Alcohol use disorder (AUD) is the most common substance use disorder worldwide. Although dopamine‐related findings were often observed in AUD, associated neurobiological mechanisms are still poorly understood. Therefore, in the present study, we investigate D2/3 receptor availability in healthy participants, participants at high risk (HR) to develop addiction (not diagnosed with AUD), and AUD patients in a detoxified stage, applying 18F‐fallypride positron emission tomography (18F‐PET). Specifically, D2/3 receptor availability was investigated in (1) 19 low‐risk (LR) controls, (2) 19 HR participants, and (3) 20 AUD patients after alcohol detoxification. Quality and severity of addiction were assessed with clinical questionnaires and (neuro)psychological tests. PET data were corrected for age of participants and smoking status. In the dorsal striatum, we observed significant reductions of D2/3 receptor availability in AUD patients compared with LR participants. Further, receptor availability in HR participants was observed to be intermediate between LR and AUD groups (linearly decreasing). Still, in direct comparison, no group difference was observed between LR and HR groups or between HR and AUD groups. Further, the score of the Alcohol Dependence Scale (ADS) was inversely correlated with D2/3 receptor availability in the combined sample. Thus, in line with a dimensional approach, striatal D2/3 receptor availability showed a linear decrease from LR participants to HR participants to AUD patients, which was paralleled by clinical measures. Our study shows that a core neurobiological feature in AUD seems to be detectable in an early, subclinical state, allowing more individualized alcohol prevention programs in the future.

<b><i>Introduction:</i></b> Reduced striatal dopamine D2/3 receptor availability in alcohol use disorder (AUD) has been demonstrated in recent clinical studies and meta-analyses. However, only a limited number of studies investigated extrastriatal D2/3 availability in AUD or in at-risk populations. In line with a dimensional understanding of addiction, extrastriatal dopaminergic neuroadaptations have been suggested to be relevant from a pathobiological perspective. <b><i>Methods:</i></b> We investigated D2/3 receptor availability via ¹⁸F-fallypride positron emission tomography applying a region of interest (ROI) approach. We selected ROIs for the prefrontal cortex (PFC) and the anterior cingulate cortex (ACC). Our sample included 19 healthy controls (low risk [LR]), 19 individuals at high risk (HR) to develop addiction, and 20 recently detoxified AUD patients. <b><i>Results:</i></b> We found significantly higher D2/3 receptor availability of HR compared to AUD in the left and right rostral ACC (rACC), as well as in the left ventrolateral PFC (vlPFC). We did not observe a significant difference between AUD and LR. After corrections for multiple comparisons none of the ROIs reached significance throughout the group comparison. The D2/3 receptor availability in the left rACC was inversely correlated with symptom severity assessed with the Alcohol Dependency Scale. <b><i>Discussion:</i></b> To our knowledge, the present work is the first study investigating extrastriatal D2/3 receptor availabilities in individuals at HR and patients with AUD. The observation that D2/3 receptor availabilities are highest in HR might suggest that their pathobiology differs from subjects with AUD. Future studies are necessary to clarify the intraindividual course of this biomarker over different disease stages and its possible role as a risk or protective factor.

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Background:The association between blunted dopaminergic neurotransmission and alcohol use disorder (AUD) is well-known. In particular, the impairment of postsynaptic dopamine 2 and 3 receptors (DRD2/3) in the ventral and dorsal striatum during the development and maintenance of alcohol addiction has been investigated in several positron emission tomography (PET) studies. However, it is unclear whether these changes are the result of adaptation or genetic predisposition. Methods: Here we investigated the association between DRD2/ankyrin repeat and kinase domain-containing 1 (ANKK1) TaqIA allele (rs1800497) status and striatal DRD2/3 availability measured by 18F-fallypride PET in 12 AUD patients and 17 sex-matched healthy controls. Age and smoking status were included as covariates. Results: Contrary to our expectations, TaqIA allele status was not associated with striatal DRD2/3 availability in either group and there was no significant difference between groups, possibly due to the relatively small sample size (N = 29). Conclusions: Nonetheless, this is the first in vivo study investigating the relationship between dopamine receptor availability and genetic factors in AUD. The pitfalls of assessing such relationships in a relatively small sample are discussed. Clinical Trial Registration: The published analysis is an additional, post hoc analysis to the preregistered trial with clinical trial number NCT01679145 available on https://clinical -trials.gov/ct2/show/NCT01679145.

ZUSAMMENFASSUNGDie Begleitung von Patienten am Lebensende ist eine klinische und ethische Herausforderung in der Gerontopsychiatrie, z. B. bei Gefährdungsaspekten oder der Ermittlung des Patientenwillens bzgl. medizinischer Entscheidungen. Eine möglicherweise inadäquate somatische Versorgung der Betroffenen sowie eine Überlastung der Mitarbeitenden können insbesondere bei fehlender Möglichkeit zur Verlegung in die somatische und palliativmedizinische Weiterbehandlung auftreten. Anhand von 5 Kasuistiken aus dem stationären Klinikalltag werden Ansätze für eine verbesserte Versorgung am Lebensende erörtert. Problemfelder in der Behandlung am Lebensende treten z. B. bei gleichzeitig bestehenden psychiatrischen und somatischen Komorbiditäten und unzureichenden strukturellen/personellen Ressourcen auf. Der Komplexität solcher Fälle kann durch interdisziplinäre und multiprofessionelle Versorgungsstrukturen im gerontopsychiatrischen Setting begegnet werden. Langfristig kann durch die Einbeziehung psychosozialer und ethischer Aspekte in die klinischen Standards die Begleitung gerontopsychiatrischer Patienten im Sterbeprozess optimiert werden.