Which neurotransmitter(s) was/were the first to be linked with schizophrenia?

Who has schizophrenia? Schizophrenia is one of the most common mental illnesses. About 1 of every 100 people (1% of the population) is affected by schizophrenia. This disorder is found throughout the world and in all races and cultures. Schizophrenia affects men and women in equal numbers, although on average, men appear to develop schizophrenia earlier than women. Generally, men show the first signs of schizophrenia in their mid 20s and women show the first signs in their late 20s. Schizophrenia has a tremendous cost to society, estimated at $32.5 billion per year in the US (statistic from Brain Facts, Society for Neuroscience, 2002).

What are the symptoms of schizophrenia?

The behavior of people with schizophrenia is often very strange and shocking. This change in behavior, when people cannot tell the difference between what is real and what is not, is called "psychosis" or a "psychotic episode." The American Psychiatric Association has published guidelines that are used to classify people with mental disorders. The most recent guidelines are contained in a book called the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (known as DSM-5 for short). The DSM-5 describes several symptoms that a person MUST have before he or she is classified as having schizophrenia. These symptoms include two or more of the following behaviors for a duration of at least one month:

• Delusions - bizarre, false beliefsThese beliefs seem real to the person with schizophrenia, but they are not real. For example, a person may believe that aliens or spies are controlling his or her behavior, mind and thoughts. Sometimes these delusions can be paranoid in nature. People with paranoia have an unreal fear or suspicion that someone is "out to get them." Delusions may also be of grandiosity. In these cases, people believe that they are someone important, such as a president, king or prime minister.
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  • Who has schizophrenia?
  • What are the symptoms of schizophrenia?
  • What occurs in the brain?
  • What are the causes of schizophenia?
  • Environment
  • Neurotransmitters
  • Which neurotransmitter imbalance occurs in a patient with schizophrenia?
  • When is the first episode of schizophrenia most likely to occur?
  • Which of the following brain abnormalities is suggested to be a cause of schizophrenia?
  • What is dopamine overactivity most like?
• Hallucinations - bizarre, unreal perceptions of the environment These hallucinations can be:
  1. Auditory (hearing voices) - sometimes the "voices" tell a person to do something
  2. Visual (seeing lights, objects or faces)
  3. Olfactory (smelling things)
  4. Tactile (for example, feelings that bugs are crawling on or under the skin)

• Disorganized SpeechPeople with schizophrenia speak very little; others have speech that is disjointed. Sometimes the person will change the topic midway through a sentence.

• Negative Symptoms - the absence of normal behaviorDelusions, hallucinations and abnormal speech indicate the presence of abnormal behavior. Negative symptoms include social withdrawal, absence of emotion and expression, reduced energy, motivation and activity. Sometimes people with schizophrenia have poor hygiene and grooming habits.

• Grossly disorganized or catatonic behavior - immobility and "waxy flexibility"Catatonia is a negative symptom where people become fixed in a single position for a long period of time. "Waxy flexibility" describes how a person's arms will remain frozen in a particular position if they are moved by someone else.

When people show any of these five symptoms, they are considered to be in the "active phase" of the disorder. Often people with schizophrenia have milder symptoms before and after the active phase.

There are three basic types of schizophrenia. All people who have schizophrenia have lost touch with reality. The three main types of schizophrenia are:

1. Disorganized Schizophrenia (previously called "hebephrenic schizophrenia") - lack of emotion, disorganized speech
2. Catatonic Schizophrenia - waxy flexibility, reduced movement, rigid posture, sometimes too much movement
3. Paranoid Schizophrenia - strong delusions or hallucinations

What occurs in the brain?

A common finding in the brains of people with schizophrenia is larger than normal lateral ventricles. The lateral ventricles are part of the ventricular system that contains cerebrospinal fluid.

The picture below shows magnetic resonance image (MRI) brain scans of a pair of twins: one with schizophrenia, one without schizophrenia. Notice that the ventricles (red arrows) are larger in the twin with schizophrenia. (Image courtesy of NIMH Clinical Brain Disorders Branch.)

A reduced size of the hippocampus, increased size of the basal ganglia, and abnormalities in the prefrontal cortex are seen in some people with schizophrenia. However, these changes are not seen in all people with schizophrenia and they may occur in people without this disorder.

What are the causes of schizophenia?

There are probably multiple causes for schizophrenia and scientists do not know all of the factors that produce this mental disorder.

Genetics

Schizophrenia does "run in the family." In other words, schizophrenia has an important genetic component. Evidence for a genetic component comes from twin studies. Monozygotic twins (identical twins) are those with exactly the same genetic makeup; dizygotic twins (fraternal twins) are those who share only half of their genetic makeup. If genetics was the ONLY factor in developing schizophrenia, then both monozygotic twins should always develop this illness.

Twin Studies

Twin studies have shown that the tendency for both monozygotic (identical) twins to develop schizophrenia is between 30-50%. The tendency for dizygotic (fraternal) twins to develop schizophrenia is about 15%. The tendency for siblings who are not twins (such as brothers of different ages) is also about 15%. Remember, schizophrenia is found in the general population at a rate of about 1%. Therefore, because the tendency for monozygotic twins is NOT 100%, genetics cannot be the only factor. However, because the tendency for monozygotic twins to have schizophrenia is much greater than the tendency for dizygotic twins, genetics DOES play a role.

Adoption Studies

Some studies have looked at the family background of people who were adopted at an early age and who later developed schizophrenia. One study (Kety et al., 1968) found that 13% of the biological relatives of the adoptees with schizophrenia also had schizophrenia, but only 2% of the relatives of "normal" adoptees had schizophrenia. These studies support the role of genetics in schizophrenia.

To learn more about the role of genetics in schizophrenia, see the Genetics and Mental Disorders page at the National Institute of Mental Health.

Environment

Nongenetic factors that may influence the development of schizophrenia include: family stress, poor social interactions, infections or viruses at an early age, or trauma at an early age. Somehow the genetic makeup of individuals combines with nongenetic (environmental) factors to cause schizophrenia.

Neurotransmitters

Many studies have investigated the possible role of brain neurotransmitters in the development of schizophrenia. Most of these studies have focused on the neurotransmitter called dopamine. The "dopamine theory of schizophrenia" states that schizophrenia is caused by an overactive dopamine system in the brain. There is strong evidence that supports the dopamine theory, but there are also some data that do not support it:

Evidence FOR the Dopamine Theory of Schizophrenia:

1. Drugs that block dopamine reduce schizophrenic symptoms.
2. Drugs that block dopamine have side effects similar to Parkinson's disease. Parkinson's disease is caused by a lack of dopamine in a parts of the brain called the basal ganglia.
3. The best drugs to treat schizophrenia resemble dopamine and completely block dopamine receptors.
4. High doses of amphetamines cause schizophrenic-like symptoms in a disorder called "amphetamine psychosis." Amphetamine psychosis is a model for schizophrenia because drugs that block amphetamine psychosis also reduce schizophrenic symptoms. Amphetamines also make the symptoms of schizophrenia worse.
5. Children at risk for schizophrenia may have brain wave patterns similar to adults with schizophrenia. These abnormal brain wave patterns in children can be reduced by drugs that block dopamine receptors.

Evidence AGAINST the Dopamine Theory of Schizophrenia:

1. Amphetamines do more than increase dopamine levels. They also alter other neurotransmitter levels.
2. Drugs that block dopamine receptors act on receptors quickly. However, these drugs sometimes take many days to change the behavior of people with schizophrenia.
3. The effects of dopamine blockers may be indirect. These drugs may influence other systems that have more impact on the schizophrenic symptoms.
4. New drugs for schizophrenia, for example, clozapine, block receptors for both serotonin and dopamine.

Possible Side Effects of Antipsychotic Drugs

1. Parkinson's disease-like symptoms - tremor, muscle rigidity, loss of facial expression
2. Dystonia - contraction of muscles
3. Restlessness
4. Tardive dyskinesia - involuntary, abnormal movements of the face, mouth, and/or body. This includes lip smacking and chewing movements. About 25-40% of patients who take antipsychotic mediations for several years develop these side effects.
5. Weight gain
6. Skin problems

Counseling

Antipsychotic medications often do not reduce all of the symptoms of schizophrenia. Also, because people with schizophrenia may have become ill during the time when they should have developed technical skills and a career, they may have difficulties working with other people. Therefore, psychological therapy, family therapy and occupational training may be used along with antipsychotic medication to help these people get back into the community.

Hear IT!	Catatonia	Delusion	Dopamine	Hallucination
Psychosis	Schizophrenia	Serotonin	Tardive Dyskinesia

References:

1. Coleman, M. and Gillberg, C. The Schizophrenias. A biological approach to the schizophrenia spectrum disorders. New York: Springer, 1996.
2. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Washington, D.C.: American Psychiatric Association, 1994.
3. Keefe, R.S.E. and Harvey, P.D. Understanding Schizophrenia. A guide to the new research in causes and treatment. New York: Free Press, 1994.
4. Kety, S.S., Rosenthal, D., Wender, P.H. and Schulsinger, F. The types and prevalence of mental illness in the biological and adoptive families of adopted people with schizophrenia. In D. Rosenthal and S.S. Kety (eds.), The Transmission of Schizophrenia, New York: Pergamon Press, 1968.
5. Smith, D.W. Schizophrenia. New York: Franklin Watts, 1993.

Which neurotransmitter imbalance occurs in a patient with schizophrenia?

When is the first episode of schizophrenia most likely to occur?

Which of the following brain abnormalities is suggested to be a cause of schizophrenia?

What is dopamine overactivity most like?