N-methyl-D-aspartate receptor availability in first-episode psychosis: a PET-MR brain imaging study.
Ontology highlight
ABSTRACT:
SUBMITTER: Beck K
PROVIDER: S-EPMC8361127 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundPositron emission tomography studies examining differences in D1-dopamine receptor binding between control subjects and patients with schizophrenia have been inconsistent, reporting higher, lower, and no difference in the frontal cortex. Exposure to antipsychotic medication has been suggested to be a likely source of this heterogeneity, and thus there is a need for studies of patients at early stages of the disorder who have not been exposed to such drugs.MethodsHere, we compared 17 healthy control subjects and 18 first-episode neuroleptic naive patients with schizophrenia or schizophreniform psychosis using positron emission tomography and the D1-dopamine receptor radioligand [11C]SCH23390.ResultsWe observed a statistically significant difference in the dorsolateral prefrontal cortex. Contrary to our expectations, patients had less D1-dopamine receptor availability with a moderate effect size. In a Bayesian analysis, we show that the data are over 50 times more likely to have occurred under the decrease as opposed to the increase hypothesis. This effect was not global, as our analysis showed that the null hypothesis was preferred over either hypothesis in the striatum.ConclusionsThis investigation represents the largest single sample of neuroleptic-naive patients examined for D1-dopamine receptor availability using PET and suggests a reduction of prefrontal D1-dopamine receptor density in the pathophysiology of schizophrenia. However, further work will be required to reach a consensus.
| S-EPMC6600463 | biostudies-literature
Project description:ObjectiveNeuroinflammation and abnormal immune responses are increasingly implicated in the pathophysiology of schizophrenia. Previous positron emission tomography (PET) studies targeting the translocator protein 18 kDa (TSPO) have been limited by high nonspecific binding of the first-generation radioligand, low-resolution scanners, small sample sizes, and psychotic patients being on antipsychotics or not being in the first episode of their illness. The present study uses the novel second-generation TSPO PET radioligand [18F]FEPPA to evaluate whether microglial activation is elevated in the dorsolateral prefrontal cortex and hippocampus of untreated patients with first-episode psychosis.MethodNineteen untreated patients with first-episode psychosis (14 of them antipsychotic naive) and 20 healthy volunteers underwent a high-resolution [18F]FEPPA PET scan and MRI. Dynamic PET data were analyzed using the validated two-tissue compartment model with arterial plasma input function with total volume of distribution (VT) as outcome measure. All analyses were corrected for TSPO rs6971 polymorphism (which is implicated in differential binding affinity).ResultsNo significant differences were observed between patients and healthy volunteers in microglial activation, as indexed by [18F]FEPPA VT, in either the dorsolateral prefrontal cortex or the hippocampus. There were no significant correlations between [18F]FEPPA VT and duration of illness, clinical presentation, or neuropsychological measures after adjusting for multiple testing.ConclusionsThe lack of significant differences in [18F]FEPPA VT between groups suggests that microglial activation is not present in first-episode psychosis.
| S-EPMC5342628 | biostudies-literature
Project description:Metacognition is impaired in schizophrenia and is an important predictor of functional outcome, but the underlying neuropathology is not clear. Studies have implicated frontal regions and there is also some evidence that the hippocampus might play a pivotal role, but findings are inconsistent. We set out to more comprehensively investigate the neural underpinnings of insight in first-episode psychosis (FEP) using 2 metacognitive measures (the Beck Cognitive Insight Scale [BCIS]) and a perceptual metacognitive accuracy task alongside structural magnetic resonance imaging (MRI). We measured cortical thickness in insula and frontal regions, hippocampal (including subfield) volumes, hippocampal microstructure (using neurite orientation dispersion and density imaging [NODDI]), and fractional anisotropy in fornix. Relative to controls, FEP showed poorer metacognitive accuracy, thinner cortex in frontal regions and lower fornix integrity. In healthy controls (but not FEP), metacognitive accuracy correlated with cortical thickness in frontal cortex and insula. Conversely, in FEP (but not controls), metacognitive accuracy correlated with hippocampal volume and microstructural indices. Subicular hippocampal subregions were particularly implicated. No structural correlates of BCIS were found. These findings suggest that the neural bases of metacognition might differ in FEP: hippocampal (rather than frontal) integrity seems to be critical. Further, the use of objectively measured metacognitive indices seems to be a more powerful method for understanding the neurocircuitry of metacognition in FEP, which has the potential to inform therapeutic strategies and improve outcome in these patients.
| S-EPMC7147593 | biostudies-literature
Project description:Impaired functional capacity is a core feature of schizophrenia and presents even in first-episode psychosis (FEP) patients. Impairments in daily functioning tend to persist despite antipsychotic therapy but their neural basis is less clear. Previous studies suggest that volume loss in frontal cortex might be an important contributor, but findings are inconsistent. We aimed to comprehensively investigate the brain structural correlates of functional capacity in FEP using MRI and a reliable objective measure of functioning [University of California, San Diego Performance-Based Skills Assessment (UPSA)]. In a sample of FEP (n = 39) and a well-matched control group (n = 21), we measured cortical thickness, gray matter volume, and white matter tract integrity (fractional anisotropy, FA) within brain regions implicated by previous work. The FEP group had thinner cortex in various frontal regions and fusiform, and reduced FA in inferior longitudinal fasciculus (ILF). In FEP, poorer functional capacity correlated with reduced superior frontal volume and lower FA in left ILF. Importantly, frontal brain volumes and integrity of the ILF were identified as the structural correlates of functional capacity in FEP, controlling for other relevant factors. These findings enhance mechanistic understanding of functional capacity deficits in schizophrenia by specifying the underlying neural correlates. In future, this could help inform intervention strategies.
| S-EPMC7560620 | biostudies-literature
Project description:ImportanceExperimental and epidemiological studies implicate the cannabinoid 1 receptor (CB1R) in the pathophysiology of psychosis. However, whether CB1R levels are altered in the early stages of psychosis and whether they are linked to cognitive function or symptom severity remain unknown.ObjectiveTo investigate CB1R availability in first-episode psychosis (FEP) without the confounds of illness chronicity or the use of illicit substances or antipsychotics.Design, setting, and participantsThis cross-sectional, case-control study of 2 independent samples included participants receiving psychiatric early intervention services at 2 independent centers in Turku, Finland (study 1) and London, United Kingdom (study 2). Study 1 consisted of 18 volunteers, including 7 patients with affective or nonaffective psychoses taking antipsychotic medication and 11 matched controls; study 2, 40 volunteers, including 20 antipsychotic-naive or antipsychotic-free patients with schizophrenia or schizoaffective disorder and 20 matched controls. Data were collected from January 5, 2015, through September 26, 2018, and analyzed from June 20, 2016, through February 12, 2019.Main outcomes and measuresThe availability of CB1R was indexed using the distribution volume (VT, in milliliters per cubic centimeter) of 2 CB1R-selective positron emission tomography radiotracers: fluoride 18-labeled FMPEP-d2 (study 1) and carbon 11-labeled MePPEP (study 2). Cognitive function was measured using the Wechsler Digit Symbol Coding Test. Symptom severity was measured using the Brief Psychiatric Rating Scale for study 1 and the Positive and Negative Syndrome Scale for study 2.ResultsA total of 58 male individuals were included in the analyses (mean [SD] age of controls, 27.16 [5.93] years; mean [SD] age of patients, 26.96 [4.55] years). In study 1, 7 male patients with FEP (mean [SD] age, 26.80 [5.40] years) were compared with 11 matched controls (mean [SD] age, 27.18 [5.86] years); in study 2, 20 male patients with FEP (mean [SD] age, 27.00 [5.06] years) were compared with 20 matched controls (mean [SD] age, 27.15 [6.12] years). In study 1, a significant main effect of group on [18F]FMPEP-d2 VT was found in the anterior cingulate cortex (ACC) (t16 = -4.48; P < .001; Hedges g = 1.2), hippocampus (t16 = -2.98; P = .006; Hedges g = 1.4), striatum (t16 = -4.08; P = .001; Hedges g = 1.9), and thalamus (t16 = -4.67; P < .001; Hedges g = 1.4). In study 2, a significant main effect of group on [11C]MePPEP VT was found in the ACC (Hedges g = 0.8), hippocampus (Hedges g = 0.5), striatum (Hedges g = 0.4), and thalamus (Hedges g = 0.7). In patients, [11C]MePPEP VT in the ACC was positively associated with cognitive functioning (R = 0.60; P = .01), and [11C]MePPEP VT in the hippocampus was inversely associated with Positive and Negative Syndrome Scale total symptom severity (R = -0.50; P = .02).Conclusions and relevanceThe availability of CB1R was lower in antipsychotic-treated and untreated cohorts relative to matched controls. Exploratory analyses indicated that greater reductions in CB1R levels were associated with greater symptom severity and poorer cognitive functioning in male patients. These findings suggest that CB1R may be a potential target for the treatment of psychotic disorders.
| S-EPMC6613300 | biostudies-literature
Project description:Background:Though olfactory deficits are well-documented in schizophrenia, fewer studies have examined olfactory performance profiles across the psychosis spectrum. The current study examined odor identification, discrimination, and detection threshold performance in first-episode psychosis (FEP) patients diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, major depression with psychotic features, and other psychotic conditions. Method:FEP patients (n = 97) and healthy adults (n = 98) completed birhinal assessments of odor identification, discrimination, and detection threshold sensitivity for lyral and citralva. Participants also completed measures of anticipatory pleasure, anhedonia, and empathy. Differences in olfactory performances were assessed between FEP patients and controls and within FEP subgroups. Sex-stratified post hoc analyses were employed for a complete analysis of sex differences. Relationships between self-report measures and olfactory scores were also examined. Results:Individuals with psychosis had poorer scores across all olfactory measures when compared to the control group. Within the psychosis cohort, patients with schizophrenia-associated psychosis had poorer odor identification, discrimination, and citralva detection threshold scores relative to controls. In schizophrenia patients, greater olfactory disturbance was associated with increased negative symptomatology, greater self-reported anhedonia, and lower self-reported anticipatory pleasure. Patients with mood-associated psychosis performed comparable to controls though men and women in this cohort showed differential olfactory profiles. Conclusions:These findings indicate that olfactory deficits extend beyond measures of odor identification in FEP with greater deficits observed in schizophrenia-related subgroups of psychosis. Studies examining whether greater olfactory dysfunction confers greater risk for developing schizophrenia relative to other forms of psychosis are warranted.
| S-EPMC5890458 | biostudies-other
Project description:Genome-wide patterns of DNA methylation were quantified using the Illumina Infinium HumanMethylationEPIC BeadChip (“EPIC array”) in DNA samples isolated from blood for schizophrenia cases, first episode psychosis patients and controls. These samples were profiled as part of a wider study where they were meta-analysed with other cohorts.
2021-04-07 | GSE152026 | GEO
Project description:There is an established, link between psychosis and metabolic abnormalities, such as altered glucose metabolism and dyslipidemia, which often precede the initiation of antipsychotic treatment. It is known that obesity-associated metabolic disorders are promoted by activation of specific cannabinoid targets (endocannabinoid system (ECS)). Our recent data suggest that there is a change in the circulating lipidome at the onset of first episode psychosis (FEP). With the aim of characterizing the involvement of the central and peripheral ECSs, and their mutual associations; here, we performed a combined neuroimaging and metabolomic study in patients with FEP and healthy controls (HC). Regional brain cannabinoid receptor type 1 (CB1R) availability was quantified in two, independent samples of patients with FEP (n = 20 and n = 8) and HC (n = 20 and n = 10), by applying three-dimensional positron emission tomography, using two radiotracers, [11C]MePPEP and [18F]FMPEP-d2. Ten endogenous cannabinoids or related metabolites were quantified in serum, drawn from these individuals during the same imaging session. Circulating levels of arachidonic acid and oleoylethanolamide (OEA) were reduced in FEP individuals, but not in those who were predominantly medication free. In HC, there was an inverse association between levels of circulating arachidonoyl glycerol, anandamide, OEA, and palmitoyl ethanolamide, and CB1R availability in the posterior cingulate cortex. This phenomenon was, however, not observed in FEP patients. Our data thus provide evidence of cross talk, and dysregulation between peripheral endocannabinoids and central CB1R availability in FEP.
| S-EPMC7450081 | biostudies-literature
Project description:Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12-35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and volume and thickness measurements was explored in patients with schizophrenia spectrum disorders (SSD), affective psychoses (AFP), and HC. Earlier SSD cases (ie, FEP before 15-20 y) showed significant volume and thickness deficits in frontal lobe, volume deficits in temporal lobe, and volume enlargements in ventricular system and basal ganglia. First-episode AFP patients had smaller cingulate cortex volume and thicker temporal cortex only at early age at FEP (before 18-20 y). The AFP group also had age-constant (12-35-y age span) volume enlargements in the frontal and parietal lobe. Our study suggests that age at first episode modulates the structural brain abnormalities found in FEP patients in a nonlinear and diagnosis-dependent manner. Future MRI studies should take these results into account when interpreting samples with different ages at onset and diagnosis.
| S-EPMC4753597 | biostudies-literature
Project description:We addressed the relationship between white matter architecture, represented by MRI fractional anisotropy (FA), and cognition in individuals with first-episode psychosis (FEP) by applying for a new methodology that allows whole brain parcellation of core and peripheral white matter in a biologically meaningful fashion. Regionally specific correlations were found in FEP between three specific domains of cognition (processing speed, attention/working memory, and executive functioning) and FA at the deep (cerebral peduncles, sagittal striatum, uncinate, internal/external capsule, cingulum) and peripheral white matter (adjacent to inferior temporal, angular, supramarginal, insula, occipital, rectus gyrus).
| S-EPMC6544495 | biostudies-literature