eMedicine Specialties > Psychiatry > Adult

Schizophrenia

Author: Frances R Frankenburg, MD, Associate Professor, Department of Psychiatry, Boston University School of Medicine; Chief of Inpatient Psychiatry and Consulting Psychiatrist, Edith Nourse Rogers Memorial Veterans Administration Medical Center; Associate Psychiatrist, McLean Hospital
Contributor Information and Disclosures

Updated: Sep 10, 2009

Introduction

Background

Schizophrenia is a severe, persistent, debilitating, and poorly understood psychiatric disorder that probably consists of several separate illnesses. Symptoms include disturbances in thoughts (or cognitions), mood (or affects), perceptions, and relationships with others. The hallmark symptoms of schizophrenia are auditory hallucinations and delusions, which are fixed false beliefs. Impaired information processing is a less vivid symptom that is highly disruptive. People with schizophrenia have lower rates of employment, marriage, and independent living than other people. For more information, see Medscape's Schizophrenia Resource Center.

Case study

John P is a 25-year-old male with the diagnosis of schizophrenia. He was a healthy child, but his parents report that he was a bedwetter and seemed slower to develop than his brothers and sisters. A maternal uncle has also been diagnosed with schizophrenia.

John had 2 brief hospitalizations in his late teens that were precipitated by anger at his boss, depression, and voices in his head. He found the hospital stays unhelpful. He was treated with haloperidol which gave him dystonic symptoms; he was then treated with olanzapine and gained 20 pounds and developed diabetes mellitus.

John smokes marijuana and tobacco frequently to calm himself; he also drinks vodka.

John's parents support him financially. His brothers are sisters are angry and frightened of him and have nothing to do with him. They are particularly upset by his lack of interest in the outside world. John lives in a boarding home and works in a sheltered workshop with difficulty.

John sees a psychiatrist for 15 minutes every 2 months but sometimes misses his appointment. He has a social worker whom he sees often. The psychiatrist would like to switch him to long-acting injectable antipsychotic treatment, but John is afraid of injections and isn't sure that he needs medication. He usually misses his appointments with his primary care physician.

Pathophysiology

Neuroimaging studies have demonstrated anatomical abnormalities in patients with schizophrenia. Bilateral ventriculomegaly and decreased brain volume exist in medial temporal areas such as the hippocampus and amygdala.¹  Because of the large overlap between the healthy and the schizophrenia brain these findings are of greater research interest than clinical use.

Interest has also focused on the various connections within the brain rather than localization in one part of the brain. Indeed, neuropsychological studies show impaired information processing in schizophrenia, and MRI studies show anatomic abnormalities in a network of neocortical and limbic regions and interconnecting white matter tracts.²

The first clearly effective antipsychotic drugs, chlorpromazine and reserpine, were structurally different from each other, but they shared antidopaminergic properties. Drugs that diminish the firing rates of mesolimbic dopamine D2 neurons are antipsychotic, and drugs that stimulate these neurons (eg, amphetamines) exacerbate psychotic symptoms. Therefore, abnormalities of the dopaminergic system are thought to exist in schizophrenia; however, little direct evidence supports this. This theory has recently undergone considerable refinement.

Hypodopaminergic activity in the mesocortical system, leading to negative symptoms, and hyperdopaminergic activity in the mesolimbic system, leading to positive symptoms, may coexist. (Negative and positive symptoms are defined below.) Moreover, the newer antipsychotic drugs block both dopamine D2 and 5-hydroxytryptamine (5-HT) receptors. Clozapine, perhaps the most effective antipsychotic agent, is a particularly weak dopamine D2 antagonist. Undoubtedly, other neurotransmitter systems, such as norepinephrine, serotonin, and gamma-aminobutyric acid (GABA), are involved. Some research focuses on the N -methyl-D-aspartate (NMDA) subclass of glutamate receptors because NMDA antagonists, such as phencyclidine hydrochloride and ketamine, can lead to psychotic symptoms in healthy subjects.³

Frequency

International

The prevalence of schizophrenia is approximately 1% worldwide.

Mortality/Morbidity

People with schizophrenia have a 10% lifetime risk of suicide. Mortality is also increased because of medical illnesses, due to a combination of unhealthy lifestyles, side effects of medication, and decreased health care.

Race

No known racial differences exist in the prevalence of schizophrenia. Some research indicates that schizophrenia is diagnosed more frequently in black people than in white people. This finding has been attributed to cultural bias of practitioners.

Sex

The prevalence of schizophrenia is about the same in men and women. The onset of schizophrenia is later and the symptomatology is less severe in women than in men. This may be because of the antidopaminergic influence of estrogen.

Age

The onset of schizophrenia usually occurs in adolescence, and symptoms remit somewhat in older patients. Most of the deterioration that occurs in patients with schizophrenia occurs in the first 5-10 years of the illness and is usually followed by decades of relative stability, although a return to baseline is unusual. Positive symptoms are more likely to remit than cognitive and negative symptoms. 

Clinical

History

• Information about the medical and psychiatric history of the family, details about pregnancy and early childhood, history of travel, and history of medications and substance abuse are all important. This information is helpful in ruling out other causes of psychotic symptoms.
• The patient usually had an unexceptional childhood but began to experience a noticeable change in personality and a decrease in academic, social, and interpersonal functioning during mid-to-late adolescence. In retrospect, family members may describe the person with schizophrenia as a physically clumsy and emotionally aloof child. The child may have been anxious and preferred to play by himself or herself. The child may have been late to learn to walk and may have been a bedwetter.^4,5
• Usually, 1-2 years pass between the onset of these vague symptoms and the first visit to a psychiatrist.⁶
• The first psychotic episode usually occurs between the late teenage years and mid 30s.
• The symptoms of schizophrenia may be divided into the following 4 domains:
  1. Positive symptoms: These include psychotic symptoms, such as hallucinations, which are usually auditory; delusions; and disorganized speech and behavior.
  2. Negative symptoms: These include a decrease in emotional range, poverty of speech, loss of interests, and loss of drive. The person with schizophrenia has tremendous inertia.
  3. Cognitive symptoms: These include neurocognitive deficits, such as deficits in working memory and attention and executive functions such as the ability to organize and abstract. Patients also have difficulty understanding nuances and subtleties of interpersonal cues and relationships. A new initiative from the National Institutes of Mental Health, known as Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) is a collaboration between various programs to develop tools for measuring cognition in clinical trials and aiding drug development that is targeted at these symptoms.
  4. Mood symptoms: Schizophrenia patients often seem cheerful or sad in a way that does not make sense to others. They often are depressed.

Physical

Findings on a general physical examination are usually not contributory. This examination is necessary to rule out other illnesses.

A neurologic examination is important to evaluate the patient for movement disorders, particularly those that might indicate Wilson disease or Huntington disease, or other disorders that are present, before the initiation of antipsychotic medications. Some patients with schizophrenia have motor disturbances before exposure to antipsychotic agents. Schizophrenia has been associated with left and mixed handedness, minor physical anomalies, and soft neurological signs.

Patients with schizophrenia may show a repertoire of strange and poorly understood behaviors that are rarely observed in others. These include water drinking to the point of intoxication, staring at oneself in the mirror, stereotyped behaviors, hoarding useless objects, self-mutilation, and a disturbed wake-sleep cycle. They often experience difficulty dealing with change.

• On a detailed mental status examination in the office, the following observations are often made when talking with a person with schizophrenia:
  • The person may be dressed oddly, such as wearing heavy jackets in the summer. The person may pay insufficient attention to personal hygiene.
  • This person may be unduly suspicious of the examiner or be very socially awkward.
  • The person may endorse a variety of odd beliefs or delusions.
  • He or she often has a flat affect, meaning that they have little range of expressed emotion.
  • The person may admit to hallucinations or respond to auditory or visual stimuli not apparent to the examiner.
  • The person may show thought blocking in which long pauses occur before answers to questions or odd pauses in the middle of answers.
  • The person's speech may be difficult to follow, because of the looseness of his or her associations. This means that the sequence of thoughts follows a logic that is clear to the patient but not to the interviewer.
  • Conversation and initiation of speech may be limited.
  • Schizophrenia patients may demonstrate their difficulty in abstract thinking by not being able to understand common proverbs. Alternatively, the patient may give an interpretation that turns out to be idiosyncratic and meaningless on further investigation.
  • The speech of a person with schizophrenia can be circumstantial, meaning that the person takes a long time and uses a lot of words in answering a question, or tangential, meaning the person speaks at length but never actually answers the question.
  • The patient often shows poor attention, disorganized thinking, and stereotyped or perseverative thinking.
  • The patient may make odd movements (which may or may not be related to neuroleptic medication).
  • The person has little insight into his or her problems (ie, anosognosia).
  • The person should always be asked about suicide, violence, and homicide—whether or not they are having any thoughts about hurting or harming themselves or others in any way and whether or not they are hearing voices telling them to do so.
  • Attention is intact. (This is important in distinguishing psychosis from delirium.)
  • Orientation (knowing their own identity, where he or she is, and what the time is) is usually intact.
• According to the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), the patient must have experienced at least 2 of the following symptoms: delusions, hallucinations, disorganized speech, disorganized or catatonic behavior, or negative symptoms. Only 1 symptom is required if the delusions are bizarre or if auditory hallucinations occur in which the voices comment in an ongoing manner on the person's behavior, or if 2 or more voices are talking with each other. The patient must experience at least 1 month of symptoms (or less if successfully treated) during a 6-month period, and social or occupational deterioration problems occur over a significant amount of time. These problems must not be attributable to another condition for the diagnosis of schizophrenia to be made.⁷

Causes

• Genetic
  • The risk of schizophrenia is elevated in biological relatives of patients but not in adopted relatives.⁸
  • The risk of schizophrenia in first-degree relatives of people with schizophrenia is 10%.
  • If both parents have schizophrenia, the risk of schizophrenia in their child is 40%.
  • Concordance for schizophrenia is about 10% for dizygotic twins and 40-50% for monozygotic twins.
  • The gene variants that have been so far implicated are responsible for only a small fraction of schizophrenia, and these findings have not always been replicated in different studies. The genes that have been found mostly change a gene’s expression or a protein’s function in a small way. Interactions with the rest of the genome and with environment will doubtless prove to be important.
  • Some loci of particular interest are the following:
    • The catechol-O-methyltransferase (COMT) gene codes for the postsynaptic intracellular enzyme, COMT, which is involved in the methylation and degradation of the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. The several allelic variants of COMT affect its activity. The valine-valine variant degrades dopamine faster than does the valine-methionine variant; subjects with 2 copies of the methionine allele were less likely to develop psychotic symptoms if they used cannabis than other cannabis-using subjects.⁹
    • The RELN gene codes for the protein reelin, which plays a role in brain development and GABAergic activity. In an international study using a genome-wide association scan, a common variant in this gene increased the risk of schizophrenia, but only in women.¹⁰
    • A Canadian group has looked at the gene for nitric oxide synthase 1 adaptor, known as NOS1AP. This gene codes for the enzyme nitric oxide synthetase, which is found in high concentration in inhibitory neurons in the brain. Nitric oxide acts as an intracellular messenger. Using a newly developed statistical technique, the posterior probability of linkage disequilibrium, the authors identified a single nucleotide polymorphism associated with higher levels of expression of this gene in postmortem brain samples.¹¹
• Perinatal
  • Women who are malnourished or who have certain viral illnesses during their pregnancy may be at greater risk of giving birth to children who later develop schizophrenia.
  • Children born to Dutch mothers who were malnourished during World War II have a high incidence of schizophrenia.
  • The 1957 influenza A2 epidemics in Japan, England, and Scandinavia resulted in an increase in schizophrenia in the offspring of women who developed this flu during their second trimester.
  • Women in California who were pregnant between 1959 and 1966 were more likely to have children who developed schizophrenia if they had flu in the first trimester of their pregnancy.¹²
  • Obstetric complications may be associated with a higher incidence of schizophrenia.
  • Children born in the winter months may be at greater risk for developing schizophrenia.¹³

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