Scientific study of disease incidence

1/3 of US population at some point in life reports symptoms of a major psychiatric disorder

Women: more depression

Men: more drug dependency/alcoholism

• "Split Mind"
• Key symptom: dissociative thinking-disturbances in thought and difficulty relating events properly
• Other symptoms: loosened associations, emotional disturbances

Described common clinical features

• Paranoia
• Grandiose delusions
• Abnormal emotional regulation
• Bizarre disturbances of thought
• Auditory hallucinations

1. Auditory hallucinations

2. Highly personalized delusions

3. Changes in affect (emotion)

Abnormal behavior states that have been gained

Hallucinations, delusions, excited motor behavior

Normal functions that have been lost

Slow/impoverished thought and speech, emotional and social withdrawal, blunted affect

• Higher instance among biological relatives
• Involves multiple genes
• Problems with family studies
  • Confuse hereditary and experimental factors
  • Depend on recollections of relatives

Concordantt: both twins suffer

Discordant: only one twin

Concordance rates:

Dizygotic (fraternal): 17%

Monozygotic: 50%

• Genes encoding neuregulin 2; participates in NMDA, GABA, and ACh receptor regulation
• Dysbindin; implicated in synaptic plasticity
• Catechol-O-methyltransferase (COMT); metabolizes dopamine
• G27; contributes to glutamatergic activity

Enlarged cerebral ventricles

Due to cell death

Especially lateral ventricles

More enlarged ventricles predict worse reaction to drug treatment

• Characteristic disorganization
• Probably results of abnormal synaptic arrangements
• Degree of cellular disorientation reflects severity of disorder

• Thicker corpus callosum
• Loss of gray matter
• Frontal lobes especially affected (some in structure but mainly in activity)

• Frontal cortical regions below normal function
• Less metabolic activity in frontal lobes when compared with posterior lobes
  • Equal activation in control subjects

• Problems in tasks such as card sorting task
• Cant plan day

Amphetamine repeated use: delusional and psychotic state with paranoia and hallucinations

Endogenous drug may link: PEA Phenylethlamine (substance with amphetamine like properties)

Promotes dopamine; blocks reuptake

Dopamine antagonist

Antidote to amphetamine psychosis

Phenothiazine family

First identified class of effective antischizophrenic drugs (neuroleptic or antipsychotic)

Block postsynaptic receptor sites for dopamine (esp. D2)

Phenothiazines

Butyrophenones (haloperidol or Haldol)

Antagonistsic activity to D2 receptors

I.e. clozapine

Lack selective high affinity for dopamine receptors

Selectively block serotonin receptors (esp 5HT2A) as well as others like D2

Just as effective

A Psychotomimetic: a drug that induces a state resembling schizophrenia

Auditory hallucinations, depersonalization, disorientation, sometimes violent

Noncompetitive NMDA receptor antagonist

Blocks NMDA receptors central calcium channel

Prevents glutamate from having its effects

Schizophrenia results from an under activation of glutamate receptors

People carrying one variant of the gene fro mGlu receptor more likely to develop schizophrenia

Interaction between genetic, developmental, and stress factors

Each life stage has its own specific feature that increases vulnerablity

Influenza, malnutrition, difficulties during delivery, more

Unhappy mood

Loss of interest, energy, and appetite

Difficulty in concentration

Restless agitation

Pessimism all the time

Depression states that alternate with normal emotional states

Estimated 13-20% of the population at any one time

Monozygotic: 60%

Dizygotic: 20%

Increase blood flow/greater activity in frontal cortex and amygdala

Decreased blood flow/activity in parietal and posterior temporal cortex and anterior cingulate

(These structures involved in attention and language)

Decreased activity in synapses of monoamine transmitters

(norepinephrine and serotonin)

Supported by effectiveness of early treatments

1. Antidepressant drugs: MAOIs (monoamine oxidase inhibitors)
2. Electroconvulsive shock therapy: releases monoamine transmitters

Deficiencies in serotonin seem to be important in depression

SSRI's such as Prozac

New treatment

Expensive and irreversible

Cushing's Syndrome: people with high levels of glucocorticoids such as cortisol are prone to depression

1. Pituitary tumors that produce excessive ACTH
2. Tumors of adrenal gland causing hypersecretion of cortisol
3. Therapeutic treatments with synthetic glucocorticoids

Reveals a tendency to release excess cortisol

Dexamethasone: suppresses early morning rise in ACTH normally

When given at night it fools hypothalamus into believing there is a high level of circulating cortisol

Normal: suppresses cortisol release

Depressed: doesn't suppress anything

Reduce brain production of neutrophic factors

Neurogenisis dorps

Neurotrophins drop

Apoptosis rises

Reduced stage 3 & 4 SWS

Increased stage 1 & 2 SWS

Enter REM sooner

More vigorous REM

Periods of depression alternating with periods of excessively expansive mood (mania)

Mania: sustained overactivity; talkativeness, strange grandiosity, increased energy

4+ distinct cycles in one year

May even show several per day

6 chromosomes that may be important

Age of onset is inherited (3 genes linked)

Gene that encodes BDNF associated

Enlarged ventricles; especially in those who have experienced repeated mood cycles

Changes probably in subcortical limbic structures like amygdala

Mood stabilizing drug

Interact with a protein that is part of a circadian molecular clock

Seems to increase volume of gray matter

• Structural and functional changes in temporal lobe
• Abnormalities: small lesions in white matter and dilation of lateral ventricles
• Number of abnormalities related to number of spontaneous attacks and age of onset

Drugs that combat anxiety

• Benzodiazepines
  • Diazepam: Valium
• Noncompetitive agonists at GABA receptors
• Enhance GABA's action at inhibitory synapses
  • Regulate permeability of membranes to Cl- ions; hyperpolarize
• Preferentially bind to GABAa receptors, esp in cerebral cortex, some subcortical areas such as hippocamus and amygdala

Serotonin 5HT1a antagonist

Provides relief from anxiety

Paroxetine (Paxil)

Fluoxetine (Prozac)

Increase stimulation of serotonin receptors

Unpleasant memories plague the victim; never feels safe

• Decreased volume in right hippocampus
• Maybe failure to forget
• Amygdala no longer suppressing fear
• Increased response to stress hormone