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Neurometabolic abnormalities in the associative striatum in antipsychotic-naive first episode psychosis patients.

ABSTRACT: Schizophrenia is a chronic, often progressive, disorder. Understanding the underlying neurobiology present in the early stages of the illness is as a pivotal step in designing targeted interventions aimed at arresting disease progression. The aim of our study was to examine neurometabolic changes in the dopamine rich associative striatum in medication-naïve first episode psychosis (FEP). We quantified neurometabolites in 14 FEP and 18 healthy controls (HC) matched on key demographic characteristics. Spectra from the voxel in the left associative striatum were acquired using a PRESS sequence (TR/TE = 2000/80 ms; 512 averages). MRS data were quantified in the time domain with AMARES in jMRUI. Choline was significantly elevated in FEP compared to HC. No significant alterations in other metabolites were observed. We did not observe correlations between metabolite levels and clinical characteristics in FEP. Here, we demonstrated elevated choline and a disruption of the relationship between N-acetyl-aspartate and Glx (glutamate + glutamine) in medication-naïve FEP patients in the left striatum indicating possible mitochondrial, membrane and glial dysfunction as an underlying pathological phenomenon. In addition, striatal choline shows promise as a biomarker for FEP that may have utility in clinical trials investigating target engagement in experimental regimens.

SUBMITTER: Sivaraman S

PROVIDER: S-EPMC7874514 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Neurometabolic abnormalities in the associative striatum in antipsychotic-naïve first episode psychosis patients.

Sivaraman Soumya S Kraguljac Nina V NV White David M DM Morgan Charity J CJ Gonzales Sara S SS Lahti Adrienne C AC

Psychiatry research. Neuroimaging 20180609

Schizophrenia is a chronic, often progressive, disorder. Understanding the underlying neurobiology present in the early stages of the illness is as a pivotal step in designing targeted interventions aimed at arresting disease progression. The aim of our study was to examine neurometabolic changes in the dopamine rich associative striatum in medication-naïve first episode psychosis (FEP). We quantified neurometabolites in 14 FEP and 18 healthy controls (HC) matched on key demographic characterist ...[more]

PMID: 30286325

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Project description:BackgroundThe neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression - how age affects clinical presentation in first-episode psychosis - has not been thoroughly investigated.MethodsUsing generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naïve individuals with first-episode psychosis (N = 340, 12-40 years, 1-12 visits), collected at the University of Pittsburgh from 1990 to 2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We tested for age-associated effects on change in positive or negative symptom severity following baseline assessment and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development.ResultsPerceptual positive symptom severity significantly decreased with increasing age (F = 7.0, p = 0.0007; q = 0.003) while non-perceptual positive symptom severity increased with age (F = 4.1, p = 0.01, q = 0.02). Anhedonia severity increased with increasing age (F = 6.7, p = 0.00035; q = 0.0003), while flat affect decreased in severity with increased age (F = 9.8, p = 0.002; q = 0.006). Findings remained significant when parental SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (all p > 0.25). Beginning at age 18, there was a statistically significant association between severity of non-perceptual and perceptual symptoms. This relationship increased in strength throughout adulthood.ConclusionsThese findings suggest that as maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced. Findings underscore how pathological brain-behavior relationships vary as a function of development.

Project description: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.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.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.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.Glutamate levels were estimated using LCModel (version 6.2-1T) and were corrected for the cerebrospinal fluid proportion within the voxel.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.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.

Dataset Information

Neurometabolic abnormalities in the associative striatum in antipsychotic-naive first episode psychosis patients.

Publications

Neurometabolic abnormalities in the associative striatum in antipsychotic-naïve first episode psychosis patients.

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