Atlas of type 2 dopamine receptors in the human brain: Age and sex dependent variability in a large PET cohort

Malén, Tuulia; Karjalainen, Tomi; Isojärvi, Janne; Vehtari, Aki; Bürkner, Paul‐Christian; Putkinen, Vesa; Kaasinen, Valtteri; Hietala, Jarmo; Nuutila, Pirjo; Rinne, Juha O.; Nummenmaa, Lauri

doi:10.1016/j.neuroimage.2022.119149

Cited by 17 publications

(24 citation statements)

References 114 publications

(133 reference statements)

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“…Brain DR is not different between lean and overweight/obese subjects and these meta‐analytic findings from patients also align with the recent large‐scale study of non‐obese healthy subjects (Malén et al, 2022). There is an effect of the variety of radiopharmaceuticals and the degree of the severity of obesity on this result, therefore, we still cannot exclude the association of brain DR with obesity.…”

Section: Discussionsupporting

confidence: 88%

Brain dopamine receptor system is not altered in obesity: Bayesian and frequentist meta‐analyses

Pak,

Nummenmaa

2023

Human Brain Mapping

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Feeding induces dopamine release in the striatum, and a dysfunction of the dopaminergic reward system can lead to overeating, and obesity. Studies have reported inconsistent findings of dopamine receptor (DR) positron emission tomography scans in obesity. Here we investigated the association between DR availability and overweight/obesity using Bayesian and frequentist meta‐analysis. We performed a systematic search of Embase, Medline, Scopus and Web of Science for studies that compared striatal DR availability between lean subjects and overweight/obese subjects. The standardized mean difference (Hedge's g) of DR availability was calculated after extraction of data from each study. Studies were divided into two groups according to the definition of overweight/obese subjects (body mass index [BMI] cutoff of 25 and 30 kg/m2). Both Bayesian and frequentist meta‐analysis was done in R Statistical Software version 4.2.2 (The R Foundation for Statistical Computing). Nine studies were eligible for inclusion in this study. Three studies with C11‐raclopride, one with C11‐PNHO, two with F18‐fallypride, one with I123‐IBZM, one with C11‐NMB and one with both C11‐raclopride and C11‐PNHO were included. In Bayesian meta‐analysis, the standardized mean difference of DR availability between lean and overweight/obese subjects markedly overlapped with zero regardless of BMI cutoff for obesity. In frequentist meta‐analysis, the pooled standardized mean difference of DR availability did not show the significant difference between lean and overweight/obese subjects. There was an effect of the radiopharmaceutical on the standardized mean difference of DR availability in meta‐analysis of BMI cutoff of 25 kg/m2. In conclusion, brain DR availability is not different between lean and overweight/obese subjects. However, the effect is dependent on the radiopharmaceutical and the degree of obesity. Further studies with multi‐radiopharmaceutical in the same individuals are needed to understand the association between DR and obesity.

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Section: Discussionsupporting

confidence: 88%

Brain dopamine receptor system is not altered in obesity: Bayesian and frequentist meta‐analyses

Pak,

Nummenmaa

2023

Human Brain Mapping

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“…Selection, Comparability, Exposure) and used the star system to summarise these findings. For Comparability, we assessed whether studies explicitly matched patient and control groups for age and sex in their study design, or adjusted for these in their analysis, as these variables are known to influence dopaminergic indices (Lavalaye et al, 2000; Malen et al, 2022). We examined the association between overall quality ratings of individual studies in the Newcastle–Ottawa Scale and effect sizes in the meta-analysis.…”

Section: Methodsmentioning

confidence: 99%

Dopamine in major depressive disorder: A systematic review and meta-analysis of in vivo imaging studies

Mizuno,

Ashok,

Bhat

et al. 2023

J Psychopharmacol

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Background: Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the magnitude and consistency of the findings are unknown. We address this by systematically reviewing in vivo imaging evidence for dopamine measures in MDD and meta-analysing these where there are sufficient studies. Methods: Studies investigating the dopaminergic system using positron emission tomography or single photon emission computed tomography in MDD and a control group were included. Demographic, clinical and imaging measures were extracted from each study, and meta-analyses and sensitivity analyses were conducted. Results: We identified 43 studies including 662 patients and 801 controls. Meta-analysis of 38 studies showed no difference in mean or mean variability of striatal D2/3 receptor availability ( g = 0.06, p = 0.620), or combined dopamine synthesis and release capacity ( g = 0.19, p = 0.309). Dopamine transporter (DAT) availability was lower in the MDD group in studies using DAT selective tracers ( g = −0.56, p = 0.006), but not when tracers with an affinity for serotonin transporters were included ( g = −0.21, p = 0.420). Subgroup analysis showed greater dopamine release ( g = 0.49, p = 0.030), but no difference in dopamine synthesis capacity ( g = −0.21, p = 0.434) in the MDD group. Striatal D1 receptor availability was lower in patients with MDD in two studies. Conclusions: The meta-analysis indicates striatal DAT availability is lower, but D2/3 receptor availability is not altered in people with MDD compared to healthy controls. There may be greater dopamine release and lower striatal D1 receptors in MDD, although further studies are warranted. We discuss factors associated with these findings, discrepancies with preclinical literature and implications for future research.

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“…Women showed higher D2 binding in all three regions, but the difference relative to men was only statistically significant for the frontal cortex. A more recent register-based study [ 95 ] investigated how age and sex influenced striatal D2 receptor availability using [11C] raclopride. The pooled data from 5 different PET scanners yielded information on 120 healthy males and 36 healthy females, aged 19 to 71.…”

Section: Pharmacokinetics Of Antipsychoticsmentioning

confidence: 99%

“…The confirmation is important because their findings were not altogether in harmony with earlier results reporting sex-dependent decline in dopamine function, with males showing steeper reduction in receptors [ 96 , 97 ]. Using radioactive olanzapine as their PET ligand, Eugene and Masiak [ 26 ] had found, like Malén et al [ 95 ], that, over various age ranges, women needed a smaller oral dose than men to achieve an occupancy of 70% D2 binding, 60% being the usual minimum required for antipsychotic efficacy. The amount of DA transporter (DAT) has been found to be higher in postmenopausal women compared to similarly aged men (age range 50–86, mean 70 years) [ 98 ].…”

Section: Pharmacokinetics Of Antipsychoticsmentioning

confidence: 99%

The Effect of Menopause on Antipsychotic Response

2022

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Background: It has been hypothesized that, whenever estrogen levels decline, psychosis symptoms in women increase. At menopause, this can happen in two main ways: (a) the loss of estrogen (mainly estradiol) can directly affect central neurotransmission, leading to increase in schizophrenia-related symptoms, and (b) the loss of estrogen can decrease the synthesis of enzymes that metabolize antipsychotic drugs, thus weakening their efficacy. Aims and Methods: The aim of this narrative review was to investigate the second possibility by searching PubMed and ClinicalTrials.gov for studies over the last two decades that investigated the metabolism of antipsychotics and their efficacy before and after menopause in women or that studied systemic and local estrogen level effects on the pharmacokinetics and pharmacodynamics of individual antipsychotic drugs. Results: The evidence suggests that symptom level in women with schizophrenia rises after menopause for many reasons beyond hormones but, importantly, there is an estrogen-dependent loss of efficacy related to antipsychotic treatment. Conclusion: Effective clinical intervention is challenging; nevertheless, several promising routes forward are suggested.

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Atlas of type 2 dopamine receptors in the human brain: Age and sex dependent variability in a large PET cohort

Cited by 17 publications

References 114 publications

Brain dopamine receptor system is not altered in obesity: Bayesian and frequentist meta‐analyses

Brain dopamine receptor system is not altered in obesity: Bayesian and frequentist meta‐analyses

Dopamine in major depressive disorder: A systematic review and meta-analysis of in vivo imaging studies

The Effect of Menopause on Antipsychotic Response

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