Bright light therapy and early morning attention, mathematical performance, electroencephalography and brain connectivity in adolescents with morning sleepiness.

Adolescents typically sleep too little and feel drowsy during morning classes. We assessed whether morning use of an LED bright light device could increase alertness in school students. Twenty-six (8M/18F) healthy, unmedicated participants, ages 13-18 years, (mean 17.1±1.4) were recruited following screenings to exclude psychopathology. Baseline assessments were made of actigraph-assessed sleep, attention, math solving ability, electroencephalography and structural and functional MRI (N = 10-11, pre-post). Participants nonrandomly received 3-4 weeks of bright light therapy (BLT) for 30 minutes each morning and used blue light blocking glasses for 2 hours before bedtime. BLT devices were modified to surreptitiously record degree of use so that the hypothesis tested was whether there was a significant relationship between degree of use and outcome. They were used 57±18% (range 23%-90%) of recommended time. There was a significant association between degree of use and: (1) increased beta spectral power in frontal EEG leads (primary measure); (2) greater post-test improvement in math performance and reduction in errors of omission on attention test; (3) reduced day-to-day variability in bed times, sleep onset, and sleep duration during school days; (4) increased dentate gyrus volume and (5) enhanced frontal connectivity with temporal, occipital and cerebellar regions during Go/No-Go task performance. BLT was associated with improvement in sleep cycle consistency, arousal, attention and functional connectivity, but not sleep onset or duration (primary measures). Although this was an open study, it suggests that use of bright morning light and blue light blocking glasses before bed may benefit adolescents experiencing daytime sleepiness. Clinical trial registration: Clinicaltrials.gov ID-NCT05383690.

Potential sensitive period effects of maltreatment on amygdala, hippocampal and cortical response to threat.

Childhood maltreatment is a leading risk factor for psychopathology, though it is unclear why some develop risk averse disorders, such as anxiety and depression, and others risk-taking disorders including substance abuse. A critical question is whether the consequences of maltreatment depend on the number of different types of maltreatment experienced at any time during childhood or whether there are sensitive periods when exposure to particular types of maltreatment at specific ages exert maximal effects. Retrospective information on severity of exposure to ten types of maltreatment during each year of childhood was collected using the Maltreatment and Abuse Chronology of Exposure scale. Artificial Intelligence predictive analytics were used to delineate the most important type/time risk factors. BOLD activation fMRI response to threatening versus neutral facial images was assessed in key components of the threat detection system (i.e., amygdala, hippocampus, anterior cingulate, inferior frontal gyrus and ventromedial and dorsomedial prefrontal cortices) in 202 healthy, unmedicated, participants (84 M/118 F, 23.2 ± 1.7 years old). Emotional maltreatment during teenage years was associated with hyperactive response to threat whereas early childhood exposure, primarily to witnessing violence and peer physical bullying, was associated with an opposite pattern of greater activation to neutral than fearful faces in all regions. These findings strongly suggest that corticolimbic regions have two different sensitive period windows of enhanced plasticity when maltreatment can exert opposite effects on function. Maltreatment needs to be viewed from a developmental perspective in order to fully comprehend its enduring neurobiological and clinical consequences.

Open assessment of the therapeutic and rate-dependent effects of brain balance center® and interactive metronome® exercises on children with attention deficit hyperactivity disorder.

The aim of this open study was to delineate domains of benefit and effect size measures to design an appropriately powered randomized control trial to assess the efficacy of Brain Balance@ exercises and Interactive Metronome@ training (BB/IM) on ADHD symptoms in children. Participants underwent an extensive 15-week, 5 time per week, at-home training program. Results were assessed in 16 youths with ADHD (14M/2F, 10.8±1.7 years) who completed the program and compared to 8 typically developing controls (4M/F4, 11.0±1.8 years). BB/IM was associated with a significant reduction of 8.3 and 8.2 points on the Conner's Parent Rating Scale - Revised and the ADHD Rating Scale - IV. BB/IM was not associated with improvement on the Quotient ADHD System but with rate-dependent effects on hyperactivity and attention that were similar to previously reported effects of low dose methylphenidate. Both therapeutic and rate-dependent effects were observed on the Tower of London. The study provides information that could be used to design a randomized control trial, which is required for proof of efficacy. A key limitation is that 59% of the 39 enrolled participants with ADHD dropped out of the study and a new study should include multiple ratings during the course of treatment.

Individual Differences in Hemispheric Emotional Valence by Computerized Test Correlate with Lateralized Differences in Nucleus Accumbens, Hippocampal and Amygdala Volumes.

Purpose: Conventional theories of hemispheric emotional valence (HEV) postulate fixed hemispheric differences in emotional processing. Schiffer's dual brain psychology proposes that there are prominent individual differences with a substantial subset showing a reversed laterality pattern. He further proposed that hemispheric differences were more akin to differences in personality than in emotional processing. This theory is supported by findings that unilateral treatments, such as transcranial magnetic stimulation, are effective if they accurately target individual differences in laterality. The aim of this paper was to assess if a computer test of hemispheric emotional valence (CTHEV) could effectively identify individual differences in HEV and to ascertain if these individual differences were associated with underlying differences in brain structure and connectivity. Patients and Methods: The CTHEV was administered to 50 (18 male/32 female) right-handed participants, aged 18-19 years, enrolled in a study assessing the neurobiological effects of childhood maltreatment. Based on a literature review, we determined whether CTHEV correlated with lateralized volumes of the nucleus accumbens, amygdala, hippocampus, and subgenual anterior cingulate as well as volume of the corpus callosum. Results: CTHEV scores correlated with laterality indices of the nucleus accumbens (p = 0.00016), amygdala (p = 0.0138) and hippocampus (p = 0.031). A positive left hemispheric valence was associated with a larger left-sided nucleus accumbens and hippocampus and a smaller left amygdala. We identified four eigenvector network centrality DTI measures that predict CTHEV, most notably the left amygdala, and found that CTHEV results correlated with total and segment-specific corpus callosal volumes. Conclusion: Individual differences in HEV can be readily assessed by computer test and correlate with differences in brain structure and connectivity that could provide a mechanistic understanding. These findings provide further support for a revised understanding of HEV and provide a tool that could be used to guide lateralized brain treatments.

Sex and sensitive period differences in potential effects of maltreatment on axial versus radial diffusivity in the corpus callosum.

Corpus callosum (CC) abnormalities have been observed in several psychiatric disorders. Maltreatment has also been associated with marked differences in CC anatomy and microstructure, though rarely controlled for in psychiatric neuroimaging studies. The aim of this study was to identify type and timing of maltreatment associated with alterations in CC microstructure and to ascertain if they differ by sex. T1 and diffusion-weighted MRIs were obtained from 345 (135 M/210 F) healthy 18-25-year-olds. The Maltreatment and Abuse Chronology of Exposure scale provided retrospective data on exposure to ten types of maltreatment across each year of childhood. AI predictive analytics were used to identify the most significant type and time risk factors. The most striking maltreatment-associated alterations in males were in axial diffusivity and were most specifically associated with exposure to emotional abuse or neglect during segment-specific sensitive periods. In contrast, maltreatment was associated with marked alteration in radial diffusivity and fractional anisotropy in females and was most specifically associated with early physical neglect during one common sensitive period involving all segments except the splenium. Overall sex differences, controlling for maltreatment, brain size, and sociodemographic factors were limited to the genu with greater fractional anisotropy in males and radial diffusivity in females. These findings suggest that maltreatment may target myelinization in females and axonal development in males and that these sex differences need to be taken into account in studies seeking to delineate the contribution of CC abnormalities and interhemispheric communication to psychiatric disorders.

An Effective and Safe Novel Treatment of Opioid Use Disorder: Unilateral Transcranial Photobiomodulation.

Background: The opioid epidemic is a global tragedy even with current treatments, and a novel, safe, and effective treatment would be welcomed. We report here our findings from our second randomized controlled trial to evaluate unilateral transcranial photobiomodulation as a treatment for opioid use disorder. Methods: We enrolled 39 participants with active opioid cravings at 2 sites, 19 received the active treatment which consisted of a 4-min twice weekly (every 3 or 4 days) application of a light-emitting diode at 810 nm with an irradiance of 250 mW/cm2 and a fluence of 60 J/cm2 to the forehead over either the left or right dorsolateral prefrontal cortex with a fluence to the brain of 2.1 J/cm2. Twenty participants received a sham treatment with the same device with foil over the bulb. The side of the treatment was based on Dual-Brain Psychology, which posits that one hemisphere is more affected by past maltreatments and is more prone to anxiety and drug cravings that the other hemisphere. We treated the hemisphere with the more positive hemispheric emotional valence (HEV) by 2 tests for HEV. Results: Our primary outcome was changes in pre-treatment opioid craving scale (OCS) minus baseline, and we found using a mixed model that the active group had a highly significant treatment * time benefit over the sham group, p < 0.0001, effect size at the last follow-up of 1.5. The active treatment benefited those not on buprenorphine as well as those not on it. The TimeLine Follow Back measure of opioid use was significantly better in the actively treated group, p = 0.0001, with an effect size of 0.45. We observed no adverse effects. Conclusion: Active unilateral transcranial photobiomodulation to the brain hemisphere with the better HEV was better than sham in the reduction of opioid cravings and opioid use to a very significant degree in a RCT of 39 participants at 2 independent sites. In the active group those on buprenorphine and those not on it both had improvements in cravings over the study. No adverse responses were reported in either group. ClinicalTrials.gov Identifier: NCT04340622.

A pilot study on amygdala volumetric changes among young adults with childhood maltreatment histories after a mindfulness intervention.

The amygdala morphometry is highly sensitive to stress and is implicated in various psychopathologies that are common among individuals with childhood maltreatment histories. This pilot study investigated bilateral amygdala volumetric changes among 15 young adults with childhood maltreatment histories undergoing an eight-week mindfulness intervention compared to 19 matched participants in a waitlist control group. Results indicated significant cross-individual variability in amygdala volumetric changes after the intervention, which resulted in no significant group by time interaction effect. Degree and direction of changes in right amygdala volume correlated with baseline volumes, with larger than average right amygdala showing an increase in volume and smaller amygdala a decrease. Increasing right amygdala volume was also associated with higher intervention compliance, and a greater increase in self-compassion. Increasing left amygdala volume was associated with more reduction in perceived stress, rejection sensitivity and interpersonal distress. Findings from the present study highlight the importance of investigating individual variability and its contributing factors in future studies on neural responses of mindfulness interventions, as well as the distinct responses of the left and right amygdala.

Genomic influences on self-reported childhood maltreatment.

Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to (1) identify genetic variation associated with self-reported childhood maltreatment, (2) estimate SNP-based heritability (h2snp), (3) assess predictive value of polygenic risk scores (PRS) for childhood maltreatment, and (4) quantify genetic overlap of childhood maltreatment with mental and physical health-related phenotypes, and condition the top hits from our analyses when such overlap is present. Genome-wide association analysis for childhood maltreatment was undertaken, using a discovery sample from the UK Biobank (UKBB) (n = 124,000) and a replication sample from the Psychiatric Genomics Consortium-posttraumatic stress disorder group (PGC-PTSD) (n = 26,290). h2snp for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression. PRS was calculated using PRSice and mtCOJO was used to perform conditional analysis. Two genome-wide significant loci associated with childhood maltreatment (rs142346759, p = 4.35 × 10-8, FOXP1; rs10262462, p = 3.24 × 10-8, FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. h2snp for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (r2 = 0.0025; p = 1.8 × 10-15). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (rg = 0.70, p = 4.65 × 10-40), although we show evidence that our top hits may be specific to childhood maltreatment. This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment. Speculatively, FOXP genes might influence externalizing traits and so be relevant to childhood maltreatment. Alternatively, these variants may be associated with a greater likelihood of reporting maltreatment. A clearer understanding of the genetic relationships of childhood maltreatment, including particular abuse subtypes, with a range of phenotypes, may ultimately be useful in in developing targeted treatment and prevention strategies.

Additional Insights into the Relationship Between Brain Network Architecture and Susceptibility and Resilience to the Psychiatric Sequelae of Childhood Maltreatment.

Childhood maltreatment is associated with increased risk for psychiatric and substance use disorders. However, some maltreated individuals appear resilient to these consequences while manifesting the same array of brain changes as maltreated individuals with psychopathology. Hence, a critical issue has been to identify compensatory brain alterations in these resilient individuals. We recently reported that maltreatment is associated with a more vulnerable structural brain network architecture. Resilient individuals have this same vulnerability but appeared to be able to effectively compensate due to reduced nodal efficiency (ability of a node to influence the global network) in 9 specific brain regions that moderate the relationship between maltreatment and psychopathology. Following up we now report that network vulnerability increases progressively during late adolescence to plateau at about 21 years of age, which may help to explain age of onset of psychopathology. Further, we found that network vulnerability was most significantly affected by parental verbal abuse between 16-18 years of age and number of types of maltreatment during childhood. Asymptomatic individuals with no history of psychopathology had more prominent alterations in nodal efficiency than asymptomatic individuals with prior history, who specifically showed reduced nodal efficiency in right amygdala and right subcallosal gyrus. Experiencing inadequate financial sufficiency during childhood increased risk of susceptibility versus resilience by 2.98-fold (95% CI 1.49-5.97, p = 0.002) after adjusting for differences in exposure to maltreatment. Interestingly, adequate-to-higher financial sufficiency appeared to be protective and was associated with reduced nodal efficiency in the right postcentral gyrus and subcallosal gyrus 'resilience' nodes.

Effects of a Mindfulness-Based Intervention on Self-Compassion and Psychological Health Among Young Adults With a History of Childhood Maltreatment.

BACKGROUND: Individuals who were maltreated during childhood are faced with increased risks for developing various psychological symptoms that are particularly resistant to traditional treatments. This pilot study investigated the effects of a mindfulness based behavioral intervention for young adults with a childhood maltreatment history. METHODS: This study looked at self-report psychological questionnaires from 20 subjects (5 males) before and after a mindfulness-based behavioral intervention, compared to 18 subjects (6 males) in the waiting list control group (age range 22-29); all subjects experienced mild-to-moderate childhood maltreatment. We analyzed changes in stress, anxiety, depression, mindfulness and self-compassion related to the intervention with linear mixed effects models; we also analyzed the relationships among questionnaire score changes with partial correlation analyses and mediation analysis. RESULTS: Linear mixed effects model analyses revealed significant group by time interaction on stress (p < 0.01), anxiety (p < 0.05), and self-compassion (p < 0.01), with the mindfulness group having significant reduction in stress and anxiety (p < 0.01), and significant increase in mindfulness (p < 0.05) and self-compassion (p < 0.001). Partial correlation analyses showed that among all subjects from both groups, changes in mindfulness positively correlated with changes in self-compassion (r = 0.578, p = 0.001), which negatively correlated with changes in depression (r = -0.374, p = 0.05) and anxiety (r = -0.395, p < 0.05). Changes in self-compassion mediated, in part, the relationship between changes in mindfulness and changes in anxiety (average causal mediation effect = -4.721, p < 0.05). We observed a dose-dependent effect of the treatment, i.e., the number of intervention sessions attended were negatively correlated with changes in stress (r = -0.674, p < 0.01), anxiety (r = -0.580, p < 0.01), and depression (r = -0.544, p < 0.05), after controlling for the individual differences in childhood maltreatment severity. CONCLUSION: Our results suggest that, to some extent, the mindfulness-based intervention can be helpful for improving self-compassion and psychological health among young adults with a childhood maltreatment history. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT02447744.

Childhood Maltreatment, Cortical and Amygdala Morphometry, Functional Connectivity, Laterality, and Psychopathology.

Child maltreatment (CM) is the most important preventable risk factor for psychopathology and there is a pressing need to understand how CM gets 'under the skin' to markedly increase risk in some individuals as well as a comparable effort to identify factors associated with better than expected outcomes in other individuals. This special issue of Child Maltreatment provides a series of sophisticated studies on the neurobiological impact of CM, of which we have chosen 4 articles to comment on.The articles by Oshri et al., and Peveril, Sheridan, Busso & McLaughlin are amygdala centric and provide important new information on the impact of CM on the morphology and functional connectivity of this highly stress susceptible structure. The article by Demers et al., presents data from a longitudinal study that illustrates the potentially disruptive effects of CM on the association between maternal relationship quality, frontal cortical development and symptomatology. Finally, the De Bellis et al., study addresses the pressing question, which we have labeled the 'ecophenotype hypothesis', that postulates that maltreated and non-maltreated individuals with the same primary DSM diagnosis are clinically and neurobiologically distinct, and provides new evidence for a specific prefrontal cortical neurobiological abnormality in the maltreated subtype.

Susceptibility or Resilience to Maltreatment Can Be Explained by Specific Differences in Brain Network Architecture.

BACKGROUND: Childhood maltreatment is a major risk factor for psychopathology. However, some maltreated individuals appear remarkably resilient to the psychiatric effects while manifesting the same array of brain abnormalities as maltreated individuals with psychopathology. Hence, a critical aim is to identify compensatory brain alterations that enable resilient individuals to maintain mental well-being despite alterations in stress-susceptible regions. METHODS: Network models were constructed from diffusion tensor imaging and tractography in physically healthy unmedicated 18- to 25-year-old participants (N = 342, n = 192 maltreated) to develop network-based explanatory models. RESULTS: First, we determined that susceptible and resilient individuals had the same alterations in global fiber stream network architecture using two different definitions of resilience: 1) no lifetime history of Axis I or II disorders, and 2) no clinically significant symptoms of anxiety, depression, anger-hostility, or somatization. Second, we confirmed an a priori hypothesis that right amygdala nodal efficiency was lower in asymptomatic resilient than in susceptible participants or control subjects. Third, we identified eight other nodes with reduced nodal efficiency in resilient individuals and showed that nodal efficiency moderated the relationship between maltreatment and psychopathology. Fourth, we found that models based on global network architecture and nodal efficiency could delineate group membership (control, susceptible, resilient) with 75%, 82%, and 80% cross-validated accuracy. CONCLUSIONS: Together these findings suggest that sparse fiber networks with increased small-worldness following maltreatment render individuals vulnerable to psychopathology if abnormalities occur in specific nodes, but that decreased ability of certain nodes to propagate information throughout the network mitigates the effects and leads to resilience.

Differential effects of childhood neglect and abuse during sensitive exposure periods on male and female hippocampus.

The hippocampus is a highly stress susceptible structure and hippocampal abnormalities have been reported in a host of psychiatric disorders including major depression and post-traumatic stress disorder (PTSD). The hippocampus appears to be particularly susceptible to early life stress with a graded reduction in volume based on number of types (multiplicity) or severity of maltreatment. We assessed whether the most important predictors of adult hippocampal volume were multiplicity, severity or duration of exposure or timing of maltreatment during developmental sensitive periods. 3T MRIs were collected on 336 unmedicated, right-handed subjects (132M/204F, 18-25 years). Exposure to broad categories of abuse and neglect during each year of childhood were assessed using the Maltreatment and Abuse Chronology of Exposure scale and evaluated using artificial intelligence and predictive analytics. Male hippocampal volume was predicted by neglect, but not abuse, up through 7 years of age. Female hippocampal volume was predicted by abuse, but not neglect, at 10, 11, 15 and 16 years. Exposure at peak age had greater predictive importance than multiplicity, severity or duration. There were also marked gender differences in subfields and portions (head, body or tail) affected by exposure. History and symptoms of major depression, PTSD or anxiety disorders were not predictive of hippocampal volume once maltreatment was accounted for. Neglect appears to foster inadequate hippocampal development in males while abuse appears to produce a stress-related deficit in females. Studies assessing hippocampal volume in psychiatric disorders need to control for the gender-specific effects of abuse and neglect.

Childhood maltreatment is associated with alteration in global network fiber-tract architecture independent of history of depression and anxiety.

Childhood maltreatment is a major risk factor for psychopathology. It is also associated with alterations in the network architecture of the brain, which we hypothesized may play a significant role in the development of psychopathology. In this study, we analyzed the global network architecture of physically healthy unmedicated 18-25 year old subjects (n=262) using diffusion tensor imaging (DTI) MRI and tractography. Anatomical networks were constructed from fiber streams interconnecting 90 cortical or subcortical regions for subjects with no-to-low (n=122) versus moderate-to-high (n=140) exposure to maltreatment. Graph theory analysis revealed lower degree, strength, global efficiency, and maximum Laplacian spectra, higher pathlength, small-worldness and Laplacian skewness, and less deviation from artificial networks in subjects with moderate-to-high exposure to maltreatment. On balance, local clustering was similar in both groups, but the different clusters were more strongly interconnected in the no-to-low exposure group. History of major depression, anxiety and attention deficit hyperactivity disorder did not have a significant impact on global network measures over and above the effect of maltreatment. Maltreatment is an important factor that needs to be taken into account in studies examining the relationship between network differences and psychopathology.

Does sleep disruption mediate the effects of childhood maltreatment on brain structure?

Background: Childhood maltreatment is associated with alterations in morphology of stress susceptible brain regions. Maltreatment is also known to markedly increase risk for psychopathology and to have an enduring disruptive effect on sleep. Objective: To determine whether abnormalities in sleep continuity have effects on brain morphometry and to evaluate the extent to which sleep impairments mediate the effects of maltreatment on brain structure. Method: Maltreatment and Abuse Chronology of Exposure (MACE) scale ratings, actigraph-assessed sleep and 3T MRI were obtained on N = 37 18-19-year-old participants recruited from the community (N = 34 with neuroimaging). Results: Fourteen participants had no history of maltreatment while N = 23 were exposed, on average, to 4.7 types of maltreatment. Multiplicity of maltreatment was strongly associated with reduced sleep efficiency, increased wake after sleep onset time and number/duration of awakenings, which were independent of effects of maltreatment on depression and anxiety. The most important predictors of impaired sleep were exposure to parental non-verbal emotional abuse at 9-10 years of age. Reduced sleep efficiency correlated with reduced grey matter volume in hippocampus including CA1 subfield, molecular layer and dentate gyrus as well as inferior frontal gyrus and insula. Sleep mediated 39-46% of the effects of maltreatment on volume of hippocampal structures and inferior frontal gyrus. Conclusions: Actigraph-assessed sleep is disrupted in maltreated late teens and mediates a significant portion of the effects of maltreatment on hippocampal volume. Studies are needed to assess whether efforts to enhance sleep in maltreated children can pre-empt or ameliorate neurobiological consequences of maltreatment.

Objetivo: determinar si las anomalías en la continuidad del sueño tienen efectos sobre la morfometría cerebral y evaluar en qué medida las alteraciones del sueño intervienen en los efectos del maltrato sobre la estructura del cerebro. Método: Se obtuvieron las puntuaciones de la Escala de cronología de la exposición al maltrato y al abuso (MACE, por sus siglas en inglés), sueño evaluado por actigraph y 3T MRI en N = 37 participantes de 18-19 años reclutados en la comunidad (N = 34 con neuroimagen). Resultados: Catorce participantes no tenían antecedentes de malos tratos mientras que N = 23 habían estado expuestos, de media, a 4.7 tipos de maltrato. La multiplicidad de los malos tratos se asoció fuertemente con una menor eficiencia del sueño, tiempo mayor de vigilia después de la hora de inicio del sueño y el número / duración de despertares, que fueron independientes de los efectos del maltrato sobre la depresión y la ansiedad. Los predictores más importantes de problemas de sueño fueron la exposición al abuso emocional no verbal de los padres a los 9-10 años de edad. La reducción de la eficiencia del sueño se correlacionó con la reducción del volumen de la materia gris en el hipocampo, incluido el subcampo CA1, la capa molecular y la circunvolución dentada, así como la circunvolución frontal inferior y la ínsula. El sueño mediaba en el 39-46% de los efectos del maltrato sobre el volumen de las estructuras del hipocampo y la circunvolución frontal inferior. Conclusiones: el sueño evaluado por Actigraph se ve alterado en adolescentes mayores maltratados y media en una parte importante de los efectos del maltrato sobre el volumen del hipocampo. Se necesitan estudios para evaluar si los esfuerzos para mejorar el sueño en los niños maltratados pueden adelantar o mejorar las consecuencias neurobiológicas del maltrato.

Childhood Maltreatment, Depression, and Suicidal Ideation: Critical Importance of Parental and Peer Emotional Abuse during Developmental Sensitive Periods in Males and Females.

BACKGROUND: The adverse childhood experience (ACE) study found that risk for depression increased as a function of number of types of childhood maltreatment, and interpret this as a result of cumulative stress. An alternative hypothesis is that risk depends on type and timing of maltreatment. This will also present as a linear increase, since exposure to more types of abuse increases likelihood of experiencing a critical type of abuse at a critical age. METHODS: 560 (223M/337F) young adults (18-25 years) were recruited from the community without regard to diagnosis and balanced to have equal exposure to 0-4 plus types of maltreatment. The Maltreatment and Abuse Chronology of Exposure Scale assessed severity of exposure to 10 types of maltreatment across each year of childhood. Major depressive disorder (MDD) and current symptoms were evaluated by SCID, interview, and self-report. Predictive analytics assessed importance of exposure at each age and evaluated whether exposure at one or two ages was a more important predictor than number, severity, or duration of maltreatment across childhood. RESULTS: The most important predictors of lifetime history of MDD were non-verbal emotional abuse in males and peer emotional abuse (EA) in females at 14 years of age, and these were more important predictors across models than number of types of maltreatment (males: t 9 = 16.39, p < 10(-7); females t 9 = 5.78, p < 10(-4)). Suicidal ideation was predicted, in part, by NVEA and peer EA at age 14, but most importantly by parental verbal abuse at age 5 in males and sexual abuse at age 18 in females. CONCLUSION: This study provides evidence for sensitive exposure periods when maltreatment maximally impacts risk for depression, and provides an alternative interpretation of the ACE study results. These findings fit with emerging neuroimaging evidence for regional sensitivity periods. The presence of sensitive exposure periods has important implications for prevention, preemption, and treatment of MDD.