Childhood overweight/obesity has been associated with negative consequences related to brain function and may involve alterations in white matter pathways important for cognitive and emotional ...processing. Aerobic physical activity is a promising lifestyle factor that could restore white matter alterations. However, little is known about either regional white matter alterations in children with overweight/obesity or the effects of aerobic physical activity targeting the obesity-related brain alterations in children. Using a large-scale cross-sectional population-based dataset of US children aged 9 to 10 years (n = 8019), this study explored the associations between overweight/obesity and microstructure of limbic white matter tracts, and examined whether aerobic physical activity may reduce the overweight/obesity-related white matter alterations in children. The primary outcome measure was restriction spectrum imaging (RSI)-derived white matter microstructural integrity measures. The number of days in a week that children engaged in aerobic physical activity for at least 60 minutes per day was assessed. We found that females with overweight/obesity had lower measures of integrity of the fimbria-fornix, a major limbic-hippocampal white matter tract, than their lean peers, while this difference was not significant in males. We also found a positive relationship between the number of days of aerobic physical activity completed in a week and integrity measures of the fimbria-fornix in females with overweight/obesity. Our results provide cross-sectional evidence of sex-specific microstructural alteration in the fimbria-fornix in children with overweight/obesity and suggest that aerobic physical activity may play a role in reducing this alteration. Future work should examine the causal direction of the relationship between childhood overweight/obesity and brain alterations and evaluate potential interventions to validate the effects of aerobic physical activity on this relationship.
Various comorbid psychiatric diagnoses, including attention deficit hyperactivity disorder (ADHD), have been reported in individuals with internet gaming disorder (IGD). Prior research has shown ...alterations in brain metabolites, including N-acetylaspartate (NAA), and combined glutamate and glutamine in patients with ADHD that were similar to those observed in patients with IGD. We hypothesized that the decreased NAA levels in the IGD group would be associated with a history of ADHD.
Forty adults participated in this study. Participants were classified as having a high risk for IGD if they had a total score higher than 21 on the IGD Scale-short form. Proton magnetic resonance spectroscopy (
H-MRS) and high-resolution structural magnetic resonance imaging (MRI) data were acquired using a 3 Tesla Siemens Prisma scanner system.
Levels of NAA within the right prefrontal cortex were lower in the IGD group than those observed in the control group. In a multiple linear regression analysis, internet addiction test scores and history of ADHD were shown to predict increased game play. In addition, history of ADHD predicted lower levels of NAA within the right prefrontal cortex.
The preliminary results of current study suggest a mediating effect of ADHD on the severity of internet game play as well as the levels of NAA within the dorsolateral prefrontal cortex (DLPFC). The inclusion of ADHD in IGD research is important and deserving of further consideration.
Posttraumatic stress disorder (PTSD) is a psychiatric condition characterized by a prolonged stress response to potentially life-threatening events long after the event has passed. Understanding ...factors related to recovery from traumatic life events may inform novel targets for intervention. There is emerging preclinical evidence that creatine (Cr), a molecule critical to brain bioenergetics, may be a neurobiological marker of stress reactivity and recovery.
25 US Veterans (8 female) completed the Life Events Checklist for DSM-5, which assessed different types of traumatic events. Veterans were also asked to rate the subjective stress of each traumatic event on a 1–10 scale currently (Current Stress) and at the time the event occurred (Past Stress). Stress recovery was quantified as the difference between Current and Past Stress. Current PTSD symptoms were also assessed using the PTSD Checklist for DSM-5. Cr concentrations in the anterior cingulate cortex (ACC) were measured in the anterior cingulate cortex using proton magnetic resonance spectroscopy (1H-MRS).
Higher levels of Cr were associated with self-reported stress recovery from participants' most traumatic life event. Cr was not related to number of different types of traumatic life events or current PTSD symptoms.
The sample size was relatively small. Stress recovery was measured via retrospective self-report. Future experimental work in humans should clarify the protective role of Cr in recovery from trauma.
ACC concentrations of Cr may be an important neurochemical factor related to stress recovery. Future work should investigate Cr as a possible protective factor against the effects of traumatic stress.
•Creatine is necessary for healthy brain metabolism and changes with stress.•Creatine levels were measured in trauma-exposed veterans.•Higher creatine levels were associated with greater recovery from trauma.•The role of creatine in posttraumatic stress disorder should be further studied.
Combat exposure (CE) and military sexual trauma (MST) are among the most common types of traumatic experiences faced by veterans and active duty servicemembers and, as such, have both garnered ...increased research focus over the past decades. However, there has not yet been a critical review of the literature to examine the distinct clinical presentations associated with different trauma types. This is particularly important, as understanding distinct clinical profiles could help researchers and clinicians refine treatment approaches based on trauma type. To address this question, we conducted a search of the available literature in PsycINFO and PubMed prior to October 2022. We identified 43 articles evaluating the distinct and overlapping clinical symptoms of CE and MST. Study findings were conceptually organized by psychiatric condition. In general, there was substantial variability in study methodology including sample size, composition, and operationalizations of CE and MST. Despite this variability, notable patterns emerged across studies. Specifically, MST and CE uniquely predicted posttraumatic stress disorder symptoms, MST was more related to depressive symptoms and suicidality than CE, and CE appeared to be more related to alcohol use and other externalizing behaviors. Gender also played a significant role in the relationship between CE, MST, and clinical variables across studies. This review suggests that individuals with a history of MST and CE likely have distinct clinical presentations and more research into these presentations could better inform assessment and treatment. Important methodological gaps in the literature are also discussed.
• Pain catastrophizing was associated with a reduction in GABA/Cre in the MPFC.• Pain intensity was negatively correlated with GABA/Cre.• No significant relationships found between Glu/Cre or Gln/Cre ...and pain measures.
Veterans experience chronic pain more frequently than civilians. Identification of neurobiological mechanisms underlying the pathophysiology of chronic pain in a veteran population may aid in the development of novel treatment targets. In this pilot proof-of-concept study, veterans with chronic pain (N = 61) and no chronic pain (N = 19) completed clinical interviews, self-report questionnaires inquiring about pain history, interference of pain with daily life, and pain catastrophizing, as well as measures of depressive and anxious symptoms. Veterans also underwent single-voxel proton (1H) magnetic resonance spectroscopy (MRS) at 3 T in the anterior cingulate cortex (ACC) using a two-dimensional (2D) J-resolved point spectroscopy sequence. We found no group difference in neurometabolites between veterans with and without chronic pain; however, pain intensity, negative thinking about pain, and description of pain in affective terms were associated with lower GABA/Cre in the ACC. In addition, the Glu/GABA ratio in the ACC was positively associated with anxiety and depressive symptoms in veterans with chronic pain. Reductions in GABA in the ACC may contribute to increased pain intensity and greater pain catastrophizing in veterans with chronic pain. Furthermore, a disturbance in the excitatory-inhibitory balance may contribute to the anxious and depressive symptoms related to chronic pain. Given the pilot nature of the study, these findings must be considered preliminary.
•Higher circulating sCD25 level is associated with greater prefrontal Glx/GABA+.•Elevated Glx/GABA+ is linked to pain catastrophizing and evaluative pain ratings.•Elevated Glx/GABA+ is also related ...to anxiodepressive symptoms in chronic pain.•The sCD25-Glx/GABA+ interaction may contribute to pain catastrophizing.
Aberrant neuronal excitability in the anterior cingulate cortex (ACC) is implicated in cognitive and affective pain processing. Such excitability may be amplified by activated circulating immune cells, including T lymphocytes, that interact with the central nervous system. Here, we conducted a study of individuals with chronic pain using magnetic resonance spectroscopy (MRS) to investigate the clinical evidence for the interaction between peripheral immune activation and prefrontal excitatory-inhibitory imbalance. In thirty individuals with chronic musculoskeletal pain, we assessed markers of peripheral immune activation, including soluble interleukin-2 receptor alpha chain (sCD25) levels, as well as brain metabolites, including Glx (glutamate + glutamine) to GABA+ (γ-aminobutyric acid + macromolecules/homocarnosine) ratio in the ACC. We found that the circulating level of sCD25 was associated with prefrontal Glx/GABA+. Greater prefrontal Glx/GABA+ was associated with higher pain catastrophizing, evaluative pain ratings, and anxiodepressive symptoms. Further, the interaction effect of sCD25 and prefrontal Glx/GABA+ on pain catastrophizing was significant, indicating the joint association of these two markers with pain catastrophizing. Our results provide the first evidence suggesting that peripheral T cellular activation, as reflected by elevated circulating sCD25 levels, may be linked to prefrontal excitatory-inhibitory imbalance in individuals with chronic pain. The interaction between these two systems may play a role as a potential mechanism underlying pain catastrophizing. Further prospective and treatment studies are needed to elucidate the specific role of the immune and brain interaction in pain catastrophizing.
The Research Domain Criteria (RDoC) initiative provides a strategy for classifying psychopathology based on behavioral dimensions and neurobiological measures. Neurodevelopment is an orthogonal ...dimension in the current RDoC framework; however, it has not yet been fully incorporated into the RDoC approach. A combination of both a neurodevelopmental and RDoC approach offers a multidimensional perspective for understanding the emergence of psychopathology during development. Environmental influence (e.g., stress) has a profound impact on the risk for development of psychiatric illnesses. It has been shown that chronic stress interacts with the developing brain, producing significant changes in neural circuits that eventually increase the susceptibility for development of psychiatric disorders. This review highlights effects of chronic stress on the adolescent brain, as adolescence is a period characterized by a combination of significant brain alterations, high levels of stress, and emergence of psychopathology. The literature synthesized in this review suggests that chronic stress-induced changes in neurobiology and behavioral constructs underlie the shared vulnerability across a number of disorders in adolescence. The review particularly focuses on depression and substance use disorders; however, a similar argument can also be made for other psychopathologies, including anxiety disorders. The summarized findings underscore the need for a framework to integrate neurobiological findings from disparate psychiatric disorders and to target transdiagnostic mechanisms across disorders.
During the past decade, the pediatric suicide rate has nearly tripled. Yet, little is known about suicide behavior (SB) in children. Identification of risk factors associated with SB during childhood ...may be critical to preventing future attempts. The purpose of this study was to examine the relationship between neurocognitive performance and suicide ideation (SI) in children.
The present study utilized baseline data from 11,875 participants in the Adolescent Brain Cognitive Development (ABCD) study, a longitudinal study that follows 9- and 10-year-old children through late adolescence to examine factors that influence developmental trajectories. Suicidality was assessed by the Kiddie Schedule for Affective Disorder and Schizophrenia (KSADS) suicide module completed by the parent. Neurocognitive ability was assessed using the NIH Toolbox Cognition measures administered to the youth.
Children with a history of SI reported by their parent or concordant parent and youth report of SI demonstrated lower performance on the NIH Toolbox Picture Sequence Memory Test compared to children without SI. The difference in performance on the memory task remained significant when including demographic characteristics, family history of suicide, and internalizing symptoms in the model as covariates.
To our knowledge, this is the first study to identify decreased episodic memory in children with SI. These findings are similar to results from adult and adolescent studies which have reported decreased memory performance among suicide attempters. Deficits in episodic memory may impact a child's ability to problem-solve and generate potential future outcomes, which may increase the risk for SB. Early identification of memory deficits in children may inform suicide prevention and intervention efforts.
Highlights
6% of parents and children reported a history of active suicide ideation in children.
Children with a history of suicide ideation had lower episodic memory performance.
Early identification of memory deficits may inform suicide intervention efforts.
The aim of this narrative review is to consolidate knowledge on the role of the hypothalamic-pituitary-adrenal (HPA) axis in depression pathophysiology at different reproductive stages across the ...female lifespan. Despite growing evidence about the impact of gonadal hormones on mood disorders, no previous review has examined the interaction between such hormonal changes and the HPA axis within the context of depressive disorders in women. We will focus on HPA axis function in depressive disorders at different reproductive stages including the menstrual cycle (e.g., premenstrual dysphoric disorder PMDD), perinatally (e.g., postpartum depression), and in perimenopausal depression. Each of these reproductive stages is characterized by vast physiological changes and presents major neuroendocrine reorganization. The HPA axis is one of the main targets of such functional alterations, and with its key role in stress response, it is an etiological factor in vulnerable windows for depression across the female lifespan. We begin with an overview of the HPA axis and a brief summary of techniques for measuring HPA axis parameters. We then describe the hormonal milieu of each of these key reproductive stages, and integrate information about HPA axis function in depression across these reproductive stages, describing similarities and differences. The role of a history of stress and trauma exposure as a contributor to female depression in the context of HPA axis involvement across the reproductive stages is also presented. This review advances the pursuit of understanding common biological mechanisms across depressive disorders among women. Our overarching goal is to identify unmet needs in characterizing stress-related markers of depression in women in the context of hormonal changes across the lifespan, and to support future research in women's mental health as it pertains to pathophysiology, early diagnosis, and treatment targets.
•Veterans with a suicide attempt had reduced left rACC WMV compared to ideators.•Reduced left rACC WMV was correlated with nonplanning impulsivity for Attempters.•Veteran ideators and attempters did ...not differ on measures of impulsivity.•Regional ACC WMV differences were associated with impulsivity and suicide attempts.
Suicide is one of the leading causes of death for military personnel and Veterans. Neuroimaging studies have revealed abnormalities in white matter tracts and brain connectivity in suicide behavior (SB); however, reports of alterations in white matter volume and its association with related behaviors are limited. The current study examined the relationship between cingulate white matter volume (WMV), impulsivity, and SB in Veterans.
Fifty-two Veterans, ages 18 to 65, underwent magnetic resonance imaging on a 3T Siemens Verio scanner. Morphometric analysis of brain images was performed to evaluate differences in WMV in cingulate regions of interest. Participants completed the Columbia Suicide Severity Rating Scale to assess lifetime suicide behavior and the Barratt Impulsivity Scale (BIS) and the Continuous Performance Test (CPT) to assess impulsivity.
Twenty-nine Veterans had a history of suicidal ideation (SI) and 23 had a history of suicide attempts (SA). Controlling for age, sex, handedness and total white matter volume, reduced WMV was observed in the left rostral anterior cingulate cortex (rACC) in Veterans with SA relative to Veterans with SI, p = .008. Additionally, non-planning on the BIS was negatively correlated with left rACC WMV for Veterans with a history of SA, p = .04. Other subregions of the ACC WMV were negatively correlated with planning and attention impulsivity (BIS) and omission and commission errors (CPT) for attempters.
Reduction in rACC WMV in Veterans with SA was negatively correlated with nonplanning measures. These findings are consistent with ACC involvement in inhibitory processes and build on evidence that SB is associated with neurobiological abnormalities and suggest that white matter changes may be related to actual attempts.