Effects of Early-Life Adversity on Hippocampal Structures and Associated HPA Axis Functions

Early-life adversity (ELA) is one of the major risk factors for serious mental and physical health risks later in life. ELA has been associated with dysfunctional neurodevelopment, especially in brain structures such as the hippocampus, and with dysfunction of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis. Children who have experienced ELA are also more likely to suffer from mental health disorders such as depression later in life. The exact interplay of aberrant neurodevelopment and HPA axis dysfunction as risks for psychopathology is not yet clear. We investigated volume differences in the bilateral hippocampus and in stress-sensitive hippocampal subfields, behavior problems, and diurnal cortisol activity in 24 children who had experienced documented ELA (including out-of-home placement) in a circumscribed duration of adversity only in their first 3 years of life in comparison to data on 25 control children raised by their biological parents. Hippocampal volumes and stress-sensitive hippocampal subfields (Cornu ammonis [CA]1, CA3, and the granule-cell layer of the dentate gyrus [GCL-DG]) were significantly smaller in children who had experienced ELA, taking psychiatric diagnoses and dimensional psychopathological symptoms into account. ELA moderated the relationship between left hippocampal volume and cortisol: in the control group, hippocampal volumes were not related to diurnal cortisol, while in ELA children, a positive linear relationship between left hippocampal volume and diurnal cortisol was present. Our findings show that ELA is associated with altered development of the hippocampus, and an altered relationship between hippocampal volume and HPA axis activity in youth in care, even after they have lived in stable and caring foster family environments for years. Altered hippocampal development after ELA could thus be associated with a risk phenotype for the development of psychiatric disorders later in life

Multidimensional assessment of neuroendocrine and psychopathological profiles in maltreated youth

It has been debated whether children who have experienced early life stress (ELS), such as early caregiver separation show elevated risk for stress-related psychiatric disorders and a multi-symptom psychopathological profile that is not fully reflected in categorical assessments. In this study, we investigated dimensional measures of stress-related psychopathology in children in permanent out-of-home care, taking into account potential neuroendocrine interactions. In the current study, 25 children who had been placed in permanent out-of-home care before age 3 (years) and 26 controls (aged 10.6 ± 1.75 years) were investigated with categorical (DSM-IV) and dimensional assessments (CBCL) of psychopathology and diurnal salivary cortisol levels were assessed. Semi-structured interviews (K-DIPS) revealed no significant group differences in full-scale psychiatric diagnoses, whereas dimensional assessment (CBCL) revealed significant group differences in externalizing and total problem behaviours within the clinical range for children with ELS. Only children with ELS showed a combined symptom profile of clinical-range internalizing and externalizing problems. Lower morning cortisol values and subsequent flatter decline was found in subjects with ELS children compared to controls, showing group differences in diurnal cortisol secretion. Lower morning cortisol values were associated with more problem behaviour in the ELS group. Results show that ELS children exhibited increased psychopathological symptom severity and complexity associated with lower morning cortisol levels, which was not fully reflected in categorical assessments. This highlights the importance of incorporating dimensional assessments and neurobiological factors into psychopathological evaluations of children in out-of-home care in order to facilitate early identification of children at high risk for stress-related disorders

Evidence for Depressogenic Spontaneous Thoughts and Altered Resting-State Connectivity in Adolescents With a Maltreatment History

OBJECTIVE: Childhood maltreatment has been associated with major depressive disorder (MDD). Atypical self-generated thoughts (SGT), lacking in positive and privileging negative content-a feature of ruminative thinking-might represent one vulnerability factor for developing depression. Rumination in MDD has been linked to alterations in resting-state functional connectivity (RSFC) of the subgenual anterior cingulate cortex (sgACC) to the default mode network and the fronto-parietal network (FPN). This study aimed to investigate online SGT content and its variability, as well as sgACC RSFC, as potential risk markers for depression in adolescents who experienced maltreatment. METHOD: Adolescents 12 to 16 years old (29 with maltreatment history [MT] and 39 with no maltreatment history [NMT]) performed an established mind-wandering task. Participants made nondemanding number discriminations during which intermittent questions probed their SGTs that were classified as off-task, positive, negative, self-related, other-related, past-oriented, or future-oriented. Resting-state data were acquired separately for 22 of 29 MT and 27 39 NMT adolescents, and seed-based functional connectivity analyses of the sgACC were performed. RESULTS: MT, relative to the NMT adolescents, generated significantly fewer positively valenced thoughts, and exhibited more extreme ratings for positively valenced thoughts. MT adolescents also showed significantly reduced RSFC between the sgACC and the FPN. Group differences in depressive symptoms between the MT and NMT adolescents were partly accounted by differences in sgACC-FPN RSFC. CONCLUSION: Adolescents who experienced maltreatment show a reduction in positively valenced spontaneous thoughts and reduced sgACC-FPN RSFC at the neural level. These may contribute to a ruminative thinking style, representing risk factors for developing depression later in life

Autobiographical memory:A candidate latent vulnerability mechanism for psychiatric disorder following childhood maltreatment

BackgroundAltered autobiographical memory (ABM) functioning has been implicated in the pathogenesis of depression and posttraumatic stress disorder and may represent one mechanism by which childhood maltreatment elevates psychiatric risk.AimsTo investigate the impact of childhood maltreatment on ABM functioning.MethodThirty-four children with documented maltreatment and 33 matched controls recalled specific ABMs in response to emotionally valenced cue words during functional magnetic resonance imaging.ResultsChildren with maltreatment experience showed reduced hippocampal and increased middle temporal and parahippocampal activation during positive ABM recall compared with peers. During negative ABM recall they exhibited increased amygdala activation, and greater amygdala connectivity with the salience network.ConclusionsChildhood maltreatment is associated with altered ABM functioning, specifically reduced activation in areas encoding specification of positive memories, and greater activation of the salience network for negative memories. This pattern may confer latent vulnerability to future depression and posttraumatic stress disorder.</jats:sec

Sex differences in socioemotional functioning, attentional bias, and gray matter volume in maltreated children: A multilevel investigation

While maltreatment is known to impact social and emotional functioning, threat processing, and neural structure, the potentially dimorphic influence of sex on these outcomes remains relatively understudied. We investigated sex differences across these domains in a large community sample of children aged 10 to 14 years (n = 122) comprising 62 children with verified maltreatment experience and 60 well-matched nonmaltreated peers. The maltreated group relative to the nonmaltreated comparison group exhibited poorer social and emotional functioning (more peer problems and heightened emotional reactivity). Cognitively, they displayed a pattern of attentional avoidance of threat in a visual dot-probe task. Similar patterns were observed in males and females in these domains. Reduced gray matter volume was found to characterize the maltreated group in the medial orbitofrontal cortex, bilateral middle temporal lobes, and bilateral supramarginal gyrus; sex differences were observed only in the supramarginal gyrus. In addition, a disordinal interaction between maltreatment exposure and sex was found in the postcentral gyrus. Finally, attentional avoidance to threat mediated the relationship between maltreatment and emotional reactivity, and medial orbitofrontal cortex gray matter volume mediated the relationship between maltreatment and peer functioning. Similar mediation patterns were observed across sexes. This study highlights the utility of combining multiple levels of analysis when studying the latent vulnerability engendered by childhood maltreatment and yields tentative findings regarding a neural basis of sex differences in long-term outcomes for maltreated children.</p