• Research

• Early Warning Signs

• The neurodevelopmental hypothesis

• Treatments

• Bibliography

Research

Researchers now agree that, while we do not yet know what "causes" schizophrenia, many pieces of the puzzle are becoming clearer. Areas of study and interest are:

·    Biochemistry -- People with schizophrenia appear to have a neurochemical imbalance. Thus, some researchers study the neurotransmitters that allow communication between brain cells. Modern antipsychotic medications now target three different neurotransmitter systems (dopamine, serotonin, and norepinephrine.)

·    Cerebral Blood Flow -- With modern brain imaging techniques (PET scans), researchers can identify areas that are activated when the brain is engaged in processing information. People with schizophrenia appear to have difficulty "coordinating" activity between different areas of the brain. For example, when thinking or speaking, most people show increased activity in their frontal lobes, and a lessening of activity in the area of the brain used for listening. People with schizophrenia show the same increase in frontal lobe activity-but there is no decrease of activity ("dampening" or "filtering") in the other area. Researchers have also been able to identify specific areas of unusual activity during hallucinations.

·    Molecular Biology -- People with schizophrenia have an irregular pattern of certain brain cells. Since these cells are formed long before a baby is born, there is speculation that

i.         this irregular pattern may point towards a possible "cause" of schizophrenia in the prenatal period; or

ii.        the pattern indicates a predisposition to acquire the disease at a later date.

·    Genetic Predisposition -- Genetic research continues, but has not identified a hereditary gene for schizophrenia. Schizophrenia does appear more regularly in some families. Then again, many people with schizophrenia have no family history of the illness.

·    Stress -- Stress does not cause schizophrenia. However, it has been proven that stress makes symptoms worse when the illness is already present.

·    Drug Abuse -- Drugs (including alcohol, tobacco, and street drugs) themselves do not cause schizophrenia. However, certain drugs can make symptoms worse or trigger a psychotic episode if a person already has schizophrenia. Drugs can also create schizophrenia-like symptoms in otherwise healthy individuals.

·    Nutritional Theories -- While proper nutrition is essential for the well-being of a person with the illness, it is not likely that a lack of certain vitamins causes schizophrenia. Claims that promote megavitamin therapy have not been substantiated.

Some people do improve while taking vitamins. However, this can be due to concurrent use of antipsychotic medication, or to the overall therapeutic effect of a good diet, vitamin and medication regime. Or -- these individuals may be part of that group who will recover no matter what treatment is used.

Early Warning Signs

The following list of warning signs was developed by people whose family members have schizophrenia. Many behaviours described are within the range of normal responses to situations. Yet families sense -- even when symptoms are mild -- that behaviour is "unusual"; that the person is "not the same."

The number and severity of these symptoms differ from person to person -- although almost everyone mentions "noticeable social withdrawal."

·         Deterioration of personal hygiene

·         Depression

·         Bizarre behaviour

·         Irrational statements

·         Sleeping excessively or inability to sleep

·         Social withdrawal, isolation, and reclusiveness

·         Shift in basic personality

·         Unexpected hostility

·         Deterioration of social relationships

·         Hyperactivity or inactivity -- or alternating between the two

·         Inability to concentrate or to cope with minor problems

·         Extreme preoccupation with religion or with the occult

·         Excessive writing without meaning

·         Indifference

·         Dropping out of activities -- or out of life in general

·         Decline in academic or athletic interests

·         Forgetting things

·         Losing possessions

·         Extreme reactions to criticism

·         Inability to express joy

·         Inability to cry, or excessive crying

·         Inappropriate laughter

·         Unusual sensitivity to stimuli (noise, light, colours, textures)

·         Attempts to escape through frequent moves or hitchhiking trips

·         Drug or alcohol abuse

·         Fainting

·         Strange posturing

·         Refusal to touch persons or objects; wearing gloves, etc.

·         Shaving head or body hair

·         Cutting oneself; threats of self-mutilation

·         Staring without blinking -- or blinking incessantly

·         Flat, reptile-like gaze

·         Rigid stubbornness

·         Peculiar use of words or odd language structures

·         Sensitivity and irritability when touched by others.

Studies show that families who are supportive, non-judgmental, and, most especially, non-critical -- can do much to help patients recover. On the other hand, patients who are around chaotic or volatile family members usually have a more difficult time, and have to return to hospital more often.

The neurodevelopmental hypothesis

The neurodevelopmental hypothesis of schizophrenia proposes that a proportion of schizophrenia is the result of an early brain insult, either pre or perinatal, which affects brain development leading to abnormalities which are expressed in the mature brain. (23-26) This idea is not new, Kraeplin and others throughout the 20th century argued that some cases of schizophrenia probably resulted from insults that cause cerebral maldevelopment. (27, 28) The cause of the brain lesion is postulated to be either from the inheritance of abnormal genes, which impair brain development, or from some fetal or neonatal adversity.

Maternal malnutrition in early gestation (141, 142) is another intrauterine environmental event which appears to increase the risk of developing schizophrenia in a dose dependent way. However, this study (142) did not control for the implication of social class both in access to food and on risk for schizophrenia.
Nevertheless, four lines of evidence support prenatal nutritional deficiencies as a plausible set of risk factors for schizophrenia: (143)

• Their effects are not incompatible with the epidemiology of schizophrenia

• They have adverse effects on brain development

• General malnutrition results in neuropathological anomalies of brain regions implicated in schizophrenia

• Prenatal malnutrition affects maternal systems critical to the developing fetal nervous system.

Most scientists now suspect that people inherit a susceptibility to the illness, which can be triggered by environmental events such as a viral infection that changes the body's chemistry, a highly stressful situation in adult life, or a combination of these.

While scientists have long known that the illness runs in families and much recent research evidence supports the linking of schizophrenia to heredity. For example, studies show that children with one parent suffering from schizophrenia have an eight to 18 percent chance of developing the illness, even if they were adopted by mentally healthy parents. If both parents suffer from schizophrenia, the risk rises to between 15 and 50 percent. Children whose biological parents are mentally healthy but whose adoptive parents suffer from schizophrenia have a one percent chance of developing the disease, the same rate as the general population.

Moreover, if one identical twin suffers from schizophrenia, there is a 50 to 60 percent chance that the sibling--who has identical genetic make-up_also has schizophrenia.

But people don't inherit schizophrenia directly, as they inherit the color of their eyes or hair. Like many genetically related illnesses, schizophrenia appears when the body is undergoing the hormonal and physical changes of adolescence. Genes govern the brain's structure and biochemistry. Because structure and biochemistry change dramatically in teen and young adult years, some researchers suggest that schizophrenia lies "dormant" during childhood. It emerges as the body and brain undergo changes during puberty.

Certain genetic combinations could mean a person doesn't produce a certain enzyme or other biochemical, and that deficiency produces illnesses ranging from cystic fibrosis to, possibly, diabetes. Other genetic combinations could mean that specific nerves don't develop correctly or completely, giving rise to genetic deafness. Similarly, a genetically determined sensitivity could mean the brain of a person with schizophrenia is more prone to be affected by certain biochemicals, or that it produces inadequate or excessive amounts of biochemicals needed to maintain mental health. Genetically determined triggers could also the development of part of the brain of a person with schizophrenia, or could cause problems with the way the person's brain screens stimuli, so that the person with schizophrenia is overwhelmed by sensory information which normal people can easily handle.

These theories arise from the ability of researchers to see the structure and activity of the brain through very sophisticated medical technology. For example

Using computer images of brain activity, scientists have learned that a part of the brain called the prefrontal cortex--which governs thought and higher mental functions--"lights up" when healthy people are given an analytical task. This area of the brain remains quiet in those with schizophrenia who are given the same task. Magnetic resonance imaging (MRI) and other techniques have suggested that the neural connections and circuits between the temporal lobe structures and the prefrontal cortex may be have an abnormal structure or may function abnormally.

• The prefrontal cortex in the brains of some schizophrenia sufferers appears to have either atrophied or developed abnormally.

• Computed axial tomography or CAT scans have shown subtle abnormalities in the brains of some people suffering from schizophrenia. The ventricles--the fluid-filled spaces within the brain--are larger in the brains of some people with schizophrenia.

• Successful use of medications that interfere with the brain's production of a biochemical called dopamine indicates that the brains of those with schizophrenia are either extraordinarily sensitive to dopamine or produce too much dopamine. This theory is strengthened by observing treatment for Parkinson's disease, caused by too little dopamine. Parkinson's patients, who are treated with medication that helps increase the amount of dopamine, may also develop psychotic symptoms.

Schizophrenia is similar in several respects to "autoimmune" illnesses -- disorders like multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS or Lou Gherig's disease), caused when the body's immune system attacks itself. Like the autoimmune diseases, schizophrenia is not present at birth but develops during adolescence or young adulthood. It comes and goes in cycles of remission and relapse, and it runs in families. Because of these similarities, scientists suspect schizophrenia could fall into the autoimmune category.

Some scientists think genetics, autoimmune illness and viral infections combine to cause schizophrenia. Genes determine the body's immune reaction to viral infection. Instead of stopping when the infection is over, the genes tell the body's immune system to continue its attack on a specific part of the body. This is similar to the theories about arthritis, in which the immune system is thought to attack the joints.

The genes of people with schizophrenia may tell the immune system to attack the brain after a viral infection. This theory is supported by the discovery that the blood of people with schizophrenia contains antibodies--immune system cells--specific to the brain. Moreover, researchers in a National Institute of Mental Health study found abnormal proteins in the fluid that surrounds the brain and spinal cord in 30 percent of people with schizophrenia but in none of the mentally healthy people they studied. These same proteins are found in 90 percent of the people who have suffered herpes simplex encephalitis, an inflammation of the brain caused by the family of viruses that causes warts and other illnesses.

Finally, some scientists suspect a viral infection during pregnancy. Many people suffering from schizophrenia were born in late winter or early spring. That timing means their mothers may have suffered from a slow virus during the winter months of their pregnancy. The virus could have infected the baby to produce pathological changes over many years after birth. Coupled with a genetic vulnerability, a virus could trigger schizophrenia.

Most psychiatrists today believe that the above--genetic predisposition, environmental factors such as viral infection, stressors from the environment such as poverty and emotional or physical abuse--form a constellation of "stress factors" that should be taken into account in understanding schizophrenia. An unsupportive home or social environment and inadequate social skills can bring on schizophrenia in those with genetic vulnerability or cause relapse in those already suffering with the disease. Psychiatrists also believe these stress factors can often be offset with "protective factors" when the person with schizophrenia receives proper maintenance doses of antipsychotic medication, and help in creating a secure network of supportive family and friends, in finding a steady and understanding place of employment, and in learning necessary social and coping skills.

Treatments

Psychiatrists have found a number of antipsychotic medications that help bring biochemical imbalances closer to normal. The medications significantly reduce the hallucinations and delusions and help the patient maintain coherent thoughts. Like all medications, however, antipsychotic drugs should be taken only under the close supervision of a psychiatrist or other physician.

Antipsychotic medications are important in reducing or eliminating the chances of relapse. One study showed that 60 to 80 percent of those who did not take medication as part of their treatment had a relapse the first year after leaving the hospital. Between 20 and 50 percent of those who did take medication were rehospitalized that first year; however, if the patients continued taking medication beyond the first year, relapse rates fell to 10 percent.

Like virtually all other medications, antipsychotic agents have side effects. While the patient's body adjusts to the medication during the first few weeks, he or she may have to contend with dry mouth, blurred vision, constipation and drowsiness. One may also experience dizziness when standing up due to a drop in blood pressure. These side effects usually disappear after a few weeks.

Other side effects include restlessness (which can resemble anxiety), stiffness, tremor, and a dampening of accustomed gestures and movements. Patients may feel muscle spasms or cramps in the head or neck, restlessness, or a slowing and stiffening of muscle activity in the face, body, arms and legs. Though discomforting, these are not medically serious and are reversible.

Because some other side effects may be more serious and not fully reversible, anyone taking these medications should be closely monitored by a psychiatrist. One such side effect is called tardive dyskinesia (TD), a condition that affects 20 to 30 percent of people taking antipsychotic drugs. TD is more common among older patients.

It begins with small tongue tremors, facial tics and abnormal jaw movements. These symptoms may progress into thrusting and rolling of the tongue, lip licking and smacking, pouting, grimacing, and chewing or sucking motions. Later, the patient may develop spasmodic movements of the hands, feet, arms, legs, neck and shoulders.

Most of these symptoms reach a plateau and do not become progressively worse. TD is severe in less than 5 percent of its victims. If medication is stopped, TD also fades away among 30 percent of all patients and in 90 percent of those younger than 40. There is also evidence that TD subsides eventually, even in patients who continue with medication. Despite the risk of TD, many suffering with schizophrenia accept medication because it so effectively ends the horrifying and painful psychoses brought on by their illness. However, the unpleasant side effects of antipsychotic medication also leads many patients to stop using medication against the advice of their psychiatrist. The refusal of patients with schizophrenia to comply with psychiatrists' treatment recommendations is a serious challenge to those specializing in the treatment of chronically mentally ill people. Psychiatrists treating people with schizophrenia must often practice with tolerance and flexibility to overcome this resistance.

There is also hope that the newer generations of antipsychotic drugs now being introduced and under development will prove to be a great help to people with schizophrenia that has been resistant to treatment in the past, with fewer side effects and greater effectiveness with schizophrenia's symptoms. Clozapine and risperidone (the first approved by the U.S. Food and Drug Administration and the second nearing approval) provide two examples. Clozapine doesn't list TD as one of its side effects and has helped many whose conditions were not substantially improved by the older generation of neuroleptic medications. Use of clozapine is restricted, however, by an expensive medical monitoring system made necessary by the fact that the medicine can cause agranulocytosis, a blood disorder that occurs in one to two percent of patients who take it and which can prove fatal if it is not observed. Risperidone may be safer than clozapine and have fewer of its side effects, including agranulocytosis. By ending or reducing the painful hallucinations, delusions and thought disorders, medications allow a patient to gain benefit from rehabilitation and counseling aimed at promoting the individual's functioning in society. Social skills training, which can be provided in group, family or individual sessions, is a structured and educational approach to learning social relationship and independent living skills. By using behavioral learning techniques, such as coaching, modeling and positive reinforcement, skills trainers have been successful in overcoming the cognitive deficits that interfere with rehabilitation. Research studies show that social skills training improves social adjustment and equips patients with means of coping with stressors, thereby reducing relapse rates by up to 50 percent.

Another type of learning-based treatment that has been documented to reduce relapse rates is behaviorally oriented, psychoeducational family therapy. Mental health professionals recognize the important role families play in treatment and should maintain open lines of communication with the families as treatment evolves over time. Providing family members, including the patient, with a better understanding of schizophrenia and its treatment, while helping them to improve their communication and problem-solving skills, is becoming a standard practice in many psychiatric clinics and mental health centers. In one study, when psychoeducational family therapy and social skills training were combined, the relapse rate during the first year of treatment was zero.

Psychiatric management and supervision of regular medication use, social skills training, behavioral and psychoeducational family therapy, and vocational rehabilitation must be delivered within the context of a community support program. The key personnel in community support programs are clinical case managers who are experienced in linking the patient to needed services, assuring that social services as well as medical and psychiatric treatment is delivered, forming solid and supportive long-term helping relationships with the patient, and advocating for patients' needs when there is a crisis or problem.

When continuing treatment and supportive care is available in the community, with a partnership of family, patient and professional caregivers, patients can learn to control their symptoms, identify early warning signs of relapse, develop a relapse prevention plan, and succeed in vocational and social rehabilitation programs. For the vast majority of persons with schizophrenia, the future is bright with optimism--new and more effective medications are on the horizon, neuroscientists are learning more and more about the function of the brain and how it goes awry in schizophrenia, and psychosocial rehabilitation programs are increasingly successful in restoring functioning and quality of life.

Ascher-Svanum, Haya and Krause, Audrey, Psychoeducational Groups for Patients with Schizophrenia: A Guide for Practitioners. Gaithersburg, MD: Aspen Publishers, 1991.

Deveson, Anne., The Me I'm Here: One Family's Experience of Schizophrenia. Penguin Books, 1991.

Howells, John G., The Concept of Schizophrenia: Historical Perspectives. Washington, DC: American Psychiatric Press, Inc., 1991.

Kuehnel TG, Liberman, RP, Storzbach D and Rose, G, Resource Book for Psychiatric Rehabilitation. Baltimore, MD: Williams & Wilkins, 1990.

Kuipers, Liz., Family Work for Schizophrenia: A Practical Guide. Washington, D.C.: American Psychiatric Press, Inc., 1992

Liberman, Robert Paul, Psychiatric Rehabilitation of Chronic Mental Patients. Washington, DC: American Psychiatric Press, 1988.

Matson, Johnny L., Ed., Chronic Schizophrenia and Adult Autism: Issues in Diagnosis, Assessment, and Psychological Treatment. New York: Springer, 1989.

Mendel, Werner, Treating Schizophrenia. San Francisco: Jossey-Bass, 1989.

Menninger, W. Walter and Hannah, Gerald, The Chronic Mental Patient. American Psychiatric Press, Inc., Washington, D.C., 1987. 224 pages.

Schizophrenia: Questions and Answers. Public Inquiries Branch, National Institute of Mental Health, Room 7C-02, 5600 Fishers Lane, Rockville, MD 20857. 1986. Free single copies. (Available in Spanish_"Esquizofrenia: Preguntas y Respuestas")

Seeman, Stanley and Greben, Mary, Eds., Office Treatment of Schizophrenia. Washington, DC: American Psychiatric Press, Inc., 1990.

Torrey, E. Fuller., Surviving Schizophrenia: A Family Manual. New York, NY: Harper and Row, 1988.

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We in the AAS would like to help in the dissemination of information on health care, especially in the cure and treatment of neurological and mental disorders, which are referred generally as brain disorders.