Rare Tumors

Background Trauma-focused psychotherapy is treatment of choice for post-traumatic stress disorder (PTSD). However, about half of patients do not respond. Recently, there is increased interest in brain criticality, which assesses the phase transition between order and disorder in brain activity. Operating close to this borderline is theorized to facilitate optimal information processing. We studied if brain criticality is related to future response to treatment, hypothesizing that treatment responders’ brains function closer to criticality. Methods Functional magnetic resonance imaging resting-state scans were acquired from 46 male veterans with PTSD around the start of treatment. Psychotherapy consisted of trauma-focused cognitive behavioral therapy, eye movement desensitization and reprocessing, or a combination thereof. Treatment response was assessed using the Clinician-Administered PTSD Scale, and criticality was assessed using an Ising temperature approach for seven canonical brain networks (ie, the visual, somatomotor, dorsal attention, ventral attention, limbic, frontoparietal and default mode networks) to measure distance to criticality. Results The brains of prospective treatment responders were closer to criticality than nonresponders (P = 0.017), while no significant interaction effect between group and brain network was observed (P = 0.486). In addition, average criticality across networks correlated with future treatment response (P = 0.028). Conclusion These results show that the brains of prospective PTSD psychotherapy treatment responders operate closer to criticality than nonresponders, and this occurs across the entire brain instead of in separate canonical brain networks. These results suggest that effective psychotherapy is mediated by brains operating closer to criticality.

Background Understanding distinct neurobiological mechanisms underlying bipolar disorder (BD) and major depressive disorder (MDD) is crucial for accurate diagnosis and the discovery of novel and more effective targeted treatments. Previous diffusion-weighted MRI studies have suggested some common frontotemporal corticolimbic system white matter (WM) abnormalities across the disorders. However, critical to the development of more precise diagnosis and treatment is identifying distinguishing abnormalities. Promising candidates include more prominent frontotemporal WM abnormalities observed in BD in the uncinate fasciculus (UF) that have been associated with frontal-amygdala functional dysconnectivity, and with suicide that is especially high in BD. Prior work also showed differentiation in metabotropic glutamate receptor 5 (mGlu5) abnormalities in BD versus MDD, which could be a mechanism affected in the frontotemporal system. However, associations between WM and mGlu5 have not been examined previously as a differentiator of BD. Using a multimodal neuroimaging approach, we examined WM integrity alterations in the disorders and their associations with mGluR5 levels. Methods Individuals with BD ( N = 21), MDD ( N = 10), and HC ( N = 25) participated in structural and diffusion-weighted MRI scanning, and imaging with [18F]FPEB PET for quantification of mGlu5 availability. Whole-brain analyses were used to assess corticolimbic WM matter fractional anisotropy (FA) across BD and MDD relative to HC; abnormalities were tested for associations with mGlu5 availability. Results FA corticolimbic reductions were observed in both disorders and altered UF WM integrity was observed only in BD. In BD, lower UF FA was associated with lower amygdala mGlu5 availability ( p < .05). Conclusions These novel preliminary findings suggest important associations between lower UF FA and lower amygdala mGlu5 levels that could represent a disorder-specific neural mechanism in which mGluR5 is associated with the frontotemporal dysconnectivity of the disorder.

Objective Post-traumatic stress disorder (PTSD) is a mental disorder that manifests after exposure to a stressful traumatic event, such as combat experience. Accumulated evidence indicates an important genetic influence in the development of PTSD. The serotonin transporter (5-HTT) gene has been identified as a candidate for PTSD and a polymorphism of the serotonin transporter-linked promoter region (5-HTTLPR) is associated with the disorder in the general population. However, whether it is associated with PTSD in active military service members has not been investigated. This study aimed to investigate the relationship between 5-HTTLPR and PTSD in service members. Methods Leucocyte genomic DNA was extracted from service members, including those with PTSD (n = 134) or without PTSD (n = 639). The 5-HTTLPR polymorphism was detected by means of 2 stages of TaqMan fluorescent PCR assay. PTSD symptoms and symptom severity were assessed using the PTSD Checklist (PCL), a 17-item, DSM-based, self-report questionnaire with well-established validity and reliability. PTSD was determined based on endorsement of DSM-IV criteria and a PCL total score ≥ 44. Results Significant differences in biallele distribution were observed between PTSD and controls (χ2 = 7.497, P = .024). The frequency of SS, SL, and LL genotypes in the PTSD group was 0.17, 0.56, and 0.27 respectively, compared to the frequencies of 0.27, 0.43, and 0.29 in non-PTSD controls. Carriers of the L allele had higher scores for reexperiencing and arousal symptoms on the PCL, compared to SS homozygote carriers ( P < .05). The triallele genotypes showed no significant differences in distribution between the PTSD and control groups ( P > .05) and no relationship with PTSD symptom severity. The interaction of triallelic genotypes of 5-HTTLPR and traumatic life events was associated with re-experiencing, avoidance, and arousal ( P < .05 for all). Multiple regression analysis revealed significant correlations between both biallelic and triallelic genotypes of 5-HTTLPR, the interaction of the number of stressful lifetime events, and 5-HTTLPR genotypes with PCL total score ( P < .001). Conclusion Our findings suggested that 5-HTT might play a minor role in PTSD, and the interaction between 5-HTTLPR and the environment had effects on PCL score, complementing and emphasizing 5-HTT for PTSD, especially in the military population.

Background Rural areas in the United States have been disproportionately burdened with high rates of substance use, mental health challenges, chronic stress, and suicide behaviors. Factors such as a lack of mental health services, decreased accessibility to public health resources, and social isolation contribute to these disparities. The current study explores risk factors to suicidal ideation, using emergency room discharge data from Maryland. Methods The current study used data from the Healthcare Cost and Utilization Project (HCUP) State Emergency Department Databases (SEDD) from the State of Maryland. Logistic regression was used to assess the association between ICD-10 coded opioid use disorder, alcohol use disorder, cannabis use disorder, major depressive disorder, and the outcome variable of suicidal ideation discharge. We controlled for income, race, age, and gender. Results Lifetime major depressive disorder diagnosis (odds ration [OR] = 79.30; 95% confidence interval [CI] 51.91-121.15), alcohol use disorder (OR = 6.87; 95% CI 4.97-9.51), opioid use disorder (OR = 5.39; 95% CI 3.63-7.99), and cannabis use disorder (OR = 2.67; 95% CI 1.37-5.18) were all positively associated with suicidal ideation. Conclusions The study highlights the strong link between prior substance use disorder, depression, and suicidal ideation visit to the emergency room, indicating the need for prevention and intervention, particularly among those in rural areas where the burden of suicidal ideation and chronic stress are high. As health disparities between rural and urban areas further widened during the COVID-19 pandemic, there is an urgent need to address these issues.

Background Evaluation stress can impair inhibitory control, limiting the ability of children to perform cognitively. However, evidence on protective factors is lacking as stress-induced cognitive impairments are poorly understood. High physical activity has been related to better inhibitory control and has the potential to buffer the response to a stressor. We investigated the association of physical activity and stress-induced changes in inhibitory control as well as its underlying cognitive control processes (i.e., conflict monitoring and resolution). Method Participants (10 to 13 y) with either low ( N = 55) or high moderate-to-vigorous physical activity ( N = 55) completed the Trier Social Stress Test for Children (TSST-C) and a control task in a randomized order. During both conditions, salivary cortisol was collected. Additionally, a computerized Stroop task was administered before and after the experimental conditions. The N200 and positive slow wave (PSW) components of event-related potentials elicited by the Stroop task were recorded using electroencephalography. Results In comparison to the control task, the TSST-C elicited a pre-to post-test decrease of accuracy on incompatible trials. Path-analyses further revealed that this decrease was related to low physical activity and a reduced PSW amplitude. However, both the N200 and PSW amplitudes did not mediate the relation between physical activity groups and performance on the Stroop task. Conclusion In children, evaluation stress decreases inhibitory control partly due to a reduced effectiveness of conflict resolution processes. Only children with high physical activity maintain inhibitory control after facing the stressor. However, this protective effect cannot be attributed to changes in conflict monitoring and resolution.

Purpose: Currently, 1 in 5 college students struggle with suicidal ideation while 7% to 44% engage in nonsuicidal self-injury. Illinois has one of the highest teenage and college student suicide rates in the United States. This pilot study assessed suicide ideation and self-harm behaviors at a public Illinois university. This is the first study to use 5 standardized psychological instruments to investigate these 2 crises in freshmen college students who are all required to reside in dormitories. The main hypothesis was to determine if the independent effects of freshmen students’ depression, Five-Factor Model, and Reasons for Living affected the dependent variables, self-harm behaviors and suicide ideation. Methods: Forty first-year college dormitory students completed the Beck Depression Inventory-II, Scale of Suicidal Ideation, Five-Factor Model, Inventory of Statements About Self-Injury, and Reasons for Living Scale in person. Results: Participants were 18 to 19 years old, predominantly female (65%), and non-White (62%). Forty percent reported self-harm behaviors and 19% reported suicidal ideation. The top reasons for contemplated suicide attempts included the inability to solve problems (33%) and attention/revenge (28%). Students experienced high levels of anxiety (55%), self-consciousness (43%), and depression (18%). Depression was associated with suicide ideation (β  = 0.05, P = .006), while neuroticism and openness were associated with self-harm behaviors ( aOR = 3.36, P = .02, aOR = 0.48, P = .047, respectively). Ninety-five percent reported “responsibility to family” as a Reason for Living. Conclusions: Preliminary evidence necessitates an examination of self-harm and suicide ideation among all freshmen, investigating both risk and protective factors. In the future, a prevention intervention should be implemented campus-wide (and eventually nationwide) for all first-year dormitory students to enhance their mental well-being.

Background In emergency psychiatry high levels of suicidality are encountered. However, empirical studies about the extent of suicidal ideation remain scarce, and data are often gathered retrospectively via medical records. The present observational study aims to assess suicidal ideation, planning, and actions experienced by patients presenting with psychiatric emergencies. Methods In a consecutive sample of 136 patients, a standard psychiatric examination including the Chronological Assessment of Suicide Events (CASE Approach) was completed. An evaluative monitoring form for the CASE Approach was designed to record and quantify the garnered information. Results Almost 60% of the patients reported suicidal ideation with some planning. Approximately 25% had experienced over 10 hours of suicidal ideation on their worst days in the past 2 months; 27% had procured their method of choice, and another 27% had practiced a small, moderate, or serious suicide attempt. Conclusion Findings suggest more intense suicidality in emergency psychiatry than has been reported in previous empirical studies.

Background Evidence from animal and human studies suggests glutamatergic dysfunction in posttraumatic stress disorder (PTSD). The purpose of this study was to investigate glutamate abnormalities in the dorsolateral prefrontal cortex (DLFPC) of individuals with PTSD using 7T MRS, which has better spectral resolution and signal-to-noise ratio than lower field strengths, thus allowing for better spectral quality and higher sensitivity. We hypothesized that individuals with PTSD would have lower glutamate levels compared to trauma-exposed individuals without PTSD and individuals without trauma exposure. Additionally, we explored potential alterations in other neurometabolites and the relationship between glutamate and psychiatric symptoms. Methods Individuals with PTSD (n = 27), trauma-exposed individuals without PTSD (n = 27), and individuals without trauma exposure (n = 26) underwent 7T MRS to measure glutamate and other neurometabolites in the left DLPFC. The severities of PTSD, depression, anxiety, and dissociation symptoms were assessed. Results We found that glutamate was lower in the PTSD and trauma-exposed groups compared to the group without trauma exposure. Furthermore, N-acetylaspartate (NAA) was lower and lactate was higher in the PTSD group compared to the group without trauma exposure. Glutamate was negatively correlated with depression symptom severity in the PTSD group. Glutamate was not correlated with PTSD symptom severity. Conclusion In this first 7T MRS study of PTSD, we observed altered concentrations of glutamate, NAA, and lactate. Our findings provide evidence for multiple possible pathological processes in individuals with PTSD. High-field MRS offers insight into the neurometabolic alterations associated with PTSD and is a powerful tool to probe trauma- and stress-related neurotransmission and metabolism in vivo.

Police officers are frequently faced with chronic and acute stressors, such as excessive workload, organizational stressors and emotionally charged reports. This study aims to examine the relationship between a form of chronic strain (ie, burnout symptoms) and a resource (ie, coping self-efficacy) in a sample of Dutch police officers. Specifically, we aim to investigate the existence of a loss cycle of resources. We use Latent Change Score modeling to investigate the potential depletion or loss cycle of coping self-efficacy as a result of burnout symptoms in a sample of 95 police officers who completed a survey on three consecutive timepoints. The lag between the measurements was approximately one year. We found that, during both one-year intervals, within-person increases in burnout symptoms were related to within-person decreases in coping self-efficacy. Also, the results emphasize the buffering role of coping self-efficacy for burnout symptoms, as within-person decreases in coping self-efficacy during the first year were associated with within-person increases in burnout symptoms during the following year. Together, the results imply that a loss cycle of coping self-efficacy and burnout symptoms may occur. For this we used Latent Change Score modeling, which is a relatively new approach which provides researchers with the opportunity to analyse multi-wave longitudinal data while focusing on within-person changes over time. Practically, police organizations are advised to monitor personnel wellbeing and resources, to maintain and promote sustainable employability of police officers and to be able to timely provide individuals with interventions. Limitations discussed are the use of self-report measures and large intervals between the measurements. Finally, future directions of research are discussed that would circumvent the reported limitations, such as multiple wave with shorter lags and incorporating confounding factors that could affect coping self-efficacy.

Background During military deployment, stress regulation is vital to protect against the development of anxiety and trauma-related symptoms. Brain endocannabinoids play an important role in stress regulation and previous research has shown that genetic variations in the FAAH rs324420 polymorphism demonstrate protective effects during stress. In addition, this polymorphism shows interactions with the CRHR1 and CNR1 polymorphisms on anxiety. The present study examines whether genetic variations of the FAAH, CRHR1 and CNR1 polymorphisms interact with the development of anxiety and trauma related symptoms in military veterans. Methods Veterans (N = 949) who went on military deployment and experienced a stressful event were genotyped for FAAH rs324420, CRHR1 rs110402 and CNR1 rs2180619. Anxiety and trauma symptoms were measured pre-deployment and 6 months after deployment. Anxiety was measured with the anxiety subscale of the Symptom Checklist-90 (SCL-90) and trauma with the Self-Rating Inventory for PTSD (SRIP). Results Covariance Pattern Models demonstrated no significant relation of genetic variations in FAAH rs324420 on anxiety and PTSD symptoms from pre-deployment to 6 months after military deployment. Additionally, we investigated interactions between the FAAH s324420, CRHR1 rs110402 and CNR1 rs2180619 polymorphisms. This also demonstrated no significant effects on anxiety and PTSD symptoms pre- to post deployment. However, the covariate of childhood trauma that was included in the models was significant in all these models. Conclusion Genetic variations in FAAH rs324420 and its interactions with CRHR1 rs110402 and CNR1 rs2180619 are not related to the development of anxiety and trauma-related symptoms. The study however, indicates the importance of considering childhood trauma in the investigation of the effects of polymorphisms that are related to the endocannabinoid system on the development of anxiety and PTSD symptoms.

Substance use disorder (SUD) is a significant health problem, and trauma exposure is a known risk factor for the escalation of substance use. However, the shared neural mechanisms through which trauma is associated with substance use are still unknown. Therefore, we systematically review neuroimaging studies focusing on three domains that may contribute to the overlapping mechanisms of SUD and trauma—reward salience, negative emotionality, and inhibition. Using PRISMA guidelines, we identified 45 studies utilizing tasks measuring these domains in alcohol, tobacco, and cannabis use groups. Greater reward, lesser regulation of inhibitory processes, and mixed findings of negative emotionality processes in individuals who use substances versus controls were found. Specifically, greater orbitofrontal cortex, ventral tegmental area, striatum, amygdala, and hippocampal activation was found in response to reward-related tasks, and reduced activation was found in the inferior frontal gyrus and hippocampus in response to inhibition-related tasks. Importantly, no studies in trauma-exposed individuals met our review criteria. Future studies examining the role of trauma-related factors are needed, and more studies should explore inhibition- and negative-emotionality domains in individuals who use substances to uncover clinically significant alterations in these domains that place an individual at greater risk for developing a SUD.

Background Greater unhelpful thinking is associated with greater musculoskeletal discomfort and incapability. Cognitive-behavioral therapy (CBT) fosters healthy thinking to help alleviate symptoms. Questions In a meta-analysis of randomized control trials (RCT) of CBT for unhelpful thinking among people with musculoskeletal symptoms, we asked: 1) Does CBT reduce unhelpful thinking and feelings of distress, and improve capability, in individuals with musculoskeletal symptoms? 2) Are outcomes affected by CBT delivery methods? Methods Following QUOROM guidelines, we searched databases using keywords of pain catastrophizing, kinesiophobia, cognitive-behavioral therapy, musculoskeletal and variations. Inclusion criteria were RCT's testing CBT among people with musculoskeletal symptoms. Study quality was assessed with Cochrane Review of Bias 2. Meta-analysis of means and standard deviations was performed. Results CBT led to modest reductions in catastrophic thinking (−0.44 CI: −0.76 to −0.12; P = .01, kinesiophobia (−0.60 CI: −1.07 to −0.14; P = .01) and anxiety symptoms (−0.23 CI: −0.36 to −0.09; P < .01) over six months compared to usual care. There were no improvements in levels capability (−0.28 CI: −0.56 to 0.01; P = .05). CBT led by mental health professionals reduced catastrophic thinking more than CBT led by other clinicians (QB Test = 4.73 P = .03). There were no differences between online and in-person sessions, group versus individual therapy, or surgical versus non-surgical interventions. Conclusion The evidence that CBT delivered by various clinicians in various settings fosters healthier thinking in people presenting for care of musculoskeletal symptoms, supports comprehensive care of musculoskeletal illness. More research is needed to develop indications and interventions that also improve levels of capability. Level-I, meta-analysis of RCT's

Anxiety disorders are the most prevalent psychiatric disorders, exhibiting strong female bias. Clinical studies implicate declining estradiol levels in the exacerbation of anxiety symptoms in the premenstrual phase of the menstrual cycle. This study aimed to simulate estradiol fluctuation-linked anxiety behavior in larval zebrafish, using an estradiol treatment withdrawal model. Contrary to model aims, estradiol treatment withdrawal decreased both basal activity and anxiety-like hyperlocomotion (ANOVA main effect of dose, P < 0.0001 and P < 0.01, respectively) in the light/dark transition test. The accuracy of the estradiol washout model was not improved by longer durations of treatment or withdrawal. Basal activity was slightly altered by supraphysiological concentrations of WAY-200070 in the absence of added estradiol. Estrogen receptor (ER) β expression was not upregulated in larvae exposed to physiologically relevant, low concentrations of estradiol. Longer exposure to low concentrations of estradiol increased antioxidant capacity ( P < 0.01). In addition, acute exposure to low concentrations of estradiol increased basal activity. Data suggest that in the current models, estradiol-associated altered activity levels were linked to more favorable redox status, rather than reflecting altered anxiety levels. As such, it is recommended that zebrafish larval behavioral analysis be conducted in parallel with mechanistic studies such as redox indicators, for investigations focused on ER signaling.

Objective Binge drinking and heavy alcohol use are highly prevalent among college students. During the COVID-19 pandemic, due to lockdown restrictions and other challenges, many college students were burdened with loneliness, which can contribute to chronic stress, and substance use. The current study explores the association between loneliness and various levels of alcohol use among college students in the rural, underserved region of Central Appalachia, USA. Methods Data were collected from a regional sample (n = 320) of college age adults, age 18-25 in the Central Appalachian region. The UCLA-3 item Loneliness Scale (UCLA-3) was used in the study to evaluate loneliness. Logistic regression analysis was conducted to assess the association between levels of loneliness and three separate outcomes, including past year binge drinking, past year heavy alcohol use, and past year weekly alcohol use. Results Overall, 25.5% of the participants reported severe loneliness, 33.6% reported moderate, and 40.9% reported low levels of loneliness. Results of the adjusted models revealed that severe loneliness was associated with higher odds of heavy alcohol use (AOR = 1.89, 95% CI [1.02, 3.50]) and binge drinking (AOR = 2.96, 95% CI [1.16, 7.51]), and not associated with weekly alcohol use. Conclusion The study found that higher levels of loneliness were linked to both binged drinking and heavy alcohol use. Further efforts for counseling and treatment among college students who are burdened with severe loneliness should be considered. The chronic stress associated with severe loneliness needs to be further addressed, particularly among emerging adults.