Biopsychology of Psychiatric Disorders

Schizophrenia

splitting of psychic functions; overlap with other psychiatric disorders and freqently changes overtime with the disorder

schizophrenia spectrum disorders

label used by the DSM-5

positive symptoms of schizophrenia

excess of typical function:

delusions, hallucination, inappropriate affect, disorganized speech/thoughts, odd behavior

negative symptoms of schizophrenia

reduction/loss of typical function:

affective flattening, avolition, catatonia

Chlorpromazine

calming effects on difficult-to-handle patients with psychosis; agitated patients were calmed and catatonia patients was activated by it

receptor blocker at dopamine synapses

Reserpine

effective antipsychotic that is made from snake root plants

no longer used due to decline in blood pressure

Similarities between antipsychotic drugs

antipsychotic effects manifest after a person is medicated for 2-3 weeks

dopamine theory of schizophrenia

the theory that schizophrenia is caused by too much dopamine and, conversely, that anti-schizophrenic drugs exert their effects by decreasing dopamine levels

Carlsson & Lindqvist (1963)

levels of dopamine were unchanged by chlorpromazine but dopamine metabolites levels increased

Synder and Co. (1970)

binding affinity of dopamine antagonist;

chlorpromazine have high affinity and bind to both D1 and D2

Haloperidol has an low affinity and bind to specifically D2

DA Theory Modifications

Schizophrenia is caused by hyperactivity at D2 receptors than at dopamine receptors in general

Atypical antipsychotics

effective against schizophrenia but don't bind strongly to D2 receptors

clozapine

affinity for D1/D4 receptors and several 5-HT/histamine receptrs

renewed interest

classsical hallucinogens mimic the positive symptoms of schizophrenia; dissociative hallucinogens mimic negative symptoms of schizophrenia by acting as an antagonist of glutamate receptors

Genetic and Epigentic Mechanisms of Schizophrenia

concordance rate of schizophrenia in identical twins is about 45%

many schizophrenia genes

early experiential factors can contribute to development of disorder

neural bases of schizophrenia

volume reductions in parts of brain

extensive brain changes apparent during first medical brain scan

brain change continues after initial diagnosis

alterations to areas of the brain develop at different rates

Hypomania

reduced need for sleep, high energy, and positive affect

Mania

delusion of grandeur, overconfidence, impulsivity, and distractibility

Bipolar Type 1

mania episodes

bipolar type ii

hypomania and severe depression

rapid cycling

fluctuating between mania and depression more than 4 times per year

lithium

first drug found to be a mood stabilizer

anticonvulsants

prevent or control seizures

Antipsychotics

drugs used in the treatment of psychotic disorders that help alleviate hallucinations and delusional thinking

Theories of Bipolar Disorder

-HPA axis

-Circadian rhythms

-Neurotransmission (GABA, glutamate,

monoamines)

-BDNF levels are lower in patients with bipolar disorder

Genetic and Epigentic Mechanisms of Bipolar

Hundreds of thousands of genes associated with disorder

Focus on identifying epigenetic mechanisms that might affect transcription of genes

MRI studies of Bipolar

medial prefrontal cortex

left anterior cingulate

left superior temporal gyrus

prefrontal regions

hippocampus

fMRI studies

frontal cortex

medial temporal lobe

basal ganglia

Depression

intense feelings of despair, hypoactive, sleep problems, withdrawal, lack of appetite, and inability to care for oneself

reactive depression

triggered by a negative experience

endogenous depression

no apparent external triggers

major depression

when symptoms of depression last longer than two weeks

Iproniazid

The first antidepressant drug; a monoamine oxidase inhibitor

Tricylic Antidepressants

block the reuptake of norepinephrine and serotonin, thereby increasing the amount of neurotransmitters in the synaptic space between neurons; safer than MAO inhibitors

imipramine

tricyclic antidepressant

Prozac

an selective monoamine reuptake inhibitor

Atypical Antidepressants

drugs that do not fit into existing categories

Bupropion

blocks uptake of dopamine and norepinephrine and blocks nicotinic acetylcholine receptors

NMDA receptor antagonist

Ketamine was shown to reduce depression by blocking NMDA receptors

rTMS (repetitive transcranial magnetic stimulation)

High frequency and low frequency rTMS to the prefrontal cortex

deep brain stimulation

chronic stimulation of the anterior cingulate gyrus

monoamine theory of depression

Depression may be due to underactivity at 5-HT and NE synapses-Most widely accepted theory

evidence; certain norepinephrine and serotonin receptors are elevated in untreated depressed patients due to low levels of transmitters eliciting a compensatory increase in receptors

neuroplasticity theory of depression

altered neuroplasticity may account for the fact that the beneficial effects of antidepressants are often not seen until weeks after treatment onset

has been observed in the prefrontal cortex, hippocampus, and amygdala

Genetic and Epigenetic Factors of Depression

many depression related genes

involves interactions between genes and environment through epigenetic mechanisms

Gray Matter Reduction

prefrontal cortex, hippocampus, amygdala, cingulate cortex

white matter reduction

frontal cortex; fMRI studies shows atypical activation in frontal, cingulate, insular cortices, and the amygdala, the striatum, and the thalamus

anxiety disorders

chronic fear that persists in the absence of any direct threat; most prevalent

severe enough to disrupt functioning

associated with tachycardia, hypertension, nausea, breathing difficulties, sleep disturbances, high glucocorticoids levels

generalized anxiety

is a stress response in the absence of an obvious stimulus

specific phobia

are caused by exposure to a specific object or situation

agoraphobia

fear of public places

panic disorders

rapid-onset attacks of extreme fear and severe symptoms of stress

Benzodiazepines

increase the binding of GABA-A to its receptors and used as hypnotics, muscle relaxants, and anticonvulsants

side effects include:

tremors, nausea, and addiction

Pregabalin

effective in treating generalized anxiety disorder

elevated plus maze test

rats are placed on a four-armed plus-sign-shaped maze that is 40 centimeters above the floor; two arms have sides and two arms have no sides; the measure of anxiety is the proportion of time the rats spend in the enclosed arms, rather than venturing onto the exposed arms

defensive-burying test

measuring the amount of time the rats spend spraying bedding material at the source of the shock with forward thrusting movements

Risk Assessment test

An animal model of anxiety. After a single brief exposure to a cat on the surface of a laboratory burrow system, rats flee to their burrows and freeze. Then they engage in a variety of risk-assessment behaviors.

Genetic and Epigenetic Factors of Anxiety

no definitive genes associated with disorders

focus on identifying environmental and epigentic mechanisms that contribute

Neural Basis of Anxiety Disorders

- GABA-A

- Serotonin

- Brain areas: hippocampus, amygdala, medial prefrontal cortex