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.

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.

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.

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.

Preliminary evidence for white matter metabolite differences in marijuana-dependent young men using 2D J-resolved magnetic resonance spectroscopic imaging at 4 Tesla.

Chronic marijuana (MRJ) use is associated with altered cognition and mood state, altered brain metabolites, and functional and structural brain changes. The objective of this study was to apply proton magnetic resonance spectroscopic imaging (MRSI) to compare proton metabolite levels in 15 young men with MRJ dependence and 11 healthy non-using (NU) young men. Spectra were acquired at 4.0 Tesla using 2D J-resolved MRSI to resolve coupled resonances in J-space and to quantify the entire J-coupled spectral surface of metabolites from voxels containing basal ganglia and thalamus, temporal and parietal lobes, and occipital white and gray matter. This method permitted investigation of high-quality spectra for regression analyses to examine metabolites relative to tissue type. Distribution of myo-inositol (mI)/creatine (Cr) was altered in the MRJ group whereas the NU group exhibited higher mI/Cr in WM than GM, this pattern was not observed in MRJ subjects. Significant relationships observed between global mI/Cr and distribution in WM, and self-reported impulsivity and mood symptoms were also unique between MRJ and NU groups. These preliminary findings suggest that mI, and distribution of this glial metabolite in WM, is altered by MRJ use and is associated with behavioral and affective features reported by young MRJ-dependent men.

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.

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.

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.

Differences in regional blood volume during a 28-day period of abstinence in chronic cannabis smokers.

Cerebral blood volume (CBV) studies have provided important insight into the effects of illicit substances such as cannabis. The present study examined changes in regional blood volume in the frontal and temporal lobe, and the cerebellum during 28 days of supervised abstinence from cannabis. Dynamic susceptibility contrast MRI (DSCMRI) data were collected on 15 current, long-term cannabis users between 6 and 36 h after the subjects' last reported cannabis use (Day 0), and again after 7 and 28 days of abstinence. Resting state CBV images were also acquired on 17 healthy comparison subjects. The present findings demonstrate that at Day 7, cannabis users continued to display increased blood volumes in the right frontal region, the left and right temporal regions, and the cerebellum. However, after 28 days of abstinence, only the left temporal area and cerebellum showed significantly increased CBV values in cannabis users. These findings suggest that while CBV levels begin to normalize with continued abstinence from cannabis, specifically in frontal areas, other temporal and cerebellar brain regions show slower CBV decreases.

Adolescent Hippocampal and Prefrontal Brain Activation During Performance of the Virtual Morris Water Task.

The frontal cortex undergoes substantial structural and functional changes during adolescence and significant developmental changes also occur in the hippocampus. Both of these regions are notably vulnerable to alcohol and other substance use, which is typically initiated during adolescence. Identifying measures of brain function during adolescence, particularly before initiation of drug or alcohol use, is critical to understanding how such behaviors may affect brain development, especially in these vulnerable brain regions. While there is a substantial developmental literature on adolescent working memory, less is known about spatial memory. Thus, a virtual Morris water task (vMWT) was applied to probe function of the adolescent hippocampus. Multiband blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) data were acquired at 3T during task performance. Participants included 32 healthy, alcohol- and drug-naïve adolescents, 13-14 years old, examined at baseline of a 3-year longitudinal MRI study. Significantly greater BOLD activation was observed in the hippocampus and surrounding areas, and in prefrontal regions involved in executive function, during retrieval relative to motor performance. In contrast, significantly greater BOLD activation was observed in components of the default mode network, including frontal medial cortex, during the motor condition (when task demands were minimal) relative to the retrieval condition. Worse performance (longer path length) during retrieval was associated with greater activation of angular gyrus/supramarginal gyrus, whereas worse performance (longer path length/latency) during motor control was associated with less activation of frontal pole. Furthermore, while latency (time to complete task) was greater in females than in males, there were no sex differences in path length (accuracy), suggesting that females required more time to navigate the virtual environment, but did so as effectively as males. These findings demonstrate that performance of the vMWT elicits hippocampal and prefrontal activation patterns in early adolescence, similar to activation observed during spatial memory retrieval in adults. Given that this task is sensitive to hippocampal function, and that the adolescent hippocampus is notably vulnerable to the effects of alcohol and other substances, data acquired using this task during healthy adolescent development may provide a framework for understanding neurobiological impact of later initiation of use.

College Binge Drinking Associated with Decreased Frontal Activation to Negative Emotional Distractors during Inhibitory Control.

The transition to college is associated with an increase in heavy episodic alcohol use, or binge drinking, during a time when the prefrontal cortex and prefrontal-limbic circuitry continue to mature. Traits associated with this immaturity, including impulsivity in emotional contexts, may contribute to risky and heavy episodic alcohol consumption. The current study used blood oxygen level dependent (BOLD) multiband functional magnetic resonance imaging (fMRI) to assess brain activation during a task that required participants to ignore background images with positive, negative, or neutral emotional valence while performing an inhibitory control task (Go-NoGo). Subjects were 23 college freshmen (seven male, 18-20 years) who engaged in a range of drinking behavior (past 3 months' binge episodes range = 0-19, mean = 4.6, total drinks consumed range = 0-104, mean = 32.0). Brain activation on inhibitory trials (NoGo) was contrasted between negative and neutral conditions and between positive and neutral conditions using non-parametric testing (5000 permutations) and cluster-based thresholding (z = 2.3), p ≤ 0.05 corrected. Results showed that a higher recent incidence of binge drinking was significantly associated with decreased activation of dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and anterior cingulate cortex (ACC), brain regions strongly implicated in executive functioning, during negative relative to neutral inhibitory trials. No significant associations between binge drinking and brain activation were observed for positive relative to neutral images. While task performance was not significantly associated with binge drinking in this sample, subjects with heavier recent binge drinking showed decreased recruitment of executive control regions under negative versus neutral distractor conditions. These findings suggest that in young adults with heavier recent binge drinking, processing of negative emotional images interferes more with inhibitory control neurocircuitry than in young adults who do not binge drink often. This pattern of altered frontal lobe activation associated with binge drinking may serve as an early marker of risk for future self-regulation deficits that could lead to problematic alcohol use. These findings underscore the importance of understanding the impact of emotion on cognitive control and associated brain functioning in binge drinking behaviors among young adults.

Altered regional blood volume in chronic cannabis smokers.

The quantitative measurement of cerebral perfusion is crucial for the study of both normal and impaired human brain function. Although cannabis is the most commonly abused illicit substance in the United States, its effects on cerebral blood volume (CBV) have not been fully examined. The objective of the present study was to examine differences in relative regional blood volume in focal regions of interest--including the frontal lobe, the temporal lobe, and the cerebellum--during a period of supervised abstinence from cannabis. Dynamic susceptibility contrast MRI data were collected on 12 current, long-term daily cannabis users between 6 and 36 hr after the subjects' last reported cannabis use. Resting-state CBV images were also acquired in 17 healthy comparison subjects. Data were acquired in the axial plane with a 1.5-Tesla GE Signa scanner following a bolus of gadolinium contrast agent. Cannabis users demonstrated significantly increased blood volumes in the right frontal area (p < .05), in the left temporal area (p < .005), and in the cerebellum (p < .005) relative to comparison subjects. Among the cannabis users, there were no significant correlations between regional blood volumes and either total lifetime episodes of smoking or urinary tetrahydrocannabinol concentrations. These findings have important implications for understanding the effects of chronic heavy cannabis use on brain function. It would be of interest to extend the investigation beyond 6-36 hr of abstinence from cannabis to determine whether increased CBV values persist for several weeks or eventually normalize.

Neurobiological signatures associated with alcohol and drug use in the human adolescent brain.

Magnetic resonance (MR) techniques provide opportunities to non-invasively characterize neurobiological milestones of adolescent brain development. Juxtaposed to the critical finalization of brain development is initiation of alcohol and substance use, and increased frequency and quantity of use, patterns that can lead to abuse and addiction. This review provides a comprehensive overview of existing MR studies of adolescent alcohol and drug users. The most common alterations reported across substance used and MR modalities are in the frontal lobe (63% of published studies). This is not surprising, given that this is the last region to reach neurobiological adulthood. Comparatively, evidence is less consistent regarding alterations in regions that mature earlier (e.g., amygdala, hippocampus), however newer techniques now permit investigations beyond regional approaches that are uncovering network-level vulnerabilities. Regardless of whether neurobiological signatures exist prior to the initiation of use, this body of work provides important direction for ongoing prospective investigations of adolescent brain development, and the significant impact of alcohol and substance use on the brain during the second decade of life.

Sex differences in spatial navigation and perception in human adolescents and emerging adults.

Males typically outperform females on spatial tasks, beginning early in life and continuing into adulthood. This study aimed to characterize age and sex differences in human spatial ability using a virtual Water Maze Task (vWMT), which is based on the classic Morris water maze spatial navigation task used in rodents. Performance on the vWMT and on a task assessing visuospatial perception, Mental Rotations Test (MRT), was examined in 33 adolescents and 39 emerging adults. For the vWMT, significant effects of age and sex were observed for path length in the target region (narrower spatial sampling), and heading error, with emerging adults performing better than adolescents, and an overall male advantage. For the MRT, males scored higher than females, but only in emerging adulthood. Overall, sex differences in visuospatial perception (MRT) emerge differently from those observed on a classic navigation task, with age and sex-specific superior vWMT performance likely related to the use of more efficient strategies. Importantly, these results extend the developmental timeline of spatial ability characterization to include adolescent males and females performing a virtual version of the classic vWMT.

Impact of family history of alcoholism on glutamine/glutamate ratio in anterior cingulate cortex in substance-naïve adolescents.

Neuroimaging studies of individuals with family histories of alcoholism provide evidence suggesting neurobiological risk factors for alcoholism. Youth family history positive (FH+) for alcoholism exhibit increased impulsivity compared to family history negative (FH-) peers in conjunction with altered functional activation in prefrontal cortex, including anterior cingulate cortex (ACC). This study examined glutamate (Glu) and glutamine (Gln), amino acids vital to protein synthesis, cellular metabolism and neurotransmission, acquired from ACC and parieto-occipital cortex (POC) using magnetic resonance spectroscopy (MRS) at 4T. Participants were 28 adolescents (13 male, 12-14 yrs) and 31 emerging adults (16 male, 18-25 yrs), stratified into FH- and FH+ groups. Significantly higher ACC Gln/Glu was observed in emerging adults versus adolescents in FH- but not FH+ groups. In FH- adolescents, higher impulsivity was significantly associated with higher ACC Gln/Glu. In FH+ emerging adults, higher impulsivity was negatively associated with ACC Gln/Glu. No differences or associations were observed for POC. These findings provide preliminary evidence that family history of alcoholism is associated with a neurochemical profile that may influence normative age differences in glutamatergic metabolites and their association with impulse control, which together could confer greater genetic risk of addiction later in life.

A Review of Magnetic Resonance Spectroscopy Studies in Marijuana using Adolescents and Adults.

Marijuana (MJ) remains the most widely used illicit drug of abuse, and accordingly, is associated with adverse effects on mental and physical health, and neurocognitive decline. Studies investigating the neurobiology of underlying MJ effects have demonstrated structural and functional alterations in brain areas that contain moderate to high concentrations of cannabinoid (CB1) receptors and that are implicated in MJ-related cognitive decrements. Proton magnetic resonance spectroscopy (1H MRS), a non-invasive imaging technique used to assess neurochemistry, has been widely applied to probe a variety of substance-abusing populations. To date, however, there is a relative paucity of MRS published studies characterizing changes in neurometabolite concentrations in MJ users. Thus, the current review provides a summary of data from the eight existing MRS studies of MJ use in adolescents and adults, as well as interpretations and implications of study findings. Future MRS studies that address additional factors such as sex differences, onset and duration of use, abstinence and age, are warranted, and would lead to a more thorough characterization of potential neurochemical correlates of chronic MJ use, which would fill critical gaps in the existing literature.