Schizophrenia and Phenotypic Plasticity: Schizophrenia may Represent a Predictive, Adaptive Response to Severe Environmental Adversity

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Published in Medical Hypotheses, 2007

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Reser, J. 2007. 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. Medical Hypotheses, Volume 69, Issue 2, 383-394.


Did you know that schizophrenia is strongly linked to stress and early environmental adversity? Did you know that schizophrenia-like symptoms can be induced in a wide range of mammals just by stressing them out? This led me to think that the schizophrenic mind state could be one that is highly fine-tuned for dealing with a stressful environment.

When you send a puff of air at a rabbit’s eye, it blinks in response. When you sound a tone just before the puff, it learns to blink in response to the tone. Now, if you take the puff away and just sound the tone, it will eventually learn to stop blinking in response to the tone. The animal comes to understand that the puff no longer follows the tone. However, rabbits, or mice, or monkeys that are badly stressed can’t do this. They cannot learn to inhibit learned defensive responses. This is a neurological symptom called a prepulse inhibition deficit.

People with schizophrenia have prepulse inhibition deficits. This means that they are not able to unlearn defensive responses and deficits like it may be fundamental to schizophrenia in general. This article looks at these deficits, and a wide range of symptoms seen in schizophrenia, and interprets them in the context of environmental adversity. It is concluded that schizophrenia is a disinhibited mind-state that may have helped hunter gatherers be more impulsive and defensive in their habitat.

The hallmarks of schizophrenia that reduce an individual’s ability to cope in modern times, such as impulsive behavior and the inability to ignore extraneous stimuli, might be advantageous in a life-threatening environment, because they heighten awareness and increase responsiveness.


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.