Higher Insulin Resistance Linked to Mental Illness in PWS, Study Suggests

Children with Prader-Willi syndrome (PWS) may be particularly prone to metabolic alterations, including greater insulin resistance, which may be linked to increased risk for mental problems such as psychosis, a study suggests.

The study, “Metabolic Parameters in Patients with Prader-Willi Syndrome and DiGeorge Syndrome with Respect to Psychopathological Manifestation,” was published in the journal Neuropsychiatric Disease and Treatment.

Previous studies have shown that changes in several metabolic markers can relate to mental illness. Alterations in the blood lipid profile, the amounts of fats or fat-like substances, have been linked to the schizophrenia spectrum. Changes in cholesterol, insulin, and glucose were seen in people who had a first episode of psychosis.

Although these changes may have environmental causes, such as antipsychotic medications or an unhealthy lifestyle, some studies indicate that even patients at an early stage of mental illness who are not being treated already have signs of metabolic syndrome.

Other reports imply that people with severe mental disorders and people with metabolic conditions, including obesity and type 2 diabetes, share genetic similarities.

Together, the reports suggest such changes may be an early sign of mental illness in patients with PWS and DiGeorge syndrome (DGS), two genetic diseases with a high risk of psychiatric problems, especially mood and psychotic disorders.

Researchers at Wroclaw Medical University in Poland compared several metabolic parameters in patients with PWS and DiGeorge syndrome to determine if alterations in metabolic markers were linked to mental problems.

They recruited 20 children with PWS and 18 with DGS, ranging in age from 7 to 18. All but one had been diagnosed with psychotic symptoms or taken psychotropic medications. The exception was a PWS patient who was on methylphenidate for attention deficit hyperactivity disorder.

Patients took blood tests to assess glucose and insulin levels, to measure inflammation via the biomarker high-sensitivity C-reactive protein (hs-CRP); and to measure the blood profile of lipids including total cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, and non-HDL cholesterol, which is the total amount of cholesterol other than HDL.

LDL and HDL are lipoproteins (meaning they contain fat and proteins) with the primary purpose of transporting cholesterol, triglycerides, and other fats throughout the body.

In parallel to blood workups, behavioral and psychiatric symptoms were assessed using a caregiver questionnaire, the Child Behavior Checklist, or CBCL.

Results showed that children with PWS had significantly higher levels of insulin and non-HDL cholesterol when compared with patients with DGS.

Scores for social problems, cognitive problems, and delinquent and aggressive behavior were also higher (worse) in PWS patients.

Thinking problems were associated with higher levels of insulin and insulin resistance, which estimates the incapacity of cells to respond properly to insulin and regulate sugar levels.

The association was confirmed even after controlling for body mass index differences among patients, and suggests that greater insulin resistance among children with PWS may be a marker of psychosis risk.

“Our results indicate that patients with PWS may be more prone to develop subclinical metabolic dysregulation, in terms of elevated non-HDL levels and insulin levels, compared to DGS patients,” the researchers wrote. “In both groups of patients, altered insulin sensitivity, even though it is not a specific risk factor, might be related to psychosis risk, which needs further research.”

The findings may also indicate that metabolic alterations are linked to psychosis regardless of other predisposing conditions, the researchers said. Larger studies and comparison with other at-risk populations are needed to confirm these hypotheses, they said.