Adolescents With a High Burden of New-Onset Mood Symptoms After Sport-Related Concussion Benefit From Prescribed Aerobic Exercise, a Secondary Analysis of 2 Randomized Controlled Trials.

OBJECTIVE: Approximately 20% of students with sport-related concussion (SRC) report new symptoms of anxiety and depression which may be associated with delayed recovery and increased risk for developing a mood disorder. Early prescribed aerobic exercise facilitates recovery in athletes with concussion-related exercise intolerance. We studied the effect of aerobic exercise treatment on new mood symptoms early after SRC. DESIGN: Exploratory secondary analysis of 2 randomized controlled trials (RCT). SETTING: Sports medicine clinics associated with UB (Buffalo, NY), CHOP (Philadelphia, PA), and Boston Children's Hospital (Boston, MA). PARTICIPANTS: Male and female adolescents (aged 13-18 years) diagnosed with SRC (2-10 days since injury). INTERVENTIONS: Participants were randomized to individualized targeted heart rate aerobic exercise (n = 102) or to a placebo intervention designed to mimic relative rest (n = 96). MAIN OUTCOME MEASURES: Incidence of Persisting Post-Concussive Symptoms (PPCS, symptoms ≥28 days). RESULTS: First RCT recruited from 2016 to 2018 and the second from 2018 to 2020. Of 198 adolescents, 156 (79%) reported a low burden (mean 1.2 ± 1.65/24) while 42 (21%) reported a high burden (mean 9.74 ± 3.70/24) of emotional symptoms before randomization. Intervention hazard ratio for developing PPCS for low burden was 0.767 (95% CI, 0.546-1.079; P = 0.128; ß = 0.085) and for high burden was 0.290 (95% CI, 0.123-0.683; P = 0.005; ß = 0.732). CONCLUSIONS: High burden of mood symptoms early after injury increases risk for PPCS, but the sports medicine model of providing early targeted aerobic exercise treatment reduces it. Nonsports medicine clinicians who treat patients with a high burden of new mood symptoms after concussion should consider prescribing aerobic exercise treatment to reduce the risk of PPCS and a mood disorder.

Recognition of adjustment disorder among patients with substance use disorders referred for suicide-related concerns in an academic hospital setting.

BACKGROUND: Persons with substance use disorders (SUDs) have a greater risk of suicide compared with the general population. Adjustment Disorder (AD) has been under-researched in SUD populations. OBJECTIVE(S): To characterize rates, and associated features, of AD among persons with SUD for whom lethality concerns arise in a general hospital setting. METHODS: Retrospective analysis of electronic medical record data from psychiatric consultations during a consecutive six-month period. RESULTS: Compared with persons with SUD classified as non-attempters, suicide attempters were significantly more likely to be diagnosed with AD. Multiple logistic regression models revealed patients with SUD referred for suicide-related concerns have an increased risk of suicide attempt if also diagnosed with AD or if they have a history of prior suicide attempt. CONCLUSIONS: These data are in line with the contention that SUD, with comorbid AD, portend significant risk for suicide. AD represents an important disorder to recognize and target in suicide prevention strategies.

Relationship between anxiety and concussion symptoms among adolescents enrolled in a randomized controlled trial of aerobic exercise.

BACKGROUND: Affective symptoms, specifically, anxiety, are often overlooked after sport-related concussion (SRC), and may contribute to prolonged recovery. OBJECTIVE: To examine the impact of anxiety during clinical recovery among adolescents (13-18y) enrolled in a randomized trial of aerobic exercise for SRC. METHODS: Patients at three sites were randomized into aerobic exercise or stretching arms, and enrolled in the 4-week intervention. The relationship between PROMIS Anxiety score at initial visit and time to symptom resolution was evaluated with survival analysis. The relationship between weekly PROMIS Anxiety score and Post-concussion Symptom Inventory (PCSI) score was evaluated with Linear Mixed Models. Analyses adjusted for study arm and baseline covariates. RESULTS: Among 54 adolescents (median age = 15.8y, initial visit PCSI score = 32, pre-injury PROMIS Anxiety score = 2), median time to symptom resolution was 10 days (25th-75th percentiles: 6-24) in the Low-PROMIS Anxiety group and 12 days (25th-75th percentiles: 5-21) in the High-PROMIS Anxiety group (p = 0.62). Each additional unit of PROMIS Anxiety score corresponded to a 1.52-unit higher PCSI total score (p <  0.01). Neither effect varied by aerobic exercise/stretching group. CONCLUSION: Higher initial PROMIS Anxiety score was not significantly associated with delayed symptom resolution. However, over time, PROMIS Anxiety score was significantly associated with elevated PCSI score, regardless of exercise/stretching group.

A high-quality homology model for the human dopamine transporter validated for drug design purposes.

The human dopamine transporter (hDAT) plays many vital functions within the central nervous system and is thus targeted by many pharmaceutical agents. Dopamine-related therapies are in current development for individuals with dopamine-related disorders including depression, Parkinson's disease, and psychostimulant addictions such as cocaine abuse. Yet, most efforts to develop new dopamine therapies are within costly structure-activity relationship studies. Through structure-based drug design techniques, the binding site of hDAT can be utilized to develop novel selective and potent dopamine therapies at reduced costs. However, no structural models of hDAT specifically validated for rational drug design purposes currently exist. Here, using the Drosophila dopamine transporter as a template, a homology model for the hDAT was developed and validated. The model was able to reproduce experimental binding modes with great accuracy, was able to rank inhibitors in the correct order of increasing potency with an R2 value of 0.81 for the test set, and it also outperformed other published hDAT models. Thus, the model can be used reliably in structure-based drug design projects.