Mood Disorders

In recent decades, the role of genetic factors in the predisposition to suicidal behavior has attracted considerable attention. Although each genetic investigation appears to be valuable, no one study on its own can comprehensively explain the etiology of suicidal behavior.. In this study, using a broad literature review, we found the suicide-associated gene coexpression network. In addition, cytoband, molecular function, biological process, cellular component, tissue-based expression, and disease/disorder enrichment analyses were carried out to determine the most central cellular and molecular infrastructures involved in suicidal behavior.. The reconstructed network consisted of 104 genes, including 91 previously known genes and 13 novel genes, and 354 interactions. Topological analysis showed that in total, CCK, INPP1, DDC, and NPY genes are the most fundamental hubs in the network. We found that suicide genes are significantly concentrated within chromosomes 11 and 6. Further analysis showed that monoaminergic signal transduction, especially through GPCRs, in the cingulate gyrus, superior prefrontal gyrus, dorsal striatum, and the cerebellum are the main, deficient routes in suicide. Moreover, it turned out that genetically, suicidal behavior is more likely in patients with mood and affective disorders.. Like other behavioral disorders, suicide has a complex and multifactorial basis and at present, the only approaches to the integrated study of such disorders are computer-based methods. The results of such studies, although subject to a degree of uncertainty, however, can pave the way for future basic and clinical studies.

Topics: Aromatic-L-Amino-Acid Decarboxylases; Cholecystokinin; Databases, Genetic; Humans; Mental Disorders; Mood Disorders; Neuropeptide Y; Phosphoric Monoester Hydrolases; Risk Factors; Suicidal Ideation; Suicide; Suicide, Attempted

The cholecystokinin (CCK) system has long been hypothesised to have a role in the pathogenesis of panic attacks. Previous research into genetic variation within the CCK gene and the genes for its two receptors, CCKAR and CCKBR, has produced mixed results. We aimed to clarify this association by investigating multiple variants within each gene and multiple phenotypes associated with panic that may have confounded the previous studies' findings.. Variants were selected for the three genes based on HapMap CEU data. Individuals from a family based cohort (n=563) were genotyped for these variations and this data was analysed in FBAT.. CCKBR showed the strongest association with panic, having multiple variants with p<0.05 (lowest: p=0.007). In CCKAR, some evidence was found for an association with panic, though further analysis suggested that the co-morbid bipolar-panic phenotype was most strongly associated. No variants in CCK were associated with panic but broader anxiety phenotypes did show associations.. Small sample size prevented thorough investigation of phenotypes, particularly pure disorders, and no correction was made for the multiple phenotypes analysed.. Our findings support the involvement of variation in the CCK system, particularly CCKBR, in the pathogenesis of panic. Our data suggest that variation in CCK may be involved in several anxiety phenotypes and CCKAR may be involved in the development of panic co-morbid with bipolar disorder. These latter findings require further investigation and highlight the importance of clearly defined phenotypes when investigating psychiatric genetics.

Topics: Adolescent; Adult; Cholecystokinin; Cohort Studies; Comorbidity; Humans; Mood Disorders; Panic Disorder; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B; Young Adult

We have recently identified a novel polymorphic short tandem repeat (STR) in the 5' upstream region of the cholecystokinin (CCK) gene and reported its association with panic disorder. A linkage study of affective disorder showed a modest linkage signal on the short arm of chromosome 3, the location of the CCK gene. Furthermore, clinical comorbidity of depression and anxiety disorders have been documented. In the present study, we examined a possible association of the CCK STR with mood disorders. We genotyped 165 subjects with mood disorders consisting of unipolar and bipolar disorders and 253 control samples. However, no significant allelic associations were detected between the STR and either the combined mood disorders (P = 0.885), the unipolar group (P = 0.296), or the bipolar group (P = 0.605). These data suggest that the CCK promoter STR is unlikely to have a major genetic effect on the development of mood disorders in the Japanese population.

Topics: Adult; Aged; Alleles; Cholecystokinin; Female; Gene Frequency; Genotype; Humans; Japan; Male; Middle Aged; Mood Disorders; Promoter Regions, Genetic; Tandem Repeat Sequences