A "Proof of Concept" Randomized Controlled Trial of a Video Game Requiring Emotional Regulation to Augment Anger Control Training.

Emotional dysregulation leading to clinically significant anger and aggression is a common and substantial concern for youth and their families. While psychotropic medications and cognitive behavioral therapies can be effective, these modalities suffer from drawbacks such as significant side effects, high rates of attrition, and lack of real-world skill translation. Regulate and Gain Emotional Control (RAGE-Control) is a video game designed as an engaging augment to existing treatments. The game facilitates emotional regulation skill building through practice modulating physiological arousal while completing a challenging inhibitory task. We compared reduction in anger, aggression, oppositionality, and global severity between two treatment conditions: Anger Control Training (ACT) augmented with RAGE-Control and ACT with a sham version of the game, in a pilot double-blind randomized controlled trial. To begin to understand mechanisms of change, we examined heart rate during game play over the course of the study and explored associations between symptom changes and heart rate changes. Materials and Methods: Forty youth with clinically significant anger dyscontrol (age 10-17) were randomly assigned to 10 sessions of ACT with RAGE-Control or ACT with sham video game. Results: Both treatments similarly reduced self-reported anger. However, ACT with RAGE-Control led to larger improvements in aggression (CI: -17 to -1.0, ES: 0.55, p = 0.015); oppositionality (CI: -9.0 to -7e-6, ES: 0.48, p = 0.032); and global severity (CI: -1.0 to -5e-6, ES: 0.51, p = 0.023) relative to sham. Participants in the RAGE-Control group saw a decrease in median heart rate during game play (ß = 1.2, p < 0.001). Larger pre to post decreases in heart rate were significantly associated with larger pre to post decreases in aggression and oppositional behaviors. Discussion: Augmenting ACT with RAGE-Control reduced behavioral expression of anger, but not the experience of angry feelings, as compared to ACT with a sham version of the game. Increased heart rate control, demonstrated by reduction in median heart rate during gameplay, was associated with decreased aggression and oppositional behavior. Together these findings support that augmenting traditional treatment with technology facilitating heart rate control through skill practice translates to enhancements in real-life behavioral change. Therefore, further exploration into engaging skill-focused games such as RAGE-Control is warranted. Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT01551732.

N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth.

Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease's pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis (n = 22), at clinical high risk (CHR) for psychosis (n = 29), and healthy controls (n = 17) to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones - mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old. Initial N100 blunting partially accounted for differences. Decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life.

Early auditory processing evoked potentials (N100) show a continuum of blunting from clinical high risk to psychosis in a pediatric sample.

BACKGROUND: The N100 is a negative deflection in the surface EEG approximately 100 ms after an auditory signal. It has been shown to be reduced in individuals with schizophrenia and those at clinical high risk (CHR). N100 blunting may index neural network dysfunction underlying psychotic symptoms. This phenomenon has received little attention in pediatric populations. METHOD: This cross-sectional study compared the N100 response measured via the average EEG response at the left medial frontal position FC1 to 150 sinusoidal tones in participants ages 5 to 17 years with a CHR syndrome (n=29), a psychotic disorder (n=22), or healthy controls (n=17). RESULTS: Linear regression analyses that considered potential covariates (age, gender, handedness, family mental health history, medication usage) revealed decreasing N100 amplitude with increasing severity of psychotic symptomatology from healthy to CHR to psychotic level. CONCLUSIONS: Longitudinal assessment of the N100 in CHR children who do and do not develop psychosis will inform whether it predicts transition to psychosis and if its response to treatment predicts symptom change.

Comparing stimulant effects in youth with ADHD symptoms and epilepsy.

To retrospectively examine response to stimulant treatment in patients with epilepsy and ADHD symptoms as predicted by seizure freedom for six months, use of methylphenidate (MPH) versus amphetamine (AMP) preparations, cognitive level, and medical records were searched for patients under the age of 18 with epilepsy and ADHD symptoms treated with MPH or AMP (n=36, age=10.4 ± 3.5; male=67%). "Responders" had a CGI-improvement score of ≤ 2 and did not stop medication because of adverse effects. "Worsened" patients discontinued medication because of agitation/emotional lability. Seizure freedom did not predict treatment response. Lower cognitive level was associated with increased rate of worsening (p=0.048). No patients who were seizure-free at the start of the medication trial experienced an increase in seizures. Of the patients having seizures at the start of trial, one patient on MPH and two patients on AMP had increased seizures during the trial. Seizures returned to baseline frequency or less after stimulant discontinuation or anticonvulsant adjustment. Methylphenidate was associated with a higher response rate, with 12 of 19 given MPH (0.62 ± 0.28 mg/kg/day) compared with 4 of 17 given AMP (0.37 ± 0.26 mg/kg/day) responding (p=0.03). Methylphenidate treatment and higher cognitive level were associated with improved treatment outcome, while seizure freedom had no clear effect. Confidence in these findings is limited by the study's small, open-label, and uncontrolled design.