Clinical and biochemical validation of two endophenotypes of schizophrenia defined by levels of polyunsaturated fatty acids in red blood cells.
BACKGROUND
Polyunsaturated fatty acids (PUFAs) are bimodally distributed in acute schizophrenia, suggesting two endophenotypes. We intended to characterize these endophenotypes clinically. Our a priori hypothesis was that low PUFA patients have more negative symptoms.


METHODS
Patients (aged 18-39) with schizophrenia, schizoaffective or schizophreniform disorders were recruited at hospital admission during an acute episode. The baseline Positive and Negative Syndrome Scale, vital signs and biochemical variables were measured in 97 patients with available RBC PUFA levels. Adjustment for multiple testing was not performed.


RESULTS
The median Negative Subscale score was higher (p=0.04) in the low PUFA (25 points, n=30) than in the high PUFA group (19 points, n=67). Among 95 patients with measurements of serum triglycerides, hypertriglyceridaemia was more prevalent (p=0.009) among low PUFA patients (66%) than high PUFA patients (36%). PUFA modified the effect of antipsychotics on triglycerides (p=0.046). Serum glucose and mean corpuscular haemoglobin were higher (p=0.03, 0.001, respectively) in low PUFA than in high PUFA patients. Low PUFA men were heavier (p=0.04) than high PUFA men.


CONCLUSIONS
During an acute episode of schizophrenia, patients with low RBC PUFA have more negative symptoms and more metabolic and haematological abnormalities than those with high PUFA. This indicates that PUFA levels define two clinically distinct endophenotypes of the disorder.
Center for Psychopharmacology, Diakonhjemmet Hospital, 0319 Oslo, Norway. havard.bentsen@medisin.uio.no
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D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use; D058068:Endophenotypes; D004912:Erythrocytes / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000139:chemically induced; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D009765:Obesity / Q000097:blood / Q000150:complications; D000077152:Olanzapine; D000069348:Quetiapine Fumarate; D012559:Schizophrenia / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D015415:Biomarkers; D003987:Dibenzothiazepines; D005231:Fatty Acids, Unsaturated; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D003024:Clozapine; D000077152:Olanzapine