cholecystokinin and Psychotic-Disorders

Patients with Parkinson's disease (PD) may develop several non-motor symptoms such as psychosis, depression, cognitive impairment, autonomic disturbances and sleep disturbances. Psychosis is one of the common non-motor symptoms, which commonly manifests as visual hallucinations and minor hallucinations such as sense of passage and presence. Though long-term dopaminergic therapy, longer duration of PD and cognitive impairment have been described as risk factors for emergence of psychosis in PD, predicting psychosis in PD remains challenging. Multiple studies have explored the genetic basis of psychosis in PD by studying polymorphisms of several genes. Most of the studies have focused on apolipoprotein E polymorphism followed by polymorphisms in cholecystokinin (CCK) system, dopamine receptors and transporters, HOMER gene, serotonin, catechol-o-methyltransferase, angiotensin converting enzyme and tau. Other than the studies on polymorphisms of CCK, most of the studies have reported conflicting results regarding association with psychosis in PD. Three out of four studies on CCK polymorphism have reported significant association of -45C>T polymorphism with the presence of hallucinations. The discrepancies in the results across the studies reviewed are possibly due to racial differences as well as differences in the patient characteristics. This review critically analyzes the published studies on genetic polymorphisms in patients with PD and psychosis.

Topics: Apolipoproteins E; Catechol O-Methyltransferase; Cholecystokinin; Databases, Bibliographic; Homer Scaffolding Proteins; Humans; Parkinson Disease; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Psychotic Disorders; Receptors, Dopamine; Serotonin; tau Proteins

Psychotic symptoms are frequent and disabling in patients with Parkinson's disease (PD). Methodological issues in the epidemiology of PD associated psychosis (PDP) include differences in the symptoms assessed, the methods of assessment, and the selection of patients. Most studies are prospective clinic-based cross-sectional studies providing point prevalence rates in samples on dopaminergic treatment. Visual hallucinations are present in about one quarter to one third of the patients, auditory in up to 20%. Tactile/somatic, and olfactory hallucinations are usually not systematically sought. Minor phenomena such as sense of presence and visual illusions affect 17 to 72% of the patients, and delusions about 5%. Lifetime prevalence of visual hallucinations reaches approximately 50%. Prospective longitudinal cohort studies suggest that hallucinations persist and worsen in individual patients, and that their prevalence increases with time. A facilitating role of treatment on PDP is demonstrated at least for dopaminergic agonists, but there is no simple dose-effect relationship between dopaminergic treatment and the presence or severity of hallucinations. The main endogenous non-modifiable risk factor is cognitive impairment. Other associated factors include older age/longer duration of PD, disease severity, altered dream phenomena, daytime somnolence, and possibly depression and dysautonomia. PDP reduces quality of life in patients and increases caregiver distress, and is an independent risk factor for nursing home placement and development of dementia.

Topics: Cholecystokinin; Cognition Disorders; Cross-Sectional Studies; Humans; Incidence; Longitudinal Studies; Parkinson Disease; Prevalence; Psychotic Disorders; Risk Factors

Topics: Benzodiazepines; Body Mass Index; Cholecystokinin; Ghrelin; Humans; Leptin; Lipids; Lipoproteins, LDL; Male; Olanzapine; Psychotic Disorders; Time Factors; Treatment Outcome; Triglycerides

The objective of the study was to investigate the change of body mass index (BMI), waist circumference, lipid profile, leptin, ghrelin, orexin, visfatin, agouti-related protein, and cholecystokinin levels during 6 weeks of olanzapine treatment in newly diagnosed first-episode drug naive, young adult, nonobese male patients with psychosis. Twenty male participants who were all first-episode drug naive psychotic patients without prominent affective signs and symptoms and 22 healthy male controls of similar age were included. BMI, waist circumference, fasting glucose, and lipid profiles were measured, and Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores were obtained at baseline, during the second and sixth week of treatment, and the aforementioned neuropeptide levels were measured at baseline and during the sixth week of treatment. Treatment was associated with significant increases in BMI, waist circumference, serum triglyceride, and low-density lipoprotein levels. BMI levels increased more than 7% in over 75% of the patients. Leptin increased, and ghrelin and orexin decreased significantly with olanzapine treatment, whereas cholecystokinin, visfatin, and agouti-related protein levels did not change significantly. In conclusion, consistent with previous studies, we found increased BMI, leptin and lipids during olanzapine treatment. Association of neuropeptide level changes with symptom improvement might be mediated by the dopaminergic and serotonergic systems.

Topics: Agouti-Related Protein; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Cholecystokinin; Disease Progression; Ghrelin; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Lipids; Male; Neuropeptides; Nicotinamide Phosphoribosyltransferase; Olanzapine; Orexins; Psychiatric Status Rating Scales; Psychotic Disorders; Time Factors; Waist Circumference; Young Adult

Systemic injections of cholecystokinin (CCK), a "gut-brain" peptide, have been shown to modulate brain dopamine function and produce neuroleptic-like effects on such dopamine-regulated behaviors as locomotor activity. However, clinical trials of CCK agonists in schizophrenia patients showed mixed results. To re-examine the antipsychotic potential of CCK-based treatments, we examined systemic injections of CCK analogs in an animal model with strong face and construct validity for sensorimotor-gating deficits seen in schizophrenia patients and with strong predictive validity for antipsychotic drug activity. Prepulse inhibition (PPI) occurs when a weak acoustic lead stimulus ("prepulse") inhibits the startle response to a sudden loud sound ("pulse"). PPI is significantly reduced in schizophrenia patients and rats treated with dopamine agonists. Antipsychotics reverse decreased PPI in rats to a degree highly correlated with their clinical efficacy. Subcutaneous (s.c.) injections of caerulein (10 micrograms/kg) a mixed CCKA/B agonist, partially reversed amphetamine-induced reduction of PPI; whereas, s.c. haloperidol (0.5 mg/kg) totally reversed amphetamine-induced disruption of PPI. Caerulein's effect on PPI was blocked by pretreatment with a CCKA antagonist (devazepide) but not a CCKB antagonist (L-365,260). CCK-4, a preferential CCKB agonist, had no significant effect on PPI. These results suggest that caerulein produces a weak neuroleptic-like effect on PPI that is mediated by stimulation of CCKA receptors. Possible circuities in this effect are discussed. In a separate experiment, s.c. caerulein produced to a more potent neuroleptic-like profile on amphetamine-induced hyperlocomotion, suggesting that selection of preclinical paradigms may be important in evaluating the antipsychotic potential of CCK-based treatments.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Ceruletide; Cholecystokinin; Gastrointestinal Agents; Haloperidol; Injections, Subcutaneous; Male; Motor Activity; Psychotic Disorders; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Reflex, Startle; Tetragastrin

Four neuropeptides (substance P, methionine-enkephalin, neurotensin and cholecystokinin) were measured by radioimmunoassays in a number of brain regions of deceased patients with mental illnesses and controls. The most striking finding in these studies was that methionine-enkephalin concentrations in caudate nuclei of chronic paranoid schizophrenic patients were reduced relative to several control groups. Neuroleptics had no obvious effects on any of the four measured neuropeptides. These findings are not inconsistent with the hypothesis that methionine-enkephalin may be involved in some of the pathology of the schizophrenic syndrome.

Topics: Adult; Aged; Alcoholism; Brain Chemistry; Cholecystokinin; Enkephalin, Methionine; Heroin Dependence; Humans; Mental Disorders; Middle Aged; Nerve Tissue Proteins; Neurotensin; Psychotic Disorders; Schizophrenia; Substance P; Suicide

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