Understanding Schizophrenia

• Schizophrenia affects approximately 7-8 out of every 1000 people at some point.
• Schizophrenia is less common than other disorders like depression, but it leads to significant compromise in quality of life.
• Schizophrenia occurs worldwide in all ethnic groups.
• Men are more commonly diagnosed with schizophrenia than women at a ratio of 7:5.
• Schizophrenia tends to be more severe in men.
• Men typically experience an earlier onset of schizophrenia, before age 20, while women tend to develop it after age 25.
• Although schizophrenia is usually diagnosed in early adulthood, mild problems often begin in childhood.
• These early issues include deficits in attention, memory, and impulse control.
• Approximately 25% of individuals with schizophrenia experience a serious disorder throughout life.
• 10-20% of individuals recover completely from a first episode, while 55-65% experience one or more remissions and relapses.
• According to the DSM-5, a diagnosis requires deterioration in everyday functioning for at least 6 months, for reasons not attributable to other disorders.
• The diagnosis requires at least two symptoms from a specified list, with at least one from the first three.
• The symptoms of schizophrenia can be delusions, hallucinations, disorganized speech, grossly disorganized behavior, and weak or absent signs of emotion, speech, and socialization.
• Delusions are unjustifiable beliefs, often of a social nature, such as the feeling that outer beings are controlling one's actions.
• Hallucinations are false sensory experiences, such as hearing voices when alone.
• Disorganized speech involves rambling or incoherent language.
• Grossly disorganized behavior is another diagnostic symptom.
• Weak or absent signs of emotion, speech, and socialization are also considered.
• "Positive" symptoms include delusions, hallucinations, disorganized speech, and disorganized behavior.
• Positive symptoms refer to behaviors that are present but should be absent.
• "Negative" symptoms include weak or absent emotions, speech, and socialization.
• Negative symptoms refer to behaviors that are absent but should be present.
• Individuals with schizophrenia can differ immensely from each other in genetic and brain abnormalities.
• Schizophrenia is associated with cognitive dysfunctions such as slow processing speed, impaired long-term memory, and difficulty processing other's emotions.
• Further cognitive dysfunctions associated with schizophrenia include, errors in perceiving other's intentions and beliefs, and Attention problems.
• Although cognitive dysfunction is common, it is not central to the diagnosis of schizophrenia.

Differential Diagnosis

• When diagnosing schizophrenia, it is necessary to rule out conditions like substance abuse, brain damage, hearing deficits, Huntington's disease and nutritional abnormalities.

Genetics

• Current evidence suggests that schizophrenia has a genetic basis, although it does not depend on a single gene.
• Three study routes of schizophrenia's genetics include family studies, adopted children who develop schizophrenia and efforts to locate a gene

Genetics: Family Studies

• A close biological relationship to someone with schizophrenia increases the probability of developing the condition.
• Being closely related to someone with bipolar disorder can also increase the risk of schizophrenia.
• Monozygotic twins share a higher concordance rate for schizophrenia than dizygotic twins.
• Twin pairs who are monozygotic but thought they are not, are more concordant compared to pairs who thought they were monozygotic, but actually are not.
• Greater similarity is apparent between dizygotic twins (17%) than between siblings (9%) despite the genetic resemblance.
• Dizygotic twins have greater environmental similarity, including a shared prenatal environment.

Genetics: Adopted Children

• For adopted children who develop schizophrenia, the disorder is more common in biological relatives.
• This suggests a genetic basis but remains consistent with a prenatal influence.
• Many women with schizophrenia have unhealthy habits during pregnancy, so if their children develop schizophrenia, it is difficult to know if it is caused by genetics.

Genetics: Efforts to Locate a Gene

• Researchers have identified hundreds of differing genetic loci between individuals with and without schizophrenia.
• These loci include many that code for proteins in the brain.
• Results vary due to genes common in some ethnicities but not others.
• People with schizophrenia have fewer children than other people, and their siblings do not compensate by having more children.
• Geneticists rarely find variants in genes because the variants decrease survival or reproduction, but such variants still occur in people with schizophrenia.
• A few rare genes are known to greatly increase the risk of schizophrenia, mostly by disrupting the development of glutamate synapses or by interfering with the immune system.
• DISC1 controls differentiation and migration of neurons in brain development.
• DISC1 controls production of dendritic spines, generation of new neurons in the hippocampus, and learning.
• Rare variants in DISC1 are more common in people with schizophrenia.
• A de novo mutation in one gene is rare, but a mutation in any of several hundred genes for brain development is not.
• Microdeletion, the deletion of a small part of a chromosome, is a likelier possibility.

Environmental Influences

• The neurodevelopmental hypothesis suggests that prenatal or neonatal influences, genetic, environmental, or both, can produce abnormalities that leave the developing brain vulnerable to disturbances.
• The disturbances that result may include highly stressful experiences.
• The "two-hit hypothesis" proposes that schizophrenia results from a combination of genetic predisposition and environmental impacts.
• The environmental impacts occur during prenatal/neonatal development, later in life, or both.
• Most cases of schizophrenia are not diagnosed until age 20 or later.

Prenatal or Early Postnatal Factors

• Prenatal or early postnatal factors include poor maternal nutrition during pregnancy, prematurity, low birth weight, and complications in delivery.
• Factors also include extreme maternal stress or prolonged illness during pregnancy, head injury during childhood, and being an Rh- mother with an Rh+ baby.
• Season of birth effect: tendency for people born in winter potentially have a slightly greater probability for schizophrenia.
• Increased incidence of influenza among mothers whose children eventually developed schizophrenia.
• A virus may or may not cross the placenta, but the mother's cytokines do cross, and excessive cytokines can impair brain development.
• Effects of prenatal or early postnatal factors may show up in adulthood, and fever slows down the division of fetal neurons.

Factors Later in Life

• Stressful experiences may contribute to the vulnerability to schizophrenia.
• Immigrants to countries like Britain or the Netherlands have an increased probability of developing schizophrenia, and so do their children.
• Entering a new country with a different language, customs, and diet can be stressful, adding to the potential of encountering unfair discrimination.
• Other factors that may contribute to the development of schizophrenia later in life include head injury during childhood, Borna disease virus, and Toxoplasma gondii.

Mild Brain Abnormalities

• Mild abnormalities in schizophrenia include less overall gray matter and white matter.
• Larger-than-average ventricles.
• Minor abnormalities in subcortical areas.
• Smaller hippocampi.
• Deficits of memory and attention that align with damage to the prefrontal cortex
• At the beginning, patients had areas of increased metabolism (i.e., increased glutamate release) in their hippocampi.
• Later these areas showed atrophy

Neurodevelopmental-Hypothesis

• Weaker connections exist between the dorsolateral prefrontal cortex and other brain area.
• Less than normal activity occurs in this area during tasks of attention and memory.
• A person preforms poorly in tasks that depend on the prefrontal cortex, such as the Wisconsin Card Sorting Test.
• Right planum temporale slightly larger.
• Lower than normal activity exists in the left hemisphere.
• A person is more likely to be left-handed.

Treatments: Antipsychotic Drugs

• Two chemical families of antipsychotic/neuroleptic drugs include phenothiazines (including chlorpromazine) and butyrophenomes (including haloperidol).
• Behavioral benefits of antipsychotic/neuroleptic drugs develop gradually over a month.
• Symptoms may or may not return after treatment cessation.

Dopamine Hypothesis

• Schizophrenia results from excess activity at dopamine synapses in certain areas of the brain, such as the basal ganglia.
• Hallucinations and delusions result from repeated large doses of amphetamines, methamphetamines, or cocaine, which prolong activity at dopamine synapses.
• People with schizophrenia have excessive activity at D2 receptors.

Glutamate Hypothesis

• Schizophrenia relates partially to deficient activity at glutamate synapses, especially in the prefrontal cortex.
• Dopamine inhibits glutamate release, alternately, glutamate stimulates neurons that inhibit dopamine release.
• Increased dopamine thus produces the same effects as decreased glutamate.
• Studies have consistently found decreased glutamate release in the prefrontal cortex of people with schizophrenia.
• PCP, a drug that inhibits NMDA glutamate receptors, produces intoxication and slurred speech at low doses.
• At high doses, PCP produces both positive and negative symptoms of schizophrenia, including hallucinations, thought disorder, loss of emotions, and memory loss.