Faculty Bibliography

AIM/OBJECTIVE:To examine whether adding the Community Reinforcement Approach for Seniors (CRA-S) to Motivational Enhancement Therapy (MET) increases the probability of treatment success in people ≥ 60 years old with alcohol use disorder (AUD). DESIGN/METHODS:A single blind multi-centre multinational randomized (1:1) controlled trial. SETTING/METHODS:Outpatient settings (municipal alcohol treatment clinics in Denmark, specialized addiction care facilities in Germany, and a primary care clinic in the USA). PARTICIPANTS/METHODS:Between January 2014 and May 2016, 693 patients aged 60+ years and fulfilling DSM-5 criteria for AUD participated in comparing MET (n=351) and MET + CRA-S (n=342). INTERVENTION AND COMPARATOR/UNASSIGNED:MET (comparator) included four manualized sessions aimed at increasing motivation to change and establishing a change plan. CRA-S (intervention) consisted of up to eight further optional, manualized sessions aimed at helping patients to implement their change plan. CRA-S included a specially designed module on coping with age and age-related problems. MEASUREMENTS/METHODS:The primary outcome was either total alcohol abstinence or an expected blood alcohol concentration of ≤ 0.05% during the 30 days preceding the 26 weeks follow-up (defined as success) or blood alcohol concentration of >0.05% during the follow-up period (defined as failure). This was assessed by self-report using the Form 90 instrument. The main analysis involved complete cases. FINDINGS/RESULTS:The follow-up rate at 26 weeks was 76.2% (76.9% in the MET group and 76.0% in the MET+CRA-S group). The success rate in the MET group was 48.9% (95%CI=42.9%-54.9%) vs. 52.3% (95%CI=46.2%-58.3%) in the MET+CRA-S group. The odds of success in the two conditions did not differ (odds ratio 1.22. 95% CI=0.86-1.75, p = 0.26, Bayes factor=0.10). Sensitivity analyses involving alternative approaches to missing values did not change the results. CONCLUSIONS:In older adults with an alcohol use disorder diagnosis, adding the 'Community Reinforcement Approach for Seniors' intervention to brief outpatient Motivational Enhancement Therapy treatment did not improve drinking outcome.

Impairment in cognitive control in alcohol use disorder (AUD) contributes to difficulty controlling alcohol use and, in many populations, difficulties with emotion regulation. However, the most reliable and robust marker of clinically-relevant deficits in cognitive control in AUD is unclear. Our aims were to measure relationships between BOLD signal during a Stroop task and AUD severity and change in BOLD signal and change in drinking over three weeks. We also aimed to explore the relationships between BOLD signal and subjective negative affect. Thirty-three individuals with AUD underwent a multisensory Stroop task during functional magnetic resonance imaging (fMRI), as well as a battery of neuropsychological tests and self-report assessments of negative affect and AUD severity. Greater activation in temporal gyrus and cerebellum during incongruent trials compared to congruent trials was observed, and percent signal change (incongruent minus congruent) in both clusters was positively correlated with AUD severity and self-reported negative affect. Neuropsychological task performance and self-reported impulsivity were not highly correlated with AUD severity. Hierarchical regression analyses indicated that percent signal change (incongruent minus congruent) in cerebellum was independently associated with negative affect after controlling for recent and chronic drinking. In a subset of individuals (n = 23) reduction in cerebellar percent signal change (incongruent minus congruent) was correlated with increases in percent days abstinent over 3 weeks. BOLD activation during this Stroop task may therefore be an important objective marker of AUD severity and negative affect. The potential importance of the cerebellum in emotion regulation and AUD severity is highlighted.

Background and aims: Given the enormous global burden of depressive illness, there is an urgent need to develop novel and more effective treatments for major depressive disorder (MDD). Recent findings have suggested that psychedelic drugs may have a role in the treatment of depressive symptoms, and a number of groups are in the process of developing protocols to study this question systematically. Given the subjective quality of both the psychedelic experience and depressive symptomatology, great care must be taken when designing a protocol to study the clinical efficacy of psychedelic drugs. This study will discuss many factors to consider when designing a clinical trial of psilocybin for MDD. Methods: We provide a thorough review of pertinent research into antidepressant clinical trial methodology and review practical considerations that are relevant to the study of psychedelic-Assisted treatment for depression. Results: We discuss participant selection (including diagnostic accuracy, exclusion criteria, characteristics of the depressive episode, and the use of concurrent medications), study interventions (including dosing regimens, placebo selection, non-pharmacological components of treatment, and the importance of blinding), trial duration, outcome measures, and safety considerations. Conclusions: Careful and transparent study design and data analysis will maximize the likelihood of generating meaningful, reproducible results, and identifying a treatment-specific effect. Meeting the highest standards for contemporary trial design may also broaden the acceptance of psychedelic research in the scientific community at large.

OBJECTIVES/OBJECTIVE:To investigate the psychometric properties of the frequently used Alcohol Dependence Scale (ADS) in older adults and the associations between ADS scores and alcohol use and DSM-5 AUD symptom counts. METHODS:Using baseline data from an international multicenter RCT on outpatient AUD treatment for adults aged 60+ with DSM-5 alcohol use disorder (AUD; n = 529), we computed Cronbach's alpha (α) and applied confirmatory (CFA) and exploratory factor analysis (EFA) to determine the underlying factor structure. A structural equation model (SEM) explored the interrelationship of latent ADS factors with alcohol use and number of DSM-5 criteria endorsed. RESULTS:Internal consistency of the ADS (α = 0.81) was good. EFA revealed a three-factor structure. Factor 1 ("Severe withdrawal symptoms") consisted of severe psychoperceptual and psychophysical consequences of excessive drinking, Factor 2 ("Loss of control") consisted of acute physical reactions of intoxication, and Factor 3 ("Obsessive-compulsive drinking") described habitual drinking. The SEM suggested that only Factor 3 had large effects on DSM-5 symptom score and drinking behavior. CONCLUSION/CONCLUSIONS:Lowering the ADS threshold or focusing on ADS items from Factor 3 may be more suitable measures of severity of alcohol dependence in treatment-seeking older adults as ADS scores are low and not closely related to DSM-5 AUD.

Traditional neuropsychological approaches emphasize the specificity of behavioral deficits and the modular organization of the brain. At the population level, however, there is emerging evidence that deficits are correlated resulting in a low dimensional structure of post-stroke neurological impairments. Here we consider the implications of low dimensionality for the three-way mapping between structural damage, altered physiology, and behavioral deficits. Understanding this mapping will be aided by large-sample studies that apply multivariate models and focus on explained percentage of variance, as opposed to univariate lesion-symptom techniques that report statistical significance. The low dimensionality of behavioral deficits following stroke is paralleled by widespread, yet relatively consistent, changes in functional connectivity (FC), including a reduction in modularity. Both are related to the structural damage to white matter and subcortical grey commonly produced by stroke. We suggest that large-scale physiological abnormalities following a stroke reduce the variety of neural states visited during task processing and at rest, resulting in a limited repertoire of behavioral states.

Studies of stroke have identified local reorganization in perilesional tissue. However, because the brain is highly networked, strokes also broadly alter the brain's global network organization. Here, we assess brain network structure longitudinally in adult stroke patients using resting state fMRI. The topology and boundaries of cortical regions remain grossly unchanged across recovery. In contrast, the modularity of brain systems i.e. the degree of integration within and segregation between networks, was significantly reduced sub-acutely (n = 107), but partially recovered by 3 months (n = 85), and 1 year (n = 67). Importantly, network recovery correlated with recovery from language, spatial memory, and attention deficits, but not motor or visual deficits. Finally, in-depth single subject analyses were conducted using tools for visualization of changes in brain networks over time. This exploration indicated that changes in modularity during successful recovery reflect specific alterations in the relationships between different networks. For example, in a patient with left temporo-parietal stroke and severe aphasia, sub-acute loss of modularity reflected loss of association between frontal and temporo-parietal regions bi-hemispherically across multiple modules. These long-distance connections then returned over time, paralleling aphasia recovery. This work establishes the potential importance of normalization of large-scale modular brain systems in stroke recovery.

The cerebellum contains the majority of neurons in the human brain and is unique for its uniform cytoarchitecture, absence of aerobic glycolysis, and role in adaptive plasticity. Despite anatomical and physiological differences between the cerebellum and cerebral cortex, group-average functional connectivity studies have identified networks related to specific functions in both structures. Recently, precision functional mapping of individuals revealed that functional networks in the cerebral cortex exhibit measurable individual specificity. Using the highly sampled Midnight Scan Club (MSC) dataset, we found the cerebellum contains reliable, individual-specific network organization that is significantly more variable than the cerebral cortex. The frontoparietal network, thought to support adaptive control, was the only network overrepresented in the cerebellum compared to the cerebral cortex (2.3-fold). Temporally, all cerebellar resting state signals lagged behind the cerebral cortex (125-380 ms), supporting the hypothesis that the cerebellum engages in a domain-general function in the adaptive control of all cortical processes.

OBJECTIVE:To examine the diagnoses, demographics, and prevalence of psychotherapy use among children and adolescents prescribed antipsychotics by psychiatric providers in a community setting. METHODS:Medical records from 1127 children aged 0 to 17 years who were prescribed antipsychotics in 2014-2015 at Pine Rest Christian Mental Health Services (PRCMHS) outpatient network were analyzed. Antipsychotics, diagnosis codes, demographics, and number of psychotherapy sessions during this time frame were analyzed using χ and logistic regression analyses. RESULTS:During this year, 50.8% of the patients attended psychotherapy, and 35.6% attended 5 or more sessions of psychotherapy. The most prevalent primary diagnosis was bipolar disorder (37.1%), followed by attention-deficit/hyperactivity disorder (19.7%). Females being treated with antipsychotics were significantly more likely to attend psychotherapy than their male peers (55.7% vs. 47.9%, P=0.01). In the fully adjusted models, patients with diagnoses of bipolar disorder or disorders first diagnosed in infancy, childhood, or adolescence were less than half as likely to attend psychotherapy as patients with depressive disorders, with adjusted odds ratios of 0.41 and 0.42, respectively. CONCLUSIONS:Approximately half of the child and adolescent patients prescribed antipsychotics in this community sample did not attend psychotherapy, and 39% of the patients did not have a diagnosis of bipolar disorder, psychotic disorder, or autistic disorder.

Cancer is highly prevalent and one of the leading causes of global morbidity and mortality. Psychological and existential suffering is common in cancer patients, associated with poor psychiatric and medical outcomes. Promising early-phase clinical research (1960s to early 1970s) suggested a therapeutic signal for serotoninergic psychedelics (e.g. psilocybin, LSD) in treating cancer-related psychiatric distress. After several decades of quiescence, research on psychedelic-assisted therapy to treat psychiatric disorders in cancer patients has resumed within the last 2 decades in the US and Europe. This review article is based on a systematic search of clinical trials from 1960-2018 researching the therapeutic use of psychedelic treatment in patients with serious or terminal illnesses and related psychiatric illness. The search found 10 eligible clinical trials, with a total of 445 participants, with the vast majority of the patients having advanced or terminal cancer diagnoses. Six open label trials, published between 1964 and 1980 (n = 341), suggested that psychedelic therapy (mostly with LSD) may improve cancer-related depression, anxiety, and fear of death. Four RCTs trials were published between 2011 and 2016 (n = 104), mostly with psilocybin treatment (n = 92), and demonstrated that psychedelic-assisted treatment can produce rapid, robust, and sustained improvements in cancer-related psychological and existential distress.

The aims of this study were to assess the impact of ceremonial use of ayahuasca-a psychedelic brew containing N,N-dimethyltryptamine (DMT) and β-carboline -and attendance at União do Vegetal (UDV) meetings on substance abuse; here we report the findings related to alcohol and tobacco use disorder. A total of 1,947 members of UDV 18+ years old were evaluated in terms of years of membership and ceremonial attendance during the previous 12 months. Participants were recruited from 10 states from all major regions of Brazil. Alcohol and tobacco use was evaluated through questionnaires first developed by the World Health Organization and the Substance Abuse and Mental Health Services Administration. Analyses compared levels of alcohol and tobacco use disorder between the UDV and a national normative sample (n = 7,939). Binomial tests for proportions indicated that lifetime use of alcohol and tobacco was higher in UDV sample compared to the Brazilian norms for age ranges of 25-34 and over 34 years old, but not for the age range of 18-24 years old. However, current use disorders for alcohol and tobacco were significantly lower in the UDV sample than the Brazilian norms. Regression analyses revealed a significant impact of attendance at ayahuasca ceremonies during the previous 12 months and years of UDV membership on the reduction of alcohol and tobacco use disorder.