Functional Connectivity in Healthy Subjects Is Nonlinearly Modulated by the COMT and DRD2 Polymorphisms in a Functional System-Dependent Manner

Tian, Tian; Qin, Wen; Liu, Bing; Jiang, Tianzi; Yu, Chunshui

doi:10.1523/jneurosci.2163-13.2013

Cited by 34 publications

(47 citation statements)

References 61 publications

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“…However, this hypothesis remains to be examined. Prior evidence that DA signaling modulates brain function in an inverted U-shaped manner (Gjedde et al 2010; Tian et al 2013) leaves open the possibility that our findings may not generalize to persons with a psychiatric diagnosis. Another limitation of the study is related to the interpretation of findings.…”

Section: Discussionmentioning

confidence: 80%

History of childhood adversity is positively associated with ventral striatal dopamine responses to amphetamine

et al. 2014

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Childhood exposure to severe or chronic trauma is an important risk factor for the later development of adult mental health problems, such as substance abuse. Even in nonclinical samples of healthy adults, persons with a history of significant childhood adversity seem to experience greater psychological distress than those without this history. Evidence from rodent studies suggests that early life stress may impair dopamine function in ways that increase risks for drug abuse. However, the degree to which these findings translate to other species remains unclear. This study was conducted to examine associations between childhood adversity and dopamine and subjective responses to amphetamine in humans. Following intake assessment, 28 healthy male and female adults, ages 18–29 years, underwent two consecutive 90-minute positron emission tomography (PET) studies with high specific activity [11C]raclopride. The first scan was preceded by intravenous saline; the second by amphetamine (AMPH 0.3 mg/kg). Consistent with prior literature, findings showed positive associations between childhood trauma and current levels of perceived stress. Moreover, greater number of traumatic events and higher levels of perceived stress were each associated with higher ventral striatal dopamine responses to AMPH. Findings of mediation analyses further showed that a portion of the relationship between childhood trauma and dopamine release may be mediated by perceived stress. Overall, results are consistent with preclinical findings suggesting that early trauma may lead to enhanced sensitivity to psychostimulants and that this mechanism may underlie increased vulnerability for drug abuse.

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Section: Discussionmentioning

confidence: 80%

History of childhood adversity is positively associated with ventral striatal dopamine responses to amphetamine

et al. 2014

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“…We found an invert U‐shape modulation of the presumed dopamine signaling on the FCD in the DAN regions and a U‐shape modulation in the other two clusters. These findings provide new evidence for the hypothesis of a network‐dependent modulation of the dopamine signaling on brain functional properties [Tian et al, ; Zhao et al, ].…”

Section: Discussionmentioning

confidence: 87%

Interaction ofCOMTrs4680 andBDNFrs6265 polymorphisms on functional connectivity density of the left frontal eye field in healthy young adults

Liu

et al. 2016

Hum. Brain Mapp.

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As modulators of dopamine availability and release in the brain, COMT and BDNF polymorphisms have demonstrated interactions on human cognition; however, the underlying neural mechanisms remain largely unknown. In this study, we aimed to investigate the interactions of COMT rs4680 and BDNF rs6265 on global functional connectivity density (gFCD) of the brain in 265 healthy young subjects. We found a significant COMT × BDNF interaction on the gFCD in the left frontal eye field (FEF), showing an inverted U-shape modulation by the presumed dopamine signaling. This finding was consistently repeated in the gFCD analyses using other four connection thresholds. Our findings reveal a COMT × BDNF interaction on the FCD in the left FEF, which may be helpful for understanding the neural mechanisms of the COMT × BDNF interactions on the FEF-related cognitive functions. Hum Brain Mapp 37:2468-2478, 2016. © 2016 Wiley Periodicals, Inc.

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“…We believe these seemingly conflicting findings can be reconciled by reports estimating that 70% of DA cells from the midbrain projecting to the posterior putamen are already lost by the time clinical symptoms are visible, even before a diagnosis is made [Damier et al, 1999;Rajput et al, 2008]. If changes in dopaminergic signaling influences this functional connectivity pattern, as previous studies suggested [Carbonell et al, 2014;Cole et al, 2013;Tian et al, 2013], then perhaps dopaminergic loss is so profound at this stage that there is a floor effect. In other words, there is perhaps insufficient between-subject variability in midbrain-posterior putamen signaling for observing a significant correlation with motor behavior.…”

Section: Figurementioning

confidence: 86%

Resting‐state functional connectivity of the striatum in early‐stage Parkinson's disease: Cognitive decline and motor symptomatology

Manza

Zhang

et al. 2015

Human Brain Mapping

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Parkinson’s disease is a neurodegenerative disorder characterized by changes to dopaminergic function in the striatum and a range of cognitive and motor deficits. Neuroimaging studies have repeatedly shown differences in activation and functional connectivity patterns of the striatum between symptomatic individuals with Parkinson’s disease and healthy controls. However, the presence and severity of cognitive and motor symptoms seem to differ dramatically among individuals with Parkinson’s disease at the early-stages. To investigate the neural basis of such heterogeneity, we examined the resting state functional connectivity patterns of caudate and putamen subdivisions in relation to cognitive and motor impairments among 62 early-stage individuals with Parkinson’s disease (21 females, 23 drug naive, ages 39–77 years, average UPDRS motor scores off medication = 18.56, average H&Y stage = 1.66). We also explored how changes in striatal connectivity relate to changes in symptomatology over a year. There are two main findings. First, higher motor deficit rating was associated with weaker coupling between anterior putamen and midbrain including substantia nigra. Intriguingly, steeper declines in functional connectivity between these regions were associated with greater declines in motor function over the course of 1 year. Second, decline in cognitive function, particularly in the memory and visuospatial domains, was associated with stronger coupling between the dorsal caudate and the rostral anterior cingulate cortex. These findings remained significant after controlling for age, medication, gender, and education. In sum, our findings suggest that cognitive decline and motor deficit are each associated with a differentiable pattern of functional connectivity of striatal subregions.

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Functional Connectivity in Healthy Subjects Is Nonlinearly Modulated by the COMT and DRD2 Polymorphisms in a Functional System-Dependent Manner

Cited by 34 publications

References 61 publications

History of childhood adversity is positively associated with ventral striatal dopamine responses to amphetamine

History of childhood adversity is positively associated with ventral striatal dopamine responses to amphetamine

Interaction ofCOMTrs4680 andBDNFrs6265 polymorphisms on functional connectivity density of the left frontal eye field in healthy young adults

Resting‐state functional connectivity of the striatum in early‐stage Parkinson's disease: Cognitive decline and motor symptomatology

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