Transdiagnostic Mood, Anxiety, and Trauma Symptom Factors in Alcohol Use Disorder: Neural Correlates Across 3 Brain Networks.

BACKGROUND: Alcohol use disorder (AUD) is associated with high rates of trauma, mood, and anxiety disorders. Across these diagnoses, individual symptoms substantially overlap, highlighting the need for a transdiagnostic approach. Furthermore, there is limited research on how transdiagnostic psychopathology impacts the neural correlates of AUD. Thus, we aimed to identify symptom factors spanning diagnoses and examine how they relate to the neurocircuitry of addiction. METHODS: Eighty-six veterans with AUD completed self-report measures and reward, incentive salience, and cognitive control functional magnetic resonance imaging tasks. Factor analysis was performed on self-reported trauma, depression, anxiety, and stress symptoms to obtain transdiagnostic symptom compositions. Neural correlates of a priori-defined regions of interest in the 3 networks were assessed. Independent sample t tests were used to compare the same nodes by DSM-5 diagnosis. RESULTS: Four symptom factors were identified: Trauma distress, Negative affect, Hyperarousal, and Somatic anxiety. Trauma distress score was associated with increased cognitive control activity during response inhibition (dorsal anterior cingulate cortex). Negative affect was related to lower activation in reward regions (right caudate) but higher activation in cognitive control regions during response inhibition (left dorsolateral prefrontal cortex). Hyperarousal was related to lower reward activity during monetary reward anticipation (left caudate, right caudate). Somatic anxiety was not significantly associated with brain activation. No difference in neural activity was found by posttraumatic stress disorder, major depressive disorder, or generalized anxiety disorder diagnosis. CONCLUSIONS: These hypothesis-generating findings offer transdiagnostic symptom factors that are differentially associated with neural function and could guide us toward a brain-based classification of psychiatric dysfunction in AUD. Results warrant further investigation of transdiagnostic approaches in addiction.

A pilot, randomized clinical trial: Left dorsolateral prefrontal cortex intermittent theta burst stimulation improves treatment outcomes in veterans with alcohol use disorder.

BACKGROUND: Transcranial magnetic stimulation (TMS) offers a promising treatment avenue to modulate brain function in alcohol use disorder (AUD). To the best of our knowledge, this pilot study is the first randomized, double-blind, sham-controlled trial to deliver intermittent theta burst stimulation to the left dorsolateral prefrontal cortex (DLPFC) among US veterans with AUD. We hypothesized that 20 sessions of real TMS are tolerable and feasible. As a secondary line of inquiry, we hypothesized that, relative to sham TMS, individuals receiving real TMS would experience greater reductions in 6-month relapse rates, anhedonia, and alcohol cue-reactivity. METHODS: Veterans (n = 17, one woman) were enrolled in a double-blind, sham-controlled trial (2-3 sessions/day; 7-10 days; 600 pulses/session; 20 sessions). Pre- and posttreatment assessments included responses to self-report questionnaires and functional magnetic resonance imaging measures of alcohol cue-reactivity. Alcohol consumption was assessed for 6 months. Linear mixed-effects models were constructed to predict posttreatment craving, mood, and cue-reactivity. RESULTS: Individuals who received active iTBS (n = 8) were less likely to relapse within 3 months after treatment than the sham-treated group (n = 9) (OR = 12.0). Greater reductions in anhedonia were observed following active iTBS (Cohen's d = -0.59), relative to sham (d = -0.25). Alcohol cue-reactivity was reduced following active iTBS and increased following sham within the left insula (d = -0.19 vs. 0.51), left thalamus (d = -0.28 vs. 0.77), right insula (d = 0.18 vs. 0.52), and right thalamus (d = -0.06 vs. 0.62). CONCLUSIONS: Relative to sham, we demonstrate that 20 sessions of real left DLPFC iTBS reduced the likelihood of relapse for at least 3 months. The potential utility of this approach is underscored by observed decreases in anhedonia and alcohol cue-reactivity-strong predictors of relapse among veterans. These initial data offer a valuable set of effect sizes to inform future clinical trials in this patient population.

Targeting the Salience Network: A Mini-Review on a Novel Neuromodulation Approach for Treating Alcohol Use Disorder.

Alcohol use disorder (AUD) continues to be challenging to treat despite the best available interventions, with two-thirds of individuals going on to relapse by 1 year after treatment. Recent advances in the brain-based conceptual framework of addiction have allowed the field to pivot into a neuromodulation approach to intervention for these devastative disorders. Small trials of repetitive transcranial magnetic stimulation (rTMS) have used protocols developed for other psychiatric conditions and applied them to those with addiction with modest efficacy. Recent evidence suggests that a TMS approach focused on modulating the salience network (SN), a circuit at the crossroads of large-scale networks associated with AUD, may be a fruitful therapeutic strategy. The anterior insula or dorsal anterior cingulate cortex may be particularly effective stimulation sites given emerging evidence of their roles in processes associated with relapse.

Evaluating the Effect of Concussion-Education Programs on Intent to Report Concussion in High School Football.

CONTEXT: Concussion underreporting leads to delays in diagnosis and treatment, prolonging recovery time. Athletes' self-reporting of concussion symptoms, therefore, reduces risk. OBJECTIVE: To evaluate the effectiveness of 3 concussion-education programs in improving concussion-reporting intention. DESIGN: Randomized controlled clinical trial. SETTING: Three high schools in California. PATIENTS OR OTHER PARTICIPANTS: A total of 118 male football players (age = 14.88 ± 1.19 years). INTERVENTION(S): Participants were randomly assigned to receive concussion education via CrashCourse (CC), Centers for Disease Control and Prevention (CDC) video education materials (CDC-Vi), or CDC written education materials (CDC-Wr). MAIN OUTCOME MEASURE(S): The primary outcome was concussion-reporting intention, which was assessed at baseline, immediately after education, and at 1-month follow-up. Secondary outcomes were concussion knowledge, concussion-reporting attitudes, perceived concussion-reporting norms, and perceived behavioral control. RESULTS: Across all education formats, a total sample of athletes improved in concussion-reporting intention at immediate and 1-month follow-ups (mean improvements = 6.8% and 11.4%, respectively; F4,224 = 11.1, P < .001). Similar findings were observed across all education formats in secondary analyses examining knowledge, attitudes, and perceived behavioral control. However, we noted differences in concussion-reporting intention by education format and time (F4,224 = 2.8, P = .03). Post hoc analysis showed that athletes who received CC had increased concussion-reporting intentions at immediate and 1-month follow-ups (baseline = 4.7, immediate follow-up = 6.1, 1-month follow-up = 6.0; F16,61.1 = 6.1, P = .007) compared with increases only at 1-month follow-up for CDC-Vi (baseline = 4.3, immediate follow-up = 5.2, 1-month follow-up = 5.8; F1.6,61.6 = 8.4, P = .001) and no improvement for CDC-Wr (P = .10). Secondary analyses indicated differences between CC and both CDC interventions in concussion knowledge and attitudes at immediate and 1-month follow-ups. We identified no differences in perceived behavioral control among interventions (F4,216 = 0.2, P = .93) or perceived concussion-reporting norms across (F4,224 = 0.3, P = .73) or among (F4,224 = 1.7, P = .15) interventions. CONCLUSIONS: All athletes exhibited an improved intent to report concussions, increased concussion knowledge, better concussion attitudes, and more perceived behavioral control at both immediate and 1-month follow-ups. However, athletes randomized to receive CC reported a greater intent to report concussion, more knowledge, and improved concussion-reporting attitudes when compared with those who received CDC-Vi and CDC-Wr.