INTEGRATIVE BIOLOGY

of Schizophrenia and Affective Disorders

INTEGRATIVE BIOLOGY
1. DESCRIBES the trait defines the phenomenon and then considers its 2. DEVELOPMENTAL biology (changes throughout ones lifespan) 3. ECOLOGY (niche, costs/benefits in context,) 4. EVOLUTION (changes between generations, ancestors, descendents, fitness; genes, memes) 5. PHYSIOLOGY (cells, tissues, organs, organ systems, organisms, and their communications with each other)

 Schizophrenia described
Schizophrenia: A serious mental disorder characterized by: Disordered thoughts Delusions of persecution or grandeur Hallucinations (mostly auditory) Behaviors (withdrawn or detached, odd movements))

 Positive symptoms: (known by their presence in excess) delusions, hallucinations, abnormal movements, or thought disorders. Negative symptoms: (characterized by deficit or absence) social withdrawal, lack of affect, and reduced motivation.

 Positive symptoms: (known by their presence in excess) delusions, hallucinations, abnormal movements, or thought disorders. Negative symptoms: (characterized by deficit or absence) social withdrawal, lack of affect, and reduced motivation.

Heritability
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.

Heritability
Evidence for heritability Concordance rates: Most studies suggest between 25-40% concordance in identical twins and about 520% in fraternal twins. Clearly, the environment is an important contribution

 Biochemical Causes
Dopamine Hypothesis: schizophrenia is caused by excessive dopamine activity in the mesolimbic system. Supporting evidence: drug treatment, amphetamine psychosis, treatment for Parkinsons disease Additional evidence: increased DA activity, increased D3 & D4 receptors in mesolimbic system,

 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

Consequences of Long-Term Drug Treatment of Schizophrenia (collateral damage?) 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.

Evidence for neurological abnormalities in schizophrenia Schizophrenics with negative symptoms have similar symptoms as those with frontal lobe damage. Frontal lobe size Ventricle size Cerebral gray matter decreases

Possible Causes of the Brain Abnormalities is schizophrenia

Epidemiology
in populations.) (The study of the distribution and causes of diseases

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: ? NEW: parasite infection?

Copyright 2004 Allyn and Bacon

Copyright 2004 Allyn and Bacon

Copyright 2004 Allyn and Bacon

Copyright 2004 Allyn and Bacon

 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 Parkinsons or Alzheimers 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)

 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

Affective Disorders
Description: mood disorder; includes sustained depression and cycling of depressive & manic episodes. May manifest irritability, hyperactivity, inflated or depressed feelings of selfesteem; ennui, sleep disturbances, gulit

Major Affective Disorders

Description: 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 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.

Genetic contributions:
Bipolar disorder may be caused by a single dominant gene. Its 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)

WHERE DRUGS might act gives clues about the components of the system Tricyclic antidepressants inhibit the reuptake of
specific neurotransmitters (norepinephrine and serotonin)

Monoamine oxidase inhibitors (MAOIs):

Prevent degradation of NT in synapse.

Serotonin specific reuptake inhibitor (SSRI):

inhibits the reuptake of serotonin without affecting the reuptake of other neurotransmitters.

WHERE PHYSIOLOGICAL TREATMENTS might act gives clues about the components of the system

Electroconvulsive therapy (ECT) involves a brief

electrical shock that induces a seizure; used therapeutically to alleviate severe depression when medication is not effective.

Transcranial Magnetic Stimulation (TMS) involves a weak electrical field and electrical current
within the brain. Has been useful in some cases of depression.

WHERE brain structures may seem atypical or damaged gives clues about the components of the system Brain abnormalities: evidence of differences in the
prefrontal cortex, basal ganglia, hippocampus, thalamus, cerebellum, and temporal lobes. increased size of the cerebral ventricles may suggest the loss of neural tissue.

Silent cerebral infarction (SCI): A small

cerebrovascular accident (stroke) that causes minor brain damage without producing obvious neurological symptoms.

WHERE environmental influences affect symptoms gives clues about the components of the system
Role of Circadian Rhythms (involving sleep/wake cycles) 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.

Total sleep deprivation has an antidepressant effect but cost is not worth the benefit

 Role of Zeitgebers Seasonal affective disorder (SAD): A mood disorder characterized by depression, lethargy, sleep disturbances, and craving for carbohydrates during the winter months Symptoms can be mitigated by daily exposure to bright light.

TO ASK GOOD QUESTIONS

1. Consider the quality of the description and
2. use your understanding of the DEEP disciplines 3. consider the level of organization and the ways these levels communicate with each other.