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      Heightened connectivity between the ventral striatum and medial prefrontal cortex as a biomarker for stress-related psychopathology: understanding interactive effects of early and more recent stress

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          Abstract

          Background

          The experience of childhood maltreatment is a significant risk factor for the development of depression. This risk is particularly heightened after exposure to additional, more contemporaneous stress. While behavioral evidence exists for this relation, little is known about biological correlates of these stress interactions. Identifying such correlates may provide biomarkers of risk for later depression.

          Methods

          Here, we leverage behavioral, experiential, and neuroimaging data from the Duke Neurogenetics Study to identify potential biomarkers of stress exposure. Based on the past research, we were specifically interested in reward-related connectivity and the interaction of early and more recent stress. We examined psychophysiological interactions between the ventral striatum and other brain regions in relation to these stress variables, as well as measures of internalizing symptomatology ( n = 926, participant age range = 18–22 years of age).

          Results

          We found relatively increased reward-related functional connectivity between the left ventral striatum and the medial prefrontal cortex in individuals exposed to greater levels of childhood maltreatment who also experienced greater levels of recent life stress ( β = 0.199, p < 0.005). This pattern of functional connectivity was further associated with elevated symptoms of depression ( β = 0.089, p = 0.006). Furthermore, using a moderated mediation framework, we demonstrate that this functional connectivity provides a biological link between cumulative stress exposure and internalizing symptomatology.

          Conclusions

          These findings suggest a novel biomarker linking cumulative stress exposure with the later experience of depressive symptoms. Our results are discussed in the context of past research examining stress exposure in relation to depression.

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          Most cited references32

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          Adverse childhood experiences and the risk of depressive disorders in adulthood.

          Research examining the association between childhood abuse and depressive disorders has frequently assessed abuse categorically, thus not permitting discernment of the cumulative impact of multiple types of abuse. As previous research has documented that adverse childhood experiences (ACEs) are highly interrelated, we examined the association between the number of such experiences (ACE score) and the risk of depressive disorders. Retrospective cohort study of 9460 adult health maintenance organization members in a primary care clinic in San Diego, CA who completed a survey addressing a variety of health-related concerns, which included standardized assessments of lifetime and recent depressive disorders, childhood abuse and household dysfunction. Lifetime prevalence of depressive disorders was 23%. Childhood emotional abuse increased risk for lifetime depressive disorders, with adjusted odds ratios (ORs) of 2.7 [95% confidence interval (CI), 2.3-3.2] in women and 2.5 (95% CI, 1.9-3.2) in men. We found a strong, dose-response relationship between the ACE score and the probability of lifetime and recent depressive disorders (P<0.0001). This relationship was attenuated slightly when a history of growing up with a mentally ill household member was included in the model, but remained significant (P<0.001). The number of ACEs has a graded relationship to both lifetime and recent depressive disorders. These results suggest that exposure to ACEs is associated with increased risk of depressive disorders up to decades after their occurrence. Early recognition of childhood abuse and appropriate intervention may thus play an important role in the prevention of depressive disorders throughout the life span.
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            The link between childhood trauma and depression: insights from HPA axis studies in humans.

            Childhood trauma is a potent risk factor for developing depression in adulthood, particularly in response to additional stress. We here summarize results from a series of clinical studies suggesting that childhood trauma in humans is associated with sensitization of the neuroendocrine stress response, glucocorticoid resistance, increased central corticotropin-releasing factor (CRF) activity, immune activation, and reduced hippocampal volume, closely paralleling several of the neuroendocrine features of depression. Neuroendocrine changes secondary to early-life stress likely reflect risk to develop depression in response to stress, potentially due to failure of a connected neural circuitry implicated in emotional, neuroendocrine and autonomic control to compensate in response to challenge. However, not all of depression is related to childhood trauma and our results suggest the existence of biologically distinguishable subtypes of depression as a function of childhood trauma that are also responsive to differential treatment. Other risk factors, such as female gender and genetic dispositions, interfere with components of the stress response and further increase vulnerability for depression. Similar associations apply to a spectrum of other psychiatric and medical disorders that frequently coincide with depression and are aggravated by stress. Taken together, this line of evidence demonstrates that psychoneuroendocrine research may ultimately promote optimized clinical care and help prevent the adverse outcomes of childhood trauma.
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              Childhood adversity, adult stressful life events, and risk of past-year psychiatric disorder: a test of the stress sensitization hypothesis in a population-based sample of adults.

              Childhood adversity (CA) is associated with adult mental disorders, but the mechanisms underlying this association remain inadequately understood. Stress sensitization, whereby CA increases vulnerability to mental disorders following adult stressful life events, has been proposed as a potential mechanism. We provide a test of the stress sensitization hypothesis in a national sample. We investigated whether the association between past-year stressful life events and the 12-month prevalence of major depression, post-traumatic stress disorder (PTSD), other anxiety disorders, and perceived stress varies according to exposure to CA. We used data from the National Epidemiological Survey of Alcohol and Related Conditions (NESARC) (n=34 653). Past-year stressful life events were associated with an increased risk of major depression, PTSD, anxiety disorders, and perceived stress. However, the magnitude of the increased risk varied according to respondents' history of CA. For example, past-year major stressors were associated with a 27.3% increase in the 12-month risk of depression among individuals with 3 CAs and a 14.8% increased risk among individuals without CAs. Stress sensitization effects were present for depression, PTSD, and other anxiety disorders in women and men, although gender differences were found in the threshold of past-year stress needed to trigger such effects. Stress sensitization was most evident among individuals with 3 CAs. CA is associated with increased vulnerability to the deleterious mental health effects of adult stressors in both men and women. High levels of CA may represent a general diathesis for multiple types of psychopathology that persists throughout the life course.
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                Author and article information

                Journal
                applab
                Psychological Medicine
                Psychol. Med.
                Cambridge University Press (CUP)
                0033-2917
                1469-8978
                December 18 2017
                :
                :
                : 1-9
                Article
                10.1017/S0033291717003348
                6301079
                29248021
                1e4207ba-9455-428e-9858-f7ffe853d09a
                © 2017
                History

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