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      Childhood adversities and bipolar disorder: a neuroimaging focus

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          Abstract

          Early-life adverse events or childhood adversities (CAs) are stressors and harmful experiences severely impacting on a child's wellbeing and development. Examples of CAs include parental neglect, emotional and physical abuse and bullying. Even though the prevalence of CAs and their psychological effects in both healthy and psychiatric populations is established, only a paucity of studies have investigated the neurobiological firms associated with CAs in bipolar disorder (BD). In particular, the exact neural mechanisms and trajectories of biopsychosocial models integrating both environmental and genetic effects are still debated. Considering the potential impact of CAs on BD, including its clinical manifestations, we reviewed existing literature discussing the association between CAs and brain alterations in BD patients. Results showed that CAs are associated with volume alterations of several grey matter regions including the hippocampus, thalamus, amygdala and frontal cortex. A handful of studies suggest the presence of alterations in the corpus callosum and the pre-fronto-limbic connectivity at rest. Alterations in these regions of the brain of patients with BD are possibly due to the effect of stress produced by CAs, being hippocampus part of the hypothalamus–pituitary–adrenal axis and thalamus together with amygdala filtering sensory information and regulating emotional responses. However, results are mixed possibly due to the heterogeneity of methods and study design. Future neuroimaging studies disentangling between different types of CAs or differentiating between BD sub-types are needed in order to understand the link between CAs and BD.

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          Most cited references41

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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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            Initial reliability and validity of a new retrospective measure of child abuse and neglect.

            This report presents initial findings on the reliability and validity of a new retrospective measure of child abuse and neglect, the Childhood Trauma Questionnaire. Two hundred eighty-six drug- or alcohol-dependent patients were given the Childhood Trauma Questionnaire as part of a larger test battery, and 40 of these patients were given the questionnaire again after an interval of 2 to 6 months. Sixty-eight of the patients were also given a structured interview for child abuse and neglect, the Childhood Trauma Interview, that was developed by the authors. Principal-components analysis of responses on the Childhood Trauma Questionnaire yielded four rotated orthogonal factors: physical and emotional abuse, emotional neglect, sexual abuse, and physical neglect. Cronbach's alpha for the factors ranged from 0.79 to 0.94, indicating high internal consistency. The Childhood Trauma Questionnaire also demonstrated good test-retest reliability over a 2- to 6-month interval (intraclass correlation = 0.88), as well as convergence with the Childhood Trauma Interview, indicating that patients' reports of child abuse and neglect based on the Childhood Trauma Questionnaire were highly stable, both over time and across type of instruments. These findings provide strong initial support for the reliability and validity of the Childhood Trauma Questionnaire.
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              The effects of childhood maltreatment on brain structure, function and connectivity.

              Maltreatment-related childhood adversity is the leading preventable risk factor for mental illness and substance abuse. Although the association between maltreatment and psychopathology is compelling, there is a pressing need to understand how maltreatment increases the risk of psychiatric disorders. Emerging evidence suggests that maltreatment alters trajectories of brain development to affect sensory systems, network architecture and circuits involved in threat detection, emotional regulation and reward anticipation. This Review explores whether these alterations reflect toxic effects of early-life stress or potentially adaptive modifications, the relationship between psychopathology and brain changes, and the distinction between resilience, susceptibility and compensation.
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                Author and article information

                Journal
                Epidemiol Psychiatr Sci
                Epidemiol Psychiatr Sci
                EPS
                Epidemiology and Psychiatric Sciences
                Cambridge University Press (Cambridge, UK )
                2045-7960
                2045-7979
                2022
                03 February 2022
                : 31
                : e12
                Affiliations
                [1 ]Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona , Verona, Italy
                [2 ]Department of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Psychology, University of Verona , Verona, Italy
                [3 ]Department of Neuroscience and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico , Milan, Italy
                [4 ]Department of Pathophysiology and Transplantation, University of Milan , Milan, Italy
                Author notes
                Author for correspondence: Paolo Brambilla, E-mail: paolo.brambilla1@ 123456unimi.it
                Author information
                https://orcid.org/0000-0002-4281-0920
                https://orcid.org/0000-0002-4021-8456
                https://orcid.org/0000-0003-1727-5396
                Article
                S2045796021000834
                10.1017/S2045796021000834
                8851064
                35109957
                40423744-b9ac-4deb-a1c9-8250bb1028bd
                © The Author(s) 2022

                This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.

                History
                : 07 December 2021
                : 21 December 2021
                : 23 December 2021
                Page count
                Figures: 1, Tables: 1, References: 42, Pages: 6
                Funding
                Funded by: Ministero della Salute, doi http://dx.doi.org/10.13039/501100003196;
                Award ID: GR-2016-02361283
                Categories
                Epidemiology for Behavioural Neurosciences

                bipolar disorder,brain imaging,childhood adversity,childhood trauma,early-life events

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