Schizophrenia

Schizophrenia is a disorder characterized by disordered thinking and odd perceptions that cause dysfunction in major activities, sometimes including withdrawal from the world, delusions, and hallucinations.

ANATOMY OR SYSTEM AFFECTED: Brain, psychic-emotional system

CAUSES: Genetic factors; possible environmental factors

SYMPTOMS: Varies; may include withdrawal, delusions, hallucinations, thought disorders, inability to show emotion or feel pleasure or pain, total apathy, lack of facial expression, depression, mania, paranoia

DURATION: Typically chronic

TREATMENTS: Psychotherapy, drug therapy

Background

Schizophrenia is a disorder affecting the brain and mind. Eugen Bleuler (1857–1939), a Swiss psychiatrist, first named the disease in a 1908 paper that he wrote titled "Dementia Praecox: Or, The Group of Schizophrenias." In 1911, he published a book with the same title describing the disease in more detail. Bleuler served as the head of an eight hundred–bed mental hospital in Switzerland and treated the worst and most chronic cases. Beginning in 1896, he embarked on a project to understand the inner world of those experiencing mental illness. He developed work therapy programs for his patients, and he visited them and talked to them almost every day. Bleuler insisted that the hospital staff show the same kind of dedication and support for his clients that he did.

Bleuler's discoveries challenged the traditional view of the causes and treatment of the disease. The traditional view, based on the work of the great German psychiatrist Emil Kraepelin (1856–1926), held that dementia, as it was called, always got worse and that the patient's mind continued to degenerate until death. Kraepelin suggested that the disease, which he called dementia praecox, was hereditary and was the result of a poisonous substance that destroyed brain cells. Bleuler's investigation of those living with the condition led him to reject this view. Instead, he argued, continuing deterioration does not always take place because the disease can stop or go into remission at any time. The disease does not always follow a downhill course. Bleuler's views promised more hope for patients diagnosed with schizophrenia.

The word "schizophrenia" can roughly be translated to mean "split mind." This does not mean, however, that individuals with schizophrenia have two or more personalities or minds. Instead, it refers to how individuals with schizophrenia experience the world: the world can be one way in their mind and another way in what is going on around them.

Symptoms and Causes

The symptoms of schizophrenia are more well known than the cause. Diagnosis is based on a characteristic set of symptoms that must last for at least several months. According to the National Institute of Mental Health, the "psychotic symptoms" include a break with reality, altered perceptions, hallucinations, delusions, or evidence of thought disorder or movement disorder. These symptoms are referred to as positive symptoms because they are highly visible and not present in people without the disease. Negative symptoms, which are less readily observed and involve a decrease in normal functions, include withdrawal from society, the inability to show emotion or to feel pleasure or pain, total apathy, and lack of facial expression or differentiated voice tones (also known as "flat affect"). A person with negative symptoms might be found simply sitting and staring blankly at the world, no matter what is happening. Various cognitive, or disorganized, symptoms may or may not be present, including difficulty paying attention, poor working memory, and limited ability to process information and make informed decisions (executive functioning).

Schizophrenia can take many forms. Over the years psychiatrists attempted to categorize the disease into distinct subtypes based on the types of symptoms displayed, and some of the terms developed entered common usage. Melancholia referred to the presentation of depression and hypochondriacal delusions, with the patient claiming to be extremely physically ill but having no appropriate symptoms. Catatonia was the generalized category in which patients become immobile and seem fixed in one rigid position for long periods of time. Paranoid schizophrenia referred to the presence of delusional states accompanied by hallucinations frequently involving imagined voices, which often scream and shout abusive and derogatory language at the patient or make outrageous demands. Hebephrenic, or disorganized, schizophrenia grouped together those who experienced disorders of thinking and frequent episodes of incoherent uttering of incomprehensible sounds or words. However, the great variety and overlap among and within cases made these classifications of little use. In 2013 the American Psychiatric Association (APA) removed all subtypes from the fifth edition of its Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

In addition to the symptoms listed above, other issues often present in schizophrenia include disconnected speech patterns, broken sentences, excessive body movement, and purposeless activity. Those living with the disease may also experience states of extreme anger and hostility. Cursing and outbursts of uncontrolled rage can result from relatively insignificant causes, such as someone looking at them "in the wrong way." Many times, anniversaries of important life experiences, such as the death of a parent or the birthday of a parent or of the patient, can set off positive and negative symptoms. Hallucinations and mania can also follow traumatic events such as childbirth or combat experiences during war.

Schizophrenia can start at different times in different people. Generally, however, the disease develops during late adolescence. Men typically show signs of schizophrenia earlier than women, usually in the late teens or early twenties. In women, symptoms may not appear until the mid-twenties and sometimes are not evident until age thirty. For both sexes, in rare cases there are signs in childhood or onset after the age of forty-five. People who later develop schizophrenia tended to be withdrawn and isolated as children and were often made fun of by others. Not all withdrawn children develop the disease, however, and there is no guaranteed way to predict who will get it and who will not. Some risk factors are thought to include use of psychoactive drugs in adolescence or young adulthood, a heightened immune system, and being exposed to dangers such as malnutrition, viruses, or toxic substances before birth.

The cause of schizophrenia is not fully understood, but it is thought to be at least partially a genetic disease due to its tendency to run in families. Individuals with the disease are more likely to have close relatives—mothers, fathers, brothers, sisters, cousins, grandmothers, or grandfathers—with the disorder. According to the US National Institute of Mental Health (NIMH) and the National Alliance on Mental Illness, schizophrenia occurs in less than 1 percent of the general population, but it occurs in roughly 10 percent of individuals with a first-degree relative (parent, sibling) who has the disorder. The risk increases most notably when one has an identical twin with schizophrenia; an individual then has about a 40 percent chance of developing the disorder. Still, many people with schizophrenia in their family do not develop the disease, and many who are diagnosed have no family history. This leads most researchers to assume that no single gene is responsible for the condition; instead, a complex interaction of genetics and other factors can trigger schizophrenia.

As to why the disease develops later in life rather than at birth, investigators provide the following information. First, the brain develops more slowly than other organs and does not stop developing until late adolescence. Many genetic diseases remain dormant until later in life, such as Huntington's disease and multiple sclerosis (MS). The brain changes triggered by puberty may also play a significant role in the onset of schizophrenia.

Schizophrenia is thought to possibly operate by disrupting the way in which brain cells communicate with each other. The neurotransmitters that carry signals from one brain cell to another might be abnormal in those with the disease. Malfunction in one of the transmitters, dopamine, seems to be a source of the problem, though the issue is not fully understood. The connection is suspected because the major medicines that are successful in the treatment of schizophrenia limit the production or carrying power of dopamine. The neurotransmitter glutamate may also be involved. Another likely suspect is serotonin, a transmitter whose presence or absence has important influences on behavior.

In 2003 researchers announced that they had discovered clues that pointed to a specific gene with a possible role in causing schizophrenia. The gene is known as dysbindin, and it is involved in the operation of the synapses, the points where one neuron wires itself to another. The team found that genetic variations in the dysbindin gene were more common among schizophrenic patients. Medical research is increasingly pinpointing regions, or loci, within chromosomes that contain genetic mutations, a task that has proven difficult in years past. Since the human genome sequence has become available, however, research groups have started to focus on the same handful of loci, suggesting that they could be seeing a true signal for the disease. The gene dysbindin has been located in these limited chromosomal regions. Moreover, Icelandic researchers discovered a gene called neuregulin-1 that also tends to cluster in specific loci. Mutations in this gene are highly correlated with schizophrenia in about 15 percent of Icelandic patients. Other disregulated genes have also been linked to schizophrenia. Scientists believe that no one single factor causes the schizophrenia; however, there are multiple "susceptibility" genes that may make a person more vulnerable to the disorder.

Treatment and Therapy

Since the 1950s, many medications have been developed that are very effective in treating the symptoms of schizophrenia. Antipsychotic drugs can be used to treat both positive and negative symptoms. Some of the early medications used to treat positive symptoms include haloperidol (Haldol), fluphenazine (Prolixin), chlorpromazine (Thorazine), thioridazine (Mellaril), tiotixene (Navane), and trifluoperazine (stelazine). These medications work by blocking the production of excess dopamine, which may cause the positive symptoms, or by stimulating the production of the neurotransmitter, which reduces negative symptoms. These drugs are nonaddictive and do not provide a high or euphoric effect of any kind.

The chief problem resulting from the use of such drugs is the strong side effects that they can produce. The most dreaded side effect, from the patient's perspective, is tardive dyskinesia (TD), which emerges only after many years of use and is characterized by involuntary movement of muscles, frequent lip-smacking, facial grimaces, and constant rocking back and forth of the arms and the body. It is completely uncontrollable. Dystonia is another side effect. Symptoms include the abrupt stiffening of muscles, such as in the arms, neck, and face. Most of these effects can be controlled or reversed with antihistamines. Some patients receiving medication are afflicted with effects similar to movements associated with Parkinson's disease. They experience the slowing of movements in their arms and legs, tremors, and muscle spasms. Their faces seem frozen into a sad, masklike expression. These effects can be treated with medication.

Another problem is akathisia, a feeling developed by many patients that they cannot sit still. Their jumpiness can be treated with benzodiazepines such as Valium or Xanax. Benzodiazepines are addictive substances, so their use must be monitored by health professionals and caregivers. Many side effects are so severe that patients cite them as the major reason that they do not take their medicine.

Because of the potentially major side effects of traditional, or typical, antipsychotic medications, various newer drugs known as atypical antipsychotics later came into favor. These drugs include aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon). Clozapine, for example, can be used for both positive and negative symptoms, as it blocks both dopamine and serotonin. However, these drugs are not without risks of their own; some patients treated with clozapine may experience agranulocytosis, or the loss of white blood cells; therefore, people using this medication should have their white blood cell counts checked frequently. Later atypical antipsychotics had lower risk of major side effects, but doctors continue to debate whether typical or atypical antipsychotics are the best treatment for schizophrenia. The lower cost of typical antipsychotics may make them more practical over the life-long course of treatment required. Antidepressants and anti-anxiety medications may also be prescribed in some cases. In addition, there are also several long-acting injectable antipsychotics, which are administered through an intramuscular or subcutaneous injection every two to four weeks. This type of medication includes aripirazole (Abilify Maintena, Aristada), fluphenazine decanoate, haloperidol decanoate, paliperidone (Invega Sustenna, Invega Trinza), and risperidone (Risperdal Consta, Perseris).

While drugs are commonly prescribed, psychotherapy can also be effective and beneficial to many patients. Some further report great value in family or rehabilitation therapy. These therapies are not intended to cure the disease or to "fix" the family dynamic. Instead, they are aimed at helping families learn how to live with and emotionally support family members with mental illness. Family support is important for those diagnosed with schizophrenia because many are unable to live on their own. Therapy can also help family members understand and deal with their own frustration that accompanies having a family member that experiences severe mental illness. Rehabilitation therapy or social skills training attempts to teach patients the social, coping, and vocational skills that they need to become more independent within society.

The results of treatment are not always positive, even with medication and therapy. According to the Substance Abuse and Mental Health Services Administration, suicide is the leading cause of premature death among patients with schizophrenia. However, new treatments that may be more effective are being developed. The problem with most antipsychotic medications is their side effects, such as movement disorders and weight gain. Muscarinic receptor antagonists stimulate receptors in the brain that play a role in schizophrenia. This reduces symptoms as well as side effects.

Perspective and Prospects

Hopes for improving the treatment of schizophrenia rest mainly on the continuing development of new drugs and therapies, as well as genetic research. Much research has focused on the potential of electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS), especially for those who do not respond to drug therapy. Studies also suggest that psychotherapy directed at improving social skills and reducing stress helps many people with the disease to improve the quality of their lives as much as drugs can. It is known that stress-related emotions lead to increases in delusions, hallucinations, social withdrawal, and apathy. Therapists can help patients find ways of dealing with stress and living in communities. They can encourage their patients to deal with feelings of hostility, rage, and distrust of other people. Various modes of family therapy can teach all members of a family how to live with a family member who experiences mental illness.

One study of ninety-seven individuals with schizophrenia who lived with their families, received individual therapy, and took their medications showed far fewer recurrences of acute symptoms than did a group that did not get such help. Among those fifty-four individuals who received therapy but lived alone or with nonfamily members, schizophrenia symptoms reappeared or worsened over the same three-year period of the study. People living alone usually had more severe symptoms to start out with and found it difficult to find housing, food, or clothing, even with therapy.

In 2015, researchers at the University of Cambridge began experimenting with a novel method for treating the cognitive impairments associated with schizophrenia. Because drugs to treat such symptoms had not yet been developed, researchers used technology to create a tablet computer app that could potentially improve the memory of patients. The game, titled Wizard, was intended to support the patient's episodic memory through a motivating, interesting, and approachable concept. This idea illustrates the variety of ongoing efforts to help those with schizophrenia live fuller lives.

Research on the social impacts of schizophrenia has also gained increasing attention. For example, in contrast to the persistent stereotype associating mental illness with violent behavior, numerous studies indicated that people with mental illness are far more likely to be victims of crime than perpetrators. Yet some studies also suggested those with schizophrenia can in some cases be at higher risk of committing a violent crime, especially when also facing substance abuse and other risk factors with complex social implications. The high-profile opioid epidemic and homelessness crisis of the 2010s and 2020s also drew further scrutiny of the ways in which schizophrenia can intersect with such issues. A 2019 meta-analysis study found high prevalence of schizophrenia and other psychotic disorders among homeless people, for instance. Other studies have found those with schizophrenia to be at higher risk of unemployment and poverty. Such social challenges can in turn further fuel stigmatization and exclusion.

Some mental health professionals and activists have aimed to help destigmatize schizophrenia by advocating for a name change of the disorder. For example, in 2002 the Japanese Society of Psychiatry and Neurology changed its terminology to "integration disorder." In a 2021 study published in Schizophrenia Research, a group of Harvard researchers argued that the name schizophrenia is prejudiced and leads to the perception that those with the disorder are violent, desperate, and dangerous. The study also argued that the literal meaning of schizophrenia, "split mind," is outdated and does not accurately describe the neurobiology behind the disorder. The authors of the study surveyed 1,190 people with either personal or professional experience with schizophrenia and found that 74.1 percent of responders favored changing the name of the disorder and that 71.4 percent agreed that the name was stigmatizing. However, experts in the field were divided on the issue, with some suggesting that changing the name of the disorder would have little positive effect and could potentially lead to complications with future diagnoses.

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