The adolescent and young adult microbiome and its association with substance use: a scoping review.

AIMS: The microbiome is a critical factor in health throughout human development. The aims of this scoping review are to (i) elucidate the differences between the youth (post-natal day 21-65 for rodents, 2-7 years for non-human primates, and 10-25 years for humans) microbiome with other life stages and (ii) identify youth-specific microbial changes associated with substance use. METHODS: Peer-reviewed studies published up to May 2023 were identified in PubMed and SCOPUS and included gut and oral microbiome studies from rodents, non-human primates, and humans (N = 1733). Twenty-six articles were determined eligible based on inclusion criteria (aim 1: n = 19, aim 2: n = 7). RESULTS: The adolescent and young adult oral and gut microbiomes are distinct compared to other life stages, within both non-human and human models. While there is limited research in this area, the microbiome appears to be vulnerable to substance use exposure earlier in life, including substances commonly initiated and escalated during adolescence and young adulthood (i.e. alcohol, cannabis, and tobacco). CONCLUSIONS: Studies across the lifespan indicate that adolescence and young adulthood are distinct periods of development, where the microbiome is sensitive to exposures, including substance use. There is a need for more studies focused on the adolescent and young adult microbiome and substance use, as well as focused on the oral microbiome during this developmental period. Understanding the gut and oral microbiome during adolescence and young adulthood may provide insight into the pathophysiology of substance use disorders.

Brain metabolite alterations related to alcohol use: a meta-analysis of proton magnetic resonance spectroscopy studies.

Alcohol misuse and alcohol use disorder (AlUD) have neurobiological consequences. This meta-analysis of proton magnetic resonance spectroscopy (MRS) studies aimed to assess the differences in brain metabolite levels in alcohol misuse and AUD relative to controls (PROSPERO registration: CRD42020209890). Hedge's g with random-effects modeling was used. Sub-group and meta-regression techniques explored potential sources of demographic and MRS parameter heterogeneity. A comprehensive literature review identified 43 studies, resulting in 69 models across gray and white matter (GM, WM). Lower N-acetylaspartate levels were found in frontal, anterior cingulate cortex (ACC), hippocampal, and cerebellar GM, and frontal and parietal WM, suggesting decreased neuronal and axonal viability. Lower choline-containing metabolite levels (all metabolites contributing to choline peak) were found in frontal, temporal, thalamic, and cerebellar GM, and frontal and parietal WM, suggesting membrane alterations related to alcohol misuse. Lower creatine-containing metabolite levels (Cr; all metabolites contributing to Cr peak) were found in temporal and occipital cortical GM, while higher levels were noted in midbrain/brainstem GM; this finding may have implications for using Cr as an internal reference. The lack of significant group differences in glutamate-related levels is possibly related to biological and methodological complexities. The few studies reporting on GABA found lower levels restricted to the ACC. Confounding variables were age, abstinence duration, treatment status, and MRS parameters (echo time, quantification type, data quality). This first meta-analysis of proton MRS studies consolidates the numerous individual studies to identify neurometabolite alterations within alcohol misuse and AUD. Future studies can leverage this new formalized information to investigate treatments that might effectively target the observed disturbances.

Artificial food coloring affects EEG power and ADHD symptoms in college students with ADHD: a pilot study.

Objectives: Removing artificial food coloring (AFC) is a common dietary intervention for children with Attention-Deficit/Hyperactivity Disorder (ADHD), but has not been tested in young adults. This pilot study examined the effects of AFC on ADHD symptoms and electroencephalography (EEG) in college students with and without ADHD.Methods: At baseline, control and ADHD participants completed the Adult ADHD Self-Report Scale (ASRS), simple and complex attention measures, and resting-state EEG recordings. ADHD participants (n = 18) and a subset of controls (extended control group or EC, n = 11) avoided AFC in their diet for 2 weeks and then were randomized to a double-blind, placebo-controlled crossover challenge. Subjects received either 225 mg AFC disguised in chocolate cookies or placebo chocolate cookies for 3 days each week, with testing on the third day each week. Baseline comparisons were made using Student's t-test or Wilcoxon rank sum tests and challenge period analyses were run using General Linear Modeling.Results: The ADHD group had significantly greater scores on the ASRS (p < 0.001), confirming a symptom differential between groups; however, there were no differences in attentional measures or EEG at baseline. The AFC challenge resulted in an increase in posterior mean gamma power (p = 0.05), a decrease in posterior relative alpha power (p = 0.04), and a marginal increase in inattentive symptoms (p = 0.08) in the ADHD group. There were no effects of AFC in the EC group.Discussion: This study indicates that AFC exposure may affect brainwave activity and ADHD symptoms in college students with ADHD. Larger studies are needed to confirm these findings.

The low glutamate diet improves cognitive functioning in veterans with Gulf War Illness and resting-state EEG potentially predicts response.

Objectives: Gulf War Illness (GWI) is a chronic, multi-symptom disorder with underlying central nervous system dysfunction and cognitive impairments. The objective of this study was to test the low glutamate diet as a novel treatment for cognitive dysfunction among those with GWI, and to explore if baseline resting-state electroencephalography (EEG) could predict cognitive outcomes.Methods: Cognitive functioning was assessed at baseline, after one-month on the diet, and across a two-week double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG) relative to placebo.Results: Significant improvements were seen after one-month on the diet in overall cognitive functioning, and in all other domains tested (FDR p < 0.05), except for memory. Challenge with MSG resulted in significant inter-individual response variability (p < 0.0001). Participants were clustered according to baseline resting-state EEG using k-means clustering to explore the inter-individual response variability. Three distinct EEG clusters were observed, and each corresponded with differential cognitive effects during challenge with MSG: cluster 1 had cognitive benefit (24% of participants), cluster 2 had cognitive detriment (42% of participants), and cluster 3 had mild/mixed effects (33% of participants).Discussion: These findings suggest that the low glutamate diet may be a beneficial treatment for cognitive impairment in GWI. Future research is needed to understand the extent to which resting-state EEG can predict response to the low glutamate diet and to explore the mechanisms behind the varied response to acute glutamate challenge.

Moving past antioxidant supplementation for the dietary treatment of multiple sclerosis.

Current research has demonstrated the definitive presence of oxidative stress in multiple sclerosis (MS). This finding has led to clinical trial research which has indicated that specific antioxidants have the ability to effectively reduce markers of oxidative stress. However, few interventions testing antioxidant supplements have shown efficacy for reducing the symptom burden in the disorder. This paper quickly reviews what is currently known about oxidative stress and antioxidants in MS, explains which nutrients are critical for the creation and maintenance of the myelin sheath, describes potential negative effectors in the diet which may be contributing to oxidative stress, and how these aspects of diet, combined with current knowledge on antioxidants, may be able to be combined into a whole food dietary intervention which can be tested for efficacy in MS.

Effect of N-acetylcysteine on neural alcohol cue reactivity and craving in adolescents who drink heavily: A preliminary randomized clinical trial.

BACKGROUND: Alcohol craving is related to problematic alcohol use; therefore, pharmacotherapies that modulate alcohol craving are of interest. N-acetylcysteine, an over-the-counter antioxidant, is a candidate pharmacotherapy for adolescent alcohol use with the potential to impact craving. Cue-reactivity paradigms using functional magnetic resonance imaging (fMRI) can identify neural regions implicated in craving and serve as a screening tool for novel pharmacotherapy options. METHODS: This preliminary study examined the effect of N-acetylcysteine on neural reactivity to alcohol cues and subjective craving among 31 non-treatment-seeking adolescents (17.6-19.9 years old, 55% female) who use alcohol heavily. In a randomized cross-over design, participants completed three fMRI sessions: baseline and after a 10-day course of N-acetylcysteine (1200 mg twice daily) and matched placebo. The primary outcome was neural response to alcohol versus non-alcohol beverage cues after N-acetylcysteine versus placebo, with a secondary outcome of self-reported subjective craving. RESULTS: In the full sample (n = 31), there was no effect of N-acetylcysteine versus placebo on neural alcohol reactivity (ps ≥ 0.49; η p 2 $$ {\upeta_{\mathrm{p}}}^2 $$ s = 0.00-0.07) or self-reported acute alcohol craving (p = 0.18, η p 2 $$ {\upeta_{\mathrm{p}}}^2 $$ = 0.06). However, N-acetylcysteine did reduce self-reported generalized alcohol craving (p = 0.03, η p 2 $$ {\upeta_{\mathrm{p}}}^2 $$ = 0.15). In a subsample of youth who met criteria for past-year alcohol use disorder (n = 19), results remained unchanged. CONCLUSIONS: N-acetylcysteine may not alter neural reactivity to alcohol cues or acute craving; however, it may reduce general subjective alcohol craving among adolescents who consume alcohol heavily.

Multi-modal neuroimaging reveals differences in alcohol-cue reactivity but not neurometabolite concentrations in adolescents who drink alcohol.

BACKGROUND: The objective of this multi-modal neuroimaging study was to identify neuroscience-informed treatment targets for adolescent alcohol use disorder (AUD) by examining potential neural alterations associated with adolescent alcohol use. METHODS: Adolescents (ages 17-19) who heavily used (n=49) or did not use alcohol (n=22) were recruited for a multi-modal neuroimaging protocol, including proton magnetic resonance spectroscopy within the dorsal anterior cingulate cortex (dACC) and an fMRI alcohol cue-reactivity task. The alcohol cue-reactivity task was analyzed across 11 a priori regions-of-interest (ROI), including the dACC, and in an exploratory whole-brain approach. Correlations were run between neurometabolite levels and alcohol cue-reactivity in the dACC. RESULTS: There were no significant group differences in absolute neurometabolite concentrations. Compared to the control group, the alcohol-using group exhibited heightened alcohol cue reactivity in the left amygdala ROI (p=0.04). The whole-brain approach identified higher alcohol cue reactivity in the alcohol-using group compared to controls in the amygdala and occipital regions, and lower reactivity in the parietal lobe. Whole-brain sex effects were noted, with females displaying higher reactivity regardless of group. No significant correlations were found between neurometabolite levels and alcohol cue-reactivity in the dACC. CONCLUSIONS: The null neurometabolic findings may be due to age, relatively low severity of alcohol use, and non-treatment-seeking status of the participants. Females showed overall higher reactivity to alcohol cues, indicating a sex effect regardless of alcohol use history. Higher amygdala reactivity in alcohol-using adolescents suggests that emotional processing related to alcohol cues may be a useful target for future adolescent AUD interventions.

Predictors of Substance Use Initiation by Early Adolescence.

OBJECTIVE: Substance use initiation during early adolescence is associated with later development of substance use and mental health disorders. This study used various domains to predict substance use initiation, defined as trying any nonprescribed substance (e.g., alcohol, tobacco, cannabis), by age 12, using a large longitudinal data set. METHODS: Substance-naive youths from the Adolescent Brain Cognitive Development Study (ages 9-10; N=6,829) were followed for 3 years. A total of 420 variables were examined as predictors of substance use initiation, using a penalized logistic regression with elastic net; domains spanned demographic characteristics, self and peer involvement with substance use, parenting behaviors, mental and physical health, culture and environment, hormones, neurocognitive functioning, and structural neuroimaging. RESULTS: By age 12, 982 (14.4%) children reported substance initiation, with alcohol being the most common. Models with only self-report predictors had similar prediction performance to models adding hormones, neurocognitive factors, and neuroimaging predictors (AUCtest=0.66). Sociodemographic factors were the most robust predictors, followed by cultural and environmental factors, physical health factors, and parenting behaviors. The top predictor was a religious preference of Mormon (coefficient=-0.87), followed by a religious preference for Jewish (coefficient=0.32), and by Black youths (coefficient=-0.32). CONCLUSIONS: Sociodemographic variables were the most robust predictors of substance use initiation. Adding resource-intensive measures, including hormones, neurocognitive assessment, and structural neuroimaging, did not improve prediction of substance use initiation. The application of these large-scale findings in clinical settings could help to streamline and tailor prevention and early intervention efforts.

Adolescent alcohol use is associated with differences in the diversity and composition of the oral microbiome.

BACKGROUND: Adolescence is a sensitive stage of oral microbial development that often coincides with the initiation and escalation of alcohol use. Thus, adolescents may be particularly susceptible to alcohol-induced alterations in the oral microbiome, though minimal research has been done in this area. Understanding the connection between the oral microbiome and alcohol use during adolescence is important to understand fully the biological consequences of alcohol use to mitigate potential adverse outcomes. METHODS: Saliva samples were collected from adolescents aged 17-19 who used alcohol heavily (n = 21, 52.4% female) and those who did not use alcohol or any other substances (n = 18, 44.4% female). We utilized 16S rRNA sequencing to examine differences in microbial diversity and composition between the groups. RESULTS: For alpha diversity, evenness was significantly lower in the drinking group than the control group as indicated by Pielou's evenness, Shannon, and Simpson indices. There were no statistically significant findings for beta diversity. Differential abundance analyses revealed higher abundances of Rothia and Corynebacterium in the alcohol-using group using both centered-log-ratio and relative abundance normalization. These genera are known for their high capacity to convert alcohol into acetaldehyde, a toxic metabolite reported to play a role in the neurobiological effects of alcohol. An unclassified Clostridia UCG-014, Streptobacillus, Comamonas, unclassified Lachnospiraceae, and Parvimonas were also identified as significantly different between groups when using only one of the normalization techniques. CONCLUSIONS: This is the first study designed specifically to compare the oral microbiome of adolescents who use alcohol with that of control participants. Our findings reveal distinct alcohol-related differences in microbial composition and taxon abundance, emphasizing the importance of understanding the impact on the oral microbiome of alcohol use during adolescence. Because the oral microbiome is malleable, this study provides foundational work for future prevention and intervention studies.

Pairwise comparisons of three medication adherence outcomes in adolescents who use alcohol.

BACKGROUND: Accurate assessment of medication adherence is important for understanding pharmacotherapy outcomes across all phases of adolescent substance use disorder (SUD) clinical trials. The objective of this study was to describe and assess the pairwise concordance between three commonly used non-biological medication adherence assessment methods in adolescents who use alcohol to inform the selection of medication adherence measures for use in future youth SUD trials. METHODS: Participants (N = 32, 17-19-years-old) took N-acetylcysteine and placebo, in a randomized cross-over design, for 10 days each. Medication adherence was assessed (20 days total) via pill count, medication videos submitted twice daily, and the Medication Event Monitoring System (MEMS®). Lin's Concordance Correlation Coefficient (CCC) assessed concordance and Bland-Altman plots are reported. Linear mixed-effects models with main effects of medication, treatment block (first medication, second medication), and sequence were also run. RESULTS: Medication videos yielded the lowest (64%) and pill count yielded the highest (89%) adherence estimates. CCC values indicated poor correspondence, except between pill count and MEMS. The Bland-Altman plots showed good pairwise agreement between all methods. Linear mixed-effects models indicated a difference between the first and second cross-over medication, with adherence estimates being lower for the second medication, regardless of whether it was N-acetylcysteine or placebo. CONCLUSIONS: The study yielded important and practical information. First, incorporating more than one method of adherence assessment may capture estimated floor and ceiling adherence in the absence of a biological marker. This is particularly relevant for remote or hybrid studies where bio-marker collection is challenging. Selection of the assessment methods will depend on study goals. Second, the continuation of medication adherence research can benefit each phase of clinical trials and inform rigorous pharmacotherapy evaluation.

N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial.

Current treatments for adolescent alcohol use disorder (AUD) are mainly psychosocial and limited in their efficacy. As such, pharmacotherapies are being investigated as potential adjunctive treatments to bolster treatment outcomes. N-acetylcysteine is a promising candidate pharmacotherapy for adolescent AUD because of its tolerability and demonstrated ability to modulate glutamatergic, GABAergic, and glutathione systems. The primary objective of this double-blind, placebo-controlled, within-subjects crossover preliminary investigation was to measure potential changes within glutamate + glutamine (Glx), GABA, and glutathione levels in the dorsal anterior cingulate cortex (dACC) using proton magnetic resonance spectroscopy during 10-days of N-acetylcysteine (1200 mg twice daily) compared to 10-days of placebo in non-treatment seeking adolescents who use alcohol heavily (N = 31; 55% female). Medication adherence was confirmed via video. Effects on alcohol use were measured using Timeline Follow-Back as an exploratory aim. Linear mixed effects models controlling for baseline metabolite levels, brain tissue composition, alcohol use, cannabis use, and medication adherence found no significant differences in Glx, GABA, or glutathione levels in the dACC after N-acetylcysteine compared to placebo. There were also no measurable effects on alcohol use; however, this finding was underpowered. Findings were consistent in the subsample of participants who met criteria for AUD (n = 19). The preliminary null findings in brain metabolite levels may be due to the young age of participants, relatively low severity of alcohol use, and non-treatment seeking status of the population investigated. Future studies can use these findings to conduct larger, well-powered studies within adolescents with AUD.

Sex and Gender Differences in Simultaneous Alcohol and Cannabis Use: a Narrative Review.

Purpose of Review: The aim is to review recent literature on sex and gender differences in patterns of use, motives, pharmacological effects, and consequences of simultaneous alcohol and cannabis use (SAC). Recent Findings: Men engage in SAC more frequently than women. Women may have more substance-specific motives for use, while men tend to consistently endorse social/enhancement motives for both alcohol and cannabis. Regarding pharmacological effects, women experience the same subjective effects as men do at lower levels of use, with some evidence that women modulate cannabis use during simultaneous use episodes to avoid greater subjective intoxication. Finally, women appear more vulnerable to experiencing a range of positive and negative consequences from SAC relative to men. Summary: Research has identified several important sex/gender differences in SAC and its correlates and consequences. However, research has primarily focused on white and cisgender populations, with a need for more research among racial/ethnic and gender minorities.

The Effect of the Low Glutamate Diet on the Reduction of Psychiatric Symptoms in Veterans With Gulf War Illness: A Pilot Randomized-Controlled Trial.

The objective of this pilot study was to examine the effects of the low glutamate diet on anxiety, post-traumatic stress disorder (PTSD), and depression in veterans with Gulf War Illness (GWI). The low glutamate diet removes dietary excitotoxins and increases consumption of micronutrients which are protective against glutamatergic excitotoxicity. This study was registered at ClinicalTrials.gov (NCT#03342482). Forty veterans with GWI completed psychiatric questionnaires at baseline and after 1-month following the low glutamate diet. Participants were then randomized into a double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG; a dietary excitotoxin) vs. placebo over three consecutive days per week, with assessments on day three. Data were analyzed across the full sample and with participants categorized by baseline symptom severity. Pre-post-dietary intervention change scores were analyzed with Wilcoxon signed-rank tests and paired sample t-tests across the full sample, and changes across symptom severity categories were analyzed using ANOVA. Crossover challenge results were analyzed with linear mixed modeling accounting for challenge material (MSG v. placebo), sequence (MSG/placebo v. placebo/MSG), period (challenge week 1 v. week 2), pre-diet baseline symptom severity category (minimal/mild, moderate, or severe), and the challenge material*symptom severity category interaction. A random effect of ID (sequence) was also included. All three measures showed significant improvement after 1 month on the diet, with significant differences between baseline severity categories. Individuals with severe psychological symptoms at baseline showed the most improvement after 1 month on the diet, while those with minimal/mild symptoms showed little to no change. Modeling results from the challenge period demonstrated a significant worsening of anxiety from MSG in only the most severe group, with no significant effects of MSG challenge on depression nor PTSD symptoms. These results suggest that the low glutamate diet may be an effective treatment for depression, anxiety, and PTSD, but that either (a) glutamate is only a direct cause of symptoms in anxiety, or (b) underlying nutrient intake may prevent negative psychiatric effects from glutamate exposure. Future, larger scale clinical trials are needed to confirm these findings and to further explore the potential influence of increased micronutrient intake on the improvements observed across anxiety, PTSD, and depression.

A scoping review of the use of cannabidiol in psychiatric disorders.

Cannabidiol (CBD) has become a fast-growing avenue for research in psychiatry, and clinicians are challenged with understanding the implications of CBD for treating mental health disorders. The goal of this review is to serve as a guide for mental health professionals by providing an overview of CBD and a synthesis the current evidence within major psychiatric disorders. PubMed and PsycINFO were searched for articles containing the terms "cannabidiol" in addition to major psychiatric disorders and symptoms, yielding 2952 articles. Only randomized controlled trials or within-subject studies investigating CBD as a treatment option for psychiatric disorders (N = 16) were included in the review. Studies were reviewed for psychotic disorders (n = 6), anxiety disorders (n = 3), substance use disorders (tobacco n = 3, cannabis n = 2, opioid n = 1), and insomnia (n = 1). There were no published studies that met inclusion criteria for alcohol or stimulant use disorder, PTSD, ADHD, autism spectrum disorder, or mood disorders. Synthesis of the CBD literature indicates it is generally safe and well tolerated. The most promising preliminary findings are related to the use of CBD in psychotic symptoms and anxiety. There is currently not enough high-quality evidence to suggest the clinical use of CBD for any psychiatric disorder.

Low glutamate diet improves working memory and contributes to altering BOLD response and functional connectivity within working memory networks in Gulf War Illness.

Gulf War Illness is a chronic multi-symptom disorder with severe cognitive impairments which may be related to glutamate excitotoxicity and central nervous system dysfunction. The low glutamate diet has been proposed as a comprehensive intervention for Gulf War Illness. We examined the effects of the low glutamate diet on verbal working memory using a fMRI N-back task. Accuracy, whole-brain blood oxygen level dependency (BOLD) response, and task-based functional connectivity were assessed at baseline and after 1 month on the diet (N = 24). Multi-voxel pattern analysis identified regions of whole-brain BOLD pattern differences after the diet to be used as seeds for subsequent seed-to-voxel functional connectivity analyses. Verbal working memory accuracy improved after the diet (+ 13%; p = 0.006). Whole-brain BOLD signal changes were observed, revealing lower activation within regions of the frontoparietal network and default mode network after the low glutamate diet. Multi-voxel pattern analysis resulted in 3 clusters comprising parts of the frontoparietal network (clusters 1 and 2) and ventral attention network (cluster 3). The seed-to-voxel analyses identified significant functional connectivity changes post-diet for clusters 1 and 2 (peak p < 0.001, cluster FDR p < 0.05). Relative to baseline, clusters 1 and 2 had decreased functional connectivity with regions in the ventral attention and somatomotor networks. Cluster 2 also had increased functional connectivity with regions of the default mode and frontoparietal networks. These findings suggest that among veterans with Gulf War Illness, the low glutamate diet improves verbal working memory accuracy, alters BOLD response, and alters functional connectivity within two networks central to working memory.

Promising vulnerability markers of substance use and misuse: A review of human neurobehavioral studies.

Substance use often begins, and noticeably escalates, during adolescence. Identifying predictive neurobehavioral vulnerability markers of substance use and related problems may improve targeted prevention and early intervention initiatives. This review synthesizes 44 longitudinal studies and explores the utility of developmental imbalance models and neurobehavioral addiction frameworks in predicting neural and cognitive patterns that are associated with prospective substance use initiation and escalation among young people. A total of 234 effect sizes were calculated and compared. Findings suggest that aberrant neural structure and function of regions implicated in reward processing, cognitive control, and impulsivity can predate substance use initiation, escalation, and disorder. Functional vulnerability markers of substance use include hyperactivation during reward feedback and risk evaluation in prefrontal and ventral striatal regions, fronto-parietal hypoactivation during working memory, distinctive neural patterns during successful (fronto-parietal hyperactivation) and failed response inhibition (frontal hypoactivation), and related cognitive deficits. Structurally, smaller fronto-parietal and amygdala volume and larger ventral striatal volume predicts prospective substance misuse. Taken together, the findings of this review suggest that neurobehavioral data can be useful in predicting future substance use behaviors. Notably, little to no research has empirically tested the underlying assumptions of widely used theoretical frameworks. To improve the reliability and utility of neurobehavioral data in predicting future substance use behaviors, recommendations for future research are provided. This article is part of the special issue on 'Vulnerabilities to Substance Abuse.'

Effect of alcohol use on the adolescent brain and behavior.

Adolescence is a particularly vulnerable neurodevelopmental period marked by high rates of engagement with risky alcohol use. This review summarizes the cognitive and neural consequences following alcohol use during adolescence from longitudinal design studies in humans and animals. Findings from human adolescent studies suggest that binge drinking and heavy alcohol use is associated with poorer cognitive functioning on a broad range of neuropsychological assessments, including learning, memory, visuospatial functioning, psychomotor speed, attention, executive functioning, and impulsivity. Alcohol use during adolescence is associated with accelerated decreases in gray matter and attenuated increases in white matter volume, and aberrant neural activity during executive functioning, attentional control, and reward sensitivity tasks, when compared to non-drinking adolescents. Animal studies in rodents and non-human primates have replicated human findings, and suggest cognitive and neural consequences of adolescent alcohol use may persist into adulthood. Novel rodent studies demonstrate that adolescent alcohol use may increase reward responsiveness of the dopamine system to alcohol later in life, as well as disrupt adolescent neurogenesis, potentially through neuroinflammation, with long-lasting neural and behavioral effects into adulthood. Larger longitudinal human cognitive and neuroimaging studies with more diverse samples are currently underway which will improve understanding of the impact of polysubstance use, as well as the interactive effects of substance use, physical and mental health, and demographic factors on cognition and neurodevelopment.

The Low Glutamate Diet Effectively Improves Pain and Other Symptoms of Gulf War Illness.

Gulf War Illness (GWI) is a multisymptom disorder including widespread chronic pain, fatigue and gastrointestinal problems. The objective of this study was to examine the low glutamate diet as a treatment for GWI. Forty veterans with GWI were recruited from across the US. Outcomes included symptom score, myalgic score, tender point count, dolorimetry and the Chalder Fatigue Scale. Subjects were randomized to the low glutamate diet or a wait-listed control group, with symptom score being compared after one month. Subjects then went onto a double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG)/placebo to test for return of symptoms. Symptom score was compared between diet intervention and wait-listed controls with an independent t-test and effect size was calculated with Cohen's d. Change scores were analyzed with Wilcoxon Signed Rank tests. Crossover challenge results were analyzed with General Linear Models and cluster analysis. The diet intervention group reported significantly less symptoms (p = 0.0009) than wait-listed controls, with a very large effect size, d = 1.16. Significant improvements in average dolorimetry (p = 0.0006), symptom score, tender point number, myalgic score and the Chalder Fatigue Scale (all p < 0.0001) were observed after the 1-month diet. Challenge with MSG/placebo resulted in significant variability in individual response. These results suggest that the low glutamate diet can effectively reduce overall symptoms, pain and fatigue in GWI, but differential results upon challenge suggest that other aspects of the diet, or underlying differences within the population, may be driving these changes. Future research is needed to identify potential nutrient effects, biomarkers, and underlying metabolic differences between responders and non-responders.

Measuring Treatment Response in Pharmacological and Lifestyle Interventions Using Electroencephalography in ADHD: A Review.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and/or impulsivity with associations to short- and long-term aversive life events. The exact etiology of the disorder is still unknown. ADHD is heterogeneous in symptomology and a single consistent, reliable biomarker has not been found. Quantitative electroencephalography (EEG) has been proposed as a potential way to differentiate those with ADHD from typically developing controls; however, the data on the diagnostic utility of this approach have been variable. Quantitative EEG has been employed in prognostic ways to assess differences in baseline spectral power profiles and pharmacological and nonpharmacological treatment effects on electrocortical activity within the ADHD population. The aim of this review is to summarize the literature investigating the degree of normalization of resting-state EEG profiles in individuals with ADHD through various interventions, including stimulant and nonstimulant medication, exercise, and diet.

The Role of Magnesium in Neurological Disorders.

Magnesium is well known for its diverse actions within the human body. From a neurological standpoint, magnesium plays an essential role in nerve transmission and neuromuscular conduction. It also functions in a protective role against excessive excitation that can lead to neuronal cell death (excitotoxicity), and has been implicated in multiple neurological disorders. Due to these important functions within the nervous system, magnesium is a mineral of intense interest for the potential prevention and treatment of neurological disorders. Current literature is reviewed for migraine, chronic pain, epilepsy, Alzheimer’s, Parkinson’s, and stroke, as well as the commonly comorbid conditions of anxiety and depression. Previous reviews and meta-analyses are used to set the scene for magnesium research across neurological conditions, while current research is reviewed in greater detail to update the literature and demonstrate the progress (or lack thereof) in the field. There is strong data to suggest a role for magnesium in migraine and depression, and emerging data to suggest a protective effect of magnesium for chronic pain, anxiety, and stroke. More research is needed on magnesium as an adjunct treatment in epilepsy, and to further clarify its role in Alzheimer’s and Parkinson’s. Overall, the mechanistic attributes of magnesium in neurological diseases connote the macromineral as a potential target for neurological disease prevention and treatment.