Schizophrenia spectrum disorders are characterized by symptom profiles consisting of positive and negative symptoms, cognitive impairment, and a plethora of genetic, epigenetic, and phenotypic biomarkers. Assorted animal models of these disorders and clinical neurodevelopmental indicators have implicated neurodegeneration as an element in the underlying pathophysiology. Physical exercise or activity regimes—whether aerobic, resistance, or endurance—ameliorate regional brain and functional deficits not only in affected individuals but also in animal models of the disorder. Cognitive deficits, often linked to regional deficits, were alleviated by exercise, as were quality-of-life, independent of disorder staging and risk level. Apoptotic processes intricate to the etiopathogenesis of schizophrenia were likewise attenuated by physical exercise. There is also evidence of manifest benefits endowed by physical exercise in preserving telomere length and integrity. Not least, exercise improves overall health and quality-of-life. The notion of scaffolding as the outcome of physical exercise implies the “buttressing” of regional network circuits, neurocognitive domains, anti-inflammatory defenses, maintenance of telomeric integrity, and neuro-reparative and regenerative processes.

The heterogeneous, chronic, and proliferating aspect of attention deficit hyperactivity disorder (ADHD) and comorbidities covers heritability, cognitive, emotional, motor, and everyday behavioral domains that place individuals presenting the condition at some considerable disadvantage. Disruption of "typical developmental trajectories" in the manifestation of gene-environment interactive predispositions implies that ADHD children and adolescents may continue to perform at defective levels as adults with regard to academic achievement, occupational enterprises, and interpersonal relationships, despite the promise of pharmacotherapeutic treatments. Physical exercise provides a plethora of beneficial effects against stress, anxiety, depression, negative affect and behavior, poor impulse control, and compulsive behavior concomitant with improved executive functioning, working memory and positive affect, as well as improved conditions for relatives and care-givers. Brain-derived neurotrophic factor, an essential element in normal brain development that promotes health-associated behaviors and quality-of-life, though reduced in ADHD, is increased markedly by the intervention of regular physical exercise. Functional, regional, and biomarker deficits, as well as hypothalamic-pituitary-adrenal disruptions, have been improved through regular and carefully applied exercise programs. In view of the complications involving ADHD with co-morbidities, such as obesity, the influence of regular physical exercise has not been found negligible. Physical exercise bestows a propensity for eventual manifestation of "redifferentiated" developmental trajectories that may equip ADHD adults with a prognosis that is more adaptive functionally, independent of the applications of other therapeutic agents and treatments.