Brainstorming diseases: Consistent classification of neuropsychiatric diseases is problematic because it can lead to misunderstanding of etiology. The Brainstorm Consortium examined multiple genome-wide association studies drawn from more than 200,000 patients for 25 brain-associated disorders and 17 phenotypes. Broadly, it appears that psychiatric and neurologic disorders share relatively little common genetic risk. However, different and independent pathways can result in similar clinical manifestations (e.g., psychosis, which occurs in both schizophrenia and Alzheimer's disease). Schizophrenia correlated with many psychiatric disorders, whereas the immunopathological affliction Crohn's disease did not, and posttraumatic stress syndrome was also largely independent of underlying traits. Essentially, the earlier the onset of a disorder, the more inheritable it appeared to be. Science , this issue p. eaap8757

Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors, have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances. However, data on the safety and efficacy of atypical antipsychotic agents in children are limited. We conducted a multisite, randomized, double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior in children 5 to 17 years old. The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions — Improvement (CGI-I) scale at eight weeks. A total of 101 children (82 boys and 19 girls; mean [±SD] age, 8.8±2.7 years) were randomly assigned to receive risperidone (49 children) or placebo (52). Treatment with risperidone for eight weeks (dose range, 0.5 to 3.5 mg per day) resulted in a 56.9 percent reduction in the Irritability score, as compared with a 14.1 percent decrease in the placebo group (P<0.001). The rate of a positive response, defined as at least a 25 percent decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale, was 69 percent in the risperidone group (34 of 49 children had a positive response) and 12 percent in the placebo group (6 of 52, P<0.001). Risperidone therapy was associated with an average weight gain of 2.7±2.9 kg, as compared with 0.8±2.2 kg with placebo (P<0.001). Increased appetite, fatigue, drowsiness, dizziness, and drooling were more common in the risperidone group than in the placebo group (P<0.05 for each comparison). In two thirds of the children with a positive response to risperidone at eight weeks (23 of 34), the benefit was maintained at six months. Risperidone was effective and well tolerated for the treatment of tantrums, aggression, or self-injurious behavior in children with autistic disorder. The short period of this trial limits inferences about adverse effects such as tardive dyskinesia.

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by multiple motor tics and 1 or more vocal tics that persist for at least 1 year.^1,2 Multiple comorbid psychiatric disorders have been reported in TS-affected individuals; when present, these conditions typically cause more distress and impairment than do tics.^3-7 High rates of comorbid attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) have been well documented and are thought to be core components of the TS phenotype.^4,8-11 Although elevated rates for mood disorders, nonobsessional anxiety disorders, and disruptive behavior disorders (DBDs) have also been reported,^4,12-17 a significant gap in knowledge still exists regarding the range, prevalence, and clinical attributes of the non-OCD, non-ADHD comorbid disorders. The few available studies were limited by small sample sizes (<200 participants),^3,7,18-20 small number of diagnoses examined, or reliance on symptom checklists and severity scales rather than DSM-based, structured diagnostic psychiatric assessments.^18,21-24

OBSESSIVE-COMPULSIVE disorder (OCD) is a psychiatric condition first described more than 100 years ago.¹ The pathognomonic features of the disorder are persistent, intrusive, senseless thoughts and impulses (obsessions) and repetitive, intentional behaviors (compulsions). Patients with the disorder recognize that their thoughts and behaviors are excessive and unreasonable, and they struggle to resist them. The lifetime prevalence of OCD is estimated to be 1% to 3%, based on population-based surveys conducted in many communities nationally and internationally.^2,3 Although the disorder affects individuals of all ages, the period of greatest risk is from childhood to middle adulthood^4,5 Patients experience a chronic or episodic course with exacerbations that can substantially impair social, occupational, and academic functioning; according to the World Health Organization, OCD is among the 10 most disabling medical conditions worldwide.⁶