Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder

Gong, Liang; Yin, Yingying; He, Cancan; Ye, Qing; Bai, Feng; Yuan, Yonggui; Zhang, Haisan; Lv, Luxian; Zhang, Hongxing; Xie, Chunming; Zhang, Zhijun

doi:10.1016/j.jpsychires.2016.09.016

Cited by 65 publications

(54 citation statements)

References 46 publications

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“…This work demonstrated that the mu opioid receptor gene, OPRD1, rs678849 single nucleotide polymorphism is associated with amygdala volume and that the OPRM1 rs1799971 single nucleotide polymorphism is associated with incidence of connections within the dorsomedial PFCamygdala-NAc white matter network (46). Interestingly, the status of NAc-PFC connectivity also contributes to depression and addiction, although these conditions appear to arise from a net decrease in functional connectivity (47)(48)(49). Small-scale clinical studies have demonstrated promising efficacy of NAc DBS for depression and sustained heroin abstinence (50)(51)(52)(53)(54), suggesting that such approaches may be used for the treatment of comorbid conditions.…”

Section: Nucleus Accumbensmentioning

confidence: 83%

The Mesolimbic Dopamine System in Chronic Pain and Associated Affective Comorbidities

Serafini

Pryce

Zachariou

2020

Biological Psychiatry

156

121

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Chronic pain is a complex neuropsychiatric disorder characterized by sensory, cognitive, and affective symptoms. Over the past 2 decades, researchers have made significant progress toward understanding the impact of mesolimbic dopamine circuitry in acute and chronic pain. These efforts have provided insights into the circuits and intracellular pathways in the brain reward center that are implicated in sensory and affective manifestations of chronic pain. Studies have also identified novel therapeutic targets as well as factors that affect treatment responsiveness. Dysregulation of dopamine function in the brain reward center may further promote comorbid mood disorders and vulnerability to addiction. This review discusses recent clinical and preclinical findings on the neuroanatomical and neurochemical adaptations triggered by prolonged pain states in the brain reward pathway. Furthermore, this discussion highlights evidence of mechanisms underlying comorbidities among pain, depression, and addiction.

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Section: Nucleus Accumbensmentioning

confidence: 83%

The Mesolimbic Dopamine System in Chronic Pain and Associated Affective Comorbidities

Serafini

Pryce

Zachariou

2020

Biological Psychiatry

156

121

View full text Add to dashboard Cite

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“…Furthermore, in response to own vs. generic baby-cry among postpartum depressed versus non-depressed mothers, caudate and NAc activity was reduced at 15–18 months postpartum [23]. Finally, major depression when not occurring in the postpartum seems to alter the functional connectivity related to the limbic system [24, 25]. …”

Section: Introductionmentioning

confidence: 99%

Depression alters maternal extended amygdala response and functional connectivity during distress signals in attachment relationship

Swain

2017

Behavioural Brain Research

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Maternal attachment-related parenting behaviors require mothers to regulate self-related and child-related distress. Emotion regulation is, in turn, influenced by maternal mood and personal developmental history. In the current study we examined how depressive mood may alter maternal limbic system function and functional connectivity underlying defensive and hedonic motivations. Twenty nine mothers were recruited to undergo a baby-cry task during a functional magnetic resonance imaging (fMRI) scan. Based on self-reported depression symptoms and clinical interview, the participants were grouped as healthy controls (n = 15) and currently depressed (n = 14). In the baby-cry task, 30s-long auditory stimuli of baby-cry sounds were presented to simulate four conditions: generic baby-cry (Just-Listen), baby-cry as if it were their own child’s cry (Your-Baby), baby-cry as if it were themselves (Self), and matched control sounds (Noise). Depressed mothers, as compared to healthy controls, showed greater Self versus Just-Listen responses in left extended amygdala and decreased functional coupling between this left extended amygdala as the seed and nucleus accumbens (NAc) in self-oriented (Self versus Just-Listen) and child-oriented (Your-Baby versus Just-Listen) distress signals. Moreover, the extended amygdala’s differential functional connectivity with dorsomedial prefrontal cortex (dmPFC) during the Your-Baby versus Self was increased for depressed mothers and decreased for healthy controls. Thus, depression may affect mothers by increasing baby-cry threat responses and dysregulating associations between threat and heathy child-oriented parenting motivations. These results are discussed in the context of attachment and self-psychology.

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“…Second, the extracted gFCD values in the brain regions exhibiting the primary outcome of the APOE genotypes and the hippocampus volume were set as the mediators (M). Third, we used the simple mediation model from the PROCESS macro in SPSS (Model 4, version 2.16.3) (Hayes, 2013;Gong et al, 2017b) and adjusted the effects of sex, age, and years of education as covariates. This model was based on 10,000 bootstrap samples for assessing the bias-corrected bootstrap confidential interval (CI).…”

Section: Statistical Analysesmentioning

confidence: 99%

The Specific Impact of Apolipoprotein E Epsilon 2 on Cognition and Brain Function in Cognitively Normal Elders and Mild Cognitive Impairment Patients

Gong

Liu

et al. 2020

Front. Aging Neurosci.

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Variants in the apolipoprotein E (APOE) gene play an important role in the development of Alzheimer's disease (AD). Specifically, the APOE ε4 allele is an established genetic risk factor for AD, while the APOE ε2 allele is a protective factor against AD. However, the mechanism underlying this impact of APOE genotype on the pathogenesis of AD remain unclear. This study sought to investigate the influence of APOE genotype on cognition and neuroimaging features in cognitively normal (CN) elderly individuals and patients with mild cognitive impairment (MCI). A total of 177 participants were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, including 101 MCI patients and 76 CN individuals. A 2 × 3 (consisting of two groups and three APOE genotypes) analysis of covariance was carried out to measure the influences of diagnosis and APOE genotype on cognition and brain features, assessed based on global functional connectivity density (gFCD) and hippocampal volume. In addition, a mediation analysis was carried out to investigate the indirect influence of neuroimaging features on the relationship between APOE genotype and cognitive performance in the MCI group. This analysis revealed that APOE genotype had an influence on brain function in the bilateral precentral gyrus, right thalamus, and posterior cingulate cortex (PCC). In addition, an interactive influence between diagnosis and APOE genotype was found on general cognition, immediate memory, executive function, hippocampal volume, and gFCD in the right dorsolateral prefrontal cortex and medial prefrontal cortex (MPFC). Finally, this mediation analysis revealed that hippocampal volume and gFCD in the thalamus may mediate the relationship between APOE genotype and cognitive performance in the MCI group. Taken together, our findings provide novel insights into the neural mechanisms underlying the genetically guided pathogenic mechanisms of AD.

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Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder

Cited by 65 publications

References 46 publications

The Mesolimbic Dopamine System in Chronic Pain and Associated Affective Comorbidities

The Mesolimbic Dopamine System in Chronic Pain and Associated Affective Comorbidities

Depression alters maternal extended amygdala response and functional connectivity during distress signals in attachment relationship

The Specific Impact of Apolipoprotein E Epsilon 2 on Cognition and Brain Function in Cognitively Normal Elders and Mild Cognitive Impairment Patients

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