SCHIZOPHRENIA

What is Schizophrenia?

According to the DSM-5 (American Psychiatric Association, 2013), to be diagnosed with schizophrenia, someone must have deteriorated in everyday functioning (work, interpersonal relations, self-care, etc.) for at least 6 months for reasons not attributable to other disorders. The person must also have at least two symptoms from the following list, including at least one from the first three:

  • Delusions (unjustifiable beliefs, such as “Beings from outer space are

  • controlling my actions”)

  • Hallucinations (false sensory experiences, such as hearing voices when alone)

  • Disorganized speech (rambling or incoherent)

  • Grossly disorganized behavior

  • Weak emotional expression, speech, and socialization

The first four items on the list—delusions, hallucinations, disorganized speech, and disorganized behavior—are called positive symptoms, meaning behaviors that are present that should be absent. Weak emotional expression, speech, and socialization are negative symptoms—behaviors that are absent that should be present.

Cognitive symptoms may include trouble maintaining and focusing attention and difficulty understanding and using abstract concepts. that is, they interpret sayings too literally. Also, memory impairments are also common, related to reduced connectivity between sensory areas of the cortex and the hippocampus.

GENETICS AND SCHIZOPHRENIA

Many researchers believed that schizophrenia might be a genetic disease in the same sense. However, accumulating evidence indicates it does not depend on any single gene. People with a closer genetic relationship to someone with schizophrenia have a higher probability of developing it themselves. (Source: Based on data from Gottesman, 1991)

THE NEURODEVELOPMENTAL HYPOTHESIS

States that prenatal or neonatal influences—genetic, environmental, or both— produce abnormalities in the developing brain. Even if these abnormalities by themselves do not cause schizophrenia, they leave the brain vulnerable to other disturbances at critical periods in childhood or adolescence. (Davis et al., 2016). The cumulative eƯect distorts brain function, and therefore behavior (Fatemi & Folsom, 2009; Weinberger, 1996).

Supporting evidence for the neurodevelopmental hypothesis includes:

  • Several kinds of prenatal or neonatal difficulties are linked to later schizophrenia.

  • People with schizophrenia have minor brain abnormalities that originate early in life.

  • Abnormalities of early development could impair behavior in adulthood.

PRENATAL AND NEONATAL ENVIRONMENT

TOXOPLASMA GONDII

This parasite reproduces only in cats, but it can infect humans and other species also. People can be exposed to the parasite by handling infected cats, by playing in soil or sand where cats have defecated, or by eating chicken or pork after those animals fed in infected soil. If the parasite infects the brain of an infant or child, it impairs brain development. Antibodies against this parasite, indicating past exposure to it, are more common than average among people who have schizophrenia, major depression, bipolar disorder, or obsessive compulsive disorder (Kramer & Bressan, 2015; Sutterland et al., 2015; Yolken, Dickerson, & Torrey, 2009).

LOW RISK FACTORS

  • Poor nutrition of the mother during pregnancy.

  • Premature birth.

  • Low birth weight.

  • Complications during delivery.

  • Head injuries in early childhood

  • Extreme stress of mother during pregnancy

  • Mother/child blood type differences increase the likelihood of

    schizophrenia.

  • If the mother has a Rh-negative blood type and the baby is Rh-positive,

    the child has about twice the probability of developing schizophrenia.

  • Response weak in first child but stronger in later pregnancies

MILD BRAIN ABNORMALITIES

Many, but not all, people with schizophrenia show mild, variable abnormalities of brain anatomy, including less than average gray matter, especially in the hippocampus, amygdala, and thalamus (van Erp et al., 2016). White matter is reduced, and the ventricles (fluid-filled spaces within the brain) are enlarged (Kochunov & Hong, 2014; Meyer Lindenberg, 2010; Wolkin et al., 1998; Wright et al., 2000) Minor abnormalities in subcortical areas are also common (Spoletini et al., 2011).

Abnormalities visible in the blood vessels of the retina imply less than average blood flow to the brain (Meier et al., 2013). The abnormalities are mild compared to those in people with Alzheimer’s disease or many other disorders. On average, brain volume is only about 5 percent smaller than average, and many people show little or no anatomical abnormality. (Woodward, 2016)

The brain areas with consistent signs of abnormality include some that mature slowly, such as the dorsolateral prefrontal cortex (Berman, Torrey, Daniel, & Weinberger, 1992; Fletcher et al., 1998; Gur et al., 2000). In addition, most patients with schizophrenia show deficits of memory and attention similar to those of people with damage to the temporal or prefrontal cortex (Park, Holzman, & Goldman-Rakic, 1995).

The season-of-birth refers to the tendency for people born in winter to have a slightly (5% to 8% greater probability of developing schizophrenia)

  • More pronounced by complication of delivery, nutritional factors, or increased likelihood of viral infection in mother

  • Viral infections in mother can:

    • Increase cytokines in mother that impair brain development of fetus.

    • Cause fever which damage the fetal brain

ARE BRAIN ABNORMALITIES IN SCHIZOPHRENIA BECOME GRADUALLY WORSE AS PEOPLE AGE?

Some studies report that a few brain areas deteriorate over age slightly more than is typical for people of the same age (van Haren et al., 2016). Most of the abnormality of both brain and behavior is present at the time of first diagnosis, with some further impairment in the next couple of years, but only slight deterioration after that in most patients. Even when further deterioration does occur, it could be a result of drug use (common in people with schizophrenia) rather than a result of schizophrenia itself.

Why are most cases not diagnosed until age 20 or later?

Dorsolateral prefrontal cortex, an area that shows consistent signs of deficit in schizophrenia, is one of the slowest brain areas to mature. Most of the people who receive a diagnosis of schizophrenia in adulthood had shown other problems since childhood, including deficits in attention, memory, and impulse control . These relatively minor problems developed into more serious problems later.

DOPAMINE HYPOTHESIS OF SCHIZOPHRENIA

Schizophrenia results from excess activity at dopamine synapses in certain brain areas. Although the concentration of dopamine in the brain as a whole is no higher than normal, dopamine release is increased in the basal ganglia, especially in response to stressful events. Extensive abuse of amphetamine, methamphetamine, or cocaine (which all increase dopamine at the synapses) induces substance-induced psychotic disorder, characterized by hallucinations and delusions. LSD, which also produces psychotic symptoms, is best known for its eƯects on serotonin synapses, but it also stimulates dopamine synapses.

GLUTAMATE HYPOTHESIS OF SCHIZOPHRENIA

The problem relates in part to deficient activity at glutamate synapses in the prefrontal cortex. In many brain areas, dopamine inhibits glutamate release, or glutamate stimulates neurons that inhibit dopamine release. Therefore, increased dopamine could produce nearly the same eƯects as decreased glutamate.