MODEL PSYCHOSES AND SCHIZOPHRENIA
ELLIOT D. LUBY M.D.,
JACQUES S. GOTTLIEB M.D.,
BERTRAM D. COHEN PH.D.,
GERALD ROSENBAUM PH.D., , and
EDWARD F. DOMINO M.D.1
1 The Lafayette Clinic and Wayne State University, Detroit, Mich.
All model psychoses may be conceptualized as resulting from disruption in the central processing or from interference with the normal sensory influx from body or distance receptors. The experimental findings of the effects of sleep deprivation, sensory isolation, drugs, and a combination of drugs and sensory isolation in control and schizophrenic subjects warrants the development of a hypothesis within this context to explain some of the mechanisms responsible for schizophrenic behavior. Such a hypothesis must be operational in the sense that its elements must be susceptible to experimental verification.
Evidence has been presented that sleep deprivation is at first accompanied by an adaptive high biologic energy turnover, but that finally a point is reached after several days when energy producing mechanisms decompensate. Moreover, it appears possible that a "stressor substance" develops in the serum of these subjects which may be responsible for the progressive failure of the mechanism of energy turnover.
While the failure in the mechanism of adaptation for supplying the needed biologic energy for sleep-deprived subjects is reversible, one may ponder about its relationship to the permanently disturbed mechanisms controlling the formation and utilization of biologic energy that characterizes the chronic schizophrenic patient. Two questions are pertinent. Do traumatic sociopsychological experiences at an early period of life when these biochemical mechanisms are in the process of maturation limit their adaptive responsivity ? Conversely, does inadequate exposure to normal sociopsychologic stressors at a critical maturational period inhibit their development?
How does the succinic oxidase inhibiting "stressor" substance in the serum of persons deprived of sleep relate to the alpha globulin in the serum of schizophrenic patients, which shifts intermediary carbohydrate metabolism to more anaerobic mechanisms? Only further study will tell, but it is conceivable that they are related.
Nevertheless, the alpha globulin isolated by Frohman and others from the plasma of schizophrenic patients apparently affects neutral transmission centrally. It alters the behavior of monkeys and rats and according to Marrazzi inhibits transcallosal synaptic conduction(27, 28). This need not necessarily imply ease of passage through blood brain barrier because the protein may act by increasing permeability or as a carrier system for a smaller molecule. Our studies on model psychoses can, perhaps, contribute to a hypothesis concerning the mechanism of action of this substance.
Meaningful exteroceptive input is necessary for normal psychological functioning, but apparently induces aversive responses in schizophrenic patients. This suggests that the central stimulus filtering and interpretation capacity of these patients is diminished. Conceivably the defect may be similar to that produced by Sernyl and involve the disruption or reduction of body input transmission and integration.
In Kubie's parlance, when the subject's image of himself, "the I," is destroyed, the ability to assess external reality or the "not I" is lost(29). As Federn suggested, depersonalization may be the core of schizophrenia (30), and disturbed body input transmission or integration may be its basis. In our hypothesis such disturbed neural integration in schizophrenia might result either from the presence of an inhibitor substance or from a defect in energy production.
Analogous situations in the animal can be produced by psychotomimetic drugs such as Sernyl or by lesions in lateral midbrain involving tracts mediating touch, proprioception, and pain. Sernyl has been shown by Lees to be an uncoupling agent (31). It may thus reduce available energy stores, although admittedly other uncoupling drugs do not produce psychotomimetic effects. That Sernyl has profound action on central reception and integration of body input is evidenced by the work of Van Meter, et al.(32), and Domino(26). At the cortical level both axosomatic and axodendritic synapses are partially blocked by the drug. There is also evidence for depression of the diffuse thalamic projection system.
Recent work on destruction of lemniscal pathways in the cat by Sprague, Chambers, and Stellar might lend additional support to our hypothesis. When the sensory afferent systems mediating proprioception, pain, and touch in these animals were cut, severe behavioral changes occurred. The cat was rendered incapable of attending to or making adaptive responses to relevant stimuli associated with eating, sexuality, or defense. Emotionality was diminished and the cats seemed flat and automaton-like. At times they appeared to be hallucinating(33).
These disrupted body input mechanist may be considered as responsible for the disturbances in psychological functioning of the schizophrenic patient. This aspect of our hypothesis could be easily subjected to direct test if the human brain were readily available for experimentation and study. Being realistic, however, we must have recourse to analogous study in animals to increase our knowledge. This prolongs and complicates the challenge.
