The voices go, but the song remains the same: how can we rescue cognition in early-onset schizophrenia?

摘要: Current treatments for psychosis in children and adolescents are sorely need of efficacy data. In the past decade we have seen a dramatic increase prescription antipsychotic medication individuals younger than 18 years1 an increased awareness that subclinical overt psychotic symptoms more prevalent pediatric populations previously believed.2 Despite its widespread implementation, exactly how pharmaceutical intervention affects cognitive psychosocial functioning youth remains unknown. The Treatment Early-Onset Schizophrenia Spectrum Disorders study,3 multisite, longitudinal investigation potential moderators treatment response with illness, has proved welcome platform informing optimizing guidelines gaining insight into pathophysiology early-onset schizophrenia (EOS). Youth diagnosed EOS (8-19 years old) were evaluated first acutely symptomatic state at baseline, 8 weeks later, 52-week follow-up. All participants randomized to one three medications baseline: risperidone or olanzapine, second-generation antipsychotics, molindone, first-generation antipsychotic. Measurements clinical symptomatology cognition administered each time point. This study addresses several important aspects EOS: Does therapy improve this population? If yes, is effect indirect result medication-related improvement symptomatology? Do different (including “first-” “second-generation” medications) differential effects on functioning? Identifying whether improves as own right, but also been shown predict future real-world EOS.4 Furthermore, because so profoundly impaired population, any may holds great promise decreasing burden. Unfortunately, although these effective symptom severity, they did not induce meaningful (beyond what might be expected from practice effects). Although small changes domains fine motor, inhibitory control, social cognition, problemsolving efficiency over course treatment, no was observed working memory, Full-Scale IQ, academic achievement. addition, there differences among groups neurocognitive domain. Although sample size group somewhat limited, lack superiority atypical antipsychotics mirrors recent findings adult-onset schizophrenia,5 suggesting benefit unlikely. This outcome particularly disappointing adolescence represent greater brain plasticity structural reorganization, 6 which presumably would present ideal intervene alter illness. However, showed quite clearly, clinically regimens improvements adolescent patients’ functioning. Clinicians researchers alike left question: can do achieve better outcomes patients EOS? In (with mean age mid-30s), remediation techniques tend show post-treatment range medium (Cohen’s d) global (d = 0.43) 0.45).7 To our knowledge, only two studies published. One find generalized improved performance measurements executive function8; other reported comparable psychoeducation control group.9 These had samples, making it difficult draw definitive conclusions EOS. Findings trials adult patients, however, underscored utility further examining EOS. The by Frazier et al.3 issue Journal points assess therapies (e.g., cognitive-behavioral therapy) serve adjunctive Studies treatments, paired intervention, adults experiencing their episode promising results, including functioning.10 Rarely neurocognition included measurement remediation. approaches, such therapy, seem less intuitive targeting common goal improving achievable multiple routes. For instance, diagnosis obsessive-compulsive disorder “normalization” function after combination therapy.11 An next step approach modification interventions taking developmental stage account measurement. In developing novel EOS, must remain mindful physiologic mechanisms underlying neurotransmitter changes, alterations gene expression) operate differently childhood adulthood,12 meaning critical pathophysiologic moving targets. Exactly given interacts physiology affect neurodevelopment additional unknown contributing complexity. Neurodevelopment highly complex, dynamic process, significant gaps knowledge brain.6 Standing against tremendous uncertainty, offers essential results suggest solution challenging find, devastating toll illness takes youth13 demands continue work toward disorders.