Above: Artwork of an unidentified schizophrenic

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Lecture by Sari Gilman Aronson M.D

Schizophrenia is one of the most perplexing group of illnesses that physicians treat and ranks among one of the most important public health problems in this country and the world. For over a century, researchers and clinicians have attempted to define the syndrome of schizophrenia in a way that would predict its outcome, course, treatment and prognosis. Emil Kraepelin (1855- 1926) differentiated schizophrenia from other mental illnesses and called it dementia praecox. He chose this name to differentiate it from the illness described by another member of his department, Alois Alzheimer. Kraepelin believed that the symptoms of hallucinations, delusions, thought disorder, abnormalities of speech, and automatic obedience began early in life and were associated with a progressively deteriorating course in intellectual abilities and emotional functioning in most patients. Kraepelin's approach to understanding schizophrenia focused on behavioral features and significantly influenced European psychiatry, particularly in Scandinavia and Great Britain.

Eugene Bleuler (1857- 1939), a colleague of Carl Jung, took a broader approach which emphasized psychological processes more than specific behavioral features. He believed that there was a basic defect whereby psychic functions were split off from each other: a disorganization of affect, thought and action. He defined the four A's as disturbances in association, affect, autism, and ambivalence. Bleuler's work set the stage for the broad concepts of schizophrenia developed by psychoanalysts and adopted by psychiatrists in the United States in the 1940s and 50s. Bleulerís concepts have fallen out of favor, however, as they are not specific to schizophrenia, and are difficult to define and research. The study of neuroscience, rather than psychoanalysis, has yielded the most important steps forward in understanding schizophrenia.

Portrait of Marilyn Monroe constructed, by a schizophrenic artist, on a piece of toilet paper with cigarette butts and match heads. It was found in the Kew Mental Hospital in the 1950s.

In these lectures about schizophrenia, we will integrate the clinical aspects of schizophrenia with the neuroscience that has allowed us to better understand and treat patients who suffer from this problem. There is much that is still unknown about schizophrenia. Sylvia Nasar wrote a biography of John Forbes Nash, Jr., a brilliant professor of mathematics and economics who developed paranoid schizophrenia when he was 30 years old and spontaneously recovered in his early 60s. For the 30 years in between (1959- 1989), Professor Nash suffered from severe delusions, hallucinations, disordered thought and feeling, and no motivation. Nasar describes him during this time as a "sad phantom who haunted the Princeton University campus where he had once been a brilliant graduate student, oddly dressed, muttering to himself, writing mysterious messages on blackboards, year after year." Treatment resulted in brief remissions and hope that lasted only a few months. After his surprising spontaneous recovery in the late 1980s, he received the Nobel Prize for Economics in 1994 for his work on game theory.

When Professor Nash first became ill, medication treatment of psychiatric disorders was in its infancy. Chlorpromazine was first noted to ameliorate psychotic processes in 1952. Widespread use of chlorpromazine as an antipsychotic did not occur until the late 1950s and early 1960s. Haloperidol, a much more potent antipsychotic, was first marketed in the United States in 1967. A major advance in antipsychotic drugs came in the 1990s with the release of the "atypical" antipsychotics which affect serotonergic as well as dopaminergic transmission. During the time that Professor Nash was ill, imaging of brain physiology was all but impossible and clinically useful imaging of brain anatomy was just developing. A technique we now take for granted, CT imaging of the brain has been available clinically for only about 25 years. MRI scans came into clinical just 15 years ago. Prior to the introduction of CT, physicians used the cerebral angiogram to image brain vasculature and the pneumoencephalogram to image ventricular spaces (this is a painful test where cerebrospinal fluid is withdrawn, air is injected, and x-rays are taken). The advent of clinically useful imaging of brain physiology is on the horizon. Neuroscience has made great strides forward in understanding brain development and regulation, neuronal communication and mutual influence, neural pathways and networks, neurotransmitters and receptors, and the pathophysiology of a variety of psychiatric and neurological disorders.

This picture is of historical value as showing the women on the "airing courts" before 1950 when it was then discovered. It shows the shapeless clothing and the unemployed and miserable patients. The surroundings help to accentuate the whole wretched picture of the old mental hospitals.


Natural History

It is often difficult to determine when the symptoms of schizophrenia actually started as the onset is often insidious. Retrospectively, many patients showed personality abnormalities present in early adolescence including excessive shyness, social awkwardness, withdrawal from social relationships, and an inability to form relationships. Some studies have shown an increased frequency of pregnancy and birth complications in individuals who later develop schizophrenia. There may academic difficulties or antisocial or delinquent tendencies. The positive symptoms usually start in the late teen or early twenties- often vague or brief in nature. Schizophrenia infrequently begins after age 40. The course of schizophrenia fluctuates with episodes of acute psychosis superimposed on a baseline which can show remission or residual symptoms. Many schizophrenics have difficulty achieving satisfactory lives and can become quite isolated. Good prognosis is associated with acute onset, past high function and excellent interpersonal adjustment, good response to antipsychotics, absence of negative symptoms, and absence of secondary affective disorder. A study done at the University of Iowa utilized DSM III type criteria. They found that thirty years after case identification, 20% of patients were asymptomatic, 25% had moderate symptoms, and 55% had severe symptoms (n=200). Severe deterioration is not always a necessary outcome of the disease.

Above: Artwork of an unidentified bipolar patient

Clinical Presentation

The clinical presentation of schizophrenia is complex and the symptoms encompass nearly all the aspects of human emotional and cognitive life. The disorder is defined by a clustering of features, no single one of which is necessarily present or pathognomonic. In an effort to bring some coherence to the relatively broad range of schizophrenic signs and symptoms, investigators have begun to group them into two major categories: Positive (florid) symptoms and negative (defect) symptoms. Positive symptoms tend to represent a distortion or exaggeration of a normal function and include delusions, hallucinations and abnormalities of language and behavior. Negative symptoms represent a diminution or loss of function including poverty of speech and content of speech (alogia), affective blunting, asociality, anhedonia, and avolition.

Classification of Symptoms of Schizophrenia

Positive Symptoms: exaggeration or distortion of normal function




Function Distorted












Inferential Thinking



Formal Thought Disorder






Behavioral Disorganization



Behavioral Control



Negative Symptoms: loss of normal functions


Function Lost


Fluency of speech

Affective Blunting

Emotional Expression


Volition and drive


Hedonic capacity

Attentional Impairment


Positive Symptoms



Positive Symptoms of Schizophrenia


Hallucinations are abnormal perceptions that occur in the absence of some identifiable external stimulus. Illusions are a misperception of an external stimulus. Auditory hallucinations: hearing voices, noises or sounds; schizophrenics typically hear voices that are unpleasant or negative. Voices that are commenting on the patient's thoughts or behaviors, conversing voices, and commanding voices (command hallucination) are often seen in schizophrenia. Visual hallucinations can occur but are more characteristic of an organic/toxic psychosis.

Above: Artwork of an unidentified patient


Delusions are abnormal thought content consisting of false beliefs that cannot be explained on the basis of the patient's cultural background. They may be held as the truth or the patient may doubt them. Evaluation of the patient must take into account the severity and power of the delusions as behavior may be influenced by them. Delusions can be: persecutory (being followed, mail being opened, room is "bugged", telephone tapped, harassed by someone); jealous; concerned with sin or guilt (concern with masturbation as a child, cause of a disaster, suffer eternal punishment from G-d); grandiose (special powers or abilities, famous person; developer of something wonderful or special- think mania and beware if patient becomes irritable or thinks someone is trying to steal ideas); religious (may be within the context of conventional religious system or new religious system, can be combined with grandiose delusions); somatic (body diseased, abnormal, changed); ideas and delusions of reference (remarks, others' behavior, events have to do with patient- can be generated by interpersonal contact, TV, radio, newspaper, magazine); control (subjective physiological experience that thoughts or behaviors are controlled by outside force); mind reading (others can read patient's mind or thoughts); thought broadcasting (belief that thoughts are broadcast so others can hear them); thought insertion (others' thoughts are inserted into patients' mind); and thought withdrawal (thoughts taken away from mind).

Bizarre behavior: unusual, weird or fantastic actions not due to alcohol or drugs. Dress may be unusual (layers of clothes, strange attire, costume, inappropriate for weather conditions), social and sexual behavior may be altered (public masturbation or urination, talking or praying in public, inappropriate sexual overtones), behaviors may be stereotyped or repetitive (ritual actions such as colored jelly bean eating, orderly dinner, message writing), or aggressive or agitated behavior may occur (may be unpredictable or start with written messages, then verbal messages followed by behaviors).

Above: Artwork of an unidentified patient

Formal thought disorder: fluent speech that communicates poorly because of problems with "thought flow". The examiner needs to listen to the patient for at least five minutes to determine if idea sequencing is well connected and comprehensible. There may be derailment or loose associations (ideas slip off track onto a related or unrelated track, often very slowly); tangentiality (replying to a question with irrelevant or slightly related answer); incoherence or word salad (incomprehensible speech with words not relating to each other in a sentence); illogicality (conclusions do not follow from "the facts" independent of delusional thinking and may be non sequiturs, faulty inductive references, faulty deductive conclusions); circumstantiality (pattern of speech which is indirect, delayed and tediously detailed); pressured (increase in rate and amount of speech, difficult to interrupt- think mania also); distractible (change of subject in response to environmental event such as a noise); and clanging (sounds govern word choice rather than idea- may rhyme or pun, e.g.: I was talking to my sister Lister Pasteur pasteurize the milk...)

Negative Symptoms of Schizophrenia

Affective Blunting or Flattening: a characteristic impoverishment in emotional expression, reactivity or feeling characterized by unchanging facial expression, decreased spontaneous movements, paucity of expressive gestures, poor eye contact, affective nonresponsivity, inappropriate affect, and lack of vocal inflections.

Alogia characterized by impoverished thinking and cognition inferred from speech poverty, poverty of thought, thought blocking, and increased response latency.

Avolition-Apathy manifested by lack of drive energy, interest not accompanied by sad or depressed affect, poor grooming and hygiene, impersistence at work or school, and physical anergia.

Anhedonia-Asociality characterized by difficulty in experiencing interest or pleasure, loss of recreational interests and activities, loss of sexual interest and activity, inability to feel intimacy or closeness, and impaired relationships with others.

Inattention characterized by social inattentiveness, inattention on MSE.

Self-Portrait by an identified mental patient

The diagnosis of schizophrenia also contains the related issue of subtypes of schizophrenia. The purpose of defining subtypes is to improve predictive validity and subsequent treatment. Subtypes identified in DSM IV include: Paranoid, Disorganized, Catatonic, Undifferentiated and residual. Dissatisfaction with these subtypes has led to alternative proposals including classifications based on CT scan structural abnormalities or PET scan metabolic abnormalities.

The Crow model subtypes schizophrenia on the basis of symptom type into Positive and Negative Schizophrenia. There is great appeal to this model as it unites phenomenology, pharmacology and pathophysiology in a comprehensive hypothesis. There is evidence to support this hypothesis, yet it cannot account for the mixture of symptoms seen in many schizophrenics and the variability of symptoms over time.

Diagnostic Variable

Neg. Schiz.

Pos. Schiz

Premorbid fcn





often acute





affective blunt




positive FTD



bizarre behavior


attentional def.





Tx Response







neuronal loss and atrophy

hyperdopaminergic transmission in limbic system


Above: Artwork of an unidentified patient

Schizophrenia Case

Daniel is an 18 year old white middle class male brought to the hospital emergency room by his parents. His parents were concerned that Daniel had been acting strangely lately, although Daniel denied any problem saying, "I've seen the light."

Daniel lives with his parents and is a sophomore at a local college. He has always been a good student, but his grades fell significantly one month ago. He has always been a rather quiet child, but seemed to socialize well with other children until about age 12. At that time, he began to withdraw from friends and family, choosing to spend alot of time alone in his room. He enjoyed reading and playing guitar. He told the examiner that he liked to read fantasy novels and that he thought highly of John Lennon. His parents said that Daniel never dated and in fact seemed intimidated by girls. Daniel stated, "females are the right hand of the devil" but he would not elaborate on that thought. His parents began to feel more concern 8 months ago during the first semester of his freshman year in college as he seemed even more withdrawn from them than usual. He also began talking about John Lennon more frequently, telling his parents that John "knew the way" and that he needed to "find his meaning in this meaningless world". Within the past two months, Daniel seemed even more preoccupied with concerns of life and death and has stopped going to class. His parents became alarmed when he told them this morning that he believes that he can communicate with John Lennon by getting Johnís "karma in my mind". In addition, he told them that "I am becoming the walrusÖI can use my tusks to read the waters of life." Daniel has not slept or eaten for the past two days. Daniel and his parents stated that he had never used drugs or alcohol.

Daniel is the eldest of 3 children with siblings age 15 and 11. He has never been seriously ill and has no history of head injury, seizures, fever, or toxic exposure. His development as an infant and young child was unremarkable except for the problems noted previously. His family denies a family history of psychiatric disorder, but remembered a maternal cousin who was unusual and spent much of his later life living alone. There was a family story about how this man used to collect thousands of magazines and lock himself in his house for months.

Mental Status Evaluation

The Mental Status Evaluation (MSE) is an assessment of a patientís appearance, behavior, speech, mood, affect, thought content, thought process, orientation, memory and other cognitive functioning, judgement and insight at one point in time. A MSE can change quickly if the patientís functioning is fluctuating, such as when a patient is delirious. The MSE will be covered in detail in the second year psychiatry course. Danielís MSE is presented to clarify his symptoms.

Daniel was dressed in tattered blue jeans, a V-neck sweater without a shirt and loafers without socks. He was unshaven and looked tired although he remained alert throughout the interview. He did not want to sit down in a chair but preferred to stand near the door, often turning his head towards it when there was some noise in the hallway. He was distant and made poor eye contact with the examiner. Daniel looked at his watch or at a book about John Lennon which he had brought with him. His speech was somewhat slowed and quiet. He seemed mildly agitated, standing still then pacing for a few minutes. Daniel did not want to describe his mood. His affect was blunted and he expressed little emotion. He denied depression and suicidal thoughts. Daniel was reluctant to discuss his thoughts. He did talk about his interest in Lennon's life as a "guide" for him, but denied thinking about dying or joining John. On one occasion, he said that he was worried that he might be killed by someone who "fought the principles of God and Lennon". Daniel had thought blocking on several occasions and had loose associations. Daniel was very guarded and suspicious and seemed to be attending to internal stimuli. At one point during the interview, he mumbled something softly but would not discuss it with the examiner. He was alert and oriented with no fluctuations in consciousness. His attention was poor as a result of his preoccupation with himself. He knew the names of 6 past presidents, was familiar with current events, and did not seem to be impaired intellectually. Daniel did not want to perform any tests of memory saying, "that's stupid- there is nothing wrong with my memory". He had little insight into his problem and showed poor judgement, i.e. "it really doesn't matter if I eat as God will provide sustenance for me".

Cafe at Arles

Questions And Discussion Points

What psychiatric problem is Daniel experiencing?

  1. Schizophrenia, probably paranoid

  2. Key Diagnostic Features of Schizophrenia

At least 2 psychotic features present for at least a month

    1. Hallucinations

    2. Delusions

    3. Disorganized speech: incoherence, frequent derailment

    4. Grossly disorganized or catatonic behavior

    5. Negative symptoms: affective blunting, anhedonia, lack of motivation

Impairment in social or occupational functioning or self-care

Duration for at least 6 months with 1 month of active symptoms (unless treated)

Symptoms not due to a mood disorder or schizoaffective disorder

Symptoms not due to a medical, neurological or substance use disorder

(Schizoaffective disorder usually diagnosed when manic or depressive symptoms are prominent and consistent part of patientís long term psychotic illness)

3. Diagnostic Subtypes of Schizophrenia

The diagnosis of schizophrenia also contains the related issue of subtypes of schizophrenia. The purpose of defining subtypes is to improve predictive validity and subsequent treatment. Subtypes identified in DSM IV include:

    1. Catatonic: motor abnormalities such as rigidity and posturing

    2. Disorganized: disorganized speech and behavior, flat affect

    3. Paranoid: paranoid symptoms in the absence of catatonic or disorganized features

    4. Undifferentiated: some combination of the above



List the symptoms that Daniel is experiencing

  1. delusions

  2. probable hallucinations

  3. social withdrawal

  4. decreased sleep and appetite

  5. impairment in functioning in school

  6. agitation

  7. blunted affect

  8. thought blocking

  9. loose associations

  10. little insight and poor judgement


Daniel was offered hospitalization which he initially refused, but decided to accept after some discussion. He said, "Iíll come in to be sure that no one shoot me like they did JohnÖhe warned me that something bad might happen." His medical work-up showed a healthy 18 year old male. He was started on haloperidol 5 mg at bedtime and discharged in 5 days to his parents home. He was seen weekly by a psychiatrist in the outpatient clinic. Within 5 days of starting medication, he was sleeping better and gaining weight. After 2 weeks, he seemed calmer, but still talked about his connection to John Lennon. His haloperidol was held at this dose for 2 more weeks as research has shown that low dose treatment takes longer to work, but is easier for patients to tolerate. Within a month, he no longer seemed to be hallucinating and was more interactive. His delusions had "softened" and he seemed less fearful of being hurt. After 4 months of treatment, Daniel stated, "I donít think about John Lennon much anymore. He is still important to me, but my mind took off on its own". He was much improved, but still was socially withdrawn and had a blunted affect.

What are some of the side effects of antipsychotics?

  1. Imbalance of dopaminergic (nigrostriatal) and cholinergic systems leading to extrapyramidal side effects (acute dystonic reaction; parkinsonian side effects such as tremor, rigidity, and bradykinesia; akathisia).

  2. Nigrostriatal dopamine receptor supersensitivity leading to tardive dyskinesia.

  3. Anticholinergic side effects such as dry mouth, sedation, difficulty with urination, blurry vision, orthostatic hypotension.

  4. Weight gain.

  5. Elevation of prolactin leading to sexual dysfunction, altered/lowered mood, loss of menses in female patients, inability to become pregnant, weight gain.

What are some of the problems that patients face when deciding to take medication?

  1. Lack of acceptance of mental disorders as diseases- the perception that mental illness is willful and psychologically driven.

  2. Inability to face the illness or a desire to run away and pretend that the illness will go away on its own.

  3. Lack of support from important others like family or mate.

  4. Realistic problems like job loss and social rejection.

  5. General fear of mind-altering medications (which may be quite irrational as the individual may not fear the use of alcohol, cigarettes, marijuana, or cocaine).

  6. The disease itself leads to fear of treatment (e.g. paranoid hallucinations telling the patient to not trust anyone or that the medication is really poison).

  7. Unhappiness with side effects of medication.

  8. Fear of tardive dyskinesia.

  9. Discomfort with the physician or other members of the treatment team.

How can these problems be ameliorated?

  1. Education of the patient about his/her disease; the probable course and risks if untreated, and the probable course and benefits/risks if medication is used.

  2. Develop an understanding of the patientís point of view about his/her disease, symptoms, hopes for the future, fears.

  3. Identify the patientís strengths and help the patient mobilize all his/her individual and social resources. Involve the family when this is helpful.

  4. Acknowledge the possible risks of medication treatment and assure the patient that he/she will be followed carefully.

  5. Encourage open communication between patient and physician.

How is tardive dyskinesia treated?

  1. Discontinue the antipsychotic and hope for the best. The patient may become ill again.

  2. Initiate clonidine (a presynaptic alpha agonist that leads to down-regulation of the DA receptors and hypotension).

  3. Initiate reserpine (depletes monoamines and may cause depression).

  4. Obtain tetrabenazine from Canada (depletes monoamines with lower risk of depression).

    Our Resources

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