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The Early Stages of SchizophreniaReview - The Early Stages of Schizophrenia
by Robert B. Zipursky and Charles S. Schulz (eds.)
American Psychiatric Association Press, 2002
Review by Jack R. Anderson, M.D.
Feb 18th 2003 (Volume 7, Issue 8)


     “First you tell ‘em what you’re gonna tell ‘em; then you tell ‘em; and then you tell ‘em what you told ‘em.” Those were my instructions as to how to deliver a lecture when I first joined an American university faculty. Doctors Zipursky and Schulz, editors of this book, follow the same order of presentation—first an introduction; then the nine journal articles that contain the substance of their argument; and then an “afterword.”

    The very last paragraph of the afterword concisely expresses their reason for putting this book together:

“The studies and experiences described in this book address a crucial stage of schizophrenia. We believe that early recognition, an assertive therapeutic approach, and continued integrated multidisciplinary treatment strategies are important for optimizing the overall outcome for these young patients and their families.”

When I read this paragraph I experienced what Yogi Berra called “Déjà vu all over again.” I went to one of my first psychiatric texts—Noyes’ “Modern Clinical Psychiatry,” published by W.B. Saunders Company in 1934, 1939 and 1948—and, sure enough, there it was, on page 386, the same opinion about early recognition and treatment expressed by Zipursky and Schulz:

 “The treatment of schizophrenia, particularly in its early stages, is undertaken with far less pessimism than formerly. Its success depends to no small degree upon the therapeutic initiative, energy and effort of the physician, although the results will be small if the psychotic methods of thinking and feeling have become habits and established forms of adjustment….Gradually it is becoming appreciated that the most desirable time to treat schizophrenia is before the patient reaches the hospital for mental diseases.”


     The credibility and readability of the book is enhanced by the editors’ organization of their material. Each of the nine chapters is a previously published journal article. All but three of the articles are multi-authored, so there are nineteen contributors in all, two of whom are the editors themselves. The book is broken down into three sections of three articles each. The first section is entitled “Early Intervention, Epidemiology, and Natural History of Schizophrenia;” the second “Management of the Early Stages of Schizophrenia;” and the third “Neurobiological Investigations of the Early Stages of Schizophrenia.”

     I thought the international flavor of the book added to its interest. The contributors and their research projects represent three different countries: Australia, Canada, and the USA. The contributors are from various disciplines, including psychiatry, psychology, social work and nursing.


     The recommended interventions during the early stages of schizophrenia are classified as prevention, treatment and maintenance. Research results indicate that psychotic episodes are usually preceded by a prodromal period of weeks, months, or even years. Intervention during this period may prevent the development of frank psychosis. However, there are no reliable indicators of the prodromal period, except retrospectively, after psychotic symptoms develop. Poor global adjustment states in childhood and adolescence are associated with earlier onset of schizophrenia, longer duration of psychotic symptoms and poorer long-term outcome, but they are not specific diagnostic indicators for schizophrenia. Bipolar disorders, psychotic depressive disorders and some organic brain disorders have adjustment states similar to the prodromal period of schizophrenia. With so many “false-positives,” identifying schizophrenia during its early stages is fraught with diagnostic difficulties.


     Schizophrenia is conceptualized by the researchers as a disorder with genetic, neurodevelopmental, and environmental factors interacting from the very moment of conception. In order to differentiate between prodromal schizophrenia and the variety of other severe psychiatric disorders that overlap with early-stage schizophrenia, the researchers used a number of different neurobiological studies, including neuropsycho-logical impairments, structural brain MRI abnormalities, proton MRI abnormalities and eye-tracking dysfunction. A number of structural brain abnormalities were identified in patients with childhood schizophrenia, but none of them were consistently found in all individuals diagnosed with childhood schizophrenia and for each finding there was considerable overlap between patients and healthy control subjects.

     Ongoing studies demonstrate convincing evidence for “clinical and biological continuity between the very-early-onset and adult-onset forms of the disorder.” Researchers are encouraged that studies have “… provided insight into a variety of risk factors and biological markers associated with the disorder that can be detected during adolescence as well as neurodevelopmental processes that may only be seen during adolescence in patients with schizophrenia.”

     Running through several of the chapters is a belief that further research may reveal the specific genetic markers and deficits in neuronal connections that have high predictive validity for the development of schizophrenia, and that early treatment with psychosocial techniques or psychotropic medication may reduce the cognitive dysfunction seen in schizophrenic patients, prevent the development of frank psychosis and improve long-term outcomes. On the other hand, there is also discussion of the possibility that schizophrenia is a progressively worsening brain disease that will ineluctably produce psychosis and disabling neurocognitive deficits in an undetermined percentage of affected patients, despite the most expert interventions.


     Although individual psychotherapy and family therapy are discussed in various chapters, they are mostly regarded as compassionate interventions, intended to reduce the suffering of patients and relatives who face the disadvantages of a chronic, socially stigmatized disorder.

     Chapter 4, “Optimal Pharmacological Management of the First Episode of Schizophrenia,” written by one of the editors, Dr. Zipursky, discusses treatment of first-episode patients with various levels of “typical” antipsychotic medications such as haloperidol and with the newer “atypical” agents—clozapine, risperidone, olanzapine, quetiapine and ziprasidone. (aripiprazole had not yet been introduced at the time the book was assembled.) Dr. Zipursky points out the advantages of the atypical agents—they are better tolerated, associated with a greater degree of compliance and carry a reduced risk of tardive dyskinesia. However he goes on to say that most of the unpleasant side effects of the typical agents are due to unnecessarily high dosage levels. 

     In the studies cited by Dr. Zipursky, patients had antipsychotic reponses to low doses of haloperidol when the dopamine D2 receptors in the brain were 70% occupied, and neuroleptic responses—EPS—when occupancy reached 80%. The “therapeutic window” of 70% to 80% occupancy was reached with dosages as low as 2 mg/day.  Dr. Zipursky goes on to conclude that “There is no evidence to date that treatment with any of the new atypical agents results in substantial advantages in long-term outcome. Trials addressing this question are under way.”


     All-in-all, “The Early Stages of Schizophrenia” is well worth reading by all of us in the various mental health disciplines, whether in hospitals, clinics or community programs. I have only touched on a few points in this short review; I intend to keep the book in my library and consult it frequently.

     On the one hand I admire the scientific rigor of the studies included in the book. On the other hand, when I remember the puzzles that still obfuscate the concept of “mental disease,”  I am reminded of Whitehead’s observations in “Adventures in ideas:”

“In the study of ideas, it is necessary to remember that insistence on hard-headed clarity issues from sentimental feeling, as if it were a mist, cloaking the perplexities of facts. Insistence on clarity at all costs is based on sheer superstition as to the mode in which human intelligence functions.  Our reasonings grasp at straws for premises and float on gossamers for deductions.”




 © 2003 Jack R. Anderson


Jack R. Anderson, M.D. is a retired psychiatrist living in Lincoln, Nebraska.


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