Prognostic factors for low‐risk drinking and relapse in alcohol use disorder: A multimodal analysis

Abstract

This study aims to specify the determinants of low‐risk alcohol drinking and relapse at different time points after detoxification in patients with severe alcohol use disorder (AUD). Fifty‐four patients with AUD and 36 healthy controls (HC) were evaluated early in abstinence (T1). They underwent clinical, neuropsychological and neuroimaging (structural MRI and 18FDG‐PET) investigations. Patients with AUD were subsequently classified as “low‐risk drinkers” (LR) or “relapsers” (R) based on their alcohol drinking at 6 months (T2) and 1 year (T3) after discharge, using their medical record or self‐reported drinking estimation at follow‐up. Based on the alcohol status at T2 and compared with HC, only R had alexithymia, lower grey matter volume in the midbrain and hypermetabolism in the cerebellum and hippocampi. Based on the alcohol status at T3 and compared with HC, only R had more severe nicotinic dependence, lower episodic and working memory performance, lower grey matter volume in the amygdala, ventromedial prefrontal cortex and anterior cingulate gyrus and hypermetabolism in cerebellum, hippocampi and anterior cingulate gyrus. Moreover, R had bilateral frontal hypometabolism, whereas LR only presented right frontal hypometabolism. Nicotine dependence, memory impairments and structural brain abnormalities in regions involved in impulsivity and decision‐making might contribute to a 1‐year relapse. Treatment outcome at 1 year may also be associated with an imbalance between a hypermetabolism of the limbic system and a hypometabolism of the frontal executive system. Finally, cerebellar hypermetabolism and alexithymia may be determinants of relapse at both 6 months and 1 year.

Dopamine and Alcohol: A Review of in vivo PET and SPECT Studies

“…Some studies reported reduced global brain metabolism and especially a hypometabolism in the frontal cortical regions of persons with AD, compared to HCs [174, 175]. Interestingly, Maillard et al [176] found a hypermetabolism in the cerebellum and hippocampus of persons with AD who relapsed within 6 months and additionally in the anterior cingulate cortex of persons with AD who relapsed after 12 months. Further (preclinical) multimodal studies combining PET and MRI in AD investigated glutamatergic but not DA neurotransmission in animal models [177, 178].…”

Insular volumetry in severe alcohol use disorder and Korsakoff's syndrome through an anatomical parcellation: Let us go back to basics

“…Noteworthy, participants were seen in the context of a large protocol, from which prior results have been published 32–38 …”

Chronic Ethanol Exposure Produces Persistent Impairment in Cognitive Flexibility and Decision Signals in the Striatum

“…The ability to make flexible decisions is substantially altered by chronic ethanol (EtOH) use and dependence across species, impairing goal-directed behavior while enhancing habitual or stimulus-oriented behavior [1][2][3][4][5][6][7] . Low cognitive flexibility may contribute to future escalation of substance use [8][9][10] , including EtOH intake in both rodents and primates [11][12][13][14] , and in heightening the risk of relapse to alcohol use in humans 15,16 .…”

“…Notably, neural signals in the DMS related to the decision outcome were enhanced, while those related to choice and choice-outcome conjunction were reduced, in EtOH-treated rats compared to the controls. These findings highlight the profound impact of chronic EtOH exposure on adaptive decision-making, pinpointing specific changes in striatal representations of actions and outcomes as underlying mechanisms for cognitive deficits.Cheng et al Page 3 10 , including EtOH intake in both rodents and primates [11][12][13][14] and in heightening the risk of relapse to alcohol use in humans 15,16 .Cognitive flexibility, evaluated through reversal learning tasks 17,18 , involves learning beneficial choice and adapting to new action-outcome contingencies. Although the cognitive and neural mechanisms underlying chronic EtOH-induced reversal deficits are not yet fully understood, studies in humans have shown persistent disruption of reversal learning during protracted withdrawal from EtOH drinking [19][20][21][22] .…”

“…Cheng et al Page 3 10 , including EtOH intake in both rodents and primates [11][12][13][14] and in heightening the risk of relapse to alcohol use in humans 15,16 .…”