Striatum-Based Circuitry of Adolescent Depression and Anhedonia

Abstract

Objective Striatum-based circuits have been implicated in both major depressive disorder (MDD) and anhedonia, a symptom that reflects deficits of reward processing. Yet adolescents with MDD often exhibit a wide range of anhedonia severity. Addressing this clinical phenomenon, we aimed to use intrinsic functional connectivity (iFC) to study striatum-based circuitry in relation to categorical diagnosis of MDD and anhedonia severity. Method A total of 21 psychotropic medication–free adolescents with MDD and 21 healthy controls (HC), group-matched for age and sex, underwent resting-state functional magnetic resonance imagining (fMRI) scans. Voxelwise maps indicating correlation strengths of spontaneous blood-oxygenation-level–dependent (BOLD) signals among 6 bilateral striatal seeds (dorsal caudate, ventral caudate, nucleus accumbens, dorsal-rostral putamen, dorsal-caudal putamen, ventral-rostral putamen) and the remaining brain regions were compared between groups. Relationships between striatal iFC and severity of MDD and anhedonia were examined in the MDD group. Analyses were corrected for multiple comparisons. Results Adolescents with MDD manifested increased iFC between all striatal regions bilaterally and the dorsomedial prefrontal cortex (dmPFC), as well as between the right ventral caudate and the anterior cingulate cortex (ACC). MDD severity was associated with iFC between the striatum and midline structures including the precuneus, posterior cingulate cortex, and dmPFC. However, distinct striatal iFC patterns involving the pregenual ACC, subgenual ACC, supplementary motor area, and supramarginal gyrus were associated with anhedonia severity. Conclusions Although MDD diagnosis and severity were related to striatal networks involving midline cortical structures, distinct circuits within the reward system were associated with anhedonia.

Common and Dissociable Dysfunction of the Reward System in Bipolar and Unipolar Depression

“…Finally, recent work in depression (Pizzagalli et al, 2005(Pizzagalli et al, , 2009Gabbay et al, 2013), and our own work in schizophrenia (Wolf et al, 2014) suggests the merit of investigating more specific components of psychopathology such as anhedonia (Treadway and Zald, 2011), amotivation, or irritability (Stringaris et al, 2009) rather than overall depression severity. While in this study we did not find a specific relationship between reward system dysfunction and anhedonia-related items on the BDI, more detailed assessments might be more sensitive; the truncated range of anhedonia items from the BDI used here may have limited detection power.…”

“…Specifically, given prior research relating anhedonia to reward system dysfunction in multiple psychiatric disorders (Juckel et al, 2006;Wolf, 2006;Harvey et al, 2007;Wolf et al, 2008;Pizzagalli et al, 2009;Treadway and Zald, 2011;Gabbay et al, 2013;Hägele et al, 2014) anhedonia was examined using a sub-set of anhedonia-related items from the BDI (Joiner et al, 2003). Furthermore, we similarly examined the relationship with BDI items unrelated to anhedonia.…”

“…Abnormalities in cortico-striatal connectivity have been associated with severity of anhedonia in adolescents with major depression (Gabbay et al, 2013), but it is unknown if such abnormalities of connectivity in critical nodes of the reward system are present in bipolar depression, and if severity of depression is related to similar dysfunction of reward circuitry across both bipolar and unipolar depression.…”

Hypoactivation of the Ventral and Dorsal Striatum During Reward and Loss Anticipation in Antipsychotic and Mood Stabilizer-Naive Bipolar Disorder

“…The VS has long been implicated in the processing of both rewarding and aversive stimuli and decreased BOLD response within the VS has been identified as a putative biological marker for vulnerability to substance use in adolescents (Peters et al, 2011). Similarly, data implicate the DS in the neurobiology of both mood-and substance-related disorders (Vollstadt-Klein et al, 2010;Hyatt et al, 2012;Dager et al, 2013;Gabbay et al, 2013;Tomasi and Volkow, 2013;Xu et al, 2014). The DS is further involved in reward-related learning and is thought to have a role in substance misuse and addictions relapse (Everitt and Robbins, 2005;Volkow et al, 2006).…”

“…Accordingly, as in previous studies, we recruited BD II and NOS participants early in their illness course and before significant clinical intervention (Chandler et al, 2009;Yip et al, 2013;Godlewska et al, 2014;Yip et al, 2014). A limitation of this methodology is that it inherently excludes very severe cases and may therefore underestimate the magnitude of observed effects.…”