Schizophrenia

Chapter 16

Schizophrenia and Affective Disorders

Schizophrenia Description

Schizophrenia:• A serious mental disorder characterized by:

Disordered thoughts

Delusions of persecution or grandeur

Hallucinations (mostly auditory)

Behaviors (withdrawn or detached, odd movements))

Schizophrenia Description

Positive symptom: (known by their presence)• delusions, hallucinations, abnormal movements,

or thought disorders.

Negative symptom: (characterized by absence)• social withdrawal, lack of affect, and reduced

motivation.

Schizophrenia

Possible Causes:• Heritability is a statistical concept that estimates the

relative contribution of genetic factors to variability in a trait (e.g., schizophrenia). It is not a measure of the amount of contribution (e.g., 60% genes vs 40% environment).

• Heritability: In its simplest form, if schizophrenia were determined by a single dominant gene, about 75% of children from schizophrenic parents would get it. If it was recessive, about 50% would inherit the disorder. An incidence less than 50% suggests that the disease is determined by multiple genes and that only a susceptibility is passed on.

Schizophrenia

Evidence for heritability• Concordance rates:

Most studies suggest between 25-40% concordance in identical twins and about 5-20% in fraternal twins.

Clearly, the environment is an important contribution.

Schizophrenia

Biochemical Causes• Dopamine Hypothesis: schizophrenia is caused

by excessive dopamine activity in the mesolimbic system.

• Supporting evidence: drug treatment, amphetamine psychosis, treatment for Parkinson’s disease

• Additional evidence: increased DA activity, increased D3 & D4 receptors in mesolimbic system,

Schizophrenia Pharmacology of Schizophrenia

Chlorpromazine: A phenothiazine• A “typical neuroleptic”; a nonspecific dopamine

receptor blocker; first prescribed antischizophrenic drug.

Clozapine:• An “atypical neuroleptic”; an antipsychotic drug

that blocks D4 receptors in the nucleus accumbens. Little effect on D2 receptors

Schizophrenia Consequences of Long-Term Drug Treatment of

Schizophrenia

Tardive dyskinesia:• A movement disorder that can occur after

prolonged treatment with antipsychotic medication, characterized by involuntary movements of the face and neck.

Supersensitivity:• The increased sensitivity of neurotransmitter

receptors; caused by damage to the afferent axons or long-term blockage of neurotransmitter release.

Schizophrenia

Evidence for neurological abnormalities Negative symptoms

Schizophrenics with negative symptoms have similar symptoms as those with fromtal lobe damage.• Frontal lobe size• Ventrical size • Cerebral gray matter decreases

Schizophrenia Possible Causes of the Brain Abnormalities

Epidemiology:• The study of the distribution and causes of

diseases in populations.

• Research suggest several environmental factors:-Season of birth: greatest during winter months-Viral epidemics: associated with viral diseases-Latitude: increased incidence further from equator-Prenatal malnutrition: ?-Rh incompatibility: ?-Maternal stress: ?

Schizophrenia

Degenerative process or sudden cell loss?

• Woods (1998) found that the cell loss in schizophrenic patients appears to occur suddenly during late adolescence or early adulthood. Schizophrenia is not a gradual degenerative disease like Parkinson’s or Alzheimer’s diseases.

• Does not appear to involve cell death and ‘gliosis’ (replacement of neural tissue by glia).

• Appears to involve loss of dendrites. Areas of tissue loss are correlated with symptoms (temporal lobes with auditory hallucinations, for example).

• The frontal cortex seems to be involved in most cases of schizophrenia (hypofrontality)

Schizophrenia

The cause of schizophrenia now appears to be a disturbance of normal brain development.

• Genetic predisposition may make individuals more susceptible

• Obstetric complications may cause individuals without genetic predisposition to develop schizophrenia

Schizophrenia

Hypofrontality (caused by a reduction in cell volume in the dorsolateral frontal cortices) is associated with negative symptoms of schizophrenia.

Hypofrontality also results in an increase in dopamine activity in the mesolimbic system which is associated with positive symptoms.

Dopamine hypothesis suggests that hypofrontality results in a disruption of normal glutamate activity from the frontal cortex to the mesolimbic system.

NMDA agonists cannot be used because they would cause seizures, but glycine may be effective in treating schizophrenics since it is also an NMDA agonist. Several studies have shown good results with negative symptoms

Major Affective Disorders Description

Major affective disorder:• A serious mood disorder; includes major

depressive disorder and bipolar disorder.

• May effect as many as 5% of US population in a given year. Perhaps as many as 25% over lifetime.

Major Affective Disorders Description

Major depressive disorder:• A serious mood disorder that consists of

unremitting depression or periods of depression that do not alternate with periods of mania.

Bipolar disorder:• A serious mood disorder characterized by

cyclical periods of mania and depression.

Major Affective Disorders Causes of Depression Genetic contributions:

• Bipolar disorder may be caused by a single dominant gene.Location still not confirmed, but heritability studies reveal strong link.

Major depressive disorder:• Less likely caused by single gene than bipolar

disorder.• Amine hypothesis: deficiencies in activity of one

or several amine neurotransmitter systems (NE, SE)

Major Affective Disorders Drug Treatment for Depression

Tricyclic antidepressants:• A class of drugs used to treat depression; inhibits the

reuptake of norepinephrine and serotonin; named for the specific molecular structure.Amitriptyline (Elavil)

Monoamine oxidase inhibitors (MAOIs):• Prevent degradation of NT in synapse.

phenelzine (Nardil) Serotonin specific reuptake inhibitor (SSRI):

• A drug that inhibits the reuptake of serotonin without affecting the reuptake of other neurotransmitters.

fluoxetine (Prozac)

Major Affective Disorders Physiological Treatments

Lithium• A chemical element; lithium carbonate is used to

treat bipolar disorder Carbamazepine:

• An anticonvulsive drug (trade name: Tegretol) that is used to treat seizures originating from a focus, also used to treat mania in bipolar disorder.

Major Affective Disorders Physiological Treatments

Electroconvulsive therapy (ECT):• A brief electrical shock that induces a seizure;

used therapeutically to alleviate severe depression when medication is not effective.

Transcranial Magnetic Stimulation (TMS):

Magnetic field causes a weak electrical field and electrical current within the brain. Has been useful in some cases of depression.

Major Affective Disorders Evidence of Brain Abnormalities

Brain abnormalities:• Research suggests abnormalities in the

prefrontal cortex, basal ganglia, hippocampus, thalamus, cerebellum, and temporal lobes.

• Some evidence suggests increased size of the cerebral ventricles may suggest the loss of neural tissue.

Major Affective Disorders Evidence of Brain Abnormalities

Silent cerebral infarction (SCI):• A small cerebrovascular accident (stroke) that

causes minor brain damage without producing obvious neurological symptoms.

Major Affective Disorders Role of Circadian Rhythms

REM Sleep Deprivation:• Selective deprivation of REM sleep through EEG

monitoring, is one of the most effective antidepressant treatments; suggests a close relationship between REM sleep and mood.

• Antidepressant effects require several weeks of deprivation.

Major Affective Disorders Role of Circadian Rhythms

Total Sleep Deprivation:• Total sleep deprivation has antidepressant effect

that are immediate; however, the procedure is not very practical.

• Some individuals do not respond to total or selective sleep deprivation.

Major Affective Disorders Role of Zeitgebers

Seasonal affective disorder (SAD):• A mood disorder characterized by depression,

lethargy, sleep disturbances, and craving for carbohydrates during the winter months.

Summer depression:• A mood disorder characterized by depression,

sleep disturbances, and loss of appetite.

Major Affective Disorders Role of Zeitgebers

Phototherapy:• Treatment of seasonal affective disorder by daily

exposure to bright light.

Schizophrenia

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