Hedonic Tone: A Bridge between the Psychobiology of Depression and its Comorbidities

Abstract

paper will present the hypothesis that low hedonic tone and associated specific neurobiologic correlates predict the presence of ADHD in MDD, thus who is at risk for poorer outcomes with selective Serotonin Reuptake Inhibitors (SSRIs). Brain Regions and CircuitsEleven key areas of the brain have been highlighted in part by their specific neurotransmitter projections of which alteration in neurotransmitter innervation has been hypothesized to create disruptions in information processing and consequently specific psychological symptoms [2]. Linking each of these functional areas is a network of neuron projections or neurotransmitter pathways from the brainstem. It is posited that when a neurotransmitter-carrying neuron projects into a specific area, it has the capacity to modulate the physiological processes of the associated circuit [2]. Thus these pathways form the substrates that "tune" the neurons within each AbstractTreatment of Major Depressive Disorder (MDD), in many cases, offers less than optimal results, resulting in loss of function and remaining impairment. This is partially explained by the high prevalence of comorbid psychiatric illnesses that share common features, likely resulting in less than adequate treatment outcomes among patients receiving traditional psychiatric treatment.The term anhedonia does not sufficiently capture the complex and multifaceted reward-associated deficits seen in neuropsychiatric disorders. Deficits in reward-related processes can lead to behaviors that may appear to be the loss of interest or pleasure, and may preclude an individual from engaging in goal-oriented action. Investigators have identified a lifelong poor hedonic responsiveness, manifested as altered sensitivity to reinforcement, in patients with Attention Deficit Hyperactivity Disorder (ADHD), and suggest it as a common endophenotype for depression and the inattentive symptoms of ADHD. Research into the neurobiology of anhedonia has focused on the centers in the brain related to reward and motivation, and has identified the dopaminergic and associated circuits as playing a key role. Studies have shown that lesions in reward and motivation circuits result in anhedonia, and that decreased activation in the medial frontal cortex is believed to underlie abnormal positive affect processing in patients.In this paper, we propose that a specific phenotype of depression, which is more likely to be described as "treatment resistant" is associated with high risk of comorbidity with dysthymia, ADHD, and substance abuse, specifically cocaine abuse. We believe these patients experience a chronically lower hedonic tone that results in chronic anhedonia (as opposed to acute state anhedonia noted in a major depressive episode) related to unique pathophysiology and requiring treatment of the dopaminergic deficiency that characterizes its unique collection of comorbidities.