Miriam R. Schäfer

Omega-3 Fatty Acids Supplementation in Children with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study

BACKGROUND There is increasing evidence that fatty acid deficiencies or imbalances may contribute to childhood neurodevelopmental disorders. METHODS We conducted a randomized, double-blind, placebo-controlled 6-week pilot trial investigating the effects of 1.5 g/d of omega-3 fatty acids (.84 g/d eicosapentaenoic acid, .7 g/d docosahexaenoic acid) supplementation in 13 children (aged 5 to 17 years) with autistic disorders accompanied by severe tantrums, aggression, or self-injurious behavior. The outcome measure was the Aberrant Behavior Checklist (ABC) at 6 weeks. RESULTS We observed an advantage of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy, each with a large effect size. Repeated-measures ANOVA indicated a trend toward superiority of omega-3 fatty acids over placebo for hyperactivity. No clinically relevant adverse effects were elicited in either group. CONCLUSIONS The results of this study provide preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism.

Emotion Recognition in Individuals at Clinical High-Risk for Schizophrenia

Problems in the perception of emotional material, in particular deficits in the recognition of negative stimuli, have been demonstrated in schizophrenia including in first-episode samples. However, it is largely unknown if emotion recognition impairment is present in people with subthreshold psychotic symptoms. Here, we examined the capacity to recognize facially expressed emotion and affective prosody in 79 individuals at ultra high-risk for psychosis, 30 clinically stable individuals with first-episode schizophrenia assessed as outpatients during the early recovery phase of illness, and 30 unaffected healthy control subjects. We compared (1) scores for a combined fear-sadness aggregate index across face and voice modalities, (2) summary scores of specific emotions across modalities, and (3) scores for specific emotions for each sensory modality. Findings supported deficits in recognition of fear and sadness across both modalities for the clinical groups (the ultra high-risk and first-episode group) as compared with the healthy controls. Furthermore, planned contrasts indicated that compared with the healthy control subjects, both clinical groups had a significant deficit for fear and sadness recognition in faces and for anger recognition in voices. Specific impairments in emotion recognition may be apparent in people at clinical high-risk for schizophrenia before the full expression of psychotic illness. The results suggest a trait deficit and an involvement of the amygdala in the pathology of ultra high-risk states.

Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study

Long-chain omega-3 polyunsaturated fatty acids (PUFAs) are essential for neural development and function. As key components of brain tissue, omega-3 PUFAs play critical roles in brain development and function, and a lack of these fatty acids has been implicated in a number of mental health conditions over the lifespan, including schizophrenia. We have previously shown that a 12-week intervention with omega-3 PUFAs reduced the risk of progression to psychotic disorder in young people with subthreshold psychotic states for a 12-month period compared with placebo. We have now completed a longer-term follow-up of this randomized, double-blind, placebo-controlled trial, at a median of 6.7 years. Here we show that brief intervention with omega-3 PUFAs reduced both the risk of progression to psychotic disorder and psychiatric morbidity in general in this study. The majority of the individuals from the omega-3 group did not show severe functional impairment and no longer experienced attenuated psychotic symptoms at follow-up.

Decreased nervonic acid levels in erythrocyte membranes predict psychosis in help-seeking ultra-high-risk individuals.

Decreased nervonic acid levels in erythrocyte membranes predict psychosis in help-seeking ultra-high-risk individuals

Effect of ω-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial

Importance A promising treatment to prevent onset and improve outcomes in patients at ultrahigh risk for psychosis is dietary supplementation with long-chain &ohgr;-3 polyunsaturated fatty acids (PUFAs). Objective To determine whether treatment with &ohgr;-3 PUFAs in combination with a high-quality psychosocial intervention (cognitive behavioral case management [CBCM]) is more effective than placebo plus CBCM. Design, Setting, and Participants NEURAPRO, a double-blind, placebo-controlled, randomized clinical trial, was conducted from March 1, 2010, to September 30, 2014, in 10 specialized early psychosis treatment services in Australia, Asia, and Europe. The primary analysis used the intention-to-treat approach. Interventions A daily dose of 1.4 g of &ohgr;-3 PUFAs or placebo (paraffin oil), plus 20 or fewer sessions of CBCM over the 6-month study period. Main Outcomes and Measures The primary outcome was transition to psychosis status at 6 months. The secondary outcomes were general levels of psychopathology and functioning, as assessed by the Brief Psychiatric Rating Scale (BPRS) (range, 24-168), Scale for the Assessment of Negative Symptoms (SANS) (range, 0-125), Montgomery-Åsberg Depression Rating Scale (MADRS) (range, 0-60), Young Mania Rating Scale (YMRS) (range, 0-44), Social and Occupational Functioning Assessment Scale (SOFAS) (range, 0-100), and the Global Functioning: Social and Role scale (range, 0-10). For SOFAS and Global Functioning: Social and Role scale, higher scores were better; for other measures, lower scores were better. Results In this study of 304 adults at ultrahigh risk for psychotic disorders, 153 (50.3%) received &ohgr;-3 PUFAs and 151 (49.7%) received placebo. In all, 139 (45.7%) were male; mean (SD) age was 19.1 (4.6) years. The Kaplan-Meier–estimated 6-month transition rates were 5.1% (95% CI, 1.3%-8.7%) in the control group and 6.7% (95% CI, 2.3%-10.8%) in the &ohgr;-3 PUFA group. At 12 months, the rates were 11.2% (95% CI, 5.5%-16.7%) in the control group and 11.5% (95% CI, 5.8%-16.9%) in the &ohgr;-3 PUFA group. No significant difference was observed between the transition rates of both groups (hazard ratio, 1.1; 95% CI, 0.55-2.23; P = .76, stratified log-rank test). Conclusions and Relevance This trial clearly failed to replicate the findings of the original single-center trial. The most likely explanation is that &ohgr;-3 PUFAs lack efficacy under these conditions. However, the lower-than-expected transition rate may have prevented a test of the main hypothesis. Given the substantial symptomatic and functional improvement in both groups, the other treatments received (ie, CBCM and antidepressants) likely produced a ceiling effect beyond which &ohgr;-3 PUFAs, even if effective, could not be shown to confer additional benefits. Nevertheless, the main conclusion is that &ohgr;-3 PUFAs are not effective under conditions where good quality, evidence-based psychosocial treatment is available. Trial Registration anzctr.org.au Identifier: 12608000475347

Facial and vocal affect perception in people at ultra-high risk of psychosis, first-episode schizophrenia and healthy controls

Aim: The study aims to investigate affect recognition in young people at different stages of psychotic illness.

Omega-3 fatty acid supplementation changes intracellular phospholipase A2 activity and membrane fatty acid profiles in individuals at ultra-high risk for psychosis

The identification of an ultra-high risk (UHR) profile for psychosis and a greater understanding of its prodrome have led to increasing interest in early intervention to delay or prevent the onset of psychotic illness. In a randomized placebo-controlled trial, we have identified long-chain ω-3 (ω-3) polyunsaturated fatty acid (PUFA) supplementation as potentially useful, as it reduced the rate of transition to psychosis by 22.6% 1 year after baseline in a cohort of 81 young people at UHR of transition to psychosis. However, the mechanisms whereby the ω-3 PUFAs might be neuroprotective are incompletely understood. Here, we report on the effects of ω-3 PUFA supplementation on intracellular phospholipase A2 (inPLA2) activity, the main enzymes regulating phospholipid metabolism, as well as on peripheral membrane lipid profiles in the individuals who participated in this randomized placebo-controlled trial. Patients were studied cross-sectionally (n=80) and longitudinally (n=65) before and after a 12-week intervention with 1.2 g per day ω-3 PUFAs or placebo, followed by a 40-week observation period to establish the rates of transition to psychosis. We investigated inPLA2 and erythrocyte membrane FAs in the treatment groups (ω-3 PUFAs vs placebo) and the outcome groups (psychotic vs non-psychotic). The levels of membrane ω-3 and ω-6 PUFAs and inPLA2 were significantly related. Some of the significant associations (that is, long-chain ω-6 PUFAs, arachidonic acid) with inPLA2 activity were in opposite directions in individuals who did (a positive correlation) and who did not (a negative correlation) transition to psychosis. Supplementation with ω-3 PUFA resulted in a significant decrease in inPLA2 activity. We conclude that ω-3 PUFA supplementation may act by normalizing inPLA2 activity and δ-6-desaturase-mediated metabolism of ω-3 and ω-6 PUFAs, suggesting their role in neuroprogression of psychosis.

Adolescents at ultra-high risk for psychosis with and without 22q11 deletion syndrome: A comparison of prodromal psychotic symptoms and general functioning

OBJECTIVE Genetic syndromes related to psychosis have become increasingly important for exploring the trajectory that leads to psychosis onset. A very significant opportunity for mapping earlier phases of the trajectory can be found in 22q11.2 deletion syndrome (22q11DS). Comparative studies have shown that schizophrenic disorder in 22q11DS largely resembles schizophrenia in the general population, but only few studies have investigated the features of prodromal symptoms in 22q11DS. The aim of the present study was to investigate differences and similarities between two samples: patients with 22q11DS clinically at risk for psychotic onset (UHR+22q11DS group) and patients at clinical high risk for psychotic onset (UHR group). METHOD The study was conducted on a sample of 30 individuals UHR+22q11DS and 81 individuals at UHR without 22q11DS. The two groups were compared on positive, negative and depressive symptoms, level of general functioning and IQ. RESULTS There was a significant group difference in negative symptoms, but no significant differences were found for positive, global and total symptoms. The UHR+22q11DS group showed a lower level of general functioning. The clinical profile of the UHR+22q11DS group was clearly more homogeneous. CONCLUSIONS Even if the two UHR groups are comparable in terms of positive symptoms, the UHR+22q11DS have a specific clinical pattern characterized by higher negative symptoms, lower general functioning and an older age of onset of the UHR state. This finding may be of clinical value for the development of specific therapeutic intervention for UHR+22q11DS, and of theoretical value since the two groups may share only some underlying etiopathogenetic mechanisms.

Omega-3 Fatty Acid Supplementation in Adolescents with Borderline Personality Disorder and Ultra-High Risk Criteria for Psychosis: A Post Hoc Subgroup Analysis of a Double-Blind, Randomized Controlled Trial

Objective: To investigate whether long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs) improve functioning and psychiatric symptoms in young people with borderline personality disorder (BPD) who also meet ultra-high risk criteria for psychosis. Methods: We conducted a post hoc subgroup analysis of a double-blind, randomized controlled trial. Fifteen adolescents with BPD (mean age 16.2 years, [SD 2.1]) were randomized to either 1.2 g/day n-3 PUFAs or placebo. The intervention period was 12 weeks. Study measures included the Positive and Negative Syndrome Scale, the Montgomery–Åsberg Depression Rating Scale, and the Global Assessment of Functioning. Side effects were documented with the Udvalg for Kliniske Undersøgelser. Fatty acids in erythrocytes were analyzed using capillary gas chromatography. Results: At baseline, erythrocyte n-3 PUFA levels correlated positively with psychosocial functioning and negatively with psychopathology. By the end of the intervention, n-3 PUFAs significantly improved functioning and reduced psychiatric symptoms, compared with placebo. Side effects did not differ between the treatment groups. Conclusions: Long-chain n-3 PUFAs should be further explored as a viable treatment strategy with minimal associated risk in young people with BPD.

Emotion recognition as a predictor of transition to a psychotic disorder in ultra-high risk participants

AIMS Recent research has shown emotion recognition to be impaired in individuals at ultra-high risk (UHR) for developing a psychotic disorder compared to healthy controls. This longitudinal study aimed to examine whether disturbed emotion recognition measured in UHR participants at baseline predicts transition to a psychotic disorder within 12months. METHODS Thirty-seven UHR participants aged 13-22years participated in the study. At baseline participants completed face and prosody emotion recognition tasks, as well as measures of psychopathology, functioning, and IQ. Transition to a psychotic disorder over 12months was the primary outcome. A series of Cox regressions was performed with emotion recognition as the predictor variable, while controlling for covariates, with time to transition to a psychotic disorder as the dependent variable. RESULTS Eleven (29.7%) of the 37 participants transitioned to a psychotic disorder over the 12-month follow-up period. Total face or prosody emotion recognition accuracy was not predictive of transition to a psychotic disorder. However, examination of recognition of specific emotions, while controlling for positive, negative and global symptoms and functioning, revealed that accuracy in identifying neutral (p=.037) and fearful (p=.015) emotion predicted transition to a psychotic disorder. Specifically, lower accuracy in identifying neutral emotion and higher accuracy in identifying fearful emotion were predictive of transition to a psychotic disorder within 12months. Examination of the separate modalities revealed that this finding held for face but not for prosody emotion recognition. CONCLUSION These findings suggest that emotion recognition abilities may be prognostic for the development of psychotic disorders, but further studies are needed.