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.

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.

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.

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.

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.

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.

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).

Clinical Outcomes Following Acute Residential Psychiatric Treatment in Transgender and Gender Diverse Adolescents.

Importance: Transgender and gender diverse (TGD) individuals, who have a gender identity that differs from their sex assigned at birth, are at increased risk of mental health problems, including depression, anxiety, self-injurious behavior, and suicidality, relative to cisgender peers. Objective: To examine mental health outcomes among TGD vs cisgender adolescents in residential treatment. Design, Setting, and Participants: This cohort study's longitudinal design was used to compare groups at treatment entry and discharge, and 1-month postdischarge follow-up. The setting was an adolescent acute residential treatment program for psychiatric disorders. Participants were TGD or cisgender adolescents enrolled in the treatment program. Statistical analysis was performed October 2019 to March 2021. Exposure: Adolescents participated in a 2-week acute residential treatment program for psychiatric disorders. Main Outcomes and Measures: Primary outcomes were depressive (the Center for Epidemiologic Studies Depression Scale [CES-D]) and anxiety (the Multidimensional Anxiety Scale for Children [MASC]) symptoms, and emotional dysregulation (the Difficulties in Emotion Regulation Scale [DERS]), measured at treatment entry and discharge, and postdischarge follow-up. Age of depression onset, suicidality, self-injury, and childhood trauma also were assessed at treatment entry. Results: Of 200 adolescent participants who completed treatment entry and discharge assessments, the mean (SD) age was 16.2 (1.5) years; 109 reported being assigned female at birth (54.5%), 35 were TGD (17.5%), and 66 (49.3%) completed 1-month follow-up. TGD participants had an earlier mean (SD) age of depression onset (TGD: 10.8 [2.4] years vs cisgender: 11.9 [2.3] years; difference: 1.07 years; 95% CI, 0.14-2.01 years; P = .02), higher mean (SD) suicidality scores (TGD: 44.4 [23.1] vs cisgender: 28.5 [25.4]; difference: 16.0; 95% CI, 6.4-25.5; P = .001), more self-injurious behavior (mean [SD] RBQ-A score for TGD: 3.1 [2.5] vs cisgender: 1.7 [1.9]; difference: 1.42; 95% CI, 0.69-2.21; P = .001) and more childhood trauma (eg, mean [SD] CTQ-SF score for emotional abuse in TGD: 12.7 [5.4] vs cisgender: 9.8 [4.7]; difference: 2.85; 95% CI, 1.06-4.64; P = .002). The TGD group also had higher symptom scores (CES-D mean difference: 7.69; 95% CI, 3.30 to 12.08; P < .001; MASC mean difference: 7.56; 95% CI, 0.46 to 14.66; P = .04; and DERS mean difference: 18.43; 95% CI, 8.39 to 28.47; P < .001). Symptom scores were significantly higher at entry vs discharge (CES-D mean difference, -12.16; 95% CI, -14.50 to -9.80; P < .001; MASC mean difference: -3.79; 95% CI, -6.16 to -1.42; P = .02; and DERS mean difference: -6.37; 95% CI, -10.80 to -1.94; P = .05) and follow-up (CES-D mean difference: -9.69; 95% CI, -13.0 to -6.42; P < .001; MASC mean difference: -6.92; 95% CI, -10.25 to -3.59; P < .001; and DERS mean difference: -12.47; 95% CI, -18.68 to -6.26; P < .001). Conclusions and Relevance: This cohort study found mental health disparities in TGD youth relative to cisgender youth, with worse scores observed across assessment time points. For all participants, primary clinical outcome measures were significantly lower at treatment discharge than at entry, with no significant differences between discharge and 1-month follow-up. Given the substantial degree of mental health disparities reported in TGD individuals, these findings warrant focused clinical attention to optimize treatment outcomes in gender minority populations.

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.

Brain Activation during Memory Retrieval is Associated with Depression Severity in Women.

Major depressive disorder (MDD) is a debilitating disorder that interferes with daily functioning, and that occurs at higher rates in women than in men. Structural and functional alterations in hippocampus and frontal lobe have been reported in MDD, which likely contribute to the multifaceted nature of MDD. One area impacted by MDD is hippocampal-mediated memory, which can be probed using a spatial virtual Morris water task (MWT). Women (n=24) across a spectrum of depression severity underwent functional magnetic resonance imaging (fMRI) during MWT. Depression severity, assessed via Beck Depression Inventory (BDI), was examined relative to brain activation during task performance. Significant brain activation was evident in areas traditionally implicated in spatial memory processing, including right hippocampus and frontal lobe regions, for retrieval > motor contrast. When BDI was included as a regressor, significantly less functional activation was evident in left hippocampus, and other non-frontal, task relevant regions for retrieval > rest contrast. Consistent with previous studies, depression severity was associated with functional alterations observed during spatial memory performance. These findings may contribute to understanding neurobiological underpinnings of depression severity and associated memory impairments, which may have implications for treatment approaches aimed at alleviating effects of depression in women.

Women versus men: A critical comparison for understanding the neurobiology of memory.

Spets and Slotnick present a meta-analysis on long-term memory and sex differences. Overall findings indicate greater brain activation in men than women during memory performance. Merits of the activation likelihood estimation meta-analysis include considering study parameters and equating performance to enhance interpretability of activation differences. Variables and concepts relevant to memory and sex differences research also are discussed. As memory is essential for survival, characterizing neurobiological profiles, parsing sex and gender, will help broaden the field of long-term memory and sex differences research.

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.

Thalamic Gamma Aminobutyric Acid Level Changes in Major Depressive Disorder After a 12-Week Iyengar Yoga and Coherent Breathing Intervention.

Objective: To determine if a 12-week yoga intervention (YI) was associated with increased gamma aminobutyric acid (GABA) levels and decreased depressive symptoms in participants with major depressive disorder (MDD). Methods: Subjects were randomized to a high-dose group (HDG) of three YIs a week and a low-dose group (LDG) of two YIs a week. Thalamic GABA levels were obtained using magnetic resonance spectroscopy at Scan-1 before randomization. After the assigned 12-week intervention, Scan-2 was obtained, immediately followed by a YI and Scan-3. Beck Depression Inventory II (BDI-II) scores were obtained before Scan-1 and Scan-3. Settings/Location: Screenings and interventions occurred at the Boston University Medical Center. Imaging occurred at McLean Hospital. Subjects: Subjects met criteria for MDD. Intervention: Ninety minutes of Iyengar yoga and coherent breathing at five breaths per minute plus homework. Outcome measures: GABA levels and the BDI-II. Results: BDI-II scores improved significantly in both groups. GABA levels from Scan-1 to Scan-3 and from Scan-2 to Scan-3 were significantly increased in the LDG (n = 15) and showed a trend in the total cohort. Post hoc, participants were divided into two groups based on having an increase in GABA levels at Scan-2. Increases in Scan-2 GABA levels were observed in participants whose mean time between their last YI and Scan-2 was 3.93 ± 2.92 standard deviation (SD) days, but not in those whose mean time between their last YI and Scan-2 was 7.83 ± 6.88 SD. Conclusions: This study tentatively supports the hypothesis that one of the mechanisms through which yoga improves mood is by increasing the activity of the GABA system. The observed increase in GABA levels following a YI that was no longer observed 8 days after a YI suggests that the associated increase in GABA after a YI is time limited such that at least one YI a week may be necessary to maintain the elevated GABA levels.

Altered corticolimbic connectivity reveals sex-specific adolescent outcomes in a rat model of early life adversity.

Exposure to early-life adversity (ELA) increases the risk for psychopathologies associated with amygdala-prefrontal cortex (PFC) circuits. While sex differences in vulnerability have been identified with a clear need for individualized intervention strategies, the neurobiological substrates of ELA-attributable differences remain unknown due to a paucity of translational investigations taking both development and sex into account. Male and female rats exposed to maternal separation ELA were analyzed with anterograde tracing from basolateral amygdala (BLA) to PFC to identify sex-specific innervation trajectories through juvenility (PD28) and adolescence (PD38;PD48). Resting-state functional connectivity (rsFC) was assessed longitudinally (PD28;PD48) in a separate cohort. All measures were related to anxiety-like behavior. ELA-exposed rats showed precocial maturation of BLA-PFC innervation, with females affected earlier than males. ELA also disrupted maturation of female rsFC, with enduring relationships between rsFC and anxiety-like behavior. This study is the first providing both anatomical and functional evidence for sex- and experience-dependent corticolimbic development.

Having a traumatic childhood increases the risk a person will develop anxiety disorders later in life. Early life adversity affects men and women differently, but scientists do not yet know why. Learning more could help scientists develop better ways to prevent or treat anxiety disorders in men and women who experienced childhood trauma. Anxiety occurs when threat-detecting brain circuits turn on. These circuits begin working in infancy, and during childhood and adolescence, experiences shape the brain to hone the body's responses to perceived threats. Two areas of the brain that are important hubs for anxiety-related brain circuits include the basolateral amygdala (BLA) and the prefrontal cortex (PFC). Now, Honeycutt et al. show that rats that experience early life adversity develop stronger connections between the BLA and PFC, and these changes occur earlier in female rats. In the experiments, one group of rats was repeatedly separated from their mothers and littermates (an early life trauma), while a second group was not. Honeycutt et al. examined the connections between the BLA and PFC in the two groups at three different time periods during their development: the juvenile stage, early adolescence, and late adolescence. The experiments showed stronger connections between the BLA and PFC begin to appear earlier in juvenile traumatized female rats. But these changes did not appear in their male counterparts until adolescence. Lastly, the rats that developed these strengthened BLA-PFC connections also behaved more anxiously later in life. This may mean that the ideal timing for interventions may be different for males and females. More work is needed to see if these results translate to humans and then to find the best times and methods to help people who experienced childhood trauma.

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.

Psychological Function, Iyengar Yoga, and Coherent Breathing: A Randomized Controlled Dosing Study.

BACKGROUND: Evidence suggests that yoga may be an effective treatment for major depressive disorder (MDD). Studies evaluating the "dosing" of yoga treatment and efficacy for MDD are needed. The goal of this study was to assess the effects of an intervention combining Iyengar yoga and coherent breathing in participants with MDD and determine the optimal intervention dose. METHODS: Thirty-two participants (18 to 65 y of age) diagnosed with MDD were randomized to a high-dose group (HDG) or a low-dose group (LDG) of yoga and coherent breathing for 12 weeks. The HDG (n=15) involved three 90-minute yoga classes and four 30-minute homework sessions per week. The LDG (n=15) involved two 90-minute yoga classes and three 30-minute homework sessions per week. Participants were evaluated at baseline, week 4, week 8, and week 12 with the following instruments: Positivity Self-Test, Spielberger State Anxiety Inventory, Patient Health Questionnaire-9, Pittsburgh Sleep Quality Index, and Exercise-induced Feeling Inventory. Data were analyzed using intent-to-treat methods. RESULTS: Significant improvements in all outcome measures were found for both groups, with acute and cumulative benefits. Although the HDG showed greater improvements on all scales, between-group differences did not reach significance, possibly due to lack of power because of the small sample size. Cumulative yoga minutes were correlated with improvement in outcome measures. LIMITATION: This dosing study did not include a non-yoga control. CONCLUSIONS: Improvement in psychological symptoms correlated with cumulative yoga practice. Both interventions reduced symptoms of depression and anxiety and increased feelings of positivity. The time commitment for yoga practice needs to be weighed against benefits when designing yoga interventions.

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.