Neurobiology of hedonic tone: the relationship between treatment-resistant depression, attention-deficit hyperactivity disorder, and substance abuse

Abstract

Anhedonia, defined as the state of reduced ability to experience feelings of pleasure, is one of the hallmarks of depression. Hedonic tone is the trait underlying one’s characteristic ability to feel pleasure. Low hedonic tone represents a reduced capacity to experience pleasure, thus increasing the likelihood of experiencing anhedonia. Low hedonic tone has been associated with several psychopathologies, including major depressive disorder (MDD), substance use, and attention-deficit hyperactivity disorder (ADHD). The main neural pathway that modulates emotional affect comprises the limbic–cortical–striatal–pallidal–thalamic circuits. The activity of various components of the limbic–cortical–striatal–pallidal–thalamic pathway is correlated with hedonic tone in healthy individuals and is altered in MDD. Dysfunction of these circuits has also been implicated in the relative ineffectiveness of selective serotonin reuptake inhibitors used to treat anxiety and depression in patients with low hedonic tone. Mood disorders such as MDD, ADHD, and substance abuse share low hedonic tone as well as altered activation of brain regions involved in reward processing and monoamine signaling as their features. Given the common features of these disorders, it is not surprising that they have high levels of comorbidities. The purpose of this article is to review the neurobiology of hedonic tone as it pertains to depression, ADHD, and the potential for substance abuse. We propose that, since low hedonic tone is a shared feature of MDD, ADHD, and substance abuse, evaluation of hedonic tone may become a diagnostic feature used to predict subtypes of MDD, such as treatment-resistant depression, as well as comorbidities of these disorders.

Adult ADHD and comorbid disorders: clinical implications of a dimensional approach

“…In part, this may be related to deficits in reward processing with altered monoamine signalling having been implicated as the underlying mechanism of this effect. This deficit in reward processing characterized as low hedonic tone [ 51 , 52 ], is hypothesized to be at least in part related to deficits in modulation of this circuitry [ 53 ]. These deficits, which result in altered sensitivity to reinforcement, have been shown in children with ADHD who have been reported to preferentially respond to immediate rewards, but not when the rewards are delayed and therefore only exhibit conditioning to immediate rewards [ 54 ], which parallels some of the anomalous changes in the neural pathways that regulate reward and motivation [ 55 ], matching those in depression.…”

The Relationship Between Harming Behavior and Substance Use Profile, and Attention Deficit Hyperactivity Disorder Symptoms in Antisocial Personality Disorder

“…Other studies also support that there is a relationship between severity of addiction and the presence of ADHD in patients with PSUD (27). In the formation of this relationship, dysfunctions in the reward pathways that play a role in the physiopathology of both disorders including cortico-talamo-striatal circuits, dopaminergic and noradrenergic systems take place (28). The presence of psychoactive substance use in some of the individuals with ADHD stemming from self medicating and the novelty-seeking behavior, besides, the frequent presence of impulsivity, behavioral problems and novelty seeking behaviors in individuals with PSUD suggests that there may be a bilateral relationship between these two clinical conditions (28,29).…”

“…In the formation of this relationship, dysfunctions in the reward pathways that play a role in the physiopathology of both disorders including cortico-talamo-striatal circuits, dopaminergic and noradrenergic systems take place (28). The presence of psychoactive substance use in some of the individuals with ADHD stemming from self medicating and the novelty-seeking behavior, besides, the frequent presence of impulsivity, behavioral problems and novelty seeking behaviors in individuals with PSUD suggests that there may be a bilateral relationship between these two clinical conditions (28,29). Another finding in our study is that the hyperactivity/impulsivity and addiction diagnosis scores of the individuals with a history of attempted suicide are higher than the ones without suicide attempts.…”

Targeting opioid receptor signaling in depression: do we need selective κ opioid receptor antagonists?

“…Anhedonia or the reduced capacity to experience pleasure, is a core feature of major depressive disorder [6,7]. The mesolimbic dopaminergic system is involved in the reward system and in mediating the degree of anhedonia and risk of developing depression [6][7][8].…”

“…The mesolimbic dopaminergic system is involved in the reward system and in mediating the degree of anhedonia and risk of developing depression [6][7][8]. Hedonic tone can be defined as the trait or genetic predisposition underlying an individual's baseline range and lifelong characteristic ability to feel pleasure [7].…”