Functional neuropsychophysiological asymmetry in schizophrenia: a review and reorientation.

In reviewing the neuropsychophysiological evidence of functional asymmetry it is proposed that schizophrenia is characterized by a greater dispersion of leftward and rightward asymmetries. The two extremes are represented by active (left greater than right) and withdrawn (right greater than left) syndromes, as is the case with psychometric schizotypy. Syndrome-asymmetry relations extended beyond fronto-temporal systems to include posterior activity, infracortical motoneuron excitability, and individual differences in interhemispheric connectivity and directional biases. Central to these are lateral imbalances in thalamo-cortical and callosal arousal systems, while centrality to schizophrenia follows evidence of reversals in asymmetry with changes in symptom profile, clinical recovery, and neuroleptic treatment. Affinities are found in intact animals from challenge-induced turning tendencies representing coordinated activity of attentional, motor, and reinforcement systems. In both patients and animals, neuroleptics have reciprocal interhemispheric effects, with a bidirectionality that depends on syndrome or endogenous turning preference. Bidirectionality implicates nonspecific thalamic system (NSTS) and not limbic projections. It is proposed that the asymmetries arise from endogenous influences of genes, hormones, and early experience including stressors on NSTS asymmetry, and these underpin approach/withdrawal behavior that is manifested in temperament, personality, and clinical syndrome, and which precedes language development.