Schizophrenia: Current Research and Treatment

Ways of Looking at Schizophrenia

“I was of three minds, like a tree

in which there are three blackbirds.”

Wallace Stevens,

Thirteen Ways of Looking at a Blackbird

It’s an interesting time, to look back and look forward, at the state of psychiatric practice in the treatment of schizophrenia, and I find I am of at least two minds, whatever direction I look. On the one hand hopeful, grateful, and excited at progress in understanding, experience and practice; and on the other worried and frustrated, while struggling not to become cynical, as I consider how our society, and government, may respond to challenges present and expected.

I am conscious, too, that my title, and opening, may sound like a pun to some, because of the popular misunderstanding of schizophrenia as a condition of “split personality.” This is, of course, a silly notion, having nothing to do with the illness, or the subjective experience of people who suffer from it, though it is remarkable in its persistence, and in view of its roots in ignorance, fear and prejudice. There has been progress in assailing that barrier of social stigmatization, though the task has really only begun. It is another aspect of two-mindedness: to look upon the nature of schizophrenia with genuine understanding, or from within the darkling mists of shame and confusion.

The term “schizophrenia” was coined by Eugen Bleuler (who also first used the term, “autism,” to describe some of the symptoms of the illness), a Swiss psychiatrist, in 1908, in a paper, and then in 1911 in his book, Dementia Praecox or the Group of Schizophrenias1. Although a too literal translation, from the Greek, has contributed to the misconception noted above, Bleuler himself, much influenced by the work of Sigmund Freud, and keenly interested, as a philosopher as much as a clinician and scientist, in the psychological experience of the people he treated at his renowned clinic, the Burghölzli Asylum, described his use of the term differently. He thought of a specific image, that of a thick tree branch that has been struck across a stone, splaying the end. The frayed fibers of the branch have not been lost, but they no longer cohere, and so have lost their structure, and their strength; like the cognitive functions, the thinking functions of the person affected by this illness.

The image is still poignantly compassionate, both for its evocation of the violence with which the illness often first afflicts the individual, and for its allusion to the helplessness that is prevalent, until the process of healthful change, and recovery, can begin. It was also a prescient, and clinically astute observation, for we now know that schizophrenia is most fundamentally a dysregulation of the relationships between parts of the brain that are crucial for cognitive (thinking) tasks: the ability to initiate, plan, and sequence behaviors; the ability to abstract a principle or problem-solving strategy; the ability to be cognitively flexible; to make certain decisions; to interpret social information, and generate useful social responses; and certain aspects of attention and what is called “working memory,” the type of memory we use especially when we are attempting to concentrate on a task and use information we have learned.


Some of these thinking problems are also found in people who are depressed, or who have Bipolar Disorder, even when they are not acutely ill. But the problems for persons who have schizophrenia are, in general, more pronounced and persistent. This does not mean that persons with schizophrenia can never make decisions, or plan activities, or complete tasks. Dysregulation implies that these functions are harder for the affected person, which tends to produce discouragement and withdrawal, and lack of effort. And effort can be influenced by a variety of factors, both psychological and physical. One of the critical things we have learned – though it is information that is unfortunately often not put into practice – is that too much of the type of medication that is useful in decreasing agitation and hallucinations (antipsychotic medication) can make these thinking problems worse, so that the right amount of medicine, generally, is that which minimizes the side effects the medicine can cause.

The changes in thinking processes I have described, which represent malfunction in some brain circuitry, produce what is termed executive dysfunction, because they are processes necessary to the brain’s ability to “execute” orders – to produce thoughts and behaviors – and involve specific areas of the brain, especially the prefrontal cortex2, and related structures, which are constantly operating as we think, without our awareness. When they are not working, we find ourselves confused, stymied, and prone to misinterpret what is happening around us.

Advances in research have illuminated much about the nature of the illness – though there is much more to learn – that will undoubtedly lead to better treatments. Clinical research has also helped us to understand more about why medications work, how and when to use them, so that the experience of taking medication is more comfortable and rewarding for most individuals than it was when I first studied psychiatry. I still remember sober researchers, and senior colleagues, insisting that high doses of antipsychotics should be used until delusions3 were eradicated. Following that advice really meant raising doses until the person stopped talking, either because they realized the consequence of mentioning their beliefs, or because the medication simply “froze” their thinking.


Toward the end of my training I remember two very different, but equally critical events, each of which changed the way schizophrenia was treated and understood. Research on the unique effectiveness of clozapine was then released, and showed that persons who had not previously responded to other medications could be helped for the first time. Though clozapine did not work for everyone, it led to the development of other medications that have greatly expanded options for health care providers and their patients. More importantly, the fact that clozapine worked differently than other medications helped to invigorate research on the physiology of the illness. In consequence, new insights have been made possible.

We know so much more now, for instance, about the nature of the disorder, as described previously, that the phrase “chemical imbalance,” once used to describe what was thought to be wrong in the brain, is justly and finally seen to be unhelpful, inaccurate and out-of-date. Rather than dealing with a simple excess, or deficiency, of a neurotransmitter (a “chemical,” in a sense, though the word has always seemed to me somewhat dehumanizing), we instead see that dysregulated brain circuits cause schizophrenic symptoms. There may be, in consequence, reduced or elevated activity within some pathways that rely on particular transmitters (egs. dopamine, or glutamate), but it is due to altered communication in a very complex system. Neurons manufacture their own neurotransmitters, and determine the amount they produce after “reading” their environment, trying to determine how much activity is going on around them, by “deciphering” instructions from the thousands of nerve cells sending them information. There are thus multiple concurrent influences on neuronal activity that affect behavior, emotion and cognition, and in turn the response of a given nerve cell can occur in a variety of ways. It may not be the absolute or relative amount of dopamine or glutamate that is abnormal, for example, but the timing of neurotransmitter release, the frequency of its “pulses” of activity, or the presence or absence of co-transmitters; all occurring in the context of the simultaneous influence of other neurons and neurotransmitters on the target neuron.

While clozapine’s advent itself encouraged me to be hopeful about my ability to help my patients, another research study affected me more than any other event in my professional life. Dr Courtney Harding had been searching for a suitable topic for her doctoral thesis in epidemiology at Yale University when she came across a forgotten study, published in the 1960’s. Dr George Brooks, who authored the earlier study, had directed an innovative program through the Vermont State Hospital that, beginning in the mid-1950’s, studied chronically ill patients in their hospital system who were provided with an intensive program of psychosocial rehabilitation. The patients, all of whom had had at best modest responses to medication (mostly chlorpromazine) were then moved into the community with equivalent support: case management, vocational support, assistance with community integration, and other services, as well as routine psychiatric care. When he published data after 5 years of follow-up, Dr Brooks found that approximately 70% of the patients had remained in the community, a truly remarkable achievement.

Dr Harding was curious about the longer-term outcome of those study patients and so contacted Dr Brooks, and arranged to revisit those patients 25 years after the original study had ended. What they found was astounding. Most of the study participants were still living in the communities to which they had been discharged many years before – Dr Harding used to quip that people in Vermont generally don’t move once they get there. What was even more notable was that almost 2/3 of the individuals, who had initially entered the study after spending years on the “back wards” of the State Hospital, were rated as “considerably improved or recovered” by clinicians who did not know their histories.

When Dr Harding came to my hospital to present her research, she showed pictures of the study subjects, living in their communities, happy, and appearing well. She shared vignettes of their lives. I, as were many in the audience, was moved to tears. It was nothing less than a triumph of hope.

I began to read, avidly, the literature on recovery, immersing myself in ideas that were so full of promise, and so much in contrast to the dourness, aversion and pessimism I found when talking to many colleagues, and especially some mentors, about schizophrenia. And so I was surprised to read of another series of studies, conducted by the World Health Organization (WHO) under the research leadership of Dr Norman Sartorius. The study was initially devised to answer social critics of the time (Thomas Szasz, R.D. Laing and others) who maintained that schizophrenia was a severe form of social alienation, caused by the ill effects of Western industrialized cultures and economies. Researchers armed with culturally sensitive instruments visited communities across the globe, rural and urban, developed and developing, those with access to modern medical care and those without such access.

The International Pilot Study of Schizophrenia (IPSS), published in 1973, found that schizophrenia was roughly as common in developed as in developing countries, seeming to disprove the contentions of the social critics. But when the researchers also noted that outcomes in developing countries, where medical care was often lacking or at best rudimentary, were significantly better, on average, than in richer countries where most of the individuals were being treated by mental health care providers, and with antipsychotic medication, there was an uproar of protest. Not least the pharmaceutical companies cried foul, as did many academics who questioned the methodology of the research.

Recognizing that the original study had limitations, Dr Sartorius organized a follow-up study, which was eventually published in 1979. Supported by more detailed research tools, more data, and more numbers of individuals studied, the follow-up study revealed that the conclusions of the first study were true.

The conclusions of the researchers were not simplistic, and they did not maintain that antipsychotic medications were unnecessary or harmful, or that outcomes in developing countries were uniformly better. Writing in a recent review article (Schizophrenia Bulletin vol. 34 no. 2 pp. 253–255, 2008), Dr Sartorius and his colleague, Dr Jablensky, reiterated their earlier conclusions: that although their findings could not prove a cause for the observed differences, their studies suggested that “culture” was the most powerful independent variable; and that what appeared to be distinguishing about culture in developing countries was a trend toward social inclusion of the affected individual.

That is not to say that those societies were free of prejudice, or that persons with schizophrenia had ideal social supports. But it did appear to investigators that those societies were better at helping persons with severe mental illness to find a useful role in their communities. The affected individuals seemed to experience themselves as performing meaningful functions, and of having a meaningful place, not just within their family, but within the larger community.

It remains surprising to me how little these studies are discussed, how often medical students and residents who I teach say that they have never heard of them. And then I think about the amount of money pharmaceutical companies provide to medical schools to support research, and I become frustrated, and briefly sad. In truth, the lessons of these studies are no less a challenge to our society as a whole than to the mental health community, and demand of us much soul-searching and debate.


We now enjoy an era of active attention to both the nature and etiology of schizophrenia, and to the development and implementation of “evidence-based” therapies, such as job coaching, “Housing First” residential programs, Assertive Community Treatment, and others. These treatments represent the fruition of the ideals, and models, of clinicians and researchers of an earlier generation, like those we have described above, who saw the value of having meaning and purpose in one’s life, and realized that one of the most devastating effects of schizophrenia occurs when it steals that sense of purpose from the individual.

Though there remain severe gaps between the theoretical availability of effective treatment models, and their actualization, there has never been more support for good ideas, within communities, advocacy groups – like the National Alliance on Mental Illness (NAMI) – and foundations – like NARSAD – than there is now. And governments have been more inclined to listen, sometimes persuaded that good care, though requiring initial investment, will eventually reduce costs.

And yet, there are signs of trouble. Our national, and global, financial crisis threatens the existence of precious treatment services, and has distressed the relationship between government and the healthcare system. New York State, in this context, has pressed forward with its long-promised PROS (Personalized Recovery-Oriented Services) initiative. The philosophy and principle animating that initiative is admirable. However, like many programs devised by government (though some groups of clinicians and consumers were invited to provide input, it is in the end a prescriptive regulation) it is burdened with requirements more likely attractive to an auditor rather than to those for whom it had purportedly been designed.

Instead of setting global budgets and outcome targets, and then encouraging creativity, PROS dictates small details of program design and operation, with demanding targets for documentation, which, if not met, even by earnest and dedicated caregivers, could, by violating compliance guidelines, put the financial viability of an entire organization at risk. The overall aim appears too heavily weighted toward cost control. The overall effect of such programs is often intimidating to caregivers, like being made to wear a futuristic robotic suit with profuse instructions: confining, awkward and not uncommonly frustrating, ultimately risking that laudable intentions may be rendered ineffectual.


One of the advantages of having worked in my community for more than 25 years is that I now, often, meet former patients, many with a history of schizophrenia, on the street, in a movie theater, or restaurant, going about their daily lives. So many of them seem well, and happy, managing active lives, and no longer burdened by illness in the way they were when I first worked with them, that I am grateful to have been privileged to have worked with them, and to have seen their growth and success. They remind me of the contented people in Courtney Harding’s presentation, their lives an active testimony to the reality of recovery, amid the healing presence of compassion, trust and hope.

So I suppose I am of three minds, after all, like the three blackbirds in the tree, from the poem I quoted at the beginning of this essay. I am sometimes in a proud and rational mind, contemplating all we have learned, and can now use to the benefit of persons with schizophrenia. At other times I dwell in a mind of apprehension and frustration, preoccupied with the nearness of a good and just community, that could care for and heal those who are ill through no fault of their own, or anyone’s; thinking that yet our communities are still so resistant to insight and change.

Finally, I come to what I can possess of wisdom, a mind that sees the human value of attempting to do what is right, in the face of obstacles, ignorance, mendacity, and greed; in which I join my labors to those of like, good people, for whom we should all be grateful, who quietly dedicate themselves to this work, in clinics, hospitals, and in our communities; and in which I, and we, stand with and for those whose hard journeys we support and honor, rejoicing in the dignity and purpose they reclaim from the clasp of despair. It is in that mind I choose to make my place.

Timothy B. Sullivan, M.D., is Clinical Chief of Services for the Seriously Mentally Ill, including the Assertive Community Treatment Team, WestCARES Program and Continuing Day Treatment Program, at St. Vincent’s Hospital Westchester in Harrison, New York. He is also a clinical assistant professor of psychiatry at New York Medical College and is a Distinguished Fellow of the American Psychiatric Association. Dr. Sullivan has published in numerous journals and is co-author of the book, Working with the Person with Schizophrenia: The Treatment Alliance.


  1. “Dementia Praecox” was a term first used by Emil Kraepelin, a German psychiatrist of the late 19th and early 20th century, whose Textbook of Psychiatry was, and remains, enormously influential. Bleuler was the first to confidently assert, in opposition to Kraepelin, that “schizophrenia” was not a true dementia.
  2. The prefrontal cortex is the area of the brain directly behind our forehead, and over our eyes. It is the area of the brain that is more developed in humans than in other primates.
  3. Delusions are different than other psychotic symptoms, like hallucinations. They represent the mind’s flawed attempt to make sense of the psychotic experience, to create a narrative. To eradicate them risks destroying what is essentially a compensatory process, an effort to create continuity, however imperfectly, out of chaos.

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