Håvard Bentsen

Bimodal Distribution of Polyunsaturated Fatty Acids in Schizophrenia Suggests Two Endophenotypes of the Disorder

BACKGROUND There is conflicting evidence of whether polyunsaturated fatty acids (PUFA) in red blood cells are bimodally distributed in schizophrenia. The purpose of this study was to examine the distribution of PUFA, as well as its links to plausible causal factors. METHODS A 16-week cohort study and a case-control study as part of a randomized controlled trial. Ninety-nine patients with DSM-IV schizophrenia, schizoaffective disorder, or schizophreniform disorder, aged 18 to 39, were consecutively included at admission to psychiatric departments of nine Norwegian hospitals. Fatty acids were measured in 97 of these patients and in 20 healthy control subjects. The primary outcome measure was the bimodality test statistic T, assessed by a χ(2) test of the likelihood of one or two normal distributions of PUFA. RESULTS At baseline, levels of polyunsaturated fatty acids were highly significantly bimodally distributed among patients. One third of patients constituted a group (low PUFA) who had PUFA levels at one fifth (p < .001) of those in high PUFA patients and healthy control subjects, which did not differ. Bimodality was mainly accounted for by docosahexaenoic acid and arachidonic acid. Bimodality was confirmed after 16 weeks. α-tocopherol was a robust predictor of PUFA at both occasions. Desaturase and elongase indexes differed between PUFA groups. Smoking, gender, antipsychotic medication, and dietary factors did not explain the bimodal distribution. CONCLUSIONS Red blood cell PUFA were bimodally distributed among acutely ill patients with schizophrenia and schizoaffective disorder. Endogenous deficiencies of redox regulation or synthesis of long-chain PUFA in the low PUFA group may explain our findings.

A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia

Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia. We examined the clinical effect of adding an omega-3 fatty acid and/or vitamins E+C to antipsychotics. It was hypothesized that lower baseline levels of polyunsaturated fatty acids (PUFAs) would predict more benefit from the add-on treatment. The trial had a multicenter, randomized, double-blind, placebo-controlled 2 × 2 factorial design. Patients aged 18–39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway. They received active or placebo ethyl-eicosapentaenoate (EPA) 2 g day−1 and active or placebo vitamin E 364 mg day−1+vitamin C 1000 mg day−1 (vitamins) for 16 weeks. The main outcome measures were Positive and Negative Syndrome Scale (PANSS) total and subscales scores, analyzed by linear mixed models. Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects. Given separately, EPA and vitamins increased drop-out rates, whereas when combined they did not differ from placebo. In low PUFA patients, EPA alone impaired the course of total PANSS (Cohen’s d=0.29; P=0.03) and psychotic symptoms (d=0.40; P=0.003), especially persecutory delusions (d=0.48; P=0.0004). Vitamins alone impaired the course of psychotic symptoms (d= 0.37; P=0.005), especially persecutory delusions (d=0.47; P=0.0005). Adding vitamins to EPA neutralized the detrimental effect on psychosis (interaction d=0.31; P=0.02). In high PUFA patients, there were no significant effects of trial drugs on PANSS scales. In conclusion, given separately during an acute episode, EPA and vitamins E+C induce psychotic symptoms in patients with low levels of PUFA. Combined, these agents seem safe.

Relatives’ emotional warmth towards patients with schizophrenia or related psychoses: demographic and clinical predictors

Despite the importance of relatives’ emotional warmth for outcome in schizophrenia, no studies to date have addressed demographic and clinical predictors of warmth. We examined a Norwegian sample of 47 recently hospitalized patients (with schizophrenia or schizophreniform disorder) and 72 key relatives. Relatives’ emotional warmth was assessed by means of the Camberwell Family Interview. Regression analyses showed that no substance abuse (especially amphetamines), better premorbid adjustment (12–15 years), a chronic social security status, and the relative not being a parent were the strongest predictors of emotional warmth. Emotional warmth was not related to patients’ symptoms.

Association between serum lipids and membrane fatty acids and clinical characteristics in patients with schizophrenia

Earlier reports indicate that patients with schizophrenia have altered lipid levels in serum and cell membranes. The purpose of this study was to determine the relationship between clinical characteristics and serum and membrane lipids.

Does guilt proneness predict acute and long-term distress in relatives of patients with schizophrenia?

Objective:  The aim of the study was to improve our understanding of guilt proneness as predictor of acute and long‐term stress responses in relatives of acutely admitted patients.

Lipid profiles in schizophrenia associated with clinical traits: a five year follow-up study

BackgroundAlterations in serum and membrane lipids may be involved in schizophrenia pathophysiology. It is not known whether lipid profiles are associated with disease severity or current symptom level.MethodsClinical and lipid data were gathered from 55 patients with schizophrenia admitted to psychiatric emergency wards in an acute stage of the disease (T1). The patients were re-examined after 5 years at a stable phase (T2). The clinical assessments included Positive and Negative Syndrome Scale (PANSS total, positive, negative) and Global Assessment of Functioning (GAF S, symptom and F, function). Serum lipids (cholesterol and triglyceride) and membrane polyunsaturated fatty acids (PUFA, LCPUFA) were measured. Healthy controls were recruited among hospital workers.ResultsSerum triglyceride was significantly higher in patients with schizophrenia compared to healthy controls both at T1 and T2 (p < 0.001), while serum cholesterol did not differ significantly. The levels of serum lipids in patients remained stable over time. At T1, serum lipids and symptoms were not significantly correlated. At T2, higher serum lipids were associated with more severe symptoms and poorer functioning. Higher serum lipid levels at T1 were associated with more severe symptoms and poorer functioning at T2; cholesterol with GAF-S (p < 0.05), triglyceride with PANSS total (p < 0.05), GAF-S (p < 0.01) and GAF-F (p < 0.01). Membrane lipids were significantly lower in the patient group compared to healthy controls at T1 (PUFA p < 0.001, LCPUFA p < 0.001), but not at T2. Membrane lipids were not significantly correlated with symptoms at T1, but significantly associated with negative symptoms and functioning at T2 as previously reported.ConclusionsThe present findings suggest different roles of membrane and serum lipids in schizophrenia pathophysiology. To further elucidate the relation of lipid biology to disease traits, replication in independent studies of longitudinal samples are warranted.

Treatment of schizophrenia: An update I. The vulnerability-stress model and biologic treatment modalities

Genetic, neuropathologic, neuroimaging, neurochemical, and psychophysiologic data give strong evidence for a biologic diathesis of schizophrenia. Environmental factors in the family of origin, especially communication deviance, is also related to an increased risk of developing schizophrenia. Physical stressors include drug abuse, coffeine, and possibly certain fatty acids. The most important psychosocial factor contributing to relapse is high level of expressed emotion. The consequences of understimulation have been much less studied. Despite the heterogeneity of this group of patients, practically all should receive neuroleptic maintenance therapy as early as possible in the course. The relapse rate when using neuroleptics is about half that when using placebo. The lowest effective dosage should be given. Continuous low-dose treatment should be tried for stable patients, and this is much safer than intermittent medication. The article suggests how to manage poor compliance, insufficient efficacy, and si...