Psychosis Transition Research Articles

Social inference in individuals at clinical high risk for psychosis.

Social cognition impairment is a hallmark of schizophrenia and contains multiple domains. The domain of social inference has been relatively understudied in schizophrenia and its risk states. Social inference was assessed in 60 clinical high-risk (CHR) patients and 28 healthy control subjects, using the video social inference task. We hypothesized a deficit in social inference in CHR participants and examined predictive value for psychosis transition. Social inference was positively associated with increasing age. Social inference did not differ significantly between CHR patients and controls, or predict transition to psychosis. Few studies have examined social inference of individuals at clinical high risk for psychosis, and findings have been inconclusive. Additional studies using a variety of measures of social inference in CHR participants are recommended.

A naturalistic longitudinal study of at-risk mental state with a 2.4 year follow-up at a specialized clinic setting in Japan

ObjectiveThe notion of at-risk mental state (ARMS) is valuable for identifying individuals in a putative prodromal state of psychosis and for reducing conversion risk by pharmacological and psychological interventions. However, further systematic study is required because 1) diagnostic reliability in various clinical settings is not yet established; 2) predictive ability is insufficient; 3) optimal interventions in diversified populations are elusive; and 4) little evidence from non-Western regions exists. MethodsA naturalistic longitudinal study was conducted at a specialized clinic for early psychosis at a university hospital in Sendai, Japan. Individuals with ARMS (n=106) were recruited and followed up with case-by-case treatment. ResultsTwo-thirds of the participants were psychiatrist referrals, and 83 were followed up for at-least 1year (mean follow-up=2.4years). Fourteen developed psychosis and the estimated (by Kaplan–Meier) cumulative transition rate was 11.1% at 12, 15.4% at 24, and 17.5% at 30months. At the end-point, about 30% of the 83 followed-up participants including 11 converters received antipsychotic medication. Compared to non-converters, converters showed more severe attenuated psychotic symptoms, including ego-boundary disturbance, formal thought disorder, and emotional disturbance. ConclusionsThe present study replicated previous major Western longitudinal studies, in terms of clinical characteristics, psychosis transition rate, and antipsychotic prescription rate. Our results emphasize the importance of phenomenological assessment of ARMS and intensive care in a clinical setting.

Comorbid Depressive and Anxiety Disorders in 509 Individuals With an At-Risk Mental State: Impact on Psychopathology and Transition to Psychosis

Background: The current diagnostic system for subjects at enhanced clinical risk of psychosis allows concurrent comorbid diagnoses of anxiety and depressive disorders. Their impact on the presenting high-risk psychopathology, functioning, and transition outcomes has not been widely researched. Methods: In a large sample of subjects with an At-Risk Mental State (ARMS, n = 509), we estimated the prevalence of DSM/SCID anxiety or depressive disorders and their impact on psychopathology, functioning, and psychosis transition. A meta-analytical review of the literature complemented the analysis. Results: About 73% of ARMS subjects had a comorbid axis I diagnosis in addition to the “at-risk” signs and symptoms. About 40% of ARMS subjects had a comorbid diagnosis of depressive disorder while anxiety disorders were less frequent (8%). The meta-analysis conducted in 1683 high-risk subjects confirmed that baseline prevalence of comorbid depressive and anxiety disorders is respectively 41% and 15%. At a psychopathological level, comorbid diagnoses of anxiety or depression were associated with higher suicidality or self-harm behaviors, disorganized/odd/stigmatizing behavior, and avolition/apathy. Comorbid anxiety and depressive diagnoses were also associated with impaired global functioning but had no effect on risk of transition to frank psychosis. Meta-regression analyses confirmed no effect of baseline anxiety and/or depressive comorbid diagnoses on transition to psychosis. Conclusions: The ARMS patients are characterized by high prevalence of anxiety and depressive disorders in addition to their attenuated psychotic symptoms. These symptoms may reflect core emotional dysregulation processes and delusional mood in prodromal psychosis. Anxiety and depressive symptoms are likely to impact the ongoing psychopathology, the global functioning, and the overall longitudinal outcome of these patients.

Striatal glutamate and the conversion to psychosis: a prospective 1H-MRS imaging study

Increased glutamate levels in the associative-striatum have been described in subjects at ultra-high risk for psychosis (UHR); nevertheless, it is unclear whether this abnormality predicts the conversion to psychosis. Nineteen subjects at UHR and 26 controls were studied using proton magnetic resonance spectroscopy. Subjects at UHR were clinically followed for 2 yr. Seven UHR subjects (37%) transitioned to a psychotic disorder and the remaining 12 did not exhibit psychotic symptoms at the most recent follow-up. The psychosis transition group had higher glutamate levels compared to both non-transition and control groups (p = 0.02 and p < 0.01, respectively; effect size 1.39). These pilot findings suggest that the conversion to psychosis is associated with increased glutamate levels in the associative-striatum.

Reliability and Validity of the Comprehensive Assessment of the at Risk Mental State, Italian Version (CAARMS-I)

The Comprehensive Assessment of the At Risk Mental State (CAARMS) is a semi-structured interview designed to assess attenuated psychotic symptoms in people at ultra high risk of developing psychosis (UHR). It is widely used worldwide but no studies have ever assessed its psychometric properties in the Italian population. Here we tested the reliability and validity of the Italian version of the CAARMS (CAARMS-I). Psychometric properties (inter-rater reliability, internal coherence, construct validity, concurrent validity and predictive validity) were assessed in an Italian sample of ARMS subjects, first-episode subjects and matched controls. We found that the CAARMS-I demonstrates adequate validity and reliability and appears to be helpful in the diagnosis of the ARMS and prediction of psychosis transition.

Neuroanatomical maps of psychosis onset: voxel-wise meta-analysis of antipsychotic-naive VBM studies.

Despite impressive advancements in early interventions in psychosis, there is an urgent need of robust neurobiological markers to improve the predictive value of psychosis transition. Available structural imaging literature in the field is undermined by several methodological caveats and a number of confounders such as exposure to antipsychotic treatment. Fourteen voxel-based morphometry studies of antipsychotic-naive subjects at enhanced clinical risk for psychosis (high risk [HR]) or experiencing a first-episode psychosis (FEP) were included. Formal meta-analysis of effect sizes and "signed differential mapping" voxel-based meta-analysis were combined to control the results for sample sizes, strength of individual findings, and confounding variables. Formal effect size meta-analysis indicated consistent gray matter (GM) reductions both in subjects at enhanced clinical risk for psychosis and in first-episode subjects when compared with control groups. Voxel-based meta-analysis showed GM reductions in the temporal, limbic prefrontal cortex within the HR group and in the temporal insular cortex and cerebellum within the FEP group. Psychosis onset was characterized by GM decreases in temporal, anterior cingulate, cerebellar, and insular regions. GM alterations in the temporal regions directly related to severity of psychotic symptoms. There was no publication bias. Heterogeneity across studies was low. Sensitivity analyses confirmed robustness of the above results. Vulnerability to psychosis is associated with consistent GM decreases in prefrontal and temporolimbic areas. The onset of full disease is accompanied by temporoinsular, anterior cingulate, and cerebellar GM reductions. Neuroanatomical alterations in temporal regions may underlie the clinical onset of psychotic symptoms.

Caudate nucleus volume in individuals at ultra-high risk of psychosis: A cross-sectional magnetic resonance imaging study

The aim of the present study was to investigate whether volumetric abnormalities of the caudate nuclei predate the onset of psychotic illness. Caudate nuclei volume (CNVs), excluding the tail, were measured using region-of-interest (ROI) tracing of magnetic resonance imaging (MRI) scans acquired on a 1.5T scanner. Subjects included 39 individuals deemed at ultra-high risk of psychosis who converted to psychosis (UHR-P) after initial MRI scanning; 39 matched individuals at ultra-high risk who did not convert to psychosis (UHR-NP); and 39 matched healthy controls. All subjects were neuroleptic-naïve. After adjusting CNVs for intracranial volume (ICV), univariate analyses of variance and repeated measures analyses of variance were undertaken to examine the relationship of CNVs to psychosis transition and to family history of psychosis. Pearson's correlations were used to investigate the relationship of psychopathological scores to CNVs. CNVs did not differ significantly between UHR individuals and healthy controls, and there was no significant difference between converters and non-converters to psychosis. In the UHR group, presence of family history of psychosis was not related to CNVs. There was no correlation between CNVs and either positive or negative symptoms of schizophrenia. Significant associations were found between larger CNV and increased errors on a spatial working memory task but better verbal fluency performance. These data suggest that the caudate is macroscopically normal prior to illness onset, while the relationship to tasks of executive function may implicate the caudate together with its connections to prefrontal regions. Future research should examine changes longitudinally together with analysis of shape to assess subregions of the caudate that connect with prefrontal cortex.

Efficacy of Using Cognitive Status in Predicting Psychosis: A 7-Year Follow-Up

Despite extensive early detection research in schizophrenic psychoses, methods for identifying at-risk individuals and predicting their transition to psychosis are still unreliable. Moreover, there are sparse data on long-term prediction. We therefore investigated long-term psychosis transition in individuals with an At Risk Mental State (ARMS) and examined the relative efficacy of clinical and neuropsychological status in optimizing the prediction of transition. Sixty-four individuals with ARMS for psychosis were identified from all referrals to our early detection clinic between March 1, 2000 and February 29, 2004. Fifty-three (83%) were followed up for up to 7 (mean 5.4) years. Twenty-one of the 53 staying in follow-up developed psychosis, corresponding to a transition rate of .34 (Kaplan-Meier estimates). Median time to transition was 10 months (range <1-55). Six of all transitions (29%) occurred only after 12 months from referral. Best transition predictors within this population were selected attenuated psychotic symptoms (suspiciousness), negative symptoms (anhedonia/asociality), and cognitive deficits (reduced speed of information processing). With these predictors in an integrated model for predicting transition to psychosis, the overall predictive accuracy was 80.9% with a sensitivity of 83.3% and a specificity of 79.3%. Follow-up of ARMS subjects should exceed the usual 12 months. Prediction of transitions could be improved by a stronger weighting of certain early symptoms and by introducing neurocognitive tests into a stepwise risk assessment. Confirmatory research will hopefully further improve risk algorithm, including psychopathology and neuropsychological performance, for clinical application in early detection clinics.