Mood Disorders

Major (unipolar) depression

Probably more than 1 type

Endogenous vs Reactive

Bipolar disorder

Major (or “unipolar”)Depression

l   sadness, feel helpless, hopeless, worthless

l   no energy, apathetic, nothing matters

l   can’t make decisions, complete tasks

l   lose appetite for food & sex, disordered sleep, move & talk slowly

l   suicidal thoughts or actions

Bipolar Disorder

l   a.k.a. manic-depressive disorder

l   over time goes from 1 mood extreme to the other

l   increased energy, activity & speech

l   decreased need for sleep; may be irritable

l   unrealistic view of their capabilities, delusional

Genetic Factors

l   Mood disorders tend to run in families(~10x more likely if you have affected relatives )

l   10-20% of the relatives of a depressed individual also suffer from the disorder

l   25% with major depression and 50% with bipolar disorder have depressed parents

Genetic Factors

l   About 70% concordance in identical twins vs about 13% in fraternal twins for major depression; about 80% for bipolar disorder

l   Adopted depressed children more likely to have depressed biological parents

l   Stronger genetic link for early, severe depression, and for females

l   Interacts with environmental factors




Monoamine Theory of Depression

l   Normal mood depends on adequate levels of monoamine activity in brain.

l   Levels too low à depression

l   Levels too highà euphoria, mania

l   Used to focus on NE, now its clear that serotonin (5HT) also critical

Tricyclic Antidepressants

l   3 best known:

»  imipramine (Tofranil)

»  amitriptyline (Elavil)

»  desipramine (Norpramin)

l   prevent reuptake of 5HT, NE & DA

l   But have some annoying & dangerous side effects

MAO Inhibitors

l   Example: phenelzine (Nardil)

l   Inhibit action of MAO, an enzyme which breaks down  5HT, DA and NE, therefore making transmitters more available

l   But: dangerous interactions with diet & stimulant drugs

Selective Serotonin Reuptake Inhibitors (SSRIs)

l    fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil),fluvoxamine (Luvox), citalopram (Celexa)

l   Block reuptake of 5HT

l   same effectiveness but fewer side effects and risks; patients much more willing to take SSRIs

Atypical Antidepressants

l   Don’t fit previous categories

l   E.g. bupropion (Wellbutrin), venlaxafine (Effexor), nefazodone (Serzone)

l   Various mechanisms of action

The Monoamine Theory

l    Availability is not enough - drugs all increase availability immediately but don’t become clinically effective for a few weeks

l    Hypothesis: improved mood depends on a slower adaptation of CNS to increased availability (“down-regulation of receptors” and altered release of transmitter)

l    Different people may have different monoamine imbalances

Circadian Changes in Depression

l   Temp cycle advanced and sleep abnormal: early REM & more REM despite early morning awakening

l   Either REM deprivation or total sleep deprivation can relieve depression

l   Antidepressants drugs also decrease REM sleep

l   SAD associated with phase delayed cycles

Other Brain Changes

l    Excess activation of HPA responses

l    High levels of cortisol which are not reduced by dexamethasone injections

l    Decreased left prefrontal (“happy”) activity

l    Right hemisphere more active

l    Individuals with left hem damage often depressed

l    Those with right hem damage may become manic

l    Electroconvulsive shock therapy limited to the right hemisphere can be effective, with little effect on memory

Another Biological Factor:
Borna Virus

l   Borna disease causes bipolar-like behavior in horses.

l   May be passed to humans

l   Studies revealed Borna in very few normal mood individuals, but is present in ~30% of severely depressed. May also increase your risk of other psychiatric problems.

Bipolar Disorder

l   Drug of choice has been lithium carbonate (e.g. Eskalith)

l   Takes 7-10 days to act, 3 or more weeks for maximal effect, but is good at preventing future attacks

Biological Basis of Schizophrenia

Characteristics of Schizophrenia

z     Hallucinations

z     Delusions

z     Disordered thought

z     Inappropriate emotion

z     Often bizarre behavior

z     “positive symptoms”

z     Decreased social interaction

z     Normal emotion lost

z     Speech often decreased

z     “negative symptoms”



z     Incidence a little over 1% of the population

z     Usual symptom onset in early adulthood; early 20’s for men, late 20’s for women

z     All “schizophrenics” do not show the same behaviors - may be several different types of schizophrenia

Genetics of Schizophrenia

z     Schizo. runs in families -  you have increased risk if you have blood relatives with schizo

z     Overall concordance in identical twins is ~45-50%, in fraternal twins its ~15-17%

z     Identical twins with same handedness have a 92% concordance rate, that of those with opposite handedness is 25%

z     6/51 kids born to nonschizo member of identical  twin pair, 5/36 kids born to twins with schizophrenia (17.4% vs 16.8%)(not true of fraternals)(suggests the unaffected twins still have “bad gene(s)”)


Genetics of Schizophrenia

z     Adoptees with schizophrenia are more likely to have schizophrenic biological parents & relatives than adoptive parents & relatives.

z     A child of a schizophrenic parent raised by a normal couple is more likely to show schizophrenia than a child of normal parents who has a schizophrenic adopted parent.

z     63 adopted schizos who had paternal half sibs who were also adopted – 8/63 of those half sibs also schizo

Dopamine Hypothesis

Schizophrenia results from

or is associated with over-

activity of DA synapses.

Drug-Induced Psychosis

z     amphetamine or cocaine use increases     DA activity and can trigger paranoid schizophrenia

z     excess l-dopa can cause symptoms of schizophrenia in Parkinson’s patients

z     amphetamine or l-dopa given to schizophrenics worsens their symptoms


Neuroleptics or Antipsychotics

z     ~ 10 phenothiazines like chlorpromazine (Thorazine)-”typical antipsychotic”

z     butyrophenones like haloperidol (Haldol)

z     all of these block DA receptors

z     seem to act on mesolimbic DA pathway

Too Much DA Blockade?

z     typical antipsychotics block DA receptors all over brain

z     anti-DA action in basal ganglia causes appearance of Parkinson’s disease symptoms and tardive dyskinesia

z     “Atypical antipsychotics” like Clozaril or Risperdal block mostly limbic receptors(D4), not basal ganglia(D2): fewer motor problems.

Problems With DA Theory

z     Most studies have found normal levels of DA in schizos. There is, however, some evidence of abnormal #’s  of different DA receptors.

z     Antipsychotics block DA immediately but therapeutic effect builds over weeks

z     Differences noted in other transmitters

Glutamate Hypothesis

z     Underlying problem in schizophrenia is underactivity of glutamate, especially in frontal lobe.

z     This does not necessarily conflict with the DA hypothesis because these neurotransmitter systems interact.

z     PCP (phencyclidine) acts by inhibiting glutamate receptors & it produces both positive and negative symptoms of schizophrenia.

PET Scans


Brain Changes

z     enlarged ventricles

z     Smaller thalamus, frontal & temporal cortex, amygdala, hippocampus, especially on left side

z     6% decrease in brain weight on average

z     loss of cells/disorganized cells, mostly in frontal & temporal lobes & hippocampus

z     Changes/disorganization present since birth and are not progressive, but effects may not become apparent until we reach the age where those brain areas mature & normally become fully functional


Functional Differences

z     less brain activity in these regions

z     less frontal activity during tasks

z     signs of less sharing across corpus callosum, less lateralization

z     problems with memory tasks

z     some of these changes also present in nonschizophrenic family members

Neurodevelopmental Theory

z     Brain abnormalities associated with schizo begin prenatally or neonatally

z     May reflect not only genetically based differences but adverse prenatal/neonatal conditions as well

z     Birth records of schizos show more “nonoptimal” signs during preg/labor (nutritional deficiencies, illness during pregnancy, Rh incompatibility, prematurity, delivery complications, low birth weight, etc.)


Season-of-Birth Effect

z     More schizophrenics are born in winter/early spring, especially those with no family history of schizophrenia

z     Higher rate of schizophrenia in those born in winters of years with fall viral epidemics

z     If a viral epidemic occurs in other seasons, there is more schizophrenia among those born 3 months later