peptide-yy and Schizophrenia

Schizophrenia is among the top half of the 25 leading causes of disabilities worldwide with a 10-20 year decrease in life expectancy. Ineffective pharmacotherapy in the management of cognitive deficits and weight gain are known to be significant contributors; therefore interventions that may mitigate one, or both, of these parameters would be highly beneficial. Manipulation of the gut microbiome using dietary supplements such as prebiotics may be one such intervention. Preclinical studies have shown that a 2-4 week dietary supplementation with a prebiotic has beneficial effects on learning and memory, and prevents pro-inflammatory signals that are detrimental to cognitive processes. Furthermore, prebiotics influence metabolism, and in obesity they increase the expression of anorexigenic gut hormones such as peptide tyrosine tyrosine, glucagon-like peptide 1 and leptin, as well as decrease levels of orexigenic hormones such as ghrelin. Despite compelling evidence for the pro-cognitive and neuroprotective effects of prebiotics in rodents, their ability to alleviate cognitive deficits or enhance cognition needs to be evaluated in humans. Here we suggest that important symptoms associated with schizophrenia, such as cognitive impairment and weight gain, may benefit from concurrent prebiotic therapy.

Topics: Cognition; Dietary Supplements; Gastrointestinal Microbiome; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Obesity; Peptide YY; Prebiotics; Schizophrenia; Weight Gain

The present study was undertaken to determine if patients with schizophrenia on clozapine monotherapy have lower serum levels of peptide YY [PYY(1-36)], which is an endogenous inhibitor of food intake, comparing to healthy controls.. Data for 24 patients (mean age 38.8 years) with paranoid schizophrenia on clozapine monotherapy and 24 healthy subjects (gender- and age-matched; mean age 39.9 years) were analyzed.. Fasting serum levels of PYY(1-36) were lower in the clozapine group (178.4±138.4 vs. 277.4±218.1 pg/mL, p=0.034). In the whole study sample PYY(1-36) levels were lower in subjects with body mass index≥25 kg/m(2) (p=0.03) and in subjects with abdominal obesity defined using International Diabetes Foundation criteria (p=0.04). There were no significant differences for metabolic syndrome, smoking, impaired fasting glucose, dyslipidemia, and homeostatic model assessment (HOMA) defined insulin resistance.. RESULTS suggest that weight is asso-ciated with levels of PYY. Patients on clozapine had higher body mass index, but not fat mass index or body weight, therefore lower levels of PYY(1-36) in patients taking clozapine may result from clozapine-induced weight gain and central -obesity.

Topics: Adult; Antipsychotic Agents; Body Composition; Body Mass Index; Body Weight; Clozapine; Electric Impedance; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Peptide YY; Schizophrenia; Smoking

Functional changes in neuropeptide Y (NPY) signaling at the Y2 receptor subtype have been widely implicated in stress-related neuropsychiatric illnesses such as depression and anxiety disorders. Altered Y2 receptor signaling may also play a role in the precipitation of behavioral and cognitive symptoms associated with schizophrenia. To seek preclinical evidence for this possibility, we explored the functional consequences of treatment with the selective Y2 receptor agonist PYY(3-36) using translational tests for the assessment of schizophrenia-relevant behavioral and cognitive deficits in mice. We found that acute systemic administration of PYY(3-36) at a low dose (1 μg/100 g body weight) or high dose (20 μg/100 g body weight) profoundly impaired social interaction without affecting innate anxiety. PYY(3-36) treatment at the high dose further led to a disruption of sensorimotor gating in the form of prepulse inhibition deficiency. This effect was fully antagonized by acute treatment with the preferential dopamine D2 receptor antagonist haloperidol, but not with clozapine. In addition, both doses of PYY(3-36) impaired selective associative learning in the latent inhibition paradigm and spatial working memory in a matching-to-position water maze test. The wide range of abnormalities induced by PYY(3-36) suggests that signaling at the Y2 subtype of NPY receptors is critical for a number of behavioral and cognitive functions, some of which are highly relevant to schizophrenia and related psychotic disorders. At least some of the behavioral deficits induced by augmentation of Y2 receptor signaling may involve increased dopaminergic activity.

Topics: Animals; Antipsychotic Agents; Clozapine; Dopamine Antagonists; Haloperidol; Inhibition, Psychological; Male; Maze Learning; Mice; Mice, Inbred C57BL; Peptide Fragments; Peptide YY; Receptors, Neuropeptide Y; Schizophrenia; Social Behavior

Postmortem investigations were performed in brains from 14 schizophrenic patients and 21 controls matched for age and autopsy latency. Concentrations of galanin, delta-sleep-inducing peptide (DSIP), corticotropin-releasing factor (CRF), arginine vasopressin (AVP), neuropeptide Y (NPY) and peptide YY (PYY) were determined in the hypothalamus and grey matter from the temporal cortex. A significant positive correlation between age and the concentrations of galanin and CRF was found in the controls. No sex differences were found except a higher mean of CRF in the hypothalamus of the women. In the temporal cortex of the schizophrenic brains, galanin, AVP, NPY and PYY were significantly reduced. DSIP reduction only bordered on significance. CRF was not reduced. Comparing neuroleptic-treated vs non-treated schizophrenics, the treatment factor could not explain the reduced concentrations of neuropeptides in the temporal lobe. A comparison of controls with schizophrenics showed no significant differences in hypothalamic neuropeptide concentrations.

Topics: Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Arginine Vasopressin; Corticotropin-Releasing Hormone; Delta Sleep-Inducing Peptide; Female; Galanin; Hospitalization; Humans; Hypothalamus; Male; Middle Aged; Neuropeptide Y; Neuropeptides; Peptide YY; Peptides; Schizophrenia; Temporal Lobe

Neuropeptide Y (NPY)-like and peptide YY (PYY)-like immunoreactivities were measured in cerebrospinal fluid (CSF) from patients with major depressive disorder or schizophrenia and from healthy volunteers without physical or mental illness. NPY-like material was significantly lower (P less than 0.001) in CSF of patients with depressive disorders than in schizophrenic patients or healthy controls. Treatment with the antidepressant, amiflamine, a selective MAO-A inhibitor, did not alter CSF peptide concentrations. In drug-free schizophrenic patients, normal NPY but reduced PYY concentrations in CSF were observed. Treatment with neuroleptics did not affect the levels of NPY or PYY in the CSF. The finding of reduced CSF concentrations of NPY in patients with major depression and of reduced PYY concentrations in schizophrenia may reflect disturbed synthesis, turnover or degradation of the peptides. These findings suggest that the reduced concentrations of NPY or PYY in the CSF may be used as trait markers of the respective illnesses.

Topics: Adolescent; Adult; Aged; Depressive Disorder; Female; Humans; Male; Middle Aged; Neuropeptide Y; Peptide YY; Peptides; Radioimmunoassay; Schizophrenia