Hyperprolactinemia and insulin resistance in drug naive patients with early onset first episode psychosis

Abstract

BackgroundHyperprolactinemia and glucose and lipid metabolism abnormalities are often found in patients with schizophrenia and are generally considered secondary to the use of antipsychotic drugs. More recent studies have shown these same neuroendocrine and metabolic abnormalities in antipsychotic naïve patients with first episode psychosis (FEP), rising the hypothesis that schizophrenia itself may be related to an abnormal regulation of prolactin secretion and to impaired glucose tolerance. The aim of this study was to compare prolactin levels, glycometabolism parameters and lipid profile between a sample of 31 drug-naive adolescents in the acute phase of FEP and a control group of 23 subjects at clinical high risk (CHR) of developing psychosis.MethodsThe assessment involved anthropometric data (weight, height, BMI index, pubertal stage) and blood tests (levels of glucose, glycated hemoglobin, serum insulin, triglycerides, total and fractionated cholesterol, prolactin). Insulin resistance (IR) was calculated through the homeostatic model of assessment (HOMA-IR), assuming a cut-off point of 3.16 for adolescent population. FEP patients and CHR controls were compared by using Student’s t-distribution (t-test) for parametric data. P < 0.05 was considered significant.ResultsSignificant higher level of prolactin was found in FEP group than in CHR group (mean = 28.93 ± 27.16 vs 14.29 ± 7.86, P = 0.009), suggesting a condition of hyperprolactinemia (HPRL). Patients with FEP were more insulin resistant compared to patients at CHR, as assessed by HOMA-IR (mean = 3.07 ± 1.76 vs 2.11 ± 1.11, P = 0.043). Differences of fasting glucose (FEP = 4.82 ± 0.71, CHR = 4.35 ± 0.62, P = 0.016) and HbA1c (FEP = 25.86 ± 13.31, CHR = 33.00 ± 2.95, P = 0.013), were not clinically significant as the mean values were within normal range for both groups. No significant differences were found for lipid profile. A BMI value within the range of normal weight was found for both groups, with no significant differences.ConclusionWe suggested that HPRL, increase in HOMA-IR, and psychotic symptoms may be considered different manifestations of the acute onset of schizophrenia spectrum psychosis, with a common neurobiological vulnerability emerging since adolescence. The influence of age and gender on clinical manifestations of psychotic onset should be considered for early prevention and treatment of both schizophrenia spectrum psychosis and neuroendocrine-metabolic dysfunctions.

Unveiling the Metabolic Profile of First-Episode Drug-Naïve Schizophrenia Patients: Baseline Characteristics of a Longitudinal Study Among Han Chinese

“…Accumulating evidence indicates that subthreshold metabolic dysregulation might be present in the premorbid phase of the illness (59) and in antipsychotic-naïve patients with firstepisode psychosis (60), which has been confirmed in our report. We did not find hypercholesterolemia but hypertriglyceridemia in FEDN patients.…”

Assessment of Appetite-Regulating Hormones Provides Further Evidence of Altered Adipoinsular Axis in Early Psychosis

“…Moreover, it has been shown that measuring the levels of fatty acids in subjects at ultrahigh risk of psychosis may improve prediction of transition to overt psychotic episode (41). Another study demonstrated that FEP patients have significantly higher levels of prolactin, fasting glucose, glycosylated hemoglobin and insulin resistance compared to individuals at clinical high risk of psychosis (42). It cannot also be excluded that results of our study simply reflect the effects of environmental factors or unhealthy lifestyle characteristics that are highly prevalent in early psychosis and include nutritional deficiencies as well as low exercise activity (43)(44)(45).…”

Transcriptomic analysis reveals new hippocampal gene networks induced by prolactin

“…In the field of psychiatry, the adverse effects of Prl remain under debate. Treatment with psychiatric drugs to manage schizophrenia and depression is frequently associated with hyperprolactinemia (HPL), suggesting the negative effects of Prl in these patients 58,59 . In contrast, in a recent study, it was shown that many patients with a first episode of psychosis presented HPL before treatment and presented elevated rates of HPL over the course of the illness 60 .…”