Editorial: The Cognitive Neuropsychological Hypothesis in Pediatric Anxiety and the Advantage of Revealing Early Changes in Brain Mechanisms Associated With Therapeutic Effects.

There is a pressing need to improve treatment, and clinical trials should not only focus on efficacy, but also on identifying the underlying mechanisms through which treatments operate.1 Treatment with a serotonergic antidepressant is commonly used to treat pediatric anxiety disorders, including generalized anxiety disorder (GAD). Serotonergic antidepressants require considerable time to induce clinically observed responses, and tolerability and efficacy are difficult to predict. Risk and precautions have been widely discussed and are weighed against urgent needs for interventions early in life that may prevent recurrent mental health complaints. Drug-induced molecular, cellular, and chemical effects result in neurocognitive changes, which are believed to occur before behavioral changes. Assessments of early neurocognitive changes may therefore be a powerful tool to reveal key mechanisms through which antidepressants work. When the neurofunctional mechanisms believed to cause the symptoms are restored, the clinical manifestation of symptom improvement is expected. The degree of symptom improvement should also follow the degree of positive changes in neurocognitive function. Many patients do not respond early enough in the course of symptom evolution,2,3 and thus assessments of early neurocognitive mechanisms may guide treatment individualization during titration of doses and effects.