Sex differences in suicidal behaviors and aggression in US Veterans.

Female Veterans are the fastest growing demographic group in the Department of Veterans Affairs. Moreover, suicide rates in female Veterans are increasing, making suicide in female Veterans a topic of vital clinical and research significance. The current study examined the association between suicide, aggression, and mood symptoms by sex. Participants consisted of 264 Veterans (female=54, male=210) ages 18-55. Veterans completed well-validated measures of suicidal behaviors, aggression, anxiety, and depression. Male Veterans reported higher physical aggression, verbal aggression, anger, hostility, and total aggression compared to female Veterans. In male Veterans, lifetime suicidal behavior including ideation and attempts was correlated with total aggression and subscales of physical aggression, verbal aggression, anger, and hostility. However, in female Veterans lifetime suicidal behavior was significantly associated with hostility and anger. There were no between-group differences in measures of suicidal behaviors, anxious or depressive symptoms. These results suggest important differences in the association between aggression and suicidal behavior by sex. These data have significant clinical implications, as males with aggressive traits and females who endorse hostility and anger may be more likely to engage in suicidal behaviors.

Neurobiological evidence of sexual dimorphism in limbic circuitry of US Veterans.

BACKGROUND: Female Veterans are an increasing patient population in the Department of Veterans Affairs and may have distinct clinical and neurobiological features compared to males. METHODS: Nineteen female and 19 male Veterans who met diagnostic criteria for depression/posttraumatic stress disorder (MDD/PTSD) completed diagnostic interviews, symptom measures, and resting-state neuroimaging. Participants completed clinical measures of mood and aggression in addition to magnetic resonance imaging on a 3.0 Tesla Siemens scanner. RESULTS: Females showed increased functional connectivity between the left and right basolateral amygdala (BLA) and the left and right cerebellar and occipital lobes. Sex differences also were evident in the relationship between affective and clinical symptoms with BLA connectivity. Females showed a correlation between revenge planning and decreased connectivity between the left BLA and left occipital lobe and also a correlation between aggression and decreased connectivity between the right BLA and right mid cingulate, right and left medial frontal lobe, and right frontal lobe. Males evidenced a relationship between increased depressive symptoms and increased connectivity between the left BLA and right and left occipital lobe, left calcarine, and other areas associated with visual memory and processing, and interpretation of sensory information. Additionally, males reported higher levels of physical aggression and revenge planning compared to females. LIMITATIONS: This study included neuroimaging and self-report clinical measures. Further studies will benefit from multimodal measures, including behavioral measures of aggression. CONCLUSIONS: Results suggest that male Veterans report more aggression than females and symptoms of aggression and mood are differentially related to BLA connectivity by sex.

Interaction of Cannabis Use and Aging: From Molecule to Mind.

Given the aging Baby Boomer generation, changes in cannabis legislation, and the growing acknowledgment of cannabis for its therapeutic potential, it is predicted that cannabis use in the older population will escalate. It is, therefore, important to determine the interaction between the effects of cannabis and aging. The aim of this report is to describe the link between cannabis use and the aging brain. Our review of the literature found few and inconsistent empirical studies that directly address the impact of cannabis use on the aging brain. However, research focused on long-term cannabis use points toward cumulative effects on multimodal systems in the brain that are similarly affected during aging. Specifically, the effects of cannabis and aging converge on overlapping networks in the endocannabinoid, opioid, and dopamine systems that may affect functional decline particularly in the hippocampus and prefrontal cortex, which are critical areas for memory and executive functioning. To conclude, despite the limited current knowledge on the potential interactive effects between cannabis and aging, evidence from the literature suggests that cannabis and aging effects are concurrently present across several neurotransmitter systems. There is a great need for future research to directly test the interactions between cannabis and aging.

The Effect of Citicoline Supplementation on Motor Speed and Attention in Adolescent Males.

OBJECTIVE: This study assessed the effects of citicoline, a nutraceutical, on attention, psychomotor function, and impulsivity in healthy adolescent males. METHOD: Seventy-five healthy adolescent males were randomly assigned to either the citicoline group ( n = 51 with 250 or 500 mg citicoline) or placebo ( n = 24). Participants completed the Ruff 2&7 Selective Attention Test, Finger Tap Test, and the Computerized Performance Test, Second Edition (CPT-II) at baseline and after 28 days of supplementation. RESULTS: Individuals receiving citicoline exhibited improved attention ( p = 0.02) and increased psychomotor speed ( p = 0.03) compared with those receiving placebo. Higher weight-adjusted dose significantly predicted increased accuracy on an attention task ( p = 0.01), improved signal detectability on a computerized attention task ( p = 0.03), and decreased impulsivity ( p = 0.01). DISCUSSION: Adolescent males receiving 28 days of Cognizin® citicoline showed improved attention and psychomotor speed and reduced impulsivity compared to adolescent males who received placebo.

Increased efficiency of brain connectivity networks in veterans with suicide attempts.

Background: Suicide is a public health concern for United States veterans and civilians. Prior research has shown neurobiological factors in suicide. However, studies of neuroimaging correlates of suicide risk have been limited. This study applied complex weighted network analyses to characterize the neural connectivity in white matter in veterans with suicide behavior. Methods: Twenty-eight veterans without suicide behavior (NS), 29 with a history of suicidal ideation only (SI), and 23 with prior suicide attempt (SA) completed diffusion tensor brain imaging, the Columbia Suicide Severity Rating Scale and Barratt Impulsiveness Scale (BIS). Structural connectivity networks among 82 parcellated brain regions were produced using whole-brain tractography. Global and nodal metrics of network topology have been calculated. Results: SA had shorter characteristic path length and greater global efficiency and mean weighted degree of global network metrics (p < 0.024). SA had more hub nodes than NS and SI. The left posterior cingulate cortex (PCC) showed significantly greater weighted degree in SA relative to others (p < 0.0003). Nonplanning subscale of BIS correlated with the weighted degrees of the left PCC within SA. In rich club connectivity, SA had higher local connections than others (p = 0.001). Conclusion: Veterans with prior suicide attempt had altered connectivity networks characteristics in the white matter. These findings may be distinctive neurobiological markers for individuals with suicide attempt. Strong connectivity in the left PCC may be implicated in impulsivity in veterans with suicide attempt.

Orbitofrontal connectivity is associated with depression and anxiety in marijuana-using adolescents.

BACKGROUND: Prevalence of marijuana (MJ) use among adolescents has been on the rise. MJ use has been reported to impact several brain regions, including frontal regions such as the orbitofrontal cortex (OFC). The OFC is involved in emotion regulation and processing and has been associated with symptoms of depression and anxiety. Therefore, we hypothesized that adolescent MJ users would show disruptions in OFC connectivity compared with healthy adolescents (HC) which would be associated with symptoms of mood and anxiety. METHODS: 43 MJ-using and 31 HC adolescents completed clinical measures including the Hamilton Anxiety Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D). Resting-state functional magnetic resonance imaging data was also acquired for all participants. RESULTS: In MJ users, increased depressive symptoms were associated with increased connectivity between the left OFC and left parietal regions. In contrast, lower ratings of anxiety were associated with increased connectivity between right and left OFC and right occipital and temporal regions. These findings indicate significant differences in OFC connectivity in MJ-using adolescents, which correlated with mood/anxiety. LIMITATIONS: Future studies with an increased number of female participants is required to address potential sex differences in connectivity patterns related to symptoms of depression and anxiety. CONCLUSIONS: This study highlights the association between OFC connectivity, MJ use, and symptoms of depression and anxiety in adolescents. These findings provide further insight into understanding the neural correlates that modulate the relationship between comorbid MJ use and mood disorders and could potentially help us better develop preventive and treatment measures.

Alterations in anterior cingulate cortex myoinositol and aggression in veterans with suicidal behavior: A proton magnetic resonance spectroscopy study.

Studies investigating the neurochemical changes that correspond with suicidal behavior (SB) have not yielded conclusive results. Suicide correlates such as aggression have been used to explore risk factors for SB. Yet the neurobiological basis for the association between aggression and SB is unclear. Aggression and SB are both prevalent in veterans relative to civilian populations. The current study evaluated the relationship between brain chemistry in the anterior (ACC) and the posterior cingulate cortex (POC), as well as the relationship between aggression and SB in a veteran population using proton magnetic resonance spectroscopy (1H-MRS). Single-voxel MRS data at 3 Tesla (T) were acquired from the ACC and POC voxels using a 2-dimensional J-resolved point spectroscopy sequence and quantified using the ProFit algorithm. Participants also completed a structured diagnostic interview and a clinical battery. Our results showed that the myoinositol (mI)/H2O ratio in the ACC and POC was significantly higher in veterans who reported SB when compared to veterans who did not. The two groups did not differ significantly with regard to other metabolites. Second, verbal aggression and SB measures positively correlated with mI/H2O in the ACC. Finally, verbal aggression mediated the relationship between mI/H2O in the ACC and SB.

Negative Mood States Correlate with Laterobasal Amygdala in Collegiate Football Players.

A number of studies have suggested that sports-related concussion (SRC) may place individuals at increased risk for depression and negative outcomes including suicide. However, the mechanisms underlying a potential relationship between brain integrity and mood remain unclear. The current study is aimed at examining the association between amygdala shape, mood state, and postconcussion symptoms in collegiate football players. Thirty members of 1 football team completed the Profile of Mood States (POMS), the postconcussion symptom scale (PCSS), and an MRI protocol during preseason camp. T1-weighted images were acquired and three-dimensional amygdala and probabilistic maps were created for shape analysis. Correlation analyses between POMS and PCSS and the relationship between POMS and amygdala shape were completed. In the amygdala, the left laterobasal subregion showed a positive relationship with the POMS total score and subscales scores. No significant relationship between PCSS and amygdala shape was found. Significant positive correlations were found between POMS subscales and PCSS. These results indicate that amygdala structure may be more closely associated with negative mood states than postconcussion symptoms. These findings suggest that premorbid individual differences in effect may provide critical insight into the relationship between negative mood and outcomes in collegiate football players with SRC.

Suicide Behavior and Chronic Pain: An Exploration of Pain-Related Catastrophic Thinking, Disability, and Descriptions of the Pain Experience.

This study examined differences in suicidal ideation (SI) and suicide attempts (SAs) among veterans with chronic pain. Pain-specific variables, including catastrophic thinking, disability, and sensory, affective, and evaluative pain descriptors, were a focus. Structured diagnostic and clinical interviews were conducted to examine SI/SA and mental health. Veterans completed the Structured Clinical Interview for DSM-IV and the Columbia-Suicide Severity Rating Scale to assess Axis I symptoms and suicidal behavior(s). Self-report questionnaires were used to evaluate the participants' subjective experience of chronic pain, which included the McGill Pain Questionnaire, Pain Catastrophizing Scale, and Pain Disability Index. The findings add to previous literature by suggesting pain-related catastrophic thinking specifically is related to elevated risk for SA, whereas affective and sensory pain are associated with SI. The study results support the need to assess pain from a multifaceted perspective and to examine the different experiences of pain, such as sensory and affective constructs, when discussing suicide risk in veterans.

Sex differences in white matter integrity in youths with attention-deficit/hyperactivity disorder: a pilot study.

Widespread disparities in white matter (WM) microstructure and organization have been found in adolescents with attention-deficit/hyperactivity disorder (ADHD); however, little is known about the role sex plays in these differences. The present diffusion tensor imaging (DTI) study performed whole-brain, tract-based, voxel-wise, and region of interest (ROI) analyses to investigate WM microstructure differences between ADHD and healthy control (HC) adolescents to examine the impact of sex on measures of fractional anisotropy (FA). Eighteen adolescents with ADHD and 24 HC were included in this study. All participants received a 64-direction DTI scan on a 3 Tesla Siemens scanner. FSL's TBSS was used to perform whole-brain, tract-based, voxel-wise analyses. Tracts demonstrating significant sex-by-diagnosis interactions were further evaluated using univariate analyses performed on mean FA data that were extracted from ROIs using the Johns Hopkins University WM tractography atlas. TBSS analyses between diagnostic groups revealed significantly increased FA in HC relative to ADHD in the bilateral superior longitudinal fasciculus (SLF), forceps major, left cingulum, and bilateral callosal regions. In addition, both TBSS and separate ROI analyses revealed significant sex-by-diagnosis interactions for the corticospinal tract (CST), inferior longitudinal fasciculus (ILF) and SLF. In the HC group, FA was increased in males relative to females for all analyses. In WM regions demonstrating a significant sex-by-diagnosis, FA was increased in females relative to males in the ADHD group. Our findings suggest that WM microstructure in several major WM tracts differs between males and females with ADHD. These differences in WM microstructure may account for some of the differences in ADHD subtypes and comorbidities seen between the sexes. Additional studies in ADHD, examining sex differences in phenotypic expression, treatment response and brain network trajectories are warranted.