Basic Definitions

Proband - an individual affected with a disorder who is the first subject in a study (as of a genetic character in a family lineage)
Proband study - studies genetics of mental illness through number of occurrences within a family tree
Concordance rates - the probability that a pair of individuals will both have a certain characteristic, given that one of the pair has the characteristic; usually means the likelihood of presence of the same trait in both members of a pair of twins
Reuptake - The reabsorption of a secreted substance by the cell that originally produced and secreted it
Catecholamines - dopamine, epinephrine, and norepinephrine

Major Depressive Disorder

Feelings of sadness and helplessness every day for at least 2 weeks
Little energy, feelings of worthlessness, contemplating suicide, trouble sleeping & concentrating
2x more women than men
Can happen across lifespan
Most cases of depression are episodic
Main neurotransmitters - dopamine, serotonin, norepinephrine

Major Depressive Disorder (Genetic Evidence)

Runs in families
Adopted children resemble biological parents
Higher risk if parents have severe, long-lasting depression before age 30
Sex difference, but hard to explain
- Questionable effects from hormones
- No differences in social influences (unreported cases)
- No isolated gene for depression

Major Depressive Disorder (Neuroanatomical and Physiological Bases)

Lateralization effects
- Happy mood elicits high activity in left prefrontal lobe
- Depressed mood elicits high activity in right prefrontal lobe
- Left hemisphere damage correlates with depression
- Right hemisphere damage correlates with mania

Antidepressant Drugs

Tricyclics
- 2nd course of treatment in depression
- Example: Tofranil
- Prevent reuptake of serotonin and catecholamines
- Increases the production of serotonin, norepinephrine, and dopamine
- Major side effects:
  - Histamine receptors - drowsiness
  - Acetylcholine receptors - dry mouth, difficulty urinating
  - Sodium channels - heart irregularities
SSRIs (Selective Serotonin Reuptake Inhibitors)
- First course of treatment in depression (and often anxiety)
- Examples: Prozac, Zoloft, Celexa, Luvox, Paxil (generics end in ‘-ine’ or ‘-pram’)
- Similar to tricyclics but specifically prevent serotonin reuptake
- Nausea, headaches, nervousness (more mild side effects)
MAOIs (Monoamine Oxidase Inhibitors)
- Last course of treatment for depression (due to side effects)
- Example: Phenelzine (Nardil)
- Blocks the enzyme Monoamine Oxidase (MAO)
- MAO inactivates catecholamines and serotonin in axon terminal
- Avoid foods containing tyramine (cheese, raisins, liver, pickles)
  - Consumption can lead to death (increases blood pressure)

Why Don’t Antidepressants Cure All Depressive Disorders?

Physiological confounds
- Mood = combination of neurotransmitters
- Time course between behavioral and psychological effects
- Mechanisms of long-term effects not characterized
- Placebo effects
Other factors
- Depression may be due to different factors in different people
- Environmental influences
Only ⅔ of patients show benefits from antidepressants

Electroconvulsive Therapy (ECT)

Bipolar Disorder

Fluctuations between mania and depression
- Mania: extreme activity, excitement, loss of inhibition
- Fluctuations and ages may vary
Possible genetic effect
Treatments:
- Lithium (a salt)
  - Mechanism not well understood (possibly on 2nd messengers)
  - Dose important - too high may be toxic
- Anticonvulsant drugs ( ex. Valproic Acid, or Depakene)
  - Blocks 2nd messenger systems

Seasonal Affective Disorder (SAD)

Depression during a particular season (winter)
Occurs most severely in areas near the poles (subtle effects in moderate climates)
Depressed patients - phase advanced
SAD patients - phase-delayed
Related to circadian rhythms (different from depression)
Treatment: very bright lights 1+ hours a day

Schizophrenia

Characterized by:
- Gross distortions of thoughts and perceptions
- Loss of contact with reality
- (Different from multiple personalities)
1% of Americans exhibit over lifetime
- Most common in United States
Equal number of men and women
Average age of onset:
- Men = 18 to 25 years old
- Women = 26 to 45 years old
Can be chronic or acute
- The more acute, the more likely a recovery can occur
Diagnosed through differential means

Schizophrenia Major Symptoms

Neuroanatomical Hypothesis of Schizophrenia

Various brain regions are smaller in schizophrenics
- Prefrontal cortex, hippocampus, amygdala, temporal cortex
- Areas involved with emotion, coherent thought, perceptions
Ventricles are larger in schizophrenics
Lateralization of schizophrenia
- Lower activity of regions on the left
- Development of larger areas (including planum temporale) on right
- Differences do not progress
Question: if this is the case, why don’t symptoms appear earlier in life?

Dopamine Hypothesis of Schizophrenia

Excess dopamine receptor activity at synapse contributes to symptoms of schizophrenia
Supporting evidence:
- Antipsychotics (ex. Thorazine), and neuroleptic drugs (ex. Haloperidol, or Haldol)
- Certain drugs = increase in dopamine activity (cocaine, amphetamines, meth, LSD)
Downsides:
- Time course discrepancies
- Receptor differences questionable

Glutamate Hypothesis of Schizophrenia

Deficient activity at glutamate synapses in the prefrontal cortex and hippocampus contribute to symptoms of schizophrenia
Supporting evidence:
- Antagonistic effects between glutamate and dopamine
  - (Supported by antipsychotic drugs)
- PCP (phencyclidine) effects are close to schizophrenia (inhibits glutamate)
  - Produces little effects in prepubescent monkeys, significant effects later on
  - Produces specific and long-lasting effects (in comparison to drugs that stimulate dopamine)
Downside:
- Glutamate treatment will overstimulate cells to death

Emotion and Physiology