Anhedonia in opioids use disorder: The role of neurocognitive profiles

Introduction: Anhedonia, as incapacity to feel pleasure in situations or activities habitually delightful, is a hallmark symptom of Major Depression, Schizophrenia and other neuropsychiatric disorders, such as Substance Use Disorder (SUD) [1]. Anhedonia may be divided into anticipatory anhedonia, consisting in the inability to anticipate a future pleasurable experience, or consummatory anhedonia, as inability to enjoy a current stimulation; besides anhedonia can be distinguished in social and physical, depending on whether it concerns the sphere of interpersonal relationships or somatosensory experiences. The neurobiological bases of anhedonia involve, among others, neurotransmitters such as dopamine and opioids. The reward system includes both the mesolimbic dopaminergic system and the mesocortical pathways. The involved prefrontal cortical areas are crucial in learning tasks and behavioural control that are impaired in the SUD [2]. Because SUD, and specifically opiate use disorder are a model of an imbalance between the dopaminergic and the opiate pathways in the reward system, it is possible that anhedonia in this population is primarly related to these biological underpinning [3,4]. Aim: The main aim of this study is to evaluate whether hedonic deficits are characteristic of opiate use disorder and whether these are related to cognitive impairments in partial remission opioid-dependent patients compared to normal healthy control subjects. Methods: We compared 46 healthy individuals with 52 opioid-dependent patients in partial remission. Half of the patients were prescribed opiate substitution therapy (OST). In addition to sociodemographic data, all subjects were required to fill out some questionnaires aimed at rating anhedonia: anticipatory and consummatory (Temporal Experience of Pleasure Scale, TEPS), physical (Physical Anhedonia Scale, PAS) and social (Revised Social Anhedonia Scale, R-SAS). They were evaluated also on depressive symptoms (Hamilton Depression Rating Scale). All participants were assessed on cognitive functions, such as abstraction reasoning (Wisconsin Card Sorting Test, WCST) and working memory (Hopkins Verbal Learning Test-Revised, HVLT-R; Spatial Span, SS; Letter Number Span, LNS). Results: When comparing healthy controls with patients the latter scored significantly worse in anticipatory anhedonia (t=3.413; p=.001), social anhedonia (t=-4.398; p<.001) and cognitive domains such as HVLT-R (t=4.005; p<.001) and LNS (t=3.272; p=.001). Interestingly the levels of SAS correlated with HVLT-R (r=-.308; p=.002). Among patients, those on OST were significantly less social anhedonic (F=5.553; p=.023) and had better cognitive functioning at WCST (completed categories: F=17.01; p<.001). Independently from the pharmacological therapy, social anhedonia was related to the abstinence period (r=.723; p=.002) and significantly increase in the long term, perhaps in correlation with the progressive deterioration of cognitive functions. Conclusion: Our result suggest that importance of targeting cognitive impairment in patients with SUD, in order to reduce the anhedonia levels. This, in fact is related to risk of relapse. Moreover, clinicians should focus on social anhedonia both as a target of therapy and a risk factor for the development of drug addiction.