Anhedonia in major depressive disorder: the role of neurocognitive profiles

Background: Anhedonia is the inability to experience pleasure, even in normally pleasant circumstances and activities. It is a fundamental symptom of Major Depressive Disorder (MDD), and it's related to a worse outcome. There are various components of the hedonic deficit: based on stimulus features it is possible to distinguish physical from social anhedonia; considering the different stages of pleasure it is possible to distinguish anticipatory from consummatory anhedonia. Pleasure perception is possible thanks to motivation and reward-gratification circuits [1], and requires memory and executive functions integrity, all of which are often compromised in MDD [2,3]. Aim: The aim of our study is to differentiate anhedonia components and cognitive impairments that could be either a state or a trait characteristic in patients with MDD, and to find correlations among these alterations. Matherials and methods: We recruited 46 healthy controls and 54 patients with MDD currently depressed; 25 of them were retested in a euthymic phase at the remission of the actual episode. All the subjects completed Physical Anhedonia Scale (PAS), Social Anhedonia Scale (SAS), Snaith-Hamilton Pleasure Scale (SHAPS) and Temporal Experience of Pleasure Scale (TEPS) that specifically assesses anticipatory and consummatory anhedonia. We evaluated working memory through Spatial Span (SS) and Letter Number Sequencing (LNS), declarative memory with Hopkins Verbal Learning Test-Revised (HVLT-R) and abstract reasoning with Wisconsin Card Sorting Test (WCST). Results and discussion: When comparing euthymic patients and healthy controls to assess trait characteristics the gap between the anticipatory and consummatory subscales of TEPS was the only parameter that remained significant after controlling for confounding variables (t=3.57; p<.001). Patients, moreover, were significantly more impaired in abstract thinking measured with WCST (t=-11.09; p<.001) and in declarative memory tested with HTLV-R (t=2.11; p=.038). The number of correct answers at WCST that is a measure of executive functions, correlated with the TEPS gap (r=-.421; p<.001) so that euthymic patients with a more impaired abstract reasoning were more unbalanced in their abilities of anticipate and experience pleasure. We then repeated the same analyses in a within design with the subset of patients that repeated the evaluations to assess state characteristics. When depressed, subjects were significantly more anhedonic at SHAPS (t=3.83; p<.001) and physically anhedonic at PAS (t=2.33; p=.028). Confirming previous results, the two groups were significantly different also in working memory assessed with SS (t=-4.22; p<.001) and in some executive functions (WCST). The conceptual level responses at WCST that is a measure of mental representation and flexibility, correlated with the PAS (r=-.332; p=.026) so that patients that were more physical anhedonic during a depressive episode were also those most impaired in abstract thinking. Conclusions: Cognitive alterations could inhibit a correct elaboration of positive stimuli and the ability to recall them, and could consequently cause these hedonic deficits. These features only partly remit at the end of the depressive episode and seem like trait characteristics that could reflect a risk factor for the development of the disorder