Baseline measures of cerebral glutamate and GABA levels in individuals at ultrahigh risk for psychosis: Implications for clinical outcome after 12 months.

BACKGROUND: Cerebral glutamate and gamma-aminobutyric acid (GABA) levels might predict clinical outcome in individuals at ultrahigh risk (UHR) for psychosis but have previously primarily been investigated in smaller cohorts. We aimed to study whether baseline levels of glutamate and GABA in anterior cingulate cortex (ACC) and glutamate in thalamus could predict remission status and whether baseline metabolites differed in the remission versus the nonremission group. We also investigated the relationship between baseline metabolite levels and severity of clinical symptoms, functional outcome, and cognitive deficits at follow-up. METHODS: About 124 UHR individuals were recruited at baseline. In this, 74 UHR individuals were clinically and cognitively assessed after 12 months, while remission status was available for 81 (25 remission/56 nonremission). Glutamate and GABA levels were assessed at baseline using 3 T proton magnetic resonance spectroscopy. Psychopathology, symptom severity, and remission were assessed with the Comprehensive Assessment of At-Risk Mental States and Clinical Global Impression and functional outcome with the Social and Occupational Functioning Assessment Scale. Cognitive function was estimated with the Cambridge Neuropsychological Test Automated Battery. RESULTS: There were no differences between baseline glutamate and GABA levels in subjects in the nonremission group compared with the remission group, and baseline metabolites could not predict remission status. However, higher baseline levels of GABA in ACC were associated with clinical global improvement (r = -0.34, N = 51, p = 0.01) in an explorative analysis. CONCLUSIONS: The variety in findings across studies suggests a probable multifactorial influence on clinical outcome in UHR individuals. Future studies should combine multimodal approaches to attempt prediction of long-term outcome.

Basic symptoms influence real-life functioning and symptoms in individuals at high risk for psychosis.

OBJECTIVE: To investigate potential clinical differences in high-risk profiles presenting with and without basic symptoms, and additionally investigate the association between basic symptoms and clinical symptoms, functioning, and cognition. METHODS: High-risk individuals (n = 133) were stratified into individuals fulfilling ultra-high-risk (UHR) criteria (n = 59) and individuals fulfilling UHR+ basic symptoms criteria (BS) (n = 74). Group differences were assessed on clinical symptoms, real-life functioning, and cognition. Regression analyses were conducted to elucidate on the relationship between BS and clinical symptoms, functioning, neurocognition, and social cognition. RESULTS: The group fulfilling both UHR+ BS criteria had significantly more symptoms and lower real-life functioning and quality of life but not more cognitive deficits. BS influenced on attenuated psychotic, depressive, and general symptoms, but only modestly on negative symptoms. No relationship between BS and neuro- and social cognition was established except for an association with emotion recognition processing speed. BS influenced real-life functioning, and this finding was sustained when controlling for the effect of negative symptoms. CONCLUSIONS: Our findings indicate that BS contribute highly to the distress and symptom load of clinical high-risk individuals. Longitudinal findings are needed to establish the predictive validity of BS on high-risk individuals' clinical and functional prognosis.

Negative symptoms mediate the relationship between neurocognition and function in individuals at ultrahigh risk for psychosis.

OBJECTIVE: Neurocognition is known to impact functioning in individuals at ultrahigh risk (UHR) for psychosis, but studies investigating potential mediators of this relationship are scarce. Building on evidence from schizophrenia spectrum disorders, the study tested whether negative symptoms and social skills act as mediators between neurocognition and functional outcome in UHR individuals. METHODS: Ultrahigh risk participants (N = 84) underwent neurocognitive testing using the Brief Assessment of Cognition in Schizophrenia. Social skills and negative symptoms were assessed using the High-Risk Social Challenge task and the Scale for the Assessment of Negative Symptoms respectively. Four instruments were used to assess overall functioning, and one instrument assessed quality of life encompassing social functioning. RESULTS: The cross-sectional analyses revealed that neurocognition was related to the measures of functioning. Negative symptoms mediated the relationship between neurocognition and four of the five measures of functioning. We did not find social skills to mediate between neurocognition and functioning. CONCLUSION: Negative symptoms appear to mediate the relationship between neurocognition and functional outcome in UHR individuals, but the finding needs to be confirmed and extended to longitudinal studies. This underscores the importance of focusing on both neurocognition and negative symptoms when aiming at improving the functional outcome of UHR individuals.