Monika Schlögelhofer

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.

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.

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.

NEURAPRO-E study protocol: a multicentre randomized controlled trial of omega-3 fatty acids and cognitive-behavioural case management for patients at ultra high risk of schizophrenia and other psychotic disorders

Recent research has indicated that preventative intervention is likely to benefit patients ‘at‐risk’ for psychosis, both in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder. The strong preliminary results for the effectiveness of omega‐3 polyunsaturated fatty acids (PUFAs), coupled with the falling transition rate in ultra high‐risk (UHR) samples, mean that further study of such benign, potentially neuroprotective interventions is clinically and ethically required. Employing a multicentre approach, enabling a large sample size, this study will provide important information with regard to the use of omega‐3 PUFAs in the UHR group.

Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis

Background Most studies provide evidence that the skin flush response to nicotinic acid (niacin) stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR) phase of psychotic disorders. Methods We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55) with healthy controls (HC n = 25) and first episode schizophrenia patients (FEP n = 25) treated with atypical antipsychotics. Results Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA), but positively correlated with phospholipase A2 (inPLA2) activity, a marker of membrane lipid repair/remodelling. Conclusions Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a “pro-inflammatory state”, whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated.

Emotion recognition in unaffected first-degree relatives of individuals with first-episode schizophrenia

OBJECTIVE Impairments in recognising negative emotions are found in individuals with first-episode and chronic schizophrenia and also in those at ultra-high risk for the illness. Whether these impairments are an endophenotype for schizophrenia is unclear. To examine the heritability of emotion recognition, the aim of this study was to examine whether facial and prosody emotion recognition deficits, particularly for negative emotions, are also present in unaffected first-degree relatives of people with schizophrenia. METHODS Face and prosody emotion recognition (ER) were examined in individuals with first-episode schizophrenia (n=30), their unaffected first-degree relatives (n=27) and healthy controls (n=30). Measures of psychopathology and IQ were also administered. RESULTS On the face ER task, first-episode schizophrenia participants performed significantly more poorly in recognising anger (p=.017), disgust (p=.033) and fear (p=.040) and first-degree relatives were significantly poorer at recognising fear (p=.003) than healthy controls. On the prosody ER task, first-episode schizophrenia participants made significantly more errors in recognising anger (p=.001) and surprise (p=.003) and first-degree relatives were significantly poorer at recognising anger (p=.005) than healthy controls. Effect sizes were medium to large. After controlling for age, IQ and symptoms, both unaffected first-degree relatives and first-episode schizophrenia patients displayed a significant deficit in facial fear recognition relative to healthy controls (p=.040 and p=.048, respectively). This deficit was not associated with current psychiatric symptoms. CONCLUSIONS These findings bolster evidence for emotion recognition (particularly for fear) as a heritable characteristic of schizophrenia. However, the diagnostic specificity of this finding requires further investigation.

Polyunsaturated fatty acids in emerging psychosis: a safer alternative?

A promising approach of indicated prevention in individuals at increased risk of psychosis was based on the finding of potential neuroprotective properties of omega‐3 polyunsaturated fatty acids (PUFAs). Considering the rising interest in omega‐3 PUFA supplementation as preventive treatment strategy in young people at risk of psychosis, the question of safety issues must be addressed.

Omega-6 to omega-3 polyunsaturated fatty acid ratio and subsequent mood disorders in young people with at-risk mental states: a 7-year longitudinal study

While cross-sectional studies suggest that patients with mood disorders have a higher ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) and lower levels of omega-3 PUFAs, it is unknown if a high n-6/3 ratio indicates vulnerability for depression. We tested this hypothesis in a 7-year follow-up study of young individuals with an ultra-high risk (UHR) phenotype. We conducted a secondary analysis of the Vienna omega-3 study, a longitudinal study of omega-3 PUFAs in individuals at UHR for psychosis (n=69). Levels of n-6 and n-3 PUFAs were measured in the phosphatidylethanolamine fraction of erythrocyte membranes at intake into the study. Mood disorder diagnosis was ascertained with the Structured Clinical Interview for DSM-IV-TR and confirmed by review of medical records and interviews of caregivers. A higher n-6/3 PUFA ratio at baseline predicted mood disorders in UHR individuals over a 7-year (median) follow-up (odds ratio=1.89, 95% CI=1.075–3.338, P=0.03). This association remained significant after adjustment for age, gender, smoking, severity of depressive symptoms at baseline and n-3 supplementation. Consistent results were obtained for individual PUFAs, including lower levels of eicosapentaenoic acid and docosahexaenoic acid. The predictive capacity of these findings was specific to mood disorders as no associations were found for any other psychiatric disorder. To our knowledge, our data provide the first prospective evidence that the n-6/3 PUFA ratio is associated with an increased risk for mood disorders in young people exhibiting an UHR phenotype. These findings may have important implications for treatment and risk stratification beyond clinical characteristics.