Coping drinking motives, neural functional coupling during emotion processing, and alcohol use in young adults with bipolar disorder.

BACKGROUND: Rates of alcohol use disorders in individuals with bipolar disorder are 3 to 5 times greater than in the general population and exceed rates of alcohol use disorders reported in other affective and anxiety disorders. Despite this high rate of comorbidity, our understanding of the psychosocial and neural mechanisms that underlie the initiation of alcohol misuse in young adults with bipolar disorder remains limited. Prior work suggests that individuals with bipolar disorder may misuse alcohol as a coping mechanism, yet the neural correlates of coping drinking motives and associated alcohol use have not been previously investigated in this population. METHODS: Forty-eight young adults (22 bipolar disorder type I, 26 typically developing; 71% women; average age ± standard deviation = 22 ± 2 years) completed the Drinking Motives and Daily Drinking Questionnaires, and a Continuous Performance Functional magnetic resonance imaging (fMRI) Task with Emotional and Neutral Distracters. We calculated the relative difference in anterior cingulate cortex (ACC) functional coupling with the anterior insula and amygdala in response to emotional distracters compared with neutral stimuli and investigated the relations with coping drinking motives and alcohol use. RESULTS: Across all participants, coping drinking motives were associated with greater quantity of recent alcohol use. In individuals with bipolar disorder, greater ACC-anterior insula functional coupling was associated with greater coping drinking motives, and greater quantity and frequency of recent alcohol use. The relative difference in ACC-anterior insula functional coupling was not associated with coping drinking motives or alcohol use in the typically developing group. Greater ACC-anterior insula functional coupling in individuals with bipolar disorder was also associated with greater anxiety symptoms and recent perceived psychological stress. Exploratory analyses suggest that the relations between ACC-anterior insula functional coupling and coping drinking motives may be confounded by anticonvulsant use. CONCLUSION: Results suggest that a difference in ACC-anterior insula functional coupling during emotion processing may underlie alcohol use as a maladaptive coping mechanism in young adults with bipolar disorder.

Peer victimization and associated alcohol and substance use: Prospective pathways for negative outcomes.

A considerable number of studies have documented associations between peer victimization and concurrent and prospective increase in alcohol and substance use. Only a handful have investigated the psychological (e.g., internalizing behavior) and biological (e.g., neural systems) factors that contribute to this relation. Emerging studies provide clues as to mechanisms that may underlie increased risk for alcohol and substance use and associated problems in peer victimized youth, which may serve as potential targets for intervention. This review proposes a conceptual framework of increased alcohol/substance use in peer victimized youth as sequelae of alterations in the structure and/or function of neural regions broadly implicated in cognitive control and emotion processing/regulation. Studies are outlined linking peer victimization with alcohol/substance use, associations with internalizing symptoms, and differential structure and function in, and connectivity among, neural regions implicated in alcohol/substance use disorders. Further, the role(s) of neuroendocrine dysfunction, comorbid mental illness, and genetics are discussed as risk factors for substance use following peer victimization. This review concludes with the identification of gaps in the literature and suggestions for further investigation, such as the need for more studies examining the neural correlates of peer victimization, including cyberbullying, and greater consistency in how peer victimization and alcohol/substance use are operationalized and measured across studies. Prospective investigations of biological and psychosocial factors that contribute to alcohol and substance use and development of alcohol/substance use problems are needed to inform novel intervention and prevention strategies in typically developing youth and in populations with high rates of peer victimization, such as individuals with comorbid mental illness and those at high risk for psychiatric disorders.

Alcohol Use and Prefrontal Cortex Volume Trajectories in Young Adults with Mood Disorders and Associated Clinical Outcomes.

(1) Background: Alcohol use in the course of mood disorders is associated with worse clinical outcomes. The mechanisms by which alcohol use alters the course of illness are unclear but may relate to prefrontal cortical (PFC) sensitivity to alcohol. We investigated associations between alcohol use and PFC structural trajectories in young adults with a mood disorder compared to typically developing peers. (2) Methods: 41 young adults (24 with a mood disorder, agemean = 21 ± 2 years) completed clinical evaluations, assessment of alcohol use, and two structural MRI scans approximately one year apart. Freesurfer was used to segment PFC regions of interest (ROIs) (anterior cingulate, orbitofrontal cortex, and frontal pole). Effects of group, alcohol use, time, and interactions among these variables on PFC ROIs at baseline and follow-up were modeled. Associations were examined between alcohol use and longitudinal changes in PFC ROIs with prospective mood. (3) Results: Greater alcohol use was prospectively associated with decreased frontal pole volume in participants with a mood disorder, but not typically developing comparison participants (time-by-group-by-alcohol interaction; p = 0.007); however, this interaction became a statistical trend in a sensitivity analysis excluding one outlier in terms of alcohol use. Greater alcohol use and a decrease in frontal pole volume related to longer duration of major depression during follow-up (p's < 0.05). (4) Conclusion: Preliminary findings support more research on alcohol use, PFC trajectories, and depression recurrence in young adults with a mood disorder including individuals with heavier drinking patterns.

Neural functional connectivity changes to psychosocial stress in young adults with bipolar disorder and preliminary associations with clinical trajectories.

BACKGROUND: Stress-related mechanisms are implicated in the pathophysiology of bipolar disorder and may contribute to heterogeneity in illness course. Yet, there is a lack of study investigating the neural mechanisms underlying the stress response in this condition. This study investigated changes in amygdala activation and functional connectivity in response to acute psychosocial stress in young adults with bipolar disorder and explored relations with clinical phenotype and prospective mood symptoms. METHODS: 42 young adults [19 with bipolar disorder, agemean  ± SD =21.4 ± 2.2 years] completed a modified version of the Montreal Imaging Stress Task. Amygdala activation and functional connectivity with prefrontal cortex (PFC) regions of interest was calculated for control and stress conditions. Main effects of group, condition, and group by condition interaction on amygdala activation and connectivity were modeled. A subset of bipolar participants completed 1-year follow-up assessments. Relations between neural responses to stress with concurrent substance use and prospective mood symptoms were explored. RESULTS: There were no between-group differences in amygdala activation or functional connectivity during the control condition. Increased right amygdala-right rostral PFC (rPFC) functional connectivity to stress was observed in bipolar disorder, compared to typically developing controls. In bipolar disorder, greater increase in right amygdala-right rPFC functional connectivity to stress was associated with less frequent cannabis use, and prospectively with shorter duration and lower severity of depression symptoms over follow-up. CONCLUSION: Results from this preliminary study suggest differences in frontolimbic functional connectivity responses to stress in young adults with bipolar disorder and associations with cannabis use and prospective mood symptoms.

Recent Perceived Stress, Amygdala Reactivity to Acute Psychosocial Stress, and Alcohol and Cannabis Use in Adolescents and Young Adults With Bipolar Disorder.

Background: Psychosocial stress negatively affects the clinical course of bipolar disorder. Studies primarily focused on adults with bipolar disorder suggest the impact of stress is progressive, i.e., stress response sensitizes with age. Neural mechanisms underlying stress sensitization are unknown. As stress-related mechanisms contribute to alcohol/substance use disorders, variation in stress response in youth with bipolar disorder may contribute to development of co-occurring alcohol/substance use disorders. This study investigated relations between psychosocial stress, amygdala reactivity, and alcohol and cannabis use in youth with bipolar disorder, compared to typically developing youth. Methods: Forty-two adolescents/young adults [19 with bipolar disorder, 23 typically developing, 71% female, agemean ± SD = 21 ± 2 years] completed the Perceived Stress Scale (PSS), Daily Drinking Questionnaire modified for heaviest drinking week, and a modified Montreal Imaging Stress functional MRI Task. Amygdala activation was measured for both the control and stress conditions. Main effects of group, condition, total PSS, and their interactions on amygdala activation were modeled. Relationships between amygdala response to acute stress with recent alcohol/cannabis use were investigated. Results: Greater perceived stress related to increased right amygdala activation in response to the stress, compared to control, condition in bipolar disorder, but not in typically developing youth (group × condition × PSS interaction, p = 0.02). Greater amygdala reactivity to acute stress correlated with greater quantity and frequency of alcohol use and frequency of cannabis use in bipolar disorder. Conclusion: Recent perceived stress is associated with changes in amygdala activation during acute stress with amygdala reactivity related to alcohol/cannabis use in youth with bipolar disorder.

Rising to the Occasion of This COVID-19-Impacted Nation: Development, Implementation, and Feasibility of the Brief Assessment-Informed Skills Intervention for COVID-19 (BASIC).

The COVID-19 pandemic has had a profound impact on the global economy, physical health, and mental health. This pandemic, like previous viral outbreaks, has resulted in spikes in anxiety, depression, and stress. Even though millions of individuals face the physical health consequences of infection by COVID-19, even more individuals are confronted with the mental health consequences of this pandemic. This significantly increased demand for mental health services cannot be easily met by existing mental health systems, which often rely on courses of therapy to be delivered over months. Single session interventions (SSIs) may be one important approach to meeting this increased demand, as they are treatments designed to be delivered over the course of a single meeting. SSIs have been found to be effective for a range of mental health challenges, with durable effects lasting months to years later. Here, we describe an SSI designed for the COVID-19 pandemic. This Brief Assessment-informed Skills Intervention for COVID-19 (BASIC) program draws upon therapeutic skills from existing empirically supported treatments to target common presenting complaints due to this pandemic. We discuss the process of developing and implementing this intervention, as well as explore feasibility and initial clinical insights. In short, BASIC is an easy-to-adopt intervention that is designed to be effective in a single session, making it well-suited for handling the increased demand for mental health services due to COVID-19.

Childhood maltreatment, prefrontal-paralimbic gray matter volume, and substance use in young adults and interactions with risk for bipolar disorder.

Childhood maltreatment is associated with adverse effects on the brain, and an increased risk for psychopathology, including mood and substance use disorders. Individuals vary on the degree to which they exhibit neurobiological and clinical differences following maltreatment. Individuals with bipolar disorder exhibit greater magnitude of maltreatment-related prefrontal-paralimbic gray matter volume (GMV) deficits compared to typically developing individuals. It is unclear if greater structural differences stem from greater neural vulnerability to maltreatment in bipolar disorder, or if they relate to presence of other clinical features associated with childhood maltreatment, e.g., elevated prevalence of comorbid substance use disorders. To investigate this, we compared young adults with a family history of bipolar disorder (n = 21), but who did not fulfill diagnostic criteria for bipolar disorder, with typically developing young adults without a family history of bipolar disorder (n = 26). Participants completed structural neuroimaging, clinical and family history interviews, and assessment of childhood maltreatment and recent alcohol and cannabis use patterns. We examined relations between childhood maltreatment and prefrontal-paralimbic GMV by modeling main effects of maltreatment and family history group by maltreatment interactions on prefrontal-paralimbic GMV. We also examined relations between maltreatment and associated GMV changes with recent alcohol and cannabis use. Childhood maltreatment correlated with lower ventral, rostral and dorsolateral prefrontal and insular cortical GMV across all participants regardless of the presence or absence of familial history of bipolar disorder. However, exploratory analyses did reveal greater maltreatment-related GMV differences in individuals with prodromal symptoms of depression. Lower insula GMV was associated with greater frequency of cannabis use across all participants and greater quantity of alcohol use only in those with familial risk for bipolar disorder. Results suggest familial risk for bipolar disorder, and presumably genetic risk, may relate to outcomes following childhood maltreatment and should be considered in prevention/early intervention strategies.

Subjective response to alcohol: Associated alcohol use and orbitofrontal gray matter volume in bipolar disorder.

BACKGROUND: Alcohol use disorders (AUDs) are highly prevalent in bipolar disorder, however the developmental etiology of this comorbidity remains unknown. Structural differences in the orbitofrontal cortex (OFC) have been linked to problematic drinking in bipolar disorder and typically developing youth, with evidence implicating variations in OFC in differential subjective response to alcohol in typical development. METHODS: Subjective response to alcohol, recent alcohol use, impulsivity, and variation in OFC gray matter volume were investigated in 48 emerging adults (24 with bipolar disorder, 24 typically developing). On average 1.5 years later, drinking patterns were reassessed and relations between subjective response and changes in alcohol use were explored. RESULTS: Groups did not differ in baseline alcohol use or subjective response. At baseline, decreased subjective response to alcohol was associated with increased alcohol use in both groups. Lower gray matter volume in medial OFC in bipolar disorder was associated with increased subjective response to alcohol, whereas lower gray matter volume in OFC in typically developing participants was associated with decreased subjective response to alcohol. Increase in alcohol use (baseline to follow-up) was associated with increased baseline subjective response to alcohol in bipolar disorder, and decreased baseline subjective response in the typically developing group. LIMITATIONS: Preliminary study with a small sample size. CONCLUSION: Underlying OFC biology may contribute to differences in alcohol sensitivity in bipolar disorder which may also relate to prospective changes in alcohol use patterns. Future studies are needed to examine how these factors prospectively relate to development of AUDs in bipolar disorder.

Review: Adjunctive pharmacologic approaches for benzodiazepine tapers.

BACKGROUND: Many patients require discontinuation of benzodiazepines due to a reduction in drug efficacy over time, the development of a sedative use disorder, or unwanted side effects. Benzodiazepine discontinuation can pose a significant challenge for prescribing clinicians due to potential withdrawal symptoms and a recurrence of psychiatric complaints. METHODS: A PubMed literature search was conducted using the medical subject heading of benzodiazepines in combination with the following key words: discontinuation, withdrawal, detoxification, cessation, dependence, addiction, substance use disorders, or long term. Twenty-one studies met the search criteria. RESULTS: Few medications facilitated the successful discontinuation of benzodiazepines or relief from benzodiazepine withdrawal symptoms. CONCLUSIONS: Studies were heterogeneous with respect to sample selection, sample size, and outcome measures. Medications targeting insomnia yielded mixed results. Similarly, studies of agents targeting anxiety symptoms demonstrated inconsistent findings in the reduction of anxiety, improvement in withdrawal symptoms, or enhancement of benzodiazepine completion rates. Anticonvulsants have supporting evidence from small case reports; carbamazepine shows some potential in assisting taper completion and reducing withdrawal severity. These conclusions should be considered in light of a number of inconsistencies across studies in the literature. The results of this review article highlight the need for additional research on optimal strategies for facilitating successful benzodiazepine tapers.

Motor plans persist to influence subsequent actions with four or more response alternatives.

Motor activity has the potential to persist after action and influence subsequent behaviour. A standard approach to isolating a motoric influence is to map two stimuli onto each response, so that response and stimulus repetition can be dissociated. A response-only response-repetition (RoRR) effect can then be assessed, arising if the same response made to two unrelated stimuli is nonetheless produced more rapidly. This kind of motoric behavioural influence of one response on the next has proved elusive in reaction time tasks involving choices between key presses, at least when stimuli mapped to each response are difficult to categorise together. However, such tasks have traditionally involved only a few response alternatives. We hypothesised that a larger load on the motor system might prevent participants from holding all possible action plans active throughout an experiment, and thus reveal trial-to-trial motor priming in the form of an RoRR effect. In our first experiment, increasing the number of response alternatives to four or eight yielded a reliable RoRR effect. This effect was replicated in Experiment 2, where it also proved persistent across practice and resistant to changes in response configuration. Our results are consistent with evidence of motoric perseveration in other kinds of motor task, such as reaching and grasping, and have implications for the generation of speeded decisions in a range of activities.