Chapter 16 - Schizophrenia and Affective disorders Flashcards
serious mental disorder characterized by disordered thoughts, delusions, hallucinations, and often bizarre behaviors
schizophrenia
Refers to the breakdown of integration of emotion, thought, and action
“Splitting of psychic functions”
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
Type of schizophrenia. Not as bad. Does not mean you will always have schizophrenia.
acute
– gradual onset, progressive deterioration
~ 1/3 of those diagnosed will show progressive deterioration
Chronic schizophrenia
: statistic which gives an estimate of the total variance in a trait that is attributable to genetic variation in a group
Heritability
Mechanisms that control the expression of genes
Epigenetics
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
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)
Activation of D1-like Rs
stimulates cAMP
Activation of D2-like R
inhibits cAMP
All DA receptors are
metabotropic
Anti-Schizophrenic Drugs
2 Classes
Phenothiazines
Butyrophenones
drug that Binds to D1 & D2 Receptors
Chlorpromazine
drug that bind to d2 receptors only
Spiroperidol
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
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
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
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
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
Possible Causes of Brain Abnormalities
Epidemiological Studies
Season of birth
Viral epidemics
Population density
Prenatal malnutrition
Maternal stressAge of Onset for schizophrenia
Symptoms rarely begin before late adolescence or early adulthood
Progression of schizophrenia
neg symptoms -> cognitive symptoms -> positive symptoms
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.
these drugs, ___ and ___ can cause positive, negative and cognitive-like symptoms
PCP and ketamine
NMDA receptor antagonists; _____ DA and metabolic activity in frontal cortex
decrease
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
_____ drugs are able to reduce ALL symptoms
atypical drugs
atypical drugs:
_____ DA activity in PFC
_____ DA activity in the NA
Increase DA activity in PFC
Reduce DA activity in the NA
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
serious mood disorder characterized by cyclical periods of mania and depression.
Bipolar disorder
serious mood disorder that consists of unremitting depression or periods of depression that do not alternate with periods of mania.
Major Depressive Disorder
inability to experience pleasure from activities usually found enjoyable,
Anhedonia
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
measures the effect of antidepressant drugs on the behaviour of rats/mice. Immobility time is decreased by antidepressants.
Porsolt swim test
Repeated exposure to an aggressive male mouse
Decrease in subsequent social interaction
Increased time immobile in the forced swim test
Social defeat
First antidepressants. MAO breaks down monoamines in the terminal buttons
Increases release of DA, NE and 5-HT (not specific)
Monoamine oxidase (MAO) inhibitors
Excess tyramine - hypertension.
Dangerous dietary interaction
MAO inhibitors: Cheese Effect
Inhibits the reuptake of norepinephrine and serotonin but also affects other neurotransmitters. Safer than MAOI’s
Tricyclic antidepressants (TCAs)
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
serotonin
Prozac, paxil
SSRIs
norepinephrine &
5-HT
SNRIs
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)
Strong localized magnetic field into the brain by passing an electrical current through a coil of wired placed on the scalp
Transmagnetic stimulation (TMS)
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)
Monamine agonists treat depression
TCAs, SSRIs, SNRIs, MAOIs
brain area involved in the expression of emotion
Amygdala
Activity in amygdala of depressed patients correlated with severity of depression
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 .
Medial Prefrontal Cortex (in depression)
Subgenual ACC lower level of activation (right) in depression
Increased during mania
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
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!
Stressful experiences that produce depression (in animals) ______ hippocampal neurogenesis
Stressful experiences that produce depression (in animals) suppress hippocampal neurogenesis
Administration of antidepressant treatments ______ neurogenesis (in animals)
Administration of antidepressant treatments increases neurogenesis (in animals)
1 of the most effective antidepressant treatment –
sleep deprivation (total or REM selective)
Attacks of depression and lethargy typically occur every winter
SEASONAL AFFECTIVE DISORDER
