Reduced Visual Cortex Gray Matter Volume and Thickness in Young Adults Who Witnessed Domestic Violence during Childhood

Exposure to interparental violence is associated with negative outcomes, such as depression, post-traumatic stress disorder and reduced cognitive abilities. However, little is known about the potential effects of witnessing domestic violence during childhood on gray matter volume (GMV) or cortical thickness. High-resolution 3.0 T volumetric scans (Siemens Trio Scanner) were obtained on 52 subjects (18–25 years) including 22 (6 males/16 females) with a history of visually witnessing episodes of domestic violence, and 30 (8 males/22 females) unexposed control subjects, with neither a current nor past DSM-IV Axis I or II disorder. Potential confounding effects of age, gender, level of parental verbal aggression, parental education, financial stress, full scale IQ, and total GMV, or average thickness were modeled using voxel based morphometry and FreeSurfer. Witnessing domestic violence subjects had a 6.1% GMV reduction in the right lingual gyrus (BA18) (P = 0.029, False Discovery Rate corrected peak level). Thickness in this region was also reduced, as was thickness in V2 bilaterally and left occipital pole. Theses regions were maximally sensitive to exposure to witnessing domestic violence between 11–13 years of age. Regional reductions in GMV and thickness were observed in both susceptible and resilient witnessing domestic violence subjects. Results in subjects witnessing domestic violence were similar to previously reported results in subjects with childhood sexual abuse, as the primary region affected was visual cortex. Brain regions that process and convey the adverse sensory input of the abuse may be specifically modified by this experience, particularly in subjects exposed to a single type of maltreatment. Exposure to multiple types of maltreatment is more commonly associated with morphological alterations in corticolimbic regions. These findings fit with preclinical studies showing that visual cortex is a highly plastic structure

ADHD in girls and boys – gender differences in co-existing symptoms and executive function measures

Background: ADHD is diagnosed and treated more often in males than in females. Research on gender differences suggests that girls may be consistently underidentified and underdiagnosed because of differences in the expression of the disorder among boys and girls. One aim of the present study was to assess in a clinical sample of medication naïve boys and girls with ADHD, whether there were significant gender x diagnosis interactions in co-existing symptom severity and executive function (EF) impairment. The second aim was to delineate specific symptom ratings and measures of EF that were most important in distinguishing ADHD from healthy controls (HC) of the same gender. Methods: Thirty-seven females with ADHD, 43 males with ADHD, 18 HC females and 32 HC males between 8 and 17 years were included. Co-existing symptoms were assessed with self-report scales and parent ratings. EF was assessed with parent ratings of executive skills in everyday situations (BRIEF), and neuropsychological tests. The three measurement domains (co-existing symptoms, BRIEF, neuropsychological EF tests) were investigated using analysis of variance (ANOVA) and random forest classification. Results: ANOVAs revealed only one significant diagnosis x gender interaction, with higher rates of self-reported anxiety symptoms in females with ADHD. Random forest classification indicated that co-existing symptom ratings was substantially better in distinguishing subjects with ADHD from HC in females (93% accuracy) than in males (86% accuracy). The most important distinguishing variable was self-reported anxiety in females, and parent ratings of rule breaking in males. Parent ratings of EF skills were better in distinguishing subjects with ADHD from HC in males (96% accuracy) than in females (92% accuracy). Neuropsychological EF tests had only a modest ability to categorize subjects as ADHD or HC in males (73% accuracy) and females (79% accuracy). Conclusions: Our findings emphasize the combination of self-report and parent rating scales for the identification of different comorbid symptom expression in boys and girls already diagnosed with ADHD. Self-report scales may increase awareness of internalizing problems particularly salient in females with ADHD

Childhood executive functions and ADHD symptoms predict psychopathology symptoms in emerging adults with and without ADHD: A 10-year longitudinal study

© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License.Deficits in executive functions (EFs) are theorized to play an important role in causing functional impairment and associated psychopathology in individuals with ADHD. The objective of this study was to examine the role of EFs and ADHD symptoms as longitudinal predictors of psychopathology symptoms in individuals with ADHD and typically developing individuals. We assessed individuals with and without ADHD (N = 135) with neuropsychological tests of EFs and scales of ADHD symptoms and psychopathology symptoms at baseline (T1; Mage = 11.59, 57.8% boys), 2-year follow-up (T2; Mage = 13.63, 97% retention), and 10-year follow-up (Mage = 21.18, 75% retention). Baseline EFs predicted psychopathology symptoms at the 2- and the 10-year follow-up, explaining 17% and 12% of the variance, respectively. Baseline EFs predicted both internalizing and externalizing symptoms, and the predictive value of EFs on psychopathology symptoms at 10-year follow-up was accounted for by cognitive flexibility. Baseline ADHD symptoms were a significant predictor of all symptom domains at all time points. Thus, childhood EFs, in particular cognitive flexibility, can predict psychopathology symptoms in emerging adulthood beyond the effect of ADHD symptoms. This supports dominating theories of ADHD stating that executive dysfunction contributes to the observed phenotype, including associated psychopathology symptoms, and suggests that EFs are important targets of interventional efforts.publishedVersio

Determination of hemispheric emotional valence in individual subjects: A new approach with research and therapeutic implications

BACKGROUND: Much has been theorized about the emotional properties of the hemispheres. Our review of the dominant hypotheses put forth by Schore, Joseph, Davidson, and Harmon-Jones on hemispheric emotional valences (HEV) shows that none are supported by robust data. Instead, we propose that individual's hemispheres are organized to have differing HEVs that can be lateralized in either direction. METHODS: Probe auditory evoked potentials (AEP) recorded during a neutral and an upsetting memory were used to assess HEV in 28 (20 F) right-handed subjects who were either victims of childhood maltreatment (N = 12) or healthy controls. In a sub-population, we determined HEV by emotional response to lateral visual field stimulation (LVFS), in which vision is limited to one, then the other hemifield. We compare a number of morphometric and functional brain measures between individuals who have right-negative versus left-negative HEV. RESULTS: Using AEPs to determine HEV, we found 62% of controls and 67% of maltreated subjects had right negative HEV. There was a strong interaction between HEV-laterality and gender, which together accounted for 60% of individual variability in total grey matter volume (GMV). HEV-laterality was associated with differences in hippocampal volume, amygdala/hippocampal ratios, and measures of verbal, visual and global memory. HEV-laterality was associated also with different constellations of symptoms comparing maltreated subjects to controls. Emotional response to LVFS provided a convenient and complementary measure of HEV-laterality that correlated significantly with the HEVs determined by AEPs. CONCLUSION: Our findings suggest that HEV-laterality, like handedness or gender, is an important individual difference with significant implications for brain and behavioral research, and for guiding lateralized treatments such as rTMS

Psychological Benefits 2 and 4 weeks After a Single Treatment with Near Infrared Light to the Forehead: A Pilot Study of 10 Patients with Major Depression and Anxiety

Background: Many studies have reported beneficial effects from the application of near-infrared (NIR) light photobiomodulation (PBM) to the body, and one group has reported beneficial effects applying it to the brain in stroke patients. We have reported that the measurement of a patient's left and right hemispheric emotional valence (HEV) may clarify data and guide lateralized treatments. We sought to test whether a NIR treatment could 1. improve the psychological status of patients, 2. show a relationship between immediate psychological improvements when HEV was taken into account, and 3. show an increase in frontal pole regional cerebral blood flow (rCBF), and 4. be applied without side effects. Methods: We gave 10 patients, (5 M/5 F) with major depression, including 9 with anxiety, 7 with a past history of substance abuse (6 with an opiate abuse and 1 with an alcohol abuse history), and 3 with post traumatic stress disorder, a baseline standard diagnostic interview, a Hamilton Depression Rating Scale (HAM-D), a Hamilton Anxiety Rating Scale (HAM-A), and a Positive and Negative Affect Scale (PANAS). We then gave four 4-minute treatments in a random order: NIR to left forehead at F3, to right forehead at F4, and placebo treatments (light off) at the same sites. Immediately following each treatment we repeated the PANAS, and at 2-weeks and at 4-weeks post treatment we repeated all 3 rating scales. During all treatments we recorded total hemoglobin (cHb), as a measure of rCBF with a commercial NIR spectroscopy device over the left and the right frontal poles of the brain. Results: At 2-weeks post treatment 6 of 10 patients had a remission (a score ≤ 10) on the HAM-D and 7 of 10 achieved this on the HAM-A. Patients experienced highly significant reductions in both HAM-D and HAM-A scores following treatment, with the greatest reductions occurring at 2 weeks. Mean rCBF across hemispheres increased from 0.011 units in the off condition to 0.043 units in the on condition, for a difference of 0.032 (95% CI: -0.016, 0.080) units, though this result did not reach statistical significance. Immediately after treatment the PANAS improved to a significantly greater extent with NIR "on" relative to NIR "off" when a hemisphere with more positive HEV was treated than when one with more negative HEV was treated. We observed no side effects. Conclusion: This small feasibility study suggests that NIR-PBM may have utility for the treatment of depression and other psychiatric disorders and that double blind randomized placebo-controlled trials are indicated. Trial registration: ClinicalTrials.gov Identifier: NCT0096145

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: t9 = 16.39, p < 10-7; females t9 = 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

Witnessing Violence Toward Siblings: An Understudied but Potent Form of Early Adversity

Research on the consequences of witnessing domestic violence has focused on inter-adult violence and most specifically on violence toward mothers. The potential consequences of witnessing violence to siblings have been almost entirely overlooked. Based on clinical experience we sought to test the hypothesis that witnessing violence toward siblings would be as consequential as witnessing violence toward mothers. The community sample consisted of unmedicated, right-handed, young adults who had siblings (n = 1,412; 62.7% female; 21.8±2.1 years of age). History of witnessing threats or assaults to mothers, fathers and siblings, exposure to parental and sibling verbal abuse and physical abuse, sexual abuse and sociodemographic factors were assessed by self-report. Symptoms of depression, anxiety, somatization, anger-hostility, dissociation and ‘limbic irritability’ were assessed by rating scales. Data were analyzed by multiple regression, with techniques to gauge relative importance; logistic regression to assess adjusted odds ratios for clinically-significant ratings; and random forest regression using conditional trees. Subjects reported witnessing violence to siblings slightly more often than witnessing violence to mothers (22% vs 21%), which overlapped by 51–54%. Witnessing violence toward siblings was associated with significant effects on all ratings. Witnessing violence toward mother was not associated with significant effects on any scale in these models. Measures of the relative importance of witnessing violence to siblings were many fold greater than measures of importance for witnessing violence towards mothers or fathers. Mediation and structural equation models showed that effects of witnessing violence toward mothers or fathers were predominantly indirect and mediated by changes in maternal behavior. The effects of witnessing violence toward siblings were more direct. These findings suggest that greater attention be given to the effects of witnessing aggression toward siblings in studies of domestic violence, abuse and early adversity

Transforming growth factor-β in breast cancer: too much, too late

The contribution of transforming growth factor (TGF)β to breast cancer has been studied from a myriad perspectives since seminal studies more than two decades ago. Although the action of TGFβ as a canonical tumor suppressor in breast is without a doubt, there is compelling evidence that TGFβ is frequently subverted in a malignant plexus that drives breast cancer. New knowledge that TGFβ regulates the DNA damage response, which underlies cancer therapy, reveals another facet of TGFβ biology that impedes cancer control. Too much TGFβ, too late in cancer progression is the fundamental motivation for pharmaceutical inhibition

Resting state brain dynamics: Associations with childhood sexual abuse and major depressive disorder

Early life stress (ELS) and major depressive disorder (MDD) share neural network abnormalities. However, it is unclear how ELS and MDD may separately and/or jointly relate to brain networks, and whether neural differences exist between depressed individuals with vs without ELS. Moreover, prior work evaluated static versus dynamic network properties, a critical gap considering brain networks show changes in coordinated activity over time. Seventy-one unmedicated females with and without childhood sexual abuse (CSA) histories and/or MDD completed a resting state scan and a stress task in which cortisol and affective ratings were collected. Recurring functional network co-activation patterns (CAPs) were examined and time in CAP (number of times each CAP is expressed) and transition frequencies (transitioning between different CAPs) were computed. The effects of MDD and CSA on CAP metrics were examined and CAP metrics were correlated with depression and stress-related variables. Results showed that MDD, but not CSA, related to CAP metrics. Specifically, individuals with MDD (N = 35) relative to HCs (N = 36), spent more time in a posterior default mode (DMN)-frontoparietal network (FPN) CAP and transitioned more frequently between posterior DMN-FPN and prototypical DMN CAPs. Across groups, more time spent in a posterior DMN-FPN CAP and greater DMN-FPN and prototypical DMN CAP transition frequencies were linked to higher rumination. Imbalances between the DMN and the FPN appear central to MDD and might contribute to MDD-related cognitive dysfunction, including rumination. Unexpectedly, CSA did not modulate such dysfunctions, a finding that needs to be replicated by future studies with larger sample sizes. &nbsp;</p