Abstract

EFFECT OF CALORIE RESTRICTION AND METFORMIN ON METABOLIC SYNDROME-ASSOCIATED INTERMITTENT EXPLOSIVE DISORDER: CLINICAL AND LABORATORY REPORTS

Dr. S. E. Oriaifo*, Prof. E. K. I. Omogbai, Dr. E. O. Okogbenin

ABSTRACT

Recent reports indicate that the impulse control disorder (ICD), intermittent explosive disorder (IED), may be linked to diabetes mellitus and eating disorders. It may also be linked to dysregulation of parainflammatory and inflammatory cascades; and of dopaminergic, serotonergic and insulin signallings. Overwhelming evidence by numerous workers has shown that hyperuricemia is a biomarker of various cardiometabolic, neuropsychiatric and renal disorders. It is also a predictive factor for pre-eclampsia and stroke. These disorders include mitochondrial and endothelial dysfunctions, the metabolic syndrome, bipolar disorder, acute and chronic renal failure. Reports have also noted that hyperuricemia may upregulate pro-inflammatory cytokines crucial in the aetiopathogenesis of impulsiveness and aggression, key constructs of IED. Clinical report is of adult Nigerian male diagnosed with metabolic syndrome and also with IED on clinical grounds using the Barratt Impulsiveness Scale (BIS-II) and the Modified Overt Aggression Scale (MOAS) as psychometric measures. Patient improved on calorie restriction and metformin which reduced the uric acid levels as well as the BIS-II and MOAS scores. Laboratory study also shows that calorie restriction and metformin more significantly (P < 0.05) lowered fructose-induced hyperuricemia in mice and reduced resident aggression in the resident intruder paradigm. Taken together, present study shows that calorie restriction and metformin which may attenuate impaired glucoregulation in critical brain circuits involved with impulsivity- and aggression- regulation and which may restore normal dopaminergic and serotonergic signallings seem attractive and credible agents for some subtypes of IED, a disease with no effective remedy at present.

Keywords: Impulsive-Aggression, Intermittent Explosive Disorder, Metabolic Syndrome, Hyperuricemia, Calorie Restriction, Metformin.