5:00 Pm Functional Outcome in People at High Risk for Psychosis Predicted by Thalamic Glutamate Levels and Prefronto-Striatal Activation

Allen, Paul; Chaddock, Christopher; Egerton, Alice; Howes, Oliver; Stone, James; Barker, Gareth; Bonoldi, Ilaria; McGuire, Philip

doi:10.1016/s0920-9964(14)70169-0

Cited by 5 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To examine the association between metabolite levels and clinical outcomes, the clinical high-risk sample was dichotomized according to transition vs nontransition to psychosis 25 and good overall functioning (GAF≥65) vs poor overall functioning (GAF<65) at follow-up. 22 Because the primary hypothesis involved the association between hippocampal glutamate levels and clinical outcomes, general linear models were used to identify group differences in glutamate levels between the respective clinical high-risk subgroups and healthy controls, as well as between the total clinical high-risk group and healthy controls. Glutamate concentrations were included as the dependent variable with group as the independent variable (2-tailed P < .05 was considered to be statistically significant).…”

Section: Discussionmentioning

confidence: 99%

“…de la Fuente Sandoval et al 21 demonstrated increased baseline glutamate levels in the striatum of clinical high-risk individuals who developed a first episode of psychosis. Allen et al 22 found that a poor functional outcome in clinical high-risk individuals was linked to lower glutamate concentrations in the thalamus at baseline, whereas Egerton et al 23 reported that lower thalamic glutamate levels were associated with a failure to achieve symptomatic remission from the clinical high-risk state.…”

Section: Discussionmentioning

confidence: 99%

“…de la Fuente Sandoval et al 21 found that glutamate levels in the striatum were elevated in clinical high-risk individuals who developed psychosis subsequent to scanning but not in clinical high-risk individuals who did not. Furthermore, in the thalamus, low baseline glutamate levels were associated with poor functioning at clinical follow-up 22 and with a failure to achieve symptomatic remission from the clinical high-risk state. 23 The primary aim of the present study was to investigate the association between hippocampal glutamate levels in clinical high-risk individuals and subsequent clinical outcomes.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Association of Hippocampal Glutamate Levels With Adverse Outcomes in Individuals at Clinical High Risk for Psychosis

et al. 2019

View full text Add to dashboard Cite

IMPORTANCE Preclinical and human data suggest that hippocampal dysfunction plays a critical role in the onset of psychosis. Neural hyperactivity in the hippocampus is thought to drive an increase in subcortical dopamine function through glutamatergic projections to the striatum. OBJECTIVE To examine the association between hippocampal glutamate levels in individuals at clinical high risk for psychosis and their subsequent clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study of 86 individuals at clinical high risk for psychosis and 30 healthy control individuals, with a mean follow-up of 18.5 months, was conducted between November 1, 2011, and November 1, 2017, at early detection services in London and Cambridge, United Kingdom. MAIN OUTCOMES AND MEASURES Concentrations of glutamate and other metabolites were measured in the left hippocampus using 3-T proton magnetic resonance spectroscopy at the first clinical presentation. At follow-up, clinical outcomes were assessed in terms of transition or nontransition to psychosis using the Comprehensive Assessment of the At-Risk Mental State criteria and the level of overall functioning using the Global Assessment of Function scale. RESULTS Of 116 total participants, 86 were at clinical high risk for psychosis (50 [58%] male; mean [SD] age, 22.4 [3.5] years) and 30 were healthy controls (14 [47%] male; mean [SD] age, 24.7 [3.8] years). At follow-up, 12 clinical high-risk individuals developed a first episode of psychosis whereas 74 clinical high-risk individuals did not; 19 clinical high-risk individuals showed good overall functioning (Global Assessment of Function Ն65), whereas 38 clinical high-risk individuals had a poor functional outcome (Global Assessment of Function <65). Compared with clinical high-risk individuals who did not become psychotic, clinical high-risk individuals who developed psychosis showed higher hippocampal glutamate levels (mean [SD], 8.33 [1.48] vs 9.16 [1.28] glutamate levels; P = .048). The clinical high-risk individuals who developed psychosis also had higher myo-inositol levels (mean [SD], 7.60 [1.23] vs 6.24 [1.36] myo-inositol levels; P = .002) and higher creatine levels (mean [SD], 8.18 [0.74] vs 7.32 [1.09] creatine levels; P = .01) compared with clinical high-risk individuals who did not become psychotic, and higher myo-inositol levels compared with healthy controls (mean [SD], 7.60 [1.23] vs 6.19 [1.51] myo-inositol levels; P = .005). Higher hippocampal glutamate levels in clinical high-risk individuals were also associated with a poor functional outcome (mean [SD], 8.83 [1.43] vs 7.76 [1.40] glutamate levels; P = .02). In the logistic regression analyses, hippocampal glutamate levels were significantly associated with clinical outcome in terms of transition and nontransition to psychosis (β = 0.48; odds ratio = 1.61; 95% CI, 1.00-2.59; P = .05) and overall functioning (β = 0.53; odds ratio = 1.71; 95% CI, 1.10-2.66; P = .02). CONCLUSIONS AND RELEVANCE The findings indicate that adverse clinical outcomes in i...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation