Hyperprolactinemia and Insulin Resistance in Drug Naive Patients with Early Onset First Episode Psychosis

Background: Hyperprolactinemia 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.

Methods: The 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.

Results: Significant 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.

Conclusion: We 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.