2 results
Reduced cortical cerebral blood flow in antipsychotic-free first-episode psychosis and relationship to treatment response
- Pierluigi Selvaggi, Sameer Jauhar, Vasileia Kotoula, Fiona Pepper, Mattia Veronese, Barbara Santangelo, Fernando Zelaya, Federico E. Turkheimer, Mitul A. Mehta, Oliver D. Howes
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- Journal:
- Psychological Medicine / Volume 53 / Issue 11 / August 2023
- Published online by Cambridge University Press:
- 25 August 2022, pp. 5235-5245
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Background
Altered cerebral blood flow (CBF) has been found in people at risk for psychosis, with first-episode psychosis (FEP) and with chronic schizophrenia (SCZ). Studies using arterial spin labelling (ASL) have shown reduction of cortical CBF and increased subcortical CBF in SCZ. Previous studies have investigated CBF using ASL in FEP, reporting increased CBF in striatum and reduced CBF in frontal cortex. However, as these people were taking antipsychotics, it is unclear whether these changes are related to the disorder or antipsychotic treatment and how they relate to treatment response.
MethodsWe examined CBF in FEP free from antipsychotic medication (N = 21), compared to healthy controls (N = 22). Both absolute and relative-to-global CBF were assessed. We also investigated the association between baseline CBF and treatment response in a partially nested follow-up study (N = 14).
ResultsThere was significantly lower absolute CBF in frontal cortex (Cohen's d = 0.84, p = 0.009) and no differences in striatum or hippocampus. Whole brain voxel-wise analysis revealed widespread cortical reductions in absolute CBF in large cortical clusters that encompassed occipital, parietal and frontal cortices (Threshold-Free Cluster Enhancement (TFCE)-corrected <0.05). No differences were found in relative-to-global CBF in the selected region of interests and in voxel-wise analysis. Relative-to-global frontal CBF was correlated with percentage change in total Positive and Negative Syndrome Scale after antipsychotic treatment (r = 0.67, p = 0.008).
ConclusionsThese results show lower cortical absolute perfusion in FEP prior to starting antipsychotic treatment and suggest relative-to-global frontal CBF as assessed with magnetic resonance imaging could potentially serve as a biomarker for antipsychotic response.
N-Methyl-D-Aspartate Receptor binding in First-Episode Psychosis: A PET brain imaging study
- Katherine Beck, Atheeshaan Arumuham, Barbara Santangelo, Mattia Veronese, Robert McCutcheon, Stephen Kaar, Colm McGinnity, Toby Pillinger, Faith Borgan, Alexander Hammers, Oliver Howes
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- Journal:
- BJPsych Open / Volume 7 / Issue S1 / June 2021
- Published online by Cambridge University Press:
- 18 June 2021, p. S7
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Aims
Evidence from genetics, post mortem and animal studies suggest that N-Methyl-D-Aspartate Receptor (NMDAR) hypofunction has an important role in the pathophysiology of psychosis. However, it is not known if NMDAR activity is altered in the early stages of psychosis or if this links to symptom severity. Our aim was to investigate NMDAR availability in first-episode psychosis (FEP) and determine if it links to symptom severity. The NMDAR hypofunction hypothesis of schizophrenia was initially proposed in the 1990s on the basis of observations that ketamine and phencyclidine (PCP) induced the full range of schizophrenia-like symptoms (positive, negative and cognitive) when given to healthy participants and also that they worsen symptoms in patients with schizophrenia.
MethodWe recruited 40 volunteers, including 21 patients with schizophrenia from early intervention services in London (12 antipsychotic-free and 9 receiving antipsychotic medication) and 19 matched healthy controls. The uptake of an NMDAR selective ligand, [18F]GE179, was measured using positron emission tomography (PET) and indexed using the distribution volume ratio (DVR) and volume of distribution (VT, in millilitres per cubic centimetre) of [18F]GE179 in the hippocampus and additional exploratory regions (anterior cingulate cortex (ACC), thalamus, striatum and temporal lobe). Symptom severity was measured using the Positive and Negative Syndrome Scale (PANSS).
ResultA total of 37 individuals were included in the analyses (mean [SD] age of controls, 26.7 [4.5] years; mean [SD] age of patients, 25.3 [4.9] years). There was a significant reduction in hippocampal DVR in the patients with schizophrenia relative to healthy controls (p = 0.02, Cohen's d = 0.81). Although the VT of [18F]GE179 was lower in absolute terms in patients, there was no significant effect of group on VT in the hippocampus (p = 0.15, Cohen's d = 0.49) or the exploratory brain regions. There was a negative association between hippocampal DVR and total PANSS symptoms (rho = –0.47, p = 0.04), depressive symptoms (rho = –0.67, p = 0.002), and general PANSS symptoms (rho = –0.74, p = 0.001).
ConclusionThese results indicate lower hippocampal NMDAR levels in schizophrenia relative to controls with a large effect size, and that lower NMDAR levels are associated with greater levels of symptom severity. These findings are consistent with the role of NMDAR hypofunction in the pathophysiology of schizophrenia; however, further work is required to test specificity and causal relationships.