Professor Clancy D. McKenzie, M.D.
www.DrMcKenzie.com 
© AMHA, August 1998

PREFACE

While attention in recent decades has focused on biological change found in those suffering from schizophrenia and depression, new indications are that biological change might be the result of the disease process and not the cause.

If this is so, then biological research alone cannot lead to etiology, prevention, understanding, or insight psychotherapy. Biological findings are critical to the Unification Model, however, because they demonstrate the reactivation of earlier developmental brain structures, confirming that portion of the flashback experience.

Knowing where one's particular area of study fits into the overall structure, enhances one's ability to further that area of research. Like pieces of a puzzle, when one finally grasps where everything goes, the pieces fall into place more quickly.

THEORY
Central to the Unification Model is the finding of delayed Posttraumatic Stress Disorders from infancy and the Two Trauma mechanism. Everyone understands when a car backfires next to a Vietnam Veteran and suddenly he begins speaking Vietnamese, grabs a gun and hides in the woods for a few days. A loud noise in the present precipitates the flashback to a loud noise in the distant past, and the veteran begins experiencing and behaving as he did at the earlier time. This is thought to occur because during combat the veteran's life was in extreme danger. The mechanism is so obvious that no one has conducted a comparative study to determine if non-combat individuals are affected by a loud noise in the same way.

What few realize is that more terrifying than war trauma to a soldier is separation from the mother to an infant. For 150 million years of patterning of the mammalian brain, separation from the mother has meant death. Thus the human infant is quick to misinterpret common events as threats of separation from its mother and therefore overwhelming threats to its survival. Then 10-20-30 years later, instead of a loud noise precipitating the flashback, it is a similar separation from some other "most important person" (husband, wife, girlfriend, boyfriend) - or group -- which precipitates the initial step back in time.

The parallel concept, when transposed from the awakening of adult war trauma in the combat veteran to the awakening of infant trauma in the schizophrenic, is more difficult to grasp. Bullets and bombs are readily understood, but moving to a new house, or the birth of a sibling - even though potentially overwhelming to the infant -- does not seem sufficiently traumatic to set the stage for the later flashback experience. Likewise, combat reality and behavior is easily recognized in the veteran, but infant reality and behavior is not as easily recognized in the adult schizophrenic.

It is puzzling why the reality and behavior of the schizophrenic is not more readily recognized as belonging to infancy. When one sees a full grown man sitting in the middle of the floor screaming "Mommy!" "Mommy!" it seems obvious. The author first observed this as a small child in 1940, when an 18 year old girl was running nude through the lawn sprinkler in the front yard, squealing with delight. It took a quarter of a century to realize this was perfectly normal behavior, but transposed in time. Had she been 18 months old instead of 18 years old, no one would have thought anything odd about her behavior. With careful scrutiny virtually every piece of bizarre reality and behavior observed in the schizophrenic can be seen to mimic that of an infant -- and with careful cumulative observation, correlating age of trauma during infancy with symptoms in the adult schizophrenic, it becomes apparent that the reality and behavior of the schizophrenic matches that of the infant at the time/age he or she was traumatized. After such cumulative study one begins to recognize a peak age and age range of origin for each symptom or disease category, and instead of unreality one begins to recognize that it is earlier reality the schizophrenic is experiencing (McKenzie,1981,1984,1986; McKenzie and Wright,1996).

BIOLOGICAL CHANGE
To expand the theory into the biological realm, let us first consider early brain development. The powerful mechanism of ontogeny recapitulating phylogeny does not stop suddenly after intra-uterine development is complete. The infant progresses phylogenetically from earlier to later developmental structures, beginning with the reptilian and old mammalian portions of the brain which are active from birth. At least a portion of the old mammalian brain must be active in order to have rutting, sucking and crying responses, but the Moro reflex and other survival mechanisms are present in reptilian brain. Critical pathways are accessed as one passes through earlier structures. Only after initial stages of development do the rudimentary higher cortical structures begin their massive growth. The language centers in the left posterior superior temporal gyrus, for example, begin their rapid growth spurt when the toddler enters its stage of rapid accumulation of new words and the ability to speak. Pearce (1977, 1985) describes a progression through age specific windows of learning which begin in the first hours after birth. Some abilities that are not accessed during the narrow range of progression through the specific early structures can not be learned later in life. Doman (1974,1984) identifies which structures are active and developing at what ages, and demonstrates the unique ability of children to learn such things as instant math or perfect pitch at specific early ages and not later in life. With instant math a child less than two years old can instantly calculate lengthy math problems that adults are not capable of learning to solve mentally.

Thus when the schizophrenic flashes back and awakens a delayed Posttraumatic Stress Disorder condition, his flashback is biologically different from that of the combat veteran who flashes back to war experiences, because the schizophrenic returns to the phylogenetically earlier developmental brain structures he was progressing through while experiencing the extreme emotional distress that accompanies the separation response.

Kardiner (1941) coined the term physioneurosis to describe physiological remembering at the cellular level, in what now is called Posttraumatic Stress Disorder. Physiological remembering at the cellular level is particularly important in the schizophrenic process. The shift of activity to the earlier developmental brain structures, depending on when during infancy the person was traumatized, can account for activation of various regions of the brain that contain proportionately more of the neurotransmitters involved in the schizophrenic process. This includes reactivation of those structures that were active when the infant/toddler was overwhelmed and perhaps in a state of terror, and it includes reactivation of the chemical/physiological processes that were taking place then. Nemeroff (1993) demonstrates long term reduced production of cortico stimulating factors in persons who experienced early separation from their mothers, and he views this as the cause of depression. According to research findings that will follow, separation traumas as experienced by the infant in the first two years of life correlate with the later development of schizophrenia, and the identical traumas in the next year of life correlate with the later development of non psychotic Major Depression. Paul MacLean, in personal correspondence regarding "The Anatomy and Psychodynamics of Psychosis" (McKenzie, 1984), agreed with the concepts and wrote: "It seems quite clear that the traumatic experiences in infancy and early childhood could set up a storm in those unstable structures of the phylogenetically old parts of the telencephalon that appear to be involved in the separation response. Somewhat analogous to an epileptogenic focus, the poorly dampened neural mechanisms would allow the storm to 'perseverate' or to be easily reactivated."

NEUROTRANSMITTERS
Earlier brain sites are reactivated as a result of the flashback to moments of extreme emotional distress. Along with the reactivation of earlier developmental sites there is an increase in levels of neurotransmitters produced there. This includes an increase in Dopamine (Breier), an elevation in CSF norepinephrine (van Kammen), changes in modulation of seratonin (Krystal) and a disruption in glutamatergic function along with an increased density of glutamate receptors (Mahlorta). Because of the reactivation of earlier portions of the mind and brain, it is not unreasonable to attribute the change in production of the neurotransmitters to the reactivation of the structures that were active at the earlier time. Change may occur as a direct result of reactivation of the structure producing the neurotransmitter, or it may occur indirectly -- i.e., instead of learning perfect pitch or instant math, the infant/toddler - during a period of excruciating distress -- may have learned how to produce the changes in neurotransmitters, and does so upon returning to the earlier gestalt later in life. The decrease in the CSF tridecapeptide Neurotensin (Nemeroff, 1994), for example, may be the result of such a process. Before drawing conclusions based on neurotransmitters alone, however, let us review other biological changes involved in the schizophrenic process and search for parallel findings.

BRAIN ATROPHY
In schizophrenia there is a shift of thought processes from those of the adult to those of the infant. Thus there is a relative deactivation of higher, rational thought processes, and a reactivation of feelings/behavior/reality belonging to the earlier time. Higher cognitive processes, memory encoding, language, speed of response, smooth eye pursuit -- all were learned as the infant/toddler was progressing through developmental stages. When the schizophrenic shifts to earlier reality and behavior, functional deficits begin to appear -- as well as atrophy of the brain structures responsible for the particular functions lost. Since the atrophy is associated with deactivation of the higher cortical structures, it is not unreasonable to attribute the atrophy to the partial disuse of those structures, as occurs in any other part of the body not being used.

Perhaps the clearest example of this is the massive development of the left posterior superior temporal gyrus at about the time when language development is at its peak. According to Crow (1990), the development is so extensive that the sulci elongate and the differences between the two hemispheres can be seen on gross examination of the brain or even on MRI. The schizophrenic shifts to a trauma that occurred prior to the peak age of development of language, and according to Crow, the left posterior superior temporal gyrus in the schizophrenic atrophies proportionately more than any other area of brain. This is simply a disuse atrophy. When the individual shifts activity to a region of brain which was active prior to the development of a second region, that second region necessarily becomes less active and undergoes disuse atrophy.

LITERATURE SUPPORT FOR INFANT SEPARATION TRAUMA
Before moving into the scientific proofs of the theory of traumatic origins of serious mental/emotional disorders, it is necessary to support the significance of infant trauma with references from the literature:

From the Posttraumatic Stress Disorder literature we learn that the younger the age at which the trauma is experienced the more severe the impact on the subject (Boros; Williams and Siegel; Kilpatrick; Hyman et al; Pynoos & Eth; Raifman; Zelikoff; van der Ploeg & Kleijn; Janet, 1919; Eth & Pynoos; Gampel, 1988, 1989; Kestenberg; Kestenberg and Brenner; Klein, 1974,1983; van der Kolk, 1988; Spitz, 1945, 1975.) The infant is the youngest of all and therefore the most susceptible to trauma.

Paul MacLean (1973,1985) identified separation from the mother as the most painful of all experiences to the mammalian infant, and MacLean's only means of eliminating the cry response was to surgically cut the connections between the old mammalian and the reptilian portions of the brain, effectively leaving the creature with the brain of a reptile.
Renee Spitz (1945) noted that in many institutions, in spite of the best of medical care, 50% of infants died if they had established a good relationship with the mother and then were separated prior to two years. Anna Freud (1953) noted that providing one constant mother figure for each group of infants, instead of a rotation of nurses, eliminated the infant deaths. Harlow (1958,1979) noted that apes reared by a terry cloth mother would not mate, and one that did simply batted her infant away when it came to feed. Bruno Bettelheim (1967,1968) attributed infantile autism to trauma during the first 18 months of life. Margaret Mahler (1979) identified trauma in the first 18 months of life as correlating with the later development of childhood schizophrenia, and considered the birth of a sibling to be very traumatic to many infants. Kraemer (1984) noted that monkeys separated from their mothers during infancy were more prone to alcoholism. Thus there are countless indications in the literature that infant traumas of separation from the mother are particularly stressful and lead to serious disorders.

LITERATURE DESCRIPTION OF DELAYED POSTTRAUMATIC STRESS DISORDERS
The next area of literature search pertains to descriptions of delayed Posttraumatic Stress Disorder. Two of the best descriptions found were by van der Kolk and Ducey (1984,1989) and by Samuel (1990). Van der Kolk and Ducey described Rorschachs in "Mr. D." before and after the original traumas of ten years earlier were awakened: "Card after card reflected the same shift from earlier bland denial to later excruciating living of past horrors." Samuel described a combat veteran with three purple hearts, whose most terrifying experience was when his company accidentally disturbed a nest of hornets in the jungles of Vietnam. They were totally defenseless as hundreds of thousands attacked, and some men had hundreds of stingers embedded in their faces. This man functioned relatively well for 15 years after returning from Vietnam. He was married, had children and was gainfully employed. His life was a success until one day, at his place of employment, he found the ceiling of the men's room covered with hornets. His life suddenly became a living nightmare as he no longer was able to work, sleep or function. This is a clear example of the delayed type Posttraumatic Stress Disorder, and it is the same mechanism found for schizophrenia and other serious mental/emotional disorders.

The development of the delayed Posttraumatic Stress Disorder in the unconscious mind prior to its awakening as a full blown syndrome is similar to the concept of isolated core nuclei of consciousness (Janet, 1886) and the concept of unconscious fantasies from early childhood that later surface as the neuroses in the adult (Freud, 1926).

In schizophrenia, once the original trauma is awakened by a major loss, separation or rejection in the present, the infant and the adult exist side by side. With all serious mental disorders, after the initial reaction is precipitated by a known psychosocial stressor, recurrences can occur with little or no additional stress. According to the former DSM III, once a Major Depression is precipitated by a known psychosocial stressor, subsequent episodes can occur without apparent further provocation. Similarly, alcoholism -- once awakened -- is reawakened with but one drink. Following an acute phobic reaction the individual has a phobia. The same holds true for anxiety attacks, panic disorders, schizophrenia and more. Thus it appears that the initial activation of an earlier core nucleus of consciousness paves the way for reactivation with little or no provocation -- and it appears that this same mechanism operates in most, if not all, serious mental/emotional disorders.

SCIENTIFIC STUDIES
It has been relatively easy to prove that separation trauma is a primary causative factor in the later development of serious mental/emotional disorders. Future studies, to identify the peak age and age range of origin for each symptom/diagnostic category, and to determine the relative risk factor for each trauma at each age, will be far more involved -- but necessary for prevention.

Researchers can begin with any trauma that causes the infant to feel threatened in its relation with its mother. The infant can feel threatened by common everyday events, such as the mother or the infant being hospitalized, the family moving to a new house, or the parents separating or divorcing. Some of the traumatic experiences are not suitable for study, however, because it is not possible to date precisely when the baby felt traumatized. Divorce, for example, can be preceded by months of disharmony, any time during which the baby can experience traumatic emotional separation.

One trauma proved ideal for study, however, because the precise date it occurred was known and recorded, and because it was traumatic to many infants. This was the birth of a sibling. In generations past, women remained five days in the hospital following delivery, producing significant trauma.

All studies conducted by the author were of patients born in this country, born in a generation prior to the advent of the working mother, and prior to managed health care - which forces mothers to leave the hospital the same day or the day after delivery. For purposes of study, this may have been fortuitous. The present one-day versus the former five-day hospital stay is far less traumatic to the older sibling at home. Another variable is the fact that separation is more traumatic after good bonding has taken place in the first 4 to 6 months (Spitz, 1945), and many mothers now are working prior to this bonding taking place.

In the first study (1981) 60 patients who were schizophrenic and who were living in group homes were polled to determine how many had a sibling <19 months younger. An equal number of super normals, who had full affect and were leading useful, productive lives, were asked the same. Of the 120 subjects, 20 had siblings <19 months younger. Of the 20, 3 were from the super normal group and 17 from the schizophrenic group. Using the binomial theorem, this reached the .001 level of significance (McKenzie & Wright, 1996). The research design was endorsed by John deCani, Chairman of the Department of Statistics at U. of Pennsylvania's Wharton Business School.

A modification of that design was applied in 1994 (McKenzie & Wright), and the first 35 middle aged to elderly schizophrenics with one sibling less than 3 years younger were polled to see how many had a sibling 1-2 years younger versus how many had a sibling 2-3 years younger. The preponderance was so great in the 1-2 year younger category that again the .001 level was achieved with the first 35 patients. The identical study was conducted using 35 non-psychotic Major Depression patients, and this time the preponderance was so great in the 2-3 year younger category that the .001 level of significance was achieved with the first 35 patients. And by mixing schizophrenic and depressed individuals and doing the same study -- looking for mutual exclusivity (i.e., Schizophrenia and Major Depression with psychotic features in the 1-2 years younger category, and Major Depression without psychotic features in the 2-3 years younger category) - the .001 level of significance again was reached with the first 35 patients.
Hearing voices was found to have its origin in emotional trauma prior to 24 months, i.e., prior to the age of origin of non psychotic Major Depression. In a study of 50 persons with very severe Major Depression, 15 had siblings born prior to 3 years, and of the 15, 7 heard voices and 8 did not. Hearing voices versus not hearing voices lined up with having a sibling before or after 24 months, in 14 of the 15 cases -- again reaching well beyond the .001 level of statistical significance.

These findings should not be surprising because we know the language centers develop primarily after 24 months, and when the patient shifts to the brain cells used prior to that time he develops the language dysfunction of hearing voices. We already considered the fact that in schizophrenia when the person returns to the area of mind and brain that was active prior to the massive development of the language centers, that region of brain - which becomes less active -- undergoes an atrophy which we attribute to disuse.
For those who require larger studies, Sarnoff Mednick was kind enough to test the birth of a sibling trauma on the 6,000 patients in the Finnish data base on schizophrenia and confirmed the author's findings for this particular trauma. The .001 can be achieved using groups of much smaller size, however.

Future studies will reduce or eliminate most genetic, familial and environmental factors, because siblings of the schizophrenics will be used as control groups. The findings related to broad age ranges can be narrowed to the identification of the peak age and age range of origin for each symptom/diagnostic category related to infant traumas -- and if not related to infant traumas the same research design will reveal that as well.

DATA FROM MAY 1997 APA MEETINGS
Having gained an overview of the concepts, let us see how they might apply to biological and neuropsychological Schizophrenia research findings. For a current cross section of research findings we will first review those presented at the 1997 APA Meetings in San Diego, omitting but a few because of redundancy:

Several of the presentations pertained to response time in schizophrenia: Parwani et al described an impaired central inhibitory mechanism in response to the acoustic startle response as measured by pre pulse inhibition; Hazlett et al found the same and attributed it to frontal lobe dysfunction because PET, coregistered with MRI, indicated lower rGMR in the superior, middle and inferior frontal gyrus bilaterally, which was proportionate to decreased pre pulse inhibition; Willis-Shore et al -- while not finding a correlation with I.Q. or frontal lobe dysfunction, found a slower reaction time in schizophrenia as measured by lexical decision tasks which was proportionate to conceptual disorganization and suspiciousness. These findings would be consistent with a shift to earlier structures and a return to less mature levels of function.

Ngan et al found attention and processing deficits in schizophrenia, correlated them with clinically observable psychomotor poverty, and postulated that the negative or deficit symptoms may be clinical manifestations of impaired cognitive processing. Kwon et al found reduced ability to maintain synchronous activity of neuronal firing at higher frequencies -- i.e., at 40HZ. Both studies indicate an immaturity of the system consistent with a shift to earlier developmental structures and levels of function.

Gendersen, using electrooculography, found an increased rate of inappropriate saccades in the eye tracking pattern in schizophrenia as opposed to affective or schizoaffective disorders. The baby learns to follow with its eyes at some point in its development but not initially. Thus once more the finding is consistent with a return to a level-of-function/ region-of-brain prior to development of the particular ability tested. The age of origin of Schizoaffective Schizophrenia is at the end of the schizophrenia spectrum, and this is followed by psychotic and then non psychotic Major Depressions. Gendersen's findings therefore indicate that the origin of schizoaffective and affective disorders is after the infant/toddler has gained a capability for smooth eye pursuit.

Meagher et al studied outcome measures and found the longer the patients were left untreated the greater were their negative symptoms and cognitive dysfunctions. This is consistent with more disuse atrophy as the patient uses fewer higher functions for longer periods of time. Kenny et al found that while attention and memory deficits are preeminent in adolescents with schizophrenia, the more global and severe deficits in memory, generative naming and visuospatial and executive functions emerge between adolescence and early adulthood. This too is consistent with a more complete progression into the earlier structures that were active at the time of the original trauma, and with a progressive disuse of the more advanced functions/structures as the person ages.

Maierhofer et al found a reduced discrimination learning capacity, particularly in disorganized as opposed to paranoid schizophrenics, which they attributed to probably a difference in temporal lobe function. Disorganized Schizophrenia has an earlier origin than Paranoid Schizophrenia (as determined by cumulative observations, correlating age of trauma and symptoms). Thus one would expect less discrimination and less temporal lobe development in Disorganized Schizophrenia because the patient shifts to earlier brain and brain function.

Amar et al found cognitive deficits present in schizophrenia and depression, but found that schizophrenics also exhibit a deficit in free recall. This additional deficit supports the finding that schizophrenia has an earlier age of origin, with a shift to earlier developmental brain structures and more immature levels of function.

Shelley et al found auditory working memory deficits in schizophrenia that were caused by abnormal encoding, and Leiderman et al found accuracy of object working memory, after a five second delay, significantly reduced in schizophrenia over normals -- which also was attributed to encoding. Once more the deficits can be attributed to a shift to earlier developmental levels of function and of inputting information.

Ventura et al found neurocognitive deficits in schizophrenia and depression to be the same, but found verbal memory and problem solving impaired in schizophrenia and not in mood disorders. Schizophrenia, for the most part, has its origin prior to the massive development of the language centers, whereas non-psychotic Major Depression has its origin later. Thus the impairment in verbal memory should be expected when the patient shifts to the areas of the brain that were active prior to its development.

Jon et al studying QEEG during memory processing found that the frontal and temporal lobes and the thalamus were not appropriately activated in the schizophrenic during memory tasks. This too is consistent with a return to earlier developmental functions and structures and a relative deactivation of those functions/structures that developed later.
Nestor et al, studying MRI and neuropsychological measures, found a positive relation between temporal lobe volume versus verbal learning and categorization, and found a positive relation between frontal lobe volume and performance on attention and working memory tasks. In schizophrenia, the volumes and functions of both are reduced -- which is precisely what one would expect when a schizophrenic patient shifts to the structures/ functions that were active prior to the development of language centers in the left posterior superior temporal gyrus and prior to the massive development of the frontal lobes.

MacQueen et al found patients with acute psychosis have impairment in selective attention. More acute illness equates with a greater shift of activity away from the frontal lobes.

Levitt et al conducted important MRI studies that revealed an increase in brainstem absolute volume among schizophrenics as opposed to normals -- which supports the concept of a shift of activity to the phylogenetically earlier brain structures, resulting in an increase in volume and an increase in neurotransmitters produced there. They also found an increase in cerebellum white matter, an increase in vermian gray and especially white matter, and an increase in vermian anterior lobule volume. Considering the fact that the schizophrenic was traumatized at about the time he was learning to walk, when the growth and development of the cerebellum was at its peak, the increase in activity there -- along with the increase in volume (as occurs in any structure that is exercised) - gives further support to the concept of a shift of activity to the function/ structure that was developing at the time/age of the original trauma.

Downhill et al (1997a) found an increase in corpus callosum size which correlated with an increase in symptoms of schizophrenia, and found that a smaller corpus callosum was associated with a greater left-right asymmetry in the cingulate, suggesting an increase in interhemispheric communication between left and right cingulate which was proportionate to an increase in symptoms of schizophrenia. The findings might indicate a compensatory mechanism caused by the reduced size[/activity] (Fodor) in the schizophrenic's right cingulate -- which would require greater utilization of the left cingulate to compensate for inactivity on the right, and thereby increase the size of the corpus callosum. This compensatory mechanism is one the author suggested to Richard Petty for his finding of an increase in size of the right posterior superior temporal gyrus in the schizophrenic (personal communication, 1996). If a person loses the use of one arm, for example, the other becomes more developed.

Downhill et al (1997b) identified a decreased temporal lobe volume in both Schizotypal Personality Disorder and in Schizophrenia. Both these disorders have origins prior to the massive development of the speech centers in the left posterior superior temporal gyrus, and a return to brain structures that were active prior to that massive development would account for the disuse atrophy.

Byne et al found that thalamic volume loss varied from 5% to 33% depending on subdivision of the thalamus. Crosson determined that the dominant thalamus is involved in verbal working memory, and that the deficit lies in the interface between semantic and lexical systems. Both logically would result from a shift to brain structures that were active prior to the massive development of the language centers, with a disuse atrophy of later developmental structures.

Jeste et al found that late onset schizophrenia had less impairment in learning, larger thalamic volume and smaller volume of lenticular nucleus as compared to early onset. The less severe impairment in learning correlates with less disuse atrophy in the dominant thalamus which is involved in verbal working memory. Other variables may apply to late onset schizophrenia, and the findings should be studied in light of the overall pattern that is emerging -- i.e., 1) activation of specific earlier developmental structures and functions, depending on time/age of original trauma, 2) disuse atrophy of later developmental structures/ functions and the pathways they use, 3) the development of neuronal pathways interconnecting the structures that are active, and 4) changes that are proportionate to intensity and duration of illness, which may include structural changes based on growth of unconscious core nuclei of conscious prior to the initial awakening of the delayed Posttraumatic Stress Disorder mechanism.

Buchsbaum et al (1997a) found significantly lower metabolic rates in the mediodorsal nucleus of the left thalamus, which is a major cortical relay from the limbic system and has connections to the prefrontal cortex. This is consistent with disuse of the prefrontal cortex, an area of brain which develops largely after the age of origin of schizophrenia.

Shihabuddin et al found a significant difference in metabolic rate between Kraepelinian and non Kraepelinian Schizophrenia. Disorders that are allowed to progress simply do so. Many of the back ward Schizophrenic patients of yesteryear no longer are seen in such great numbers simply because the natural progression of the illness has been interrupted.

Ghanem et al, correlating SPECT and WCST, found Schizophrenics with more negative symptoms had a greater decrease in rCBF in the right frontal, temporal and right and left parietal lobes, while a decrease in left frontal rCBF occurred equally with positive or negative symptoms. Cumulative observations correlating age of origin with symptoms reveal a progressive and substantial reduction in affect among those traumatized prior to 18 months. Thus a patient with more negative symptoms would have an origin prior to those with more positive symptoms, and would use earlier developmental brain structures. Negative symptomotology also may reflect further progression into the illness.

Gupta et al, using MRI coregistered with PET, found a positive correlation between ventricular volume and duration of the illness, and a significant negative correlation between ventricular volume and metabolic rate - in the angular gyrus and the primary visual cortex. These changes are consistent with disuse, as would occur in any other part of the body.

Buchsbaum et al (1997b), utilizing a new visualization technique for analyzing white matter tracts, demonstrated evidence of diminished communication in frontostriatal pathways in schizophrenia. Since there is relatively less activity in the frontal cortex, it should be expected that interconnecting pathways would be atrophied.

Quinn et al, studying histopathology of glial archectecture of human cortex, found a disruption of caudate astrocyte function and hypothesized this could have neurocognitive sequellae in schizophrenia. While this is true, the high correlation with infant trauma indicates that the disruption of caudate astrocyte function more likely is caused by the schizophrenic process, and in accordance with the mechanisms described.

Kang et al, found an alteration in monoamine metabolism, especially in female schizophrenics with symptoms of depression and anxiety, and Gerdsen et al found a hemispheric asymmetry of benzodiazepine receptor binding sites in schizophrenia, using SPECT. While these changes are a part of a chain of reactions which cause other reactions to occur, the high correlation between infant traumas and the later development of the disorder leads one to suspect that it is the trauma that sets the process in motion.

Murray, in the Adolph Meyer Award Lecture, summarizes current thinking, attributing early onset schizophrenia to neurodevelopmental impairment. Neurostructural changes are present, but it is not yet determined what portion may be precursor versus what portion is the result of the disease process. The high correlation between schizophrenia and infant traumas indicate most brain changes more likely are the result of the disease process and not the cause. Age of onset is viewed by the present author more as a function of when the precipitating trauma occurred, but it is recognized that the more vulnerable the individual the sooner he encounters a trauma that can awaken the earlier traumatic gestalt. Murray attributes familial cases to a genetic defect in control of development of normal cortical asymmetry. This transposition is commonplace, but it may be in error. Familial is not genetic until proven to be so. Murray cites prenatal and perinatal factors, such as viral infections and hypoxia, postulating that the dysplastic neural network may be responsible for delayed milestones in preschizophrenic children, and acknowledging that it is not known whether the abnormal factors are the cause of the process or whether they are risk factors for it. Indeed the pre and perinatal factors might alter structure but can also serve as the antecedent traumas that cause the infant traumas to be experienced as more severe. Both would represent risk factors.

DATA FROM FEBRUARY 1998 NINTH BIENNIAL WINTER WORKSHOP ON SCHIZOPHRENIA IN DAVOS, SWITZERLAND
Devoted exclusively to Schizophrenia, the conference hosted approximately 75 lectures and 500 poster presentations describing the latest research findings. It would be redundant to review each one, but to the author, none of the biological findings appeared incongruous with a shift of brain activity to earlier developmental structures.

To mention but a few, the schizophrenic loses normal asymmetry (Purdon, Zaidel, Crow) [because there is a shift of brain activity to an age prior to the development of specialization.] Brain atrophy relates to smaller cells, not fewer (Garey) [indicating disuse atrophy, not cell death]. There is an increase in size of lamina II pyramidal cells in the entorhinal cortex (Longson) [because of increased activity in this earlier developmental layer.]

SUMMARY
The view of the present author is that genetic factors represent predisposition to Schizophrenia and other disorders, and eventually the precise level of contribution will be determined.

Pre and perinatal factors along with obstetric and birth traumas represent antecedent traumas, setting the stage for subsequent traumas to be more severe, and they also can impact directly on brain development. Infant separation traumas - because they represented death to the mammalian species for 150 million years - are much more significant than previously suspected, and set the stage for the later development of delayed Posttraumatic Stress Disorders.

In delayed PTSD, a second trauma, similar to the first, partially awakens the entire earlier gestalt, setting the process in motion. The flashback is to the earlier mind / brain / reality / feelings / behavior / chemistry / physiology and neuroanatomical sites that were active and developing at the time/age of the original trauma, and from this reactivation of earlier sites there is a release of neurotransmitters produced by those sites; there is the development of aberrant neuronal pathways which interconnect the new areas of activity; and there is disuse atrophy of the later developmental structures and their interconnecting pathways -- as would occur in any other part of the body not used.

Any stressor can cause intensification of the original trauma or of the subsequent trauma that reactivates the earlier gestalt. This can include anything in the environment that causes stress. Viral factors might fit into this category or might be non-causally related.
The important research findings presented in San Diego (1997) and in Davos (1998) are more meaningful when viewed under one roof and in relation to one another. There has been an explosion of knowledge in recent decades, with each particle moving farther from the core. Without a unified working model, professionals and lay persons alike are left with isolated concepts that Schizophrenia is a chemical imbalance, or a genetic disorder, or a brain disease, or a biopsychosocial disorder, or many diseases with many causes. Each finding instead must be integrated within the framework of one unified construct in order to bring understanding to a new level. Genetics can be viewed as predisposition, with biochemical, structural and psychosocial change viewed primarily as the result of a single disease process. The concept of delayed Posttraumatic Stress Disorders from infancy, with a partial shift of activity to earlier mind / brain / reality / feelings / behavior / chemistry / physiology and neuroanatomic sites, and the resultant interaction of that earlier gestalt with adult brain functions/structures, may be the best working model we have at the present time for integrating and understanding all the complexities of the disease process. O. Spurgeon English, in his Foreword to McKenzie and Wright (1996), referred to this model as "the new unification theory of mental illness."

It is hoped that this work, in addition to bringing fourth new understanding to serious mental/emotional disorders, will help unify the field and bring the many disciplines together. The process of unification already is taking place slowly, one study at a time, as newer studies coregister PET with MRI and bring in neuropsychological testing, for example, but the field can advance exponentially, with the pieces of the puzzle rapidly falling into place, if there is a structural framework that enables each researcher to maintain a larger view and understand his or her contribution in relation to the entire disease process. The new Unification Theory, backed by research studies and references in the literature, is the most inclusive model at the present time, and provides a clear, equal and logical place for each discipline.

BIBLIOGRAPHY
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