Individual Variations in Nucleus Accumbens Responses Associated with Major Depressive Disorder Symptoms

Abstract

Abnormal reward-related responses in the nucleus accumbens (NAcc) have been reported for major depressive disorder (MDD) patients. However, variability exists in the reported results, which could be due to heterogeneity in neuropathology of depression. To parse the heterogeneity of MDD we investigated variation of NAcc responses to gain and loss anticipations using fMRI. We found NAcc responses to monetary gain and loss were significantly variable across subjects in both MDD and healthy control (HC) groups. The variations were seen as a hyperactive response subtype that showed elevated activation to the anticipation of both gain and loss, an intermediate response with greater activation to gain than loss, and a suppressed-activity with reduced activation to both gain and loss compared to a non-monetary condition. While these response variability were seen in both MDD and HC subjects, specific symptoms were significantly associated with the right NAcc variation in MDD. Both the hyper- and suppressed-activity subtypes of MDD patients had severe suicidal ideation and anhedonia symptoms. The intermediate subjects had less severity in these symptoms. These results suggest that differing propensities in reward responsiveness in the NAcc may affect the development of specific symptoms in MDD.

Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression

“…Striatal‐subcortical connectivity was mainly altered among subjects with PTSD‐MDD, and the NAcc‐THA pathway negatively correlated with MDD symptoms. The NAcc has been consistently reported as the key reward network region affected in MDD during reward processing (Misaki et al., ), and has been a target of deep brain stimulation for treatment‐resistant MDD patients (Nauczyciel et al., ). The NAcc receives massive projections directly from the thalamus, and the NAcc‐thalamus circuit is involved in regulating affective and motivational function (Haber & Calzavara, ).…”

“…Striatalsubcortical connectivity was mainly altered among subjects with PTSD-MDD, and the NAcc-THA pathway negatively correlated with MDD symptoms. The NAcc has been consistently reported as the key reward network region affected in MDD during reward processing (Misaki et al, 2016), and has been a target of deep brain stimulation for treatment-resistant MDD patients (Nauczyciel et al, 2013). The…”

The Effect of Emotion and Reward Contingencies on Relational Memory in Major Depression: An Eye-Movement Study with Follow-Up

“…Our previous results also indicated a greater influence of reward in MD (Must et al, 2006). This seeming contradiction might be explained by individual variations in neuronal activation patterns (Misaki et al, 2016), genetic variations and personality traits (Must et al, 2007; Byrne et al, 2016) or false recollection affecting the cognitive evaluation of rewarding stimuli (Davidson et al, 2002). Antidepressive therapy has also been found to have an enhancing effect on positive information processing (Wells et al, 2014).…”

Anhedonia in depression and schizophrenia: A transdiagnostic challenge

“…Neuroimaging studies further elucidate the complexity of reward processing by utilizing behavioral tasks designed to assess specific aspects of reward, including anticipation, motivation, and expectation . The neural pathway and task performance probed by various reward paradigms suggests there are a series of possible deficits that could lead to the clinical presentation of anhedonia . A simple schematic adapted from Kring and Barch outlines the various aspects of the reward process (Figure ), where a deficit in each of the areas could lead to overall dysregulation of the reward circuit …”

“…9 The neural pathway and task performance probed by various reward paradigms suggests there are a series of possible deficits that could lead to the clinical presentation of anhedonia. 5,10 A simple schematic adapted from Kring and Barch 11 outlines the various aspects of the reward process (Figure 1), where a deficit in each of the areas could lead to overall dysregulation of the reward circuit. 5,11 Anhedonia is one of the core symptoms of MDD.…”