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.

Personality features in ultra-high risk for psychosis: a comparative study with schizophrenia and control subjects using the Temperament and Character Inventory-Revised (TCI-R).

Several variables have been identified as risk factors for conversion to overt psychosis in ultra-high risk for psychosis (UHR) individuals. Although almost two-thirds of them do not experience a transition to psychosis, they still exhibit functional disabilities. Other subjective developmental features may be useful for a more precise identification of individuals at UHR. Avoidant behaviors are consistently reported in schizophrenia and in UHR individuals and may be the reflection of a pattern of personality. Thus, personality features in UHR individuals deserves further research. The objective of the present study was to compare temperament and character dimensions between UHR individuals, patients with schizophrenia and healthy controls. One hundred participants (25 UHR individuals, 25 schizophrenia patients and 50 control subjects) where evaluated with the Temperament and Character Inventory-Revised (TCI-R). Univariate ANOVAs followed by Bonferroni tests were used. UHR individuals and schizophrenia patients exhibited higher levels of Harm Avoidance (HA) when compared to control subjects. For HA1 Anticipatory worry vs Uninhibited optimism and HA4 Fatigability & asthenia, UHR and schizophrenia groups showed similar scores and both groups were higher compared to control subjects. With respect to Cooperativeness (CO), UHR and schizophrenia reported lower scores than control subjects, in particular CO2 Empathy vs Social disinterest and CO3 Helpfulness vs unhelpfulness. This study replicates and extends the consideration of HA as a psychopathological related endophenotype and gives us further information of the possible role of personality features in the expression of some of the social dysfunctions observed both in prodromal subjects and schizophrenia patients.

Abnormal white matter integrity in antipsychotic-naïve first-episode psychosis patients assessed by a DTI principal component analysis.

INTRODUCTION: Diffusion tensor imaging (DTI) studies in patients with schizophrenia have shown abnormalities in the microstructure of white matter tracts. Specifically, reduced fractional anisotropy (FA) has been described across multiple white matter tracts, in studies that have mainly included patients treated with antipsychotic medications. OBJECTIVE: To compare FA in antipsychotic-naïve patients experiencing a first episode of psychosis (FEP) to FA in healthy controls to demonstrate that the variance of FA can be grouped, in a coincidental manner, in four predetermined factors in accordance with a theoretical partition of the white matter tracts, using a principal components analysis (PCA). METHODS: Thirty-five antipsychotic-naïve FEP patients and 35 age- and gender-matched healthy controls underwent DTI at 3T. Analysis was performed using a tract-based spatial statistics (TBSS) method and exploratory PCA. RESULTS: DTI analysis showed extensive FA reduction in white matter tracts in FEP patients compared with the control group. The PCA grouped the white matter tracts into four factors explaining 66% of the total variance. Comparison of the FA values within each factor highlighted the differences between FEP patients and controls. DISCUSSION: Our study confirms extensive white matter tracts anomalies in patients with schizophrenia, more specifically, in drug-naïve FEP patients. The results also indicate that a small number of white matter tracts share common FA anomalies that relate to deficit symptoms in FEP patients. Our study adds to a growing body of literature emphasizing the need for treatments targeting white matter function and structure in FEP patients.

Glutamate levels in the associative striatum before and after 4 weeks of antipsychotic treatment in first-episode psychosis: a longitudinal proton magnetic resonance spectroscopy study.

IMPORTANCE: Increased glutamate levels in the right associative striatum have been described in patients during a first episode of psychosis. Whether this increase would persist after effective antipsychotic treatment is unknown. OBJECTIVES: To compare the glutamate levels in antipsychotic-naive patients with first-episode psychosis in the right associative striatum and right cerebellar cortex using proton magnetic resonance spectroscopy before and 4 weeks after antipsychotic treatment and to compare these results with normative data from sex-matched healthy control subjects. DESIGN, SETTING, AND PARTICIPANTS: Before-after trial in an inpatient psychiatric research unit among 24 antipsychotic-naive patients with first-episode psychosis and 18 healthy controls matched for age, sex, handedness, and cigarette smoking. INTERVENTIONS: Participants underwent 2 proton magnetic resonance spectroscopy studies: patients were imaged at baseline and after 4 weeks of antipsychotic treatment, while controls were imaged at baseline and at 4 weeks after the baseline measurement. Patients were treated with oral risperidone (open label) for 4 weeks with dosages that were titrated on the basis of clinical judgment. MAIN OUTCOMES AND MEASURES: Glutamate levels were estimated using LCModel (version 6.2-1T) and were corrected for the cerebrospinal fluid proportion within the voxel. RESULTS: Patients with first-episode psychosis had higher levels of glutamate in the associative striatum and the cerebellum during the antipsychotic-naive condition compared with controls. After clinically effective antipsychotic treatment, glutamate levels significantly decreased in the associative striatum, with no significant change in the cerebellum. No differences in glutamate levels were observed between groups at 4 weeks. CONCLUSIONS AND RELEVANCE: Increased glutamate levels observed at baseline in patients with first-episode psychosis normalized after 4 weeks of clinically effective antipsychotic treatment. These results provide support for the hypothesis that improvement in clinical symptoms might be related to a decrease in glutamate levels.