PDA III Schizophrenia background

General features of schizophrenia

-Important psychological functions are "split" apart (thought, emotion, motivation)

-Not split personality disorder

-No defined neuropathology or genetic cause: vary between pts

-Type of psychosis

-Chronic condition

-1% of population uniformly across cultures

-Onset is in late teens or early twenties: consequence of abhorrent brain development

Psychosis

-Disruption and distortion of thought and perception

-Loss of reality

Abhorrent brain development

-Construction of the brain was a little off

-Explains why onset occurs after puberty

Schizophrenia symptom classifications

-Positive symptoms: pt has, that a healthy person doesn't have

-Negative symptoms: pt doesn't have, that a healthy person does have

-Cognitive deficits

Positive symptoms

-Hallucinations (usually auditory, usually negative)

-Delusions (strong beliefs not based on reality, usually of persecution/grandeur)

-Paranoia

-Disconnected and illogical speech: sentences that don't make sense

Negative symptoms

-Reduced speech

-Flat or inappropriate affect (emotions)

-Avolition (loss of motivation/initiative)

-Social withdrawal

-Anhedonia (loss of pleasure)

-Lack of personal hygiene

Cognitive deficits

-Impaired working memory: very short term memory loss

-Impaired executive function:

Executive function

-Prefrontal cortex of the brain: makes you who you are

-Emotions, thoughts, knowledge, rules of society, manners, strategy

Lifetime risks of developing schizophrenia

-Strong genetic factor

-Some environmental factor: the womb, complications in birth (siblings vs dizygotic twins)

Schizophrenia hypothesis

-Occurs during times of rapid brain development (birth and puberty)

-Neural disorder of brain development

Neurochemical basis (2 hypotheses)

-DA hypothesis

-Glutamate hypothesis

-Serotonin hypothesis

DA hypothesis

-Symptoms (especially positive symptoms) are due to excessive dopamine activity in the brain

-Amphetamine and cocaine worsen positive symptoms

-All antipsychotics block D2 receptors (two exceptions)

-Some negative symptoms and cognitive deficits seem to be due to decreased dopamine function in the prefrontal cortex

Decreased DA relation to negative symptoms and cognitive deficits

-In monkeys, toxins that deplete DA produce working memory deficits similar to schizophrenia

-In PD (loss of DA neurons), there is a flat affect and avolition

Dopamine concentration graph

-As it takes more drug to bind, the amount of drug needed to control symptoms goes up

-Bottom left has high affinity and high potency

-Linear relationship

-Drugs don't have a linear relationship in any other receptor in the brain

Serotonin concentration graph

-No correlation

Glutamate hypothesis

-Phencyclidine (PCP) is a psychotomimetic (drug that causes psychosis)

-PCP produces both positive and negative symptoms

-Mechanism of PCP is to block glutamate receptors: suggests that glutamate receptors are dysfunctional in schiz

-No drugs

Serotonin hypothesis

-Hallucinogenic drugs (LSD< mescaline, psilocybin, ecstasy) activate 5-HT receptors

-Second gen antipsychnotics block D2 and 5-HT2A receptors

-Second gen antipsychotics just as efficacious as older ones for positive symptoms

-More efficacious for negative and cognitive symptoms

Four key DA pathways

-Nigrostriatal pathway: S. Nigra to striatum

-Mesolimbic pathway

-Mesocortical pathway

-Tuberoinfundibular pathway

Nigrostriatal pathway

-Substantia nigra to striatum

-Striatum is aka dorsal striatum, motor striatum

-Modulates movement

-Associated w/ motor side effects of anti-psychotics (parkinsonism)

-Pathway a

Mesolimbic pathway

-Tegmentum to nucleus accumbens in the limbic system (and others)

-Nucleus accumbens is a part of the striatum (may call it the ventral striatum or the emotional striatum)

-Hyperactive in schizophrenia (associated w/ positive symptoms)

-Pathway b

Mesocortical pathway

-Tegmentum to cortex

-DLPFC: dorsolateral prefrontal cortex

-VMPFC: ventromedial prefrontal cortex

-Hypoactive in schizophrenia (associated with negative symptoms and cognitive deficits)

-Pathway c

Tuberoinfundibular pathway

-ALA tuberohypophyseal pathway

-Hypothalamus to pituitary

-Pathway inhibits prolactin production and secretion

-Associated with neuroendocrine side effects of anti-psychotics

-Pathway d

Ventral tegmental area

-Refers to both mesolimbic and mesocortical pathways