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Links between central CB1-receptor availability and peripheral endocannabinoids in patients with first episode psychosis.

ABSTRACT: 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.

SUBMITTER: Dickens AM

PROVIDER: S-EPMC7450081 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Links between central CB1-receptor availability and peripheral endocannabinoids in patients with first episode psychosis.

Dickens Alex M AM Borgan Faith F Laurikainen Heikki H Lamichhane Santosh S Marques Tiago T Rönkkö Tuukka T Veronese Mattia M Lindeman Tuomas T Hyötyläinen Tuulia T Howes Oliver O Hietala Jarmo J Orešič Matej M

NPJ schizophrenia 20200826 1

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 inv ...[more]

PMID: 32848142

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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.

Project description:BackgroundThough 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.MethodFEP 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.ResultsIndividuals 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.ConclusionsThese 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.

Dataset Information

Links between central CB1-receptor availability and peripheral endocannabinoids in patients with first episode psychosis.

Publications

Links between central CB1-receptor availability and peripheral endocannabinoids in patients with first episode psychosis.

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