Predictors of functional outcome in individuals at high clinical risk for psychosis at six years follow-up

BackgroundThe long-term functional status of subjects at ultra high risk for psychosis (HR) is relatively under investigated. This study explores baseline predictors of long-term functional outcome in HR subjects who did not convert to psychosis during a 6 years follow-up period.MethodsA total of 154 HR were followed up for an average of 6 years. The primary outcome variable was global assessment of functioning at the last follow-up visit as assessed with the Global Assessment of Functioning tool. A multinomial logistic regression was performed to identify potential predictors of functional outcome.ResultsBaseline and follow-up data on functioning was available for 92 HR. Twenty-four (43%) individuals who did not convert to psychosis reported poor functioning at follow-up. Baseline scores in the GAF (Exp(b) = 0.857; 95% CIs: 0.75/0.97), employment status (Exp(b) = 0.029; 95% CIs: 0.00/0.268), and CAARMS total scores (Exp(b) = 1.976; 95% CIs: 1.00/1.14) predicted functional outcome in HR subjects at 6 years.ConclusionsDespite the preventive treatments received, many individuals who did not convert to full-blown psychosis in the longer term do not functionally remit. These individuals are lower functioning, unemployed and have higher symptom loading at the time of their presentation to the prodromal clinic. Our study suggests the need for innovative treatments targeting long term functional status beyond the prevention of psychosis onset in the HR population.     

Basic self-disturbance trajectories in clinical high risk for psychosis: a one-year follow-up study

European Archives of Psychiatry and Clinical Neuroscience - Basic self-disturbance (BSD) has been proposed as a driver of symptom development in schizophrenia spectrum disorders (SSDs). In a...     

Social dysfunction predicts two years clinical outcome in people at ultra high risk for psychosis

The experience of a first psychotic episode is associated with a marked impairment in psychosocial functioning. However, the decline may be already evident in the pre-psychotic phases and play a significant role in the etiopathology of the disease onset. A sample of subjects at ultra high clinical risk for psychosis (“At Risk Mental State”, ARMS, n = 152) was compared with a demographically-matched general population (n = 98,072) on different measures of psychosocial functioning. The proportion of subjects with an ARMS living in communal establishments or living at home with their parents was significantly higher than that of the local population (p < 0.001). Subjects with an ARMS showed also higher rates of unemployment as compared to the general population (p < 0.001). GAF scores at baseline were significantly lower in unemployed ARMS as compared to students and employed ARMS (p = 0.002). ARMS subjects living in communal establishments presented higher rates of co-morbid psychiatric conditions (p = 0.007) and lower GAF scores at baseline (p = 0.017). Finally, baseline unemployment and living in a communal establishment were associated with an increased risk of developing a psychotic episode within the following two years (p < 0.05). We concluded that the “At Risk Mental State” is a clinical condition which is characterized by marked psychosocial impairment and by an increased vulnerability to psychosis. Unemployment at the first contact with the prodromal service may be a risk factor for the development of a psychotic episode.     

Voxel-wise meta-analysis of fMRI studies in patients at clinical high risk for psychosis

Background

Reliable neurofunctional markers of increased vulnerability to psychosis are needed to improve the predictive value of psychosis risk syndrome and inform preventive interventions.

Methods

I performed a signed differential mapping (SDM) voxel-wise meta-analysis of functional magnetic resonance imaging (fMRI) studies of patients at clinical high risk for psychosis.

Results

Ten studies were included in the analysis. Compared with controls, high-risk patients showed reduced neural activation in the left inferior frontal gyrus (Brodmann area [BA] 9) and in a cluster spanning the bilateral medial frontal gyrus (BA 8,6), bilateral superior frontal gyrus (BA 8,6) and the left anterior cingulate (BA 32). There was no publication bias. Heterogeneity across studies was low. Sensitivity analysis confirmed the robustness of the findings.

Limitations

The cross-sectional nature of the included studies prevented the comparison of high-risk patients who later experienced a psychotic episode with those who did not. Other caveats are reflected in methodologic heterogeneity across tasks employed by different individual imaging studies.

Conclusion

Reduced neurofunctional activation in prefrontal regions may represent a neurophysiologic correlate of increased vulnerability to psychosis.     

Early detection of psychosis: finding those at clinical high risk

Aim: In early detection work, recruiting individuals who meet the prodromal criteria is difficult. The aim of this paper was to describe the development of a research clinic for individuals who appear to be at risk of developing a psychosis and the process for educating the community and obtaining referrals. Methods: The outcome of all referrals to the clinic over a 4‐year period was examined. Results: Following an ongoing education campaign that was over inclusive in order to aid recruitment, approximately 27% of all referrals met the criteria for being at clinical high risk of psychosis. Conclusions: We are seeing only a small proportion of those in the community who eventually go on to develop a psychotic illness. This raises two important issues, namely how to remedy the situation, and second, the impact of this on current research in terms of sampling bias and generalizability of research findings.     

Negative symptoms in individuals at clinical high risk of psychosis

Negative symptoms are present in the psychosis prodrome. However, the extent to which these symptoms are present prior to the onset of the first episode of psychosis remains under-researched. The goal of this study is to examine negative symptoms in a sample of individuals at clinical high risk (CHR) for psychosis and to determine if they are predictive of conversion to psychosis. Participants (n=138) were all participants in the North American Prodrome Longitudinal Study (NAPLS 1) project. Negative symptoms were assessed longitudinally using the Scale of Prodromal Symptoms. The mean total negative symptom score at baseline was 11.0, with 82.0% of the sample scoring at moderate severity or above on at least one negative symptom. Over the course of 12 months, the symptoms remained in the above moderate severity range for 54.0% of participants. Associations between individual symptoms were moderate, and a factor analysis confirmed that all negative symptoms loaded heavily on one factor. Negative symptoms were more severe and persistent overtime in those who converted to psychosis, significantly predicting the likelihood of conversion. Thus, early and persistent negative symptoms may represent a vulnerability for risk of developing psychosis.     

Affect recognition in people at clinical high risk of psychosis

Individuals with schizophrenia demonstrate stable deficits in affect recognition. Similar deficits in affect recognition have been observed in those who are at clinical high risk (CHR) of developing psychosis. The current project aimed to longitudinally examine affect processing in CHR individuals, to determine if affect processing predicted later conversion to psychosis and if affect processing deficits were unique to those who met established criteria for prodromal syndromes. The sample consisted of 172 CHR and 100 help-seeking individuals (HS) who were followed for up to 24 months. All CHR individuals met the Criteria of Prodromal Syndromes (COPS) based on the Structured Interview for Prodromal Symptoms (SIPS). The SIPS was used to determine conversion to psychosis. Affect recognition was assessed using two facial affect recognition tasks and a measure of affective prosody. In comparison to previously published data from non-psychiatric controls, both CHR and HS groups demonstrated deficits in affect recognition. By 2 years 25 CHR participants converted to psychosis. Interestingly, there were no differences between converters and non-converters on any affect recognition tasks. This is one of the first studies to longitudinally examine affect processing and its relationship to later conversion to psychosis in individuals at-risk for psychosis. While poorer affect recognition may be associated with vulnerability for psychosis, the current results suggest that it may not be a marker of developing a psychotic illness.     

Social functioning in individuals at clinical high risk for psychosis

Poor social functioning is a hallmark of schizophrenia. The purpose of this study was to examine social functioning in individuals at clinical high risk for psychosis. Social functioning was assessed in a sample of 86 clinical high risk (CHR) individuals and compared to that of 50 first-episode of psychosis (FE) subjects, 53 multi-episode schizophrenia subjects (ME) and 55 non-psychiatric controls (NPC). Subjects were assessed on the Social Functioning Scale (SFS), the Role Functioning subscale of the Quality of Life Scale (QLS-role), and the premorbid functioning scale. On the SFS, the CHR group did not differ significantly from the FE and ME groups and all were impaired relative to the NPCs. On QLS-role, the CHR group performed significantly better than the ME patients and significantly worse than NPCs. CHR subjects did not differ from patients in terms of premorbid functioning. This study demonstrates that even at the pre-psychotic phase of the illness, these young people are demonstrating significant deficits in social functioning, supporting that social deficits are present long before the onset of psychotic symptoms.     

Treating young individuals at clinical high risk for psychosis

Background: Typically, studies investigating those at clinical high risk for psychosis have focused on predictors of conversion and treatments that might prevent conversion to full‐blown psychosis. Few studies have followed those who do not go on to develop a psychotic illness. Methods: Participants were 48 young people who were at risk for developing psychosis based on the Structured Interview for Prodromal Symptoms criteria and participated in a treatment programme where they were offered up to 6 months of psychosocial treatment and psychiatric management. Attenuated psychotic symptoms, negative symptoms, depression, anxiety, social functioning, alcohol and drug use, and meta‐cognitive beliefs were assessed at baseline, 6, 12 and 18 months. Personality characteristics were assessed at baseline. Medication use was tracked and psychiatric visits were logged over the 18‐month study period. Results: On average, participants attended 12 sessions of psychosocial treatment and had one meeting with the psychiatrist every 6 months. Only 24% were ever prescribed any psychotropic medications, and antipsychotics were not used. Significant improvements were found over time in attenuated positive symptoms, negative symptoms, depression, anxiety, meta‐cognitions and social functioning with most improvement occurring in the first 6 months. There was no change in the level of substance use. For personality assessment, participants generally scored high on neuroticism and openness and had low scores on extraversion, agreeableness and conscientiousness. Conclusion: With minimal treatment and no antipsychotics, young people who present as being at risk for developing a psychotic disorder demonstrate clinical improvement over time. However, a few continued to have the liability of ongoing attenuated psychotic symptoms.