Alterations in BNST Intrinsic Functional Connectivity in Early Abstinence from Alcohol Use Disorder.

AIMS: Maintaining abstinence from alcohol use disorder (AUD) is extremely challenging, partially due to increased symptoms of anxiety and stress that trigger relapse. Rodent models of AUD have identified that the bed nucleus of the stria terminalis (BNST) contributes to symptoms of anxiety-like behavior and drug-seeking during abstinence. In humans, however, the BNST's role in abstinence remains poorly understood. The aims of this study were to assess BNST network intrinsic functional connectivity in individuals during abstinence from AUD compared to healthy controls and examine associations between BNST intrinsic functional connectivity, anxiety and alcohol use severity during abstinence. METHODS: The study included resting state fMRI scans from participants aged 21-40 years: 20 participants with AUD in abstinence and 20 healthy controls. Analyses were restricted to five pre-selected brain regions with known BNST structural connections. Linear mixed models were used to test for group differences, with sex as a fixed factor given previously shown sex differences. RESULTS: BNST-hypothalamus intrinsic connectivity was lower in the abstinent group relative to the control group. There were also pronounced sex differences in both the group and individual analyses; many of the findings were specific to men. Within the abstinent group, anxiety was positively associated with BNST-amygdala and BNST-hypothalamus connectivity, and men, not women, showed a negative relationship between alcohol use severity and BNST-hypothalamus connectivity. CONCLUSIONS: Understanding differences in connectivity during abstinence may help explain the clinically observed anxiety and depression symptoms during abstinence and may inform the development of individualized treatments.

Anterior cingulate metabolite levels, memory, and inhibitory control in abstinent men and women with alcohol use disorder.

Alcohol use disorder (AUD) has been shown to have harmful cognitive and physiological effects, including altered brain chemistry. Further, although men and women may differ in vulnerability to the neurobiological effects of AUD, the results of existing studies have been conflicting. We examined brain metabolite levels and cognitive functions in a cross-section of men with AUD (AUDm) and women with AUD (AUDw) to determine the degree of abnormalities after extended periods of abstinence (mean, 6 years) and to evaluate gender differences in neuropsychological and metabolite measures. Participants were 40 abstinent individuals with AUD (22 AUDw, 18 AUDm) and 50 age-equivalent non-AUD comparison participants (26 NCw, 24 NCm). Proton magnetic resonance spectroscopy (MRS) was employed at 3 Tesla to acquire metabolite spectra from the dorsal anterior cingulate cortex (dACC). Brain metabolites N-acetyl aspartate (NAA), choline (Cho), myo-Inositol (mI), and glutamate & glutamine (Glx) were examined relative to measures of memory and inhibitory control. Metabolite levels did not differ significantly between AUD and NC groups. Memory and inhibitory-control impairments were observed in the AUD group. There also were significant group-specific associations between metabolite ratios and measures of inhibitory control. There were no group-by-gender interactions for the four metabolite ratios. These findings demonstrate that brain metabolite levels in men and women with AUD, following long-term abstinence, do not differ from individuals without AUD. The data also provide preliminary evidence of sustained associations between metabolite levels and measures of inhibitory control, a functional domain important for curtailing harmful drinking.

Religious affiliation protects against alcohol/substance use initiation: A prospective study among healthy adolescents.

BACKGROUND: A substantial volume of the literature suggests that religious factors buffer against alcohol/substance use among adults, but research among adolescents is sparse. Further, few studies in this area have been prospective, and therefore it is unclear how religion may impact less alcohol/substance use among adolescents. METHOD: We prospectively evaluated effects of religious affiliation on initiation of alcohol/substance use in a sample of 81 psychiatrically healthy 13-14-year-olds from New England, over a 3-year period (from November 2015 to January 2019). Known risk factors were also evaluated including anxiety, depression, and impulsivity; family history of mental illness and alcohol/substance misuse; and volume of brain regions implicated in adolescent alcohol/substance misuse (assessed by Magnetic Resonance Imaging). RESULTS: Religiously affiliated adolescents were significantly less likely to initiate use of alcohol/substances (hazard ratio [HR] = 0.38). The addition of family history of alcohol/substance misuse to the model increased the predictive value of religious affiliation (HR = 0.34). Other risk factors did not diminish nor increase observed effects. CONCLUSIONS: These findings support and extend the current research by suggesting that religious affiliation protects against initiation of alcohol/substance use during early adolescence, particularly in individuals with elevated risk.

Large-scale brain network activation during emotional inhibitory control: Associations with alcohol misuse in college freshmen.

BACKGROUND: The transition to college is associated with increased risk of alcohol misuse and a consequent increase in negative, alcohol-related social and health impacts. Traits associated with ongoing brain maturation during this period, including impulsivity in emotional contexts, could contribute to risky alcohol use. METHODS: This functional magnetic resonance imaging (fMRI) study examined brain network activation strength during an emotional inhibitory control task (Go-NoGo), which required participants to ignore background images with negative or neutral emotional valence during performance. Participants were 60 college freshmen (aged 18-20 years, 33 women). Survey measures, completed at baseline and one-year follow-up (follow-up n = 52, 29 women), assessed alcohol misuse alcohol use disorders identification test (AUDIT), alcohol/substance use counseling center assessment of psychological symptoms (C-CAPS), and negative consequences of alcohol use young adult alcohol consequences questionnaire (YAACQ). Measures were examined relative to network activation strength, on the Negative NoGo > Neutral NoGo contrast, of four large-scale brain networks implicated in top-down regulation of cognition and attention: right and left lateral frontoparietal networks (rL-FPN; lL-FPN), dorsal attention network (DAN), and salience network (SN). RESULTS: Activation strength of DAN was negatively associated with scores on the AUDIT (p = 0.013) and YAACQ (p = 0.004) at baseline, and with C-CAPS score at baseline and follow-up (p = 0.002; p = 0.005), and positively associated with accuracy on NoGo trials with negative backgrounds (p = 0.014). Activation strength of rL-FPN was positively associated with C-CAPS score at follow-up (p = 0.003). SN activation strength was negatively associated with accuracy on NoGo trials with negative (p < 0.001) and neutral (p = 0.002) backgrounds and with the accuracy difference between negative versus neutral NoGo trials (p = 0.003). CONCLUSION: These findings suggest that less engagement of large-scale brain circuitry that supports top-down attentional control, specifically during negative emotions, is associated with more problematic drinking in emerging adults who attend college. This pattern of network activation may serve as a risk marker for ongoing self-regulation deficits during negative emotion that could increase risk of problematic alcohol use and negative impacts of drinking.

Alterations in connectivity of the bed nucleus of the stria terminalis during early abstinence in individuals with alcohol use disorder.

BACKGROUND: For individuals with Alcohol Use Disorder (AUD), long-term recovery is difficult in part due to symptoms of anxiety that occur during early abstinence and can trigger relapse. Research in rodent models of AUD has identified the bed nucleus of the stria terminalis (BNST), a small, sexually dimorphic, subcortical region, as critical for regulating anxiety-like behaviors during abstinence, particularly in female mice. Furthermore, prolonged alcohol use and subsequent abstinence alter BNST afferent and efferent connections to other brain regions. To our knowledge, however, no studies of early abstinence have investigated BNST structural connectivity in humans during abstinence; this study addresses that gap. METHODS: Nineteen participants with AUD currently in early abstinence and 20 healthy controls completed a diffusion tensor imaging (DTI) scan. BNST structural connectivity was evaluated using probabilistic tractography. A linear mixed model was used to test between-groups differences in BNST network connectivity. Exploratory analyses were conducted to test for correlations between BNST connectivity and alcohol use severity and anxiety within the abstinence group. Sex was included as a factor for all analyses. RESULTS: The BNST showed stronger structural connectivity with the BNST network in early abstinence women than in control women, which was not seen in men. Women also showed region-specific differences, with stronger BNST-hypothalamus structural connectivity but weaker vmPFC-BNST structural connectivity than men. Exploratory analyses also demonstrated a relationship between alcohol use severity and vmPFC-BNST structural connectivity that was moderated by sex. CONCLUSIONS: This study is the first to demonstrate BNST structural connectivity differences in early abstinence and revealed key sex differences. The sex-specific differences in BNST structural connectivity during early abstinence could underlie known sex differences in abstinence symptoms and relapse risk and help to inform potential sex-specific treatments.

Anxiety during abstinence from alcohol: A systematic review of rodent and human evidence for the anterior insula's role in the abstinence network.

Alcohol Use Disorder (AUD) is a chronic, relapsing disease that impacts almost a third of Americans. Despite effective treatments for attaining sobriety, the majority of patients relapse within a year, making relapse a substantial barrier to long-term treatment success. A major factor contributing to relapse is heightened negative affect that results from the combination of abstinence-related increases in stress-reactivity and decreases in reward sensitivity. Substantial research has contributed to the understanding of reward-related changes in AUD. However, less is known about anxiety during abstinence, a critical component of understanding addiction as anxiety during abstinence can trigger relapse. Most of what we know about abstinence-related negative affect comes from rodent studies which have identified key brain regions responsible for abstinence-related behaviors. This abstinence network is composed of brain regions that make up the extended amygdala: the nucleus accumbens (NAcc), the central nucleus of the amygdala (CeA), and the bed nucleus of the stria terminalis (BNST). More recently, emerging evidence from rodent and human studies suggests a fourth brain region, the anterior insula, might be part of the abstinence network. Here, we review current rodent and human literature on the extended amygdala's role in alcohol abstinence and anxiety, present evidence for the anterior insula's role in the abstinence network, and provide future directions for research to further elucidate the neural underpinnings of abstinence in humans. A better understanding of the abstinence network is critical toward understanding and possibly preventing relapse in AUD.

Denoising scanner effects from multimodal MRI data using linked independent component analysis.

Pooling magnetic resonance imaging (MRI) data across research studies, or utilizing shared data from imaging repositories, presents exceptional opportunities to advance and enhance reproducibility of neuroscience research. However, scanner confounds hinder pooling data collected on different scanners or across software and hardware upgrades on the same scanner, even when all acquisition protocols are harmonized. These confounds reduce power and can lead to spurious findings. Unfortunately, methods to address this problem are scant. In this study, we propose a novel denoising approach that implements a data-driven linked independent component analysis (LICA) to identify scanner-related effects for removal from multimodal MRI to denoise scanner effects. We utilized multi-study data to test our proposed method that were collected on a single 3T scanner, pre- and post-software and major hardware upgrades and using different acquisition parameters. Our proposed denoising method shows a greater reduction of scanner-related variance compared with standard GLM confound regression or ICA-based single-modality denoising. Although we did not test it here, for combining data across different scanners, LICA should prove even better at identifying scanner effects as between-scanner variability is generally much larger than within-scanner variability. Our method has great promise for denoising scanner effects in multi-study and in large-scale multi-site studies that may be confounded by scanner differences.

Morphometric Biomarkers of Adolescents With Familial Risk for Alcohol Use Disorder.

BACKGROUND: While many adolescents exhibit risky behavior, teenagers with a family history (FH+) of an alcohol use disorder (AUD) are at a heightened risk for earlier initiation of alcohol use, a more rapid escalation in frequency and quantity of alcohol consumption and developing a subsequent AUD in comparison with youth without such family history (FH-). Neuroanatomically, developmentally normative risk-taking behavior parallels an imbalance between more protracted development of the prefrontal cortex (PFC) and earlier development of limbic regions. Magnetic resonance imaging (MRI)-derived volumetric properties were obtained for these structures in FH+ and FH- adolescents. METHODS: Forty-two substance-naïve adolescents (13- to 14-year-olds), stratified into FH+ (N = 19, 13 girls) and FH- (N = 23, 11 girls) age/handedness-matched groups, completed MRI scanning at 3.0T, as well as cognitive and clinical testing. T1 images were processed using FreeSurfer to measure PFC and hippocampi/amygdalae subfields/nuclei volumes. RESULTS: FH+ status was associated with larger hippocampal/amygdala volumes (p < 0.05), relative to FH- adolescents, with right amygdala results appearing to be driven by FH+ boys. Volumetric differences also were positively associated with family history density (p < 0.05) of having an AUD. Larger subfields/nuclei volumes were associated with higher anxiety levels and worse auditory verbal learning performance (p < 0.05). CONCLUSIONS: FH+ risk for AUD is detectable via neuromorphometric characteristics, which precede alcohol use onset and the potential onset of a later AUD, that are associated with emotional and cognitive measures. It is plausible that the development of limbic regions might be altered in FH+ youth, even prior to the onset of alcohol use, which could increase later risk. Thus, targeted preventative measures are warranted that serve to delay the onset of alcohol use in youth, particularly in those who are FH+ for an AUD.

Sex Differences in the Association between Heavy Drinking and Behavioral Distress Tolerance and Emotional Reactivity Among Non-Depressed College Students.

BACKGROUND: Heavy episodic drinking (HED) is a common behavior among college students that is associated with severe negative consequences. Negative reinforcement processes have been applied to elucidate mechanisms underlying relationships between consumption of alcohol and the desire to alleviate negative feelings. Distress tolerance (DT) and emotional reactivity are two mechanisms that are consistent with the self-medication model that may contribute to HED. The current study investigated relationships between DT, emotional reactivity, defined as frustration reactivity and irritability reactivity, and HED in a non-depressed college population. Given differential patterns of consumption and motivation for drinking between males and females, sex differences were also examined. SHORT SUMMARY: The study examined two constructs consistent with negative reinforcement processes, behavioral distress tolerance (DT) and emotional reactivity (frustration reactivity and irritability reactivity), to explain heavy episodic drinking (HED) among non-depressed college students. Behavioral DT and frustration reactivity independently predicted HED. Higher HED was associated with higher frustration reactivity and lower behavioral DT in women, but nor in men. METHODS: One-hundred-ten college students without depressive symptoms completed alcohol use measures and the Paced Auditory Serial Attention Task (PASAT-C) to assess behavioral DT and emotional reactivity. RESULTS: DT and frustration reactivity independently predicted HED. The association between DT and HED was moderated by sex such that higher levels of DT predicted higher HED among females, but not among males. Higher frustration reactivity scores were associated with a greater number of HED. CONCLUSIONS: Results provide supporting evidence that DT and emotional reactivity are distinct factors, and that they predict HED independently. Results underscore the importance of examining sex differences when evaluating the association between HED and negative reinforcement processes in this population.

Treatment of Major Depressive Disorder with Iyengar Yoga and Coherent Breathing: A Randomized Controlled Dosing Study.

Objectives: The aims of this study were to assess the effects of an intervention of Iyengar yoga and coherent breathing at five breaths per minute on depressive symptoms and to determine optimal intervention yoga dosing for future studies in individuals with major depressive disorder (MDD). Methods: Subjects were randomized to the high-dose group (HDG) or low-dose group (LDG) for a 12-week intervention of three or two intervention classes per week, respectively. Eligible subjects were 18-64 years old with MDD, had baseline Beck Depression Inventory-II (BDI-II) scores ≥14, and were either on no antidepressant medications or on a stable dose of antidepressants for ≥3 months. The intervention included 90-min classes plus homework. Outcome measures were BDI-II scores and intervention compliance. Results: Fifteen HDG (Mage=38.4±15.1 years) and 15 LDG (Mage=34.7±10.4 years) subjects completed the intervention. BDI-II scores at screening and compliance did not differ between groups (p=0.26). BDI-II scores declined significantly from screening (24.6±1.7) to week 12 (6.0±3.8) for the HDG (-18.6±6.6; p < 0.001), and from screening (27.7±2.1) to week 12 (10.1±7.9) in the LDG (-17.7±9.3; p < 0.001). There were no significant differences between groups, based on response (i.e., >50% decrease in BDI-II scores; p=0.65) for the HDG (13/15 subjects) and LDG (11/15 subjects) or remission (i.e., number of subjects with BDI-II scores <14; p=1.00) for the HDG (14/15 subjects) and LDG (13/15 subjects) after the 12-week intervention, although a greater number of subjects in the HDG had 12-week BDI-II scores ≤10 (p=0.04). Conclusion: During this 12-week intervention of yoga plus coherent breathing, depressive symptoms declined significantly in patients with MDD in both the HDG and LDG. Both groups showed comparable compliance and clinical improvements, with more subjects in the HDG exhibiting BDI-II scores ≤10 at week 12.

Binge alcohol consumption in emerging adults: anterior cingulate cortical "thinness" is associated with alcohol use patterns.

BACKGROUND: The brain undergoes dynamic and requisite changes into the early 20s that are associated with improved cognitive efficiency, particularly in prefrontal regions that are still undergoing neuromaturation. As alcohol consumption is typically initiated and progresses to binge drinking (BD) during this time, the objective of the present study was to investigate the impact of binge alcohol consumption on frontal lobe cortical thickness in emerging adults. METHODS: Twenty-three binge drinking (11 females, mean age 22.0 ± 1.2) and 31 light drinking (15 females, mean age 21.5 ± 1.6) emerging adults underwent high-resolution magnetic resonance imaging at 3 Tesla. Cortical surface reconstruction and thickness estimation were performed using FreeSurfer for 3 a priori brain regions of interest: bilateral anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and parieto-occipital sulcus (POS). Cortical thickness measurements were then compared between binge drinker (BD) and light drinker (LD) groups. RESULTS: Cortical thickness was significantly lower in BD than LD in the right middle ACC (mid-ACC; p ≤ 0.05) and in the left dorsal PCC (dPCC; p ≤ 0.01). No significant differences in cortical thickness were observed in the POS. Cortical thickness in the mid-ACC correlated negatively with higher quantity and frequency of drinks consumed (p < 0.01) and positively with the number of days elapsed since most recent use (p < 0.05). Furthermore, less cortical thickness in the mid-ACC in the BD group alone correlated with reported patterns of high quantity and frequency of alcohol consumption (p ≤ 0.05). CONCLUSIONS: Findings suggest that past and recent patterns of intermittent heavy alcohol consumption are associated with less frontal cortical thickness (i.e., "thinness") of the right mid-ACC and left dPCC in emerging adults, but not the POS. While cortical thinness could have predated binge drinking, this pattern of maladaptive consumption may have acute neurotoxic effects that interfere with the finalization of neuromaturational processes in the vulnerable frontal cortex, resulting in increased microarchitectural pruning.

Altered anterior cingulate neurochemistry in emerging adult binge drinkers with a history of alcohol-induced blackouts.

BACKGROUND: Binge alcohol consumption is associated with multiple neurobiological consequences, including altered neurophysiology, brain structure, and functional activation. Magnetic resonance spectroscopy (MRS) studies have demonstrated neurochemical alterations in the frontal lobe of alcohol users, although most studies focused on older, alcohol-dependent subjects. METHODS: In this study, neurochemical data were acquired using MRS at 4.0 Tesla from emerging adults (18 to 24 years old) who were binge alcohol drinkers (BD, n = 23) or light drinkers (LD, n = 31). Since binge drinking is also associated with increased prevalence of experiencing an alcohol-induced blackout, BD were stratified into alcohol-induced blackout (BDBO) and non-blackout (BDN) groups. RESULTS: Overall, BD had significantly lower gamma amino-butyric acid (GABA) and N-acetyl-aspartate (NAA) in the anterior cingulate cortex (ACC) than LD. When stratified by blackout history, BDBO also had lower ACC glutamate (Glu) than LD. No group differences in MRS metabolites were observed in the parietal-occipital cortex. Lower ACC GABA and Glu remained significant after accounting for lower gray matter content in BD, however, NAA differences were no longer evident. In addition, low ACC GABA levels were associated with greater alcohol use consequences, and worse response inhibition and attention/mental flexibility in BD. CONCLUSIONS: These data indicate that binge drinking affects frontal lobe neurochemistry, more so in those who had experienced an alcohol-induced blackout. Characterization of the neurochemical profiles associated with binge alcohol consumption and blackout history may help identify unique risk factors for the later manifestation of alcohol abuse and dependence, in young individuals who are heavy, frequent drinkers, but who do not meet the criteria for alcohol abuse disorders.

Insula and anterior cingulate GABA levels in posttraumatic stress disorder: preliminary findings using magnetic resonance spectroscopy.

BACKGROUND: Increased reactivity of the insular cortex and decreased activity of the dorsal anterior cingulate cortex (ACC) are seen in functional imaging studies of posttraumatic stress disorder (PTSD), and may partly explain the persistent fear and anxiety proneness that characterize the disorder. A possible neurochemical correlate is altered function of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). We report results from what we believe is the first study applying proton magnetic resonance spectroscopy ((1) H-MRS) to measure brain GABA in PTSD. METHODS: Thirteen adults with DSM-IV PTSD and 13 matched healthy control subjects underwent single voxel (1) H-MRS at 4 Tesla. GABA was measured in the right anterior insula and dorsal ACC, using Mescher-Garwood Point-Resolved Echo Spectroscopy Sequence (MEGAPRESS) spectral editing. Subjects were interviewed with the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale, and also completed the State and Trait Anxiety Inventory. RESULTS: Insula GABA was significantly lower in PTSD subjects than in controls, and dorsal ACC GABA did not differ significantly between the groups. Insula GABA was not significantly associated with severity of PTSD symptoms. However, lower insula GABA was associated with significantly higher state and trait anxiety in the subject sample as a whole. CONCLUSIONS: PTSD is associated with reduced GABA in the right anterior insula. This preliminary evidence of the (1) H-MRS GABA metabolite as a possible biomarker of PTSD encourages replication in larger samples and examination of relations with symptom dimensions. Future studies also should examine whether insula GABA is a marker of anxiety proneness, cutting across clinical diagnostic categories.

Contributions of magnetic resonance spectroscopy to understanding development: potential applications in the study of adolescent alcohol use and abuse.

A growing body of research has documented structural and functional brain development during adolescence, yet little is known about neurochemical changes that occur during this important developmental period. Magnetic resonance spectroscopy (MRS) is a well-developed technology that permits the in vivo quantification of multiple brain neurochemicals relevant to neuronal health and functioning. However, MRS technology has been underused in exploring normative developmental changes during adolescence and the onset of alcohol and drug use and abuse during this developmental period. This review begins with a brief overview of normative cognitive and neurobiological development during adolescence, followed by an introduction to MRS principles. The subsequent sections provide a comprehensive review of the existing MRS studies of development and cognitive functioning in healthy children and adolescents. The final sections of this article address the potential application of MRS in identifying neurochemical predictors and consequences of alcohol use and abuse in adolescence. MRS studies of adolescent populations hold promise for advancing our understanding of neurobiological risk factors for psychopathology by identifying the biochemical signatures associated with healthy brain development, as well as neurobiological and cognitive correlates of alcohol and substance use and abuse.

Why is Spiritual Psychotherapy for Inpatient, Residential, and Inpatient Treatment (SPIRIT) more effective when provided by nonreligious clinicians?

Previous research suggests that patients receiving spiritual psychotherapy may have better outcomes when treatment is provided by nonreligious clinicians, compared to religious clinicians. We examined these effects within a large and clinically heterogeneous sample of patients (N = 1,443) receiving Spiritual Psychotherapy for Inpatient, Residential, and Intensive Treatment (SPIRIT; Rosmarin et al., 2019) by a diverse sample of clinicians (n = 22). In addition to demographics, patients completed a brief measure of their experience in SPIRIT; clinicians completed measures of previous mental health training, previous training in spiritual psychotherapy, and attitudes toward spiritual psychotherapy, and also provided details regarding modalities, clinical interventions, and spiritual interventions utilized at each SPIRIT session. Perceived benefit of SPIRIT was greater when treatment was delivered by non-religious clinicians. Mediating factors on these effects were evaluated using correlations and multiple regression analyses. Of 26 potential explanatory factors, only 4 were significant, all of which related to the therapeutic process. Nonreligious clinicians were more likely to utilize dialectical behavior therapy (DBT), facilitate coping, encourage spiritual coping, and explore the relevance of spirituality to mental health, all of which also predicted better perceived benefit from SPIRIT. All four variables jointly, but not severally, mediated relationships between clinician religion and perceived benefit of SPIRIT. These findings suggest that DBT may be the most effective modality for delivering spiritual psychotherapy to acute patients, particularly in a group setting. Future research should further examine preferences for clinical modalities and techniques among religious and nonreligious clinicians, and effects of such preferences on perceived benefit, in a variety of settings. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Regional specificity and clinical correlates of cortical GABA alterations in posttraumatic stress disorder.

Gamma-aminobutyric acid (GABA) metabolism is implicated in posttraumatic stress disorder (PTSD) and may be altered in prefrontal-limbic brain regions involved in arousal regulation. This study used proton magnetic resonance spectroscopy (MRS) to test the hypothesis that PTSD and trauma-exposed non-PTSD comparison (TENC) adults have significantly different GABA than healthy comparison (HC) subjects in two brain areas implicated in arousal (medial prefrontal cortex, insula) but not in a control brain area (posterior temporal cortex). We also examined whether GABA alterations correlated with hyperarousal and dissociation symptoms. One hundred and fourteen participants (39 PTSD, 34 TENC, 41 HC) underwent 3T MRS of the medial prefrontal, right insular, and right posterior temporal cortices, and the GABA plus macromolecule signal (GABA+) was normalized to creatine (Cr). The Clinician Administered PTSD Scale measured hyperarousal symptoms, including sleep disruption. The Dissociative Experiences Scale assessed dissociation symptoms. PTSD and TENC participants had significantly lower mPFC GABA+/Cr than HC participants, and this deficit was significantly correlated with greater dissociation. Compared with HC, PTSD patients but not TENC had significantly lower insula GABA+/Cr. Total hyperarousal symptoms and sleep disruption were not significantly associated with GABA+/Cr alterations in either region. Our findings point to lower GABA in cortical areas implicated in arousal regulation in PTSD and suggest that GABA alterations are associated with symptoms of trauma-related psychopathology but not always a biomarker of diagnosis. These findings also add to evidence that dissociation has distinct neural correlates within PTSD, including high excitability of medial prefrontal cortex.

Effects of Sexual Orientation on Spiritual Psychotherapy for Inpatient, Residential & Intensive Treatment.

Objectives: Spiritual psychotherapy addresses mental health concerns by integrating spirituality/religion into treatment. There is scant research on how such approaches interact with sexual minority status. We sought to identify and compare how sexual minority and heterosexual patients respond to spiritual psychotherapy. Method: We collected data from heterosexual (n = 66) and sexual minority (n = 15) patients who self-referred to participate in Spiritual Psychotherapy for Inpatient Residential & Intensive Treatment (SPIRIT), a spiritually-integrated, group-based, cognitive-behavioral treatment. Results: We did not find significant differences between heterosexual and sexual minority patients across demographic/clinical variables, spiritual/religious characteristics, or effects of SPIRIT. Both groups reported notable perceived benefit of SPIRIT. Conclusions: Although not specifically tailored for sexual minority patients, or intended to reconcile spiritual/religious conflicts around sexual identity, programs like SPIRIT may benefit sexual minority patients by providing a safe space to explore both sexual orientation and religious identity. In turn, this may help sexual minority patients develop frameworks to recruit spirituality/religion in the process of coping with distress, as a catalyst for clinical change.

Forgiveness Mediates the Relationship Between Middle Frontal Gyrus Volume and Clinical Symptoms in Adolescents.

Dispositional forgiveness is positively associated with many facets of wellbeing and has protective implications against depression and anxiety in adolescents. However, little work has been done to examine neurobiological aspects of forgiveness as they relate to clinical symptoms. In order to better understand the neural mechanisms supporting the protective role of forgiveness in adolescents, the current study examined the middle frontal gyrus (MFG), which comprises the majority of the dorsolateral prefrontal cortex (DLPFC) and is associated with cognitive regulation, and its relationship to forgiveness and clinical symptoms in a sample of healthy adolescents. In this cross-sectional study (n = 64), larger MFG volume was significantly associated with higher self-reported dispositional forgiveness scores and lower levels of depressive and anxiety symptoms. Forgiveness mediated the relationship between MFG volume and both depressive and anxiety symptom levels. The mediating role of forgiveness in the relationship between MFG volume and clinical symptoms suggests that one way that cognitive regulation strategies supported by this brain region may improve adolescent mental health is via increasing a capacity for forgiveness. The present study highlights the relevance of forgiveness to neurobiology and their relevance to emotional health in adolescents. Future longitudinal studies should focus on the predictive quality of the relationship between forgiveness, brain volume and clinical symptoms and the effects of forgiveness interventions on these relationships.

Perceived stress and rejection associated with functional network strength during memory retrieval in adolescents.

The brain undergoes substantial structural and functional remodeling during adolescence, including alterations in memory-processing regions influenced by stress. This study evaluated brain activation using functional magnetic resonance imaging (fMRI) during spatial memory performance using a virtual Morris water task (MWT) and examined the associations between default mode network (DMN) activation, task performance, and perceived stress and rejection. Functional magnetic resonance imaging data were acquired at 3 Tesla from 59 (34 female) adolescents (13-14 years). The NIH Emotion Toolbox was used to measure perceived stress and rejection. During the MWT, hippocampus and prefrontal cortex showed greater activation during memory retrieval relative to motor performance. Templates of brain functional networks from the Human Connectome Project study were used to extract individual participants' brain network activation strengths for the retrieval > motor contrast for two sub-networks of the default mode network: medial temporal lobe (MTL-DMN) and dorsomedial prefrontal (dMPFC-DMN). For the MTL-DMN sub-network only, activation was significantly associated with worse MWT performance (p = .008) and greater perceived stress (p = .008) and perceived rejection (p = .002). Further, MWT performance was negatively associated with perceived rejection (p = .007). These findings suggest that perceived stress and rejection are related to engagement of MTL-DMN during spatial memory and that engagement of this network impacts performance. These findings also demonstrate the utility of examining task-related network activation strength to identify the impact of perceived stress and rejection on large-scale brain network functioning during adolescence.