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.

The effects of childhood maltreatment on brain structure, function and connectivity

BACKGROUND: Childhood maltreatment is the most important preventable cause of psychopathology accounting for about 45% of the population attributable risk for childhood onset psychiatric disorders. A key breakthrough has been the discovery that maltreatment alters trajectories of brain development. METHODS: This review aims to synthesize neuroimaging findings in children who experienced caregiver neglect as well as from studies in children, adolescents and adults who experienced physical, sexual and emotional abuse. In doing so, we provide preliminary answers to questions regarding the importance of type and timing of exposure, gender differences, reversibility and the relationship between brain changes and psychopathology. We also discuss whether these changes represent adaptive modifications or stress-induced damage. RESULTS: Parental verbal abuse, witnessing domestic violence and sexual abuse appear to specifically target brain regions (auditory, visual and somatosensory cortex) and pathways that process and convey the aversive experience. Maltreatment is associated with reliable morphological alterations in anterior cingulate, dorsal lateral prefrontal and orbitofrontal cortex, corpus callosum and adult hippocampus, and with enhanced amygdala response to emotional faces and diminished striatal response to anticipated rewards. Evidence is emerging that these regions and interconnecting pathways have sensitive exposure periods when they are most vulnerable. CONCLUSIONS: Early deprivation and later abuse may have opposite effects on amygdala volume. Structural and functional abnormalities initially attributed to psychiatric illness may be a more direct consequence of abuse. Childhood maltreatment exerts a prepotent influence on brain development and has been an unrecognized confound in almost all psychiatric neuroimaging studies. These brain changes may be best understood as adaptive responses to facilitate survival and reproduction in the face of adversity. Their relationship to psychopathology is complex as they are discernible in both susceptible and resilient individuals with maltreatment histories. Mechanisms fostering resilience will need to be a primary focus of future studies. Language: en

/pdf/annual-research-review-enduring-neurobiological-effects-of-zgj55unir1.pdf

Annual Research Review: Enduring neurobiological effects of childhood abuse and neglect

How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans

Neural correlates of dysfunctional emotion regulation in major depressive disorder. A systematic review of neuroimaging studies.

http://europepmc.org/articles/PMC6380948?pdf=render

The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology

Objective. The interplay of genetic and early environmental factors is recognized as an important factor in the aetiology of major depressive disorder (MDD). The aim of the present study was to examine whether reduced volume of hippocampus and frontal brain regions involved in emotional regulation are already present in unaffected healthy individuals at genetic risk of suffering MDD and to investigate whether early life adversity is a relevant factor interacting with these reduced brain structures. Method. Twenty unaffected first-degree relatives of patients with MDD (FHP: family history positive) and 20 healthy controls (FHN: family history negative) underwent high-resolution magnetic resonance imaging. Manual tracing of hippocampal sub-regions and voxel-based morphometry was used to compare groups and find association to early life adversity. Results. FHP subjects with history of emotional abuse had significantly smaller left and right hippocampal heads. VBM also showed smaller dorsolateral prefrontal c...

Early life adversity is associated with brain changes in subjects at family risk for depression

Background: Family history of major depressive disorder (MDD) increases individuals’ vulnerability to depression and alters the way de pression manifests itself. Emotion processing and attention shifting are functions altered by MDD and family history of the disease; there fore, it is important to recognize the neural correlates of these functions in association with both factors. Methods: Our study determines neural correlates of emotion processing and attention shifting for healthy individuals and patients with MDD with and without family history of depression. We compared the performance and neural activity in a functional magnetic resonance imaging experiment examining emo tion processing and attention shifting in all participants. Results: Our sample included 4 study groups: healthy controls without family hist ory of depression ( n = 25), patients with MDD without family history of the disease ( n = 20), unaffected healthy first-degree relatives of pa tients with MDD ( n = 21) and patients with MDD with family history of MDD ( n = 30). Compared with healthy controls, unaffected first-degree relatives overactivate the somatosensory cortex and the attention controlling areas during both emotion processing and atten tion shifting. Patients with family history of MDD have stronger neural activation in subcortical areas during shifting attention from negative stimuli. Patients without family history of MDD have less activation in the paralimbic regions and more activation in core limbic areas, espe cially during emotion processing. Limitations: The conclusions about the intergroup differences in activation can be drawn only about neural areas engaged in the task. Conclusion: Unaffected first-degree relatives of patients with MDD overreact to external emotional cues and compensate for the vulnerability with increased involvement of executive control. Patients with a family history of MDD have less ex ecutive control over their attentional shifts in the face of negative stimuli. Patients without a family history of MDD process emotional stimuli in a more visceral way than controls.

Recruitment of the left hemispheric emotional attention neural network in risk for and protection from depression.

Background: Relatives of patients with major depressive disorder (MDD) and people who experienced early-life adversity are at risk for MDD. The aim of our study was to investigate whether unaffected first-degree healthy relatives (UHRs) of patients with MDD show changes in white matter fibre connections compared with healthy controls and whether there are interactions between early-life adver sity and these microstructural changes. Methods: Unaffected, healthy first-degree relatives of patients with MDD and healthy controls without any family history for a psychiatric disease underwent high angular resolution diffusion imaging with 61 diffusion directions. Data were analyzed with tract-based spatial statistics, and findings were confirmed with tractography. Results: Twenty-one UHRs and 24 controls participated in our study. The UHRs showed greater fractional anisotropy than controls in the body and splenium of the cor pus callosum, inferior fronto-occipital fasciculus (IFO), left superior longitudinal fasciculus (SLF) and right fornix. The UHRs who experienced more early-life adversity had greater fractional anisotropy than those with less early-life adversity in the splenium of the corpus callosum, fornix, IFO and SLF; in controls, early-life adversity was found to be associated with decreased fractional anisotropy in these fibre tracts. Limitations: Studying participants’ strategies for coping with early-life adversity would have been helpful. Crossing fibres in tracts are a general limitation of the method used. Conclusion: Altogether, our findings provide evidence for greater fractional anisotropy in UHRs and for interaction between early-life adversity and family risk on white matter tracts involved in cognitive‐ emotional processes. Whether stronger neural fibre connections are associated with more resilience against depression needs to be addressed in future studies.

/pdf/effects-of-early-life-adversity-on-white-matter-diffusivity-503xnq9v9a.pdf

Effects of early-life adversity on white matter diffusivity changes in patients at risk for major depression.

The aim of this study is to investigate the impact of the coronavirus pandemic on teenage psychiatry referrals following crisis presentation to the adult emergency department (ED) of an Irish tertiary hospital. In doing so, this study will specifically examine the effect of COVID-19 on self-injurious behaviour, suicidality and substance use among older adolescents (age 16/17 years).This is a retrospective descriptive analysis of acute adolescent psychiatry referrals assessed out-of-hours via the adult ED psychiatry service across three consecutive time points (during the months of March, April and May) from pre-pandemic, 2019 (T1); initial pandemic, 2020 (T2); and peak pandemic, 2021 (T3). Data were obtained via the hospital's ED-specific electronic database, review of original assessment notes and cross-referenced by manually extracting data logged in the on-call register.Crisis psychiatry assessments of teenagers during on-call hours trebled during the period of this study (p < 0.001). Although ED/crisis referrals initially decreased overall at the start of the pandemic, the rate of teenage referrals remained constant, before increasing as restrictions tightened in lockdown. The negative impact of COVID-19 on teenagers' ability to cope was found to be statistically significant (p = 0.001). Changes in rates of self-harming and/or suicidal behaviours were not statistically significant between 2019, 2020 and 2021 (p = 0.082). Alcohol misuse occurred in up to one-third of cases across each timeframe and remained virtually constant throughout the pandemic. Drug misuse decreased from onset of COVID-19 (p = 0.01).To our knowledge, this is the first study to specifically examine the impact of COVID-19 on suicidality, self-harming behaviours, substance misuse and on-call ED presentations of teenagers in Ireland. This study demonstrates that coronavirus-related stress is associated with negative mental health sequelae for vulnerable at-risk older adolescents, as evidenced by a rise in ED presentations and on-call referrals since the onset of the pandemic. Presentation of increased numbers of under-18's for psychiatry assessment at the adult ED/general hospital indicates a deepening chasm between available and aspirational emergency (adolescent-specific) psychiatric care in the community. Mobilising resilience factors and maximising coping skills for at-risk youth will inform tailored intervention and support strategies along with adequate resourcing of services for vulnerable adolescents in the community. 

/pdf/locked-in-and-locked-out-sequelae-of-a-pandemic-for-2nzbzmja.pdf

Locked in and locked out: sequelae of a pandemic for distressed and vulnerable teenagers in Ireland

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Early life adversity is associated with brain changes in subjects at family risk for depression

Recruitment of the left hemispheric emotional attention neural network in risk for and protection from depression.

Effects of early-life adversity on white matter diffusivity changes in patients at risk for major depression.

Locked in and locked out: sequelae of a pandemic for distressed and vulnerable teenagers in Ireland