Vanessa B. Puetz

Neural Response to Social Rejection in Children With Early Separation Experiences

OBJECTIVE Nonhuman and human studies have documented the adverse effects of early life stress (ELS) on emotion regulation and underlying neural circuitry. Less is known about how these experiences shape social processes and neural circuitry. In this study, we thus investigated how ELS affects childrens perception of, and neural response to, negative social experiences in a social exclusion paradigm (Cyberball). METHOD Twenty-five foster or adopted children with ELS (age 10.6 ± 1.8 years, 13 male and 12 female) and 26 matched nonseparated controls (age 10.38 ± 1.7 years, 12 male and 14 female) took part in a Cyberball paradigm during functional magnetic resonance imaging (fMRI). RESULTS During peer rejection, children with ELS reported significantly more feelings of exclusion and frustration than nonseparated controls. On the neural level, children with ELS showed reduced activation in the dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (dlPFC), and reduced connectivity between dlPFC-dACC, areas previously implicated in affect regulation. Conversely, children with ELS showed increased neural activation in brain regions involved in memory, arousal, and threat-related processing (middle temporal gyrus, thalamus, ventral tegmental area) relative to controls during social exclusion. The number of separation experiences before entering the permanent family predicted reductions in fronto-cingulate recruitment. The relationship between early separations and self-reported exclusion was mediated by dlPFC activity. CONCLUSION The findings suggest that ELS leads to alterations in neural circuitry implicated in the regulation of socioemotional processes. This neural signature may underlie foster childrens differential reactivity to rejection in everyday life and could increase risk for developing affective disorders.

Altered neural response to rejection-related words in children exposed to maltreatment.

Background Children exposed to maltreatment show neural sensitivity to facial cues signalling threat. However, little is known about how maltreatment influences the processing of social threat cues more broadly, and whether atypical processing of social threat cues relates to psychiatric risk. Methods Forty‐one 10‐ to 14‐year‐old children underwent a social rejection‐themed emotional Stroop task during functional magnetic resonance imaging: 21 children with a documented history of maltreatment (11 F) and 19 comparison children with no maltreatment history (11 F). Groups were matched on age, pubertal status, gender, IQ, socioeconomic status, ethnicity and reading ability. Classic colour Stroop stimuli were also administered in the same paradigm to investigate potential differences in general cognitive control. Results Compared with their peers, children who had experienced maltreatment showed reduced activation in the Rejection versus Neutral condition, across circuitry previously implicated in abuse‐related posttraumatic stress disorder (PTSD), including the left anterior insula, extending into left ventrolateral prefrontal cortex/orbitofrontal cortex; left amygdala; left inferior parietal cortex (STS); and bilateral visual association cortex, encompassing the cuneus and lingual gyrus. No group differences in neural or behavioural responses were found for the classic colour Stroop conditions. Significant negative associations between activity in bilateral cuneus and STS during the rejection‐themed Stroop and higher self‐reported PTSD symptomatology, including dissociation, were observed in children exposed to maltreatment. Conclusion Our findings indicate a pattern of altered neural response to social rejection cues in maltreated children. Compared to their peers, these children displayed relative hypoactivation to rejection cues in regions previously associated with PTSD, potentially reflecting an avoidant coping response. It is suggested that such atypical processing of social threat may index latent vulnerability to future psychopathology in general and PTSD in particular.

Altered brain network integrity after childhood maltreatment: a structural connectomic DTI-study

Childhood maltreatment is associated with alterations in neural architecture that potentially put these children at increased risk for psychopathology. Alterations in white matter (WM) tracts have been reported, however no study to date has investigated WM connectivity in brain networks in maltreated children to quantify global and local abnormalities through graph theoretical analyses of DTI data. We aimed for a multilevel investigation examining the DTI‐based structural connectome and its associations with basal cortisol levels of 25 children with documented maltreatment experiences before age 3, and 24 matched controls (age: 10.6 ± 1.75 years). On the global and lobar level, maltreated children showed significant reductions in global connectivity strength, local connectivity and increased path length, suggesting deviations from the small‐world network architecture previously associated with psychopathology. Reductions in global connectivity were associated with placement instability, attenuated cortisol secretion and higher levels of internalizing and externalizing behaviours. Regional measures revealed lower connectivity strength especially in regions within the ventromedial prefrontal cortex (vMPFC) in maltreated children. These findings show that childhood maltreatment is associated with systemic global neurodevelopmental alterations in WM networks next to regional alterations in areas involved in the regulation of affect. These alterations in WM organization could underlie global functional deficits and multi‐symptom patterns frequently observed in children with maltreatment experiences. Hum Brain Mapp 38:855–868, 2017.

Exploring the Relationship Between Childhood Maltreatment and Addiction: A Review of the Neurocognitive Evidence

Childhood maltreatment has been shown to increase the risk of a range of psychiatric disorders including substance use disorders (SUDs) and is associated with the onset, course and severity of illness. We review the evidence for alterations in brain structure and neurocognitive processing in individuals who have experienced childhood maltreatment, focusing specifically on changes related to reward processing, executive functioning and affect processing. Changes in these neurocognitive systems have been documented in adults presenting with SUDs, who are typically characterized by heightened subcortico-striatal responses to salient stimuli and impairments in fronto-cingulate regulation. Maltreatment-specific effects in these processing domains may account for the particularly severe clinical presentation of SUDs in adults with histories of maltreatment in childhood. The findings are considered in relation to the theory of latent vulnerability, which contends that alterations in these neurocognitive systems may reflect calibration to early risk environments that in turn increases the risk of developing of SUDs later in life.

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

Background Altered autobiographical memory (ABM) functioning has been implicated in the pathogenesis of depression and post-traumatic stress disorder and may represent one mechanism by which childhood maltreatment elevates psychiatric risk. Aims To investigate the impact of childhood maltreatment on ABM functioning. Method Thirty-four children with documented maltreatment and 33 matched controls recalled specific ABMs in response to emotionally valenced cue words during functional magnetic resonance imaging. Results Children 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. Conclusions Childhood 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 post-traumatic stress disorder.

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.

Neuropsychological deficits in the prodromal phase and course of an early-onset schizophrenia. A case report.

OBJECTIVES Although clear advances have been achieved in the study of early-onset schizophrenia (EOS), little is known to date about premorbid and prodromal neuropsychological functioning in EOS. METHOD Here, we report on a case of an adolescent male with EOS who underwent neuropsychological testing before and after illness onset. RESULTS Marked cognitive deficits in the domains of attention, set-shifting, and verbal memory were present both pre-onset and during the course of schizophrenia, though only deficits in verbal memory persisted after illness-onset and antipsychotic treatment. CONCLUSION The findings of this case study suggest that impairments in the verbal memory domain are particularly prominent symptoms of cognitive impairment in prodromal EOS and persist in the course of the disorder, which further demonstrates the difficult clinical situation of adequate schooling opportunities for adolescent patients with EOS.

Risk-taking, peer-influence and child maltreatment: a neurocognitive investigation

Abstract Maltreatment is associated with increased risk of a range of psychiatric disorders, many of which are characterized by altered risk-taking propensity. Currently, little is known about the neural correlates of risk-taking in children exposed to maltreatment, nor whether their risk-taking is atypically modulated by peer influence. Seventy-five 10- to 14-year-old children [maltreated (MT) group: N = 41; non-maltreated Group (NMT): N = 34] performed a Balloon Analogue Risk Task (BART), under three different peer influence conditions: while alone, while being observed by a peer and while being encouraged by a peer to take risks. The MT group engaged in less risk-taking irrespective of peer influence. There was no differential effect of peer influence on risk-taking behaviour across groups. At the neural level, the right anterior insula (rAI) exhibited altered risk sensitivity across conditions in the MT group. Across groups and conditions, rAI risk sensitivity was negatively associated with risk-taking and within the MT group greater rAI risk sensitivity was related to more anxiety symptoms. These findings suggest that children with a history of maltreatment show reduced risk-taking but typical responses to peer influence. Abnormal rAI functioning contributes to the pattern of reduced risk-taking and may predispose children exposed to maltreatment to develop future psychopathology.

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.

A neurocomputational investigation of reinforcement-based decision making as a candidate latent vulnerability mechanism in maltreated children

Alterations in reinforcement-based decision making may be associated with increased psychiatric vulnerability in children who have experienced maltreatment. A probabilistic passive avoidance task and a model-based functional magnetic resonance imaging analytic approach were implemented to assess the neurocomputational components underlying decision making: (a) reinforcement expectancies (the representation of the outcomes associated with a stimulus) and (b) prediction error signaling (the ability to detect the differences between expected and actual outcomes). There were three main findings. First, the maltreated group (n = 18; mean age = 13), relative to nonmaltreated peers (n = 19; mean age = 13), showed decreased activity during expected value processing in a widespread network commonly associated with reinforcement expectancies representation, including the striatum (especially the caudate), the orbitofrontal cortex, and medial temporal structures including the hippocampus and insula. Second, consistent with previously reported hyperresponsiveness to negative cues in the context of childhood abuse, the maltreated group showed increased prediction error signaling in the middle cingulate gyrus, somatosensory cortex, superior temporal gyrus, and thalamus. Third, the maltreated group showed increased activity in frontodorsal regions and in the putamen during expected value representation. These findings suggest that early adverse environments disrupt the development of decision-making processes, which in turn may compromise psychosocial functioning in ways that increase latent vulnerability to psychiatric disorder.