Chapter 16 - Schizophrenia and Affective disorders Flashcards Preview

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Flashcards in Chapter 16 - Schizophrenia and Affective disorders Deck (55):
1

serious mental disorder characterized by disordered thoughts, delusions, hallucinations, and often bizarre behaviors

schizophrenia

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Refers to the breakdown of integration of emotion, thought, and action

"Splitting of psychic functions"

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Diagnosis of schizophrenia

The recurrence of only 2 symptoms for one month
1 symptom is necessary if the person exhibits delusions that are particularly bizarre or hallucinations that include 1 voice providing a running commentary or 2 voices conversing

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Type of schizophrenia. Not as bad. Does not mean you will always have schizophrenia.

acute

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– gradual onset, progressive deterioration
~ 1/3 of those diagnosed will show progressive deterioration

Chronic schizophrenia

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: statistic which gives an estimate of the total variance in a trait that is attributable to genetic variation in a group

Heritability

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Mechanisms that control the expression of genes

Epigenetics

8

Antipsychotic drug side effects suggests role for dopamine – drugs work by decreasing dopamine levels; positive symptoms of schizophrenia are associated with dopamine overactivity
Reserpine depletes brain of dopamine and other monoamines by making vesicles leaky
Amphetamine, cocaine and L-dopa are dopamine agonists and produce psychosis

Dopamine Theory of Schizophrenia

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Major CNS dopaminergic systems include

Nigrostriatal System (role in movement)
Mesolimbic System (role in reinforcement/reward)
Mesocortical System (role in short-term memory, planning, and problem solving)

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Activation of D1-like Rs

stimulates cAMP

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Activation of D2-like R

inhibits cAMP

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All DA receptors are

metabotropic

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Anti-Schizophrenic Drugs
2 Classes

Phenothiazines
Butyrophenones

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drug that Binds to D1 & D2 Receptors

Chlorpromazine

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drug that bind to d2 receptors only

Spiroperidol

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Revised DA Theory of Schizophrenia

Schizophrenia is caused by hyperactivity at D2 Rs, rather than DA Rs in general
1) Based on 2 findings:
2) Selective binding of butyrophenones to D2 Rs
Butyrophenones greater potency in the clinic.

Brains of schizophrenics have an abnormally high # of D2 Rs
Higher level of occupancy of those Rs by DA
Suggest both pre & postsynaptic abnormalities

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long term side effect of using anti-psychotic drugs

Tardive Dyskinesia
Tardus – slow
Dyskinesia- faulty movement
Late-developing
TD: unable to stop moving
Supersensitivity: possible that DA receptors become hypersensitive if they are blocked for long periods of time
D2 receptors in caudate and putamen

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Problems with the D2 Theory

Schizophrenia associated with brain damage
Little damage to dopamine circuitry
Damage not explained by dopamine theory
It takes several weeks of neuroleptic therapy to alleviate schizophrenic symptoms
Conventional neuroleptics (D2 blockers) mainly effective for positive symptoms
Negative and cognitive symptoms might be caused by brain damage
May be best to think of schizophrenia as multiple disorders with multiple causes

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Schizophrenia as a neurological disorder
Predisposing factors (genetic, environmental, or both) give rise to

Abnormalities in both DA transmission and PFC
Abnormalities in DA transmission that cause abnormalities in PFC
Abnormalities in PFC cause abnormalities in DA transmission

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Schizophrenia: Brain Abnormalities

Evidence of brain damage
Negative and cognitive symptoms
Loss of brain tissue
Lateral ventricles more than twice as large in schizophrenic patients than control subjects

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Possible Causes of Brain Abnormalities

Epidemiological Studies
Season of birth
Viral epidemics
Population density
Prenatal malnutrition
Maternal stress

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Age of Onset for schizophrenia

Symptoms rarely begin before late adolescence or early adulthood

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Progression of schizophrenia

neg symptoms -> cognitive symptoms -> positive symptoms

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Abnormal Brain Development (Schizophrenia)

Hypofrontality and Negative and Cognitive Symptoms
Decreased activity of the prefrontal cortex (dlPFC); believed to be responsible for the negative symptoms of schizophrenia.

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these drugs, ___ and ___ can cause positive, negative and cognitive-like symptoms

PCP and ketamine

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NMDA receptor antagonists; _____ DA and metabolic activity in frontal cortex

decrease

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Role of D2 Receptors in Development of Schizophrenia

Abnormalities in the striatal DA system may be the cause of schizophrenia
Virus inserted into striatum that increased D2 recpetors
Caused the development of behavioral deficits characteristic of schizophrenia
Abnormal activity of dlPFC

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_____ drugs are able to reduce ALL symptoms

atypical drugs

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atypical drugs:
_____ DA activity in PFC
_____ DA activity in the NA

Increase DA activity in PFC
Reduce DA activity in the NA

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Partial DA agonist

High affinity for receptor but less than ligand
Can act like an antagonist
- Nucleus accumbens
Can act like an agonist
- Prefrontal cortex

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serious mood disorder characterized by cyclical periods of mania and depression.

Bipolar disorder

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serious mood disorder that consists of unremitting depression or periods of depression that do not alternate with periods of mania.

Major Depressive Disorder

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inability to experience pleasure from activities usually found enjoyable,

Anhedonia

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Sense of euphoria not justified by circumstances
Nonstop speech and motor activity
Delusions
Full of their own importance & become angry or defensive if contradicted
Long periods without sleep
Working on “unrealistic” projects

MANIA

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measures the effect of antidepressant drugs on the behaviour of rats/mice. Immobility time is decreased by antidepressants.

Porsolt swim test

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Repeated exposure to an aggressive male mouse
Decrease in subsequent social interaction
Increased time immobile in the forced swim test

Social defeat

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First antidepressants. MAO breaks down monoamines in the terminal buttons
Increases release of DA, NE and 5-HT (not specific)

Monoamine oxidase (MAO) inhibitors

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Excess tyramine - hypertension.
Dangerous dietary interaction

MAO inhibitors: Cheese Effect

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Inhibits the reuptake of norepinephrine and serotonin but also affects other neurotransmitters. Safer than MAOI’s

Tricyclic antidepressants (TCAs)

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No more effective than TCAs, but side effects are few and they are effective at treating other disorders
‘Selective’ is relative as they still have effects on both 5-HT and NE though range in affinity:
Affinity for 5-HT:NE
Milnacipran 1:1
Venlafaxine 1:30

‘Selective’ Reuptake Inhibitors

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serotonin
Prozac, paxil

SSRIs

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norepinephrine &
5-HT

SNRIs

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brief electrical shock, applied to the head, that results in an electrical seizure; used to treat depression.
May exert effects through activation of inhibitory neurotransmitter systems
Increased GABA & Neuropeptide Y
Potential cognitive impairments

Electroconvulsive Therapy (ECT)

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Strong localized magnetic field into the brain by passing an electrical current through a coil of wired placed on the scalp

Transmagnetic stimulation (TMS)

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blocks the activity that transporters that fill synaptic vesicles in monoaminergic terminals with NTs. blocks release of NA and 5-HT

Reserpine (lower blood pressure)

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Monamine agonists treat depression

TCAs, SSRIs, SNRIs, MAOIs

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brain area involved in the expression of emotion

Amygdala
Activity in amygdala of depressed patients correlated with severity of depression

48

Metabolic activity of amygdala _____ in normal Ss when they look at faces with expressions of sadness.
Metabolic activity in amygdala _____ when depressed Ss remember episodes in their lives that made them sad

Metabolic activity of amygdala increases in normal Ss when they look at faces with expressions of sadness.
Metabolic activity in amygdala increases when depressed Ss remember episodes in their lives that made them sad .

49

Medial Prefrontal Cortex (in depression)

Subgenual ACC lower level of activation (right) in depression
Increased during mania

50

5-HT transporter (5-HTT)

The promoter region that codes for the 5-HTT comes in two forms:
Short
Long
Three possible combinations:
S-S
S-L
L-L

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The Role of the 5-HT Transporter

People with 2 long alleles tend to respond better to drug treatment.

Depressed people with 2 long alleles treated with antidepressants have better long-term outcome.

People with higher levels of 5-HT transporter in amygdala showed less activation of the amygdala when the people looked at emotional faces.

Several meta-analyses of studies investigating the role of 5-HTT promotor in depression
No significant effects!

52

Stressful experiences that produce depression (in animals) ______ hippocampal neurogenesis

Stressful experiences that produce depression (in animals) suppress hippocampal neurogenesis

53

Administration of antidepressant treatments ______ neurogenesis (in animals)

Administration of antidepressant treatments increases neurogenesis (in animals)

54

1 of the most effective antidepressant treatment –

sleep deprivation (total or REM selective)

55

Attacks of depression and lethargy typically occur every winter

SEASONAL AFFECTIVE DISORDER