Schizophrenia and phenotypic plasticity: schizophrenia may represent a predictive, adaptive response to severe environmental adversity that allows both bioenergetic thrift and a defensive behavioral strategy.

摘要

It is well recognized that investigation into the relationship between early life programming and subsequent neurological disorders may have powerful implications for understanding the human vulnerability to psychopathology. The present article will propose that schizophrenia may be adaptively programmed by early environmental adversity permitting physiological and behavioral characteristics that would have created a fitness advantage in the ancestral environment under conditions of nutritional scarcity and severe environmental stress. This proposition will be analyzed in terms of phenotypic plasticity theory which explains how and why specific environmental stressors can alter normal gene expression resulting in an alternative phenotype that is better suited for an adverse environment. The primary neurophysiological symptoms of schizophrenia can be induced in animals through exposure to prenatal and postnatal stressors, and that schizophrenia itself is known to be associated with exposure to stress during development, supports the view that the "disorder" may represent a predictive, adaptive response to adversity. In fact, maternal malnutrition, maternal stress, multiparity, short birth interval and stress provoking postnatal events are well recognized epidemiological risk factors for schizophrenia that may represent cues for the initiation of epigenetic programming. Behavioral and physiological characteristics of schizophrenia will be analyzed and interpreted as protective in the context of environmental hardship. For instance, the hypometabolic areas of the schizophrenic brain--the hippocampus and the frontal lobes--are the same areas that are known to become adaptively hypometabolic in response to starvation, stress and variations in ecological rigor in birds and mammals. Individuals with schizophrenia are also highly genetically inclined to develop the metabolic syndrome, which is widely thought to allow developmentally deprived mammals to conserve energy under poor circumstances. It is well known that schizophrenia features an up-regulated hypothalamic-pituitary-adrenal axis and an exaggerated stress response--both alterations thought to represent predictive, adaptive responses to stress in mammals--which may have increased attentiveness to the environment and created a defensive, vigilance-based behavioral strategy. The habituation deficits characteristic of schizophrenia--which can be induced in other mammals through stress--may represent a cognitive strategy that alerts the organism to salient, potentially informative stimuli and that permits it to be more impulsive and vigilant. Inability to calm instinctual drives, ignore arousing stimuli, and inhibit transient desires are all core characteristics of the disorder, which predict social and vocational disabilities in modern times, but may have amounted to a robust, selfish strategy in prehistoric times.