Preliminary evidence that negative symptom severity relates to multilocus genetic profile for dopamine signaling capacity and D2 receptor binding in healthy controls and in schizophrenia

Abstract

Deficits in central, subcortical dopamine (DA) signaling may underlie negative symptom severity, particularly anhedonia, in healthy individuals and in schizophrenia. To investigate these relationships, we assessed negative symptoms with the Schedule for the Assessment of Negative Symptoms and the Brief Negative Symptom Scale (BNSS) and self-reported anhedonia with the Scales for Physical and Social Anhedonia (SPSA), Temporal Experience of Pleasure Scale, and Snaith-Hamilton Pleasure Scale in 36 healthy controls (HC), 27 siblings (SIB) of individuals with schizophrenia, and 66 individuals with schizophrenia or schizoaffective disorder (SCZ). A subset of participants (N = 124) were genotyped for DA-related polymorphisms in genes for DRD4, DRD2/ANKK1, DAT1, and COMT, which were used to construct biologically-informed multi-locus genetic profile (MGP) scores reflective of subcortical dopaminergic signaling. DA receptor type 2 (D2R) binding was assessed among a second subset of participants (N = 23) using PET scans with the D2R-selective, non-displaceable radioligand (N-[11C]methyl)benperidol. Higher MGP scores, reflecting elevated subcortical dopaminergic signaling capacity, were associated with less negative symptom severity, as measured by the BNSS, across all participants. In addition, higher striatal D2R binding was associated with less physical and social anhedonia, as measured by the SPSA, across HC, SIB, and SCZ. The current preliminary findings support the hypothesis that subcortical DA function may contribute to negative symptom severity and self-reported anhedonia, independent of diagnostic status.

A Transdiagnostic Perspective on Social Anhedonia

“…The first emphasizes the role of dopamine in reward processes and social bonding (157). Evidence linking dopamine and social anhedonia can be drawn from genetic association studies in relatives of patients with schizophrenia (158) and dopamine D2 receptor binding availability along the psychosis continuum (159). Furthermore, in Parkinson’s disease (characterized by the breakdown of dopamine-producing neurons), consummatory anhedonia is specifically blunted (160) independently of depression (161); however, social anhedonia is yet to receive specific attention.…”

CLASH-VLT: a full dynamical reconstruction of the mass profile of Abell S1063 from 1 kpc out to the virial radius

“…To date, there are inconsistent results from several association studies of ANKK1 polymorphism with schizophrenia and its clinical phenotypes (Alfimova et al, 2017(Alfimova et al, , 2018Arab & Elhawary, 2015;Eisenstein et al, 2017;Nkam et al, 2017;Parsons et al, 2007;Ponce et al, 2009;Wishart et al, 2011;Yao, Pan, Ding, Pang, & Wang, 2015;Zhang et al, 2014). It has been hypothesized that rs1800497 polymorphism is likely to have a modifying effect rather than causative effect on schizophrenia (Zhang et al, 2014).…”

The interaction effect of ANKK1/DRD2 TaqIA and HTR2C Cys23Ser on approach motivation in schizophrenic patients and normals

“…Относительно вклада генетических факторов в оценки TEPS имеются лишь единичные работы [40,41]. В пилотном исследовании 124 человек, включавшем больных шизофренией, их родственников и контроль, не было выявлено ассоциации показателей TEPS с аддитивным влиянием полиморфизма генов дофаминергической системы, включая DRD2/ANKK1 [41], что согласуется с нашими данными.…”

“…D2-рецепторы являются мишенью действия типичных нейролептиков, в связи с чем их избыточную активность при шизофрении связывают с позитивной симптоматикой [17]. Роль DRD2 в нарушении процесса мотивации при шизофрении изучалась преимущественно в рамках анализа негативного синдрома [18][19][20], без учета сложной структуры мотивационных процессов, включающей, по меньшей мере, гедоническую и активационную составляющие [21,22]. В связи с поиском механизмов мотивации, помимо рецепторов D2, интерес представляют рецепторы серотонина типа 2C (5-HTR2C).…”