Announcement - PowerPoint PPT Presentation

1 / 31
About This Presentation
Title:

Announcement

Description:

The following material related to the visual system will not be tested on the December exam: Lecture s: Lecture 28, s 15-24 (on- and off-center cells ... – PowerPoint PPT presentation

Number of Views:66
Avg rating:3.0/5.0
Slides: 32
Provided by: psyclab1P
Category:

less

Transcript and Presenter's Notes

Title: Announcement


1
Announcement
The following material related to the visual
system will not be tested on the December
exam Lecture slides Lecture 28, slides 15-24
(on- and off-center cells, simple cortical cells,
complex cortical cells). Textbook Bottom half of
p. 294 bottom half of p. 300 figure 10.15
bottom half of p. 302 and top half of p. 303the
spatial-frequency filter model, presented on p.
303-305 of the textbook.
2
Biopsychology of Psychiatric Disorders
Guest LecturerNaghmeh Shafiei
  • Schizophrenia,
  • Affective disorders,
  • Anxiety disorders

3
Psychiatric disorders
  • What are Psychiatric disorders (Symptoms)?
  • What are some causal contributors?
  • What are some hypothesis about why how they
    develop?
  • What are some treatment options?

4
Outline
  • Schizophrenia
  • Symptoms
  • Epidemiology
  • Causes
  • Heredity
  • Cognitive deficiencies
  • Neural abnormalities
  • Cognitive abnormalities in schizophrenia
  • The dopamine hypothesis
  • Problems with typical antipsychotics
  • Problems with the dopamine hypothesis
  • The Glutamate hypothesis
  • Neural Circuitry Implicated in Schizophrenia
  • A new hypothesis

5
Schizophrenia
  • Schizophrenia
  • Paranoid Schizophrenic
  • Disorganized schizophrenic
  • Catatonic schizophrenic
  • There are also
  • Schizoaffective disorder
  • Schizophreniform disorder

6
Symptoms
  • Schizophrenia as defined by DSM IV
  • Delusions Hallucinations
  • Incoherence Disorganized or
    Catatonic
  • Negative symptom
  • 6 months duration, psychotic for 1 month
  • Course
  • Continuous
  • Episodic, with or without residuals
  • Single episode, partial or full remission

7
SchizophreniaSymptoms
  • Negative Symptoms Behavioral deficits
  • Social withdrawal
  • Flat affect, Apathy
  • Anhedonia, lack of pleasure
  • Reduced focus and motivation
  • Catatonia

8
SchizophreniaEpidemiology
  • Onset
  • Late teenage years-early adulthood
  • Earlier onset in males (20-28) than in females
    (26-32)
  • Rare onset in childhood and late adulthood
  • Lifetime prevalence of 1.

9
CausesCausescauses
  • Heredity
  • Twin studies
  • Family studies
  • Adoption Studies

10
CausesCausescauses
  • These findings indicate
  • There is a strong genetic component to
    schizophrenia, but
  • Altered genes are NOT the only cause of the
    disease
  • Genetic component not linked to just one gene,
    there may be dozens that are altered.
  • So why some and not others?
  • Birth complications, Early infections, Autoimmune
    reactions, Toxins, Traumatic injuries, Stress

11
CausesCausescauses
  • Alterations throughout development
  • In utero influence includes
  • Poor nutrition during pregnancy,
  • Premature birth/low birth weight
  • Physical and immune stressors during pregnancy

12
Cognitive deficiencies
  • Cognitive functioning is the 1 predictor of long
    term outcome (better function better prognosis)
  • Seven primary domains of cognition that are
    affected
  • Speed of Processing Attention/Vigilance
  • Working Memory Verbal Learning/Memory
  • Visual Learning/Memory Reasoning/Problem
    Solving
  • Social Cognition

13
Neural abnormalities
  • Enlarged Ventricles

14
Neural abnormalities
  • Hippocampus brain region in temporal lobe
    critical for memory formation.
  • Some schizophrenics have enlarged lateral
    ventricles, due to smaller hippocampus and other
    temporal lobe regions
  • Closer inspection reveals organization of
    hippocampal neurons is altered in the
    schizophrenic brain (neural organization occurs
    during development)

15
Neural abnormalitiesNeural abnormalities
Neural abnormalities
  • Not brain damage per se changes in the neural
    organization can disrupt the way brain regions
    process information


16
Neural abnormalities
  • Prefrontal Cortex (PFC) frontal lobe region
    critical for higher order cognition (short term
    memory, planning, behavioural flexibility,
    abstract thinking)
  • Neurons in the PFC of schizophrenics have reduced
    number of dendrites, which in turn reduces
    processing power of these cells.

17
Neural abnormalities
  • Cortical gray matter loss in adolescence in the
    case of early onset Schizophrenia
  • No major structural abnormalities in the frontal
    lobes.

18
Cognitive Abnormalities in Schizophrenia
Wisconsin Card Sorting Task A classic PFC
task Test behavioural flexibility (ability to
change strategies)
19
Cognitive Abnormalities in Schizophrenia
  • Subjects initially sort cards by one dimension
    (e.g., number)
  • Then task switches, subjects must ignore old
    strategy and switch to new one (e.g., shape)
  • Damage to PFC impairs switching strategies,
    patients keep sorting cards by first dimension
    (keep sorting by number)
  • Schizophrenics also impaired on this task

20
Cognitive Abnormalities in Schizophrenia
  • Brain activation studies schizophrenics and
    discordant identical twin controls performed
    Wisconsin Card Sort
  • Schizophrenics had activation of the PFC at
    rest showed no increase when performing task,
    unlike controls
  • Other brain regions were activated similarly in
    both groups
  • Schizophrenics show a dramatic decrease in PFC
    function, but not other cortical regions

21
Cognitive Abnormalities in Schizophrenia
During card sorting task
  • Hypofrontality (reduced PFC function) is a
    characteristic negative symptom of schizophrenia

22
The Dopamine hypothesisTreatments
  • Most of the dopamine in the brain is produced in
    small nuclei in the midbrain
  • 1950s Chlorpromazine found to be antipsychotic
    causes Parkinsons symptoms in healthy subjects
  • Brains of Parkinsons patients found to be
    depleted of dopamine
  • 1960s Drugs that increase dopamine release
    (e.g. amphetamine) could induce psychotic
    symptoms
  • Chlorpromazine and other antipsychotics found to
    block dopamine receptors (Typical antipsychotics)
  • 1970s Dopamine receptor subtypes discovered
    antipsychotic potency of a drug correlated with
    binding to D2 receptors (not D1)
  • THUS, The dopamine hypothesis was born
  • Schizophrenia is caused by an abnormal increase
    in dopamine transmission, leading to
    overstimulation of D2 receptors

23
The Dopamine hypothesisTreatments
  • How are D2 receptors being overstimulated?
  • More D2 receptors?
  • Unlikely Some post mortem studies report D2
    receptors in
  • schizophrenic brains, others failed to
    find this effect
  • Changes may be due to chronic antipsychotic
    medication
  • More dopamine being produced?
  • Probably not Schizophrenics do not show
    differences in dopamine
  • metabolites in CSF
  • More dopamine being released?
  • Study imaging allows for non-invasive measure of
    dopamine release in human brain
  • Give amphetamine to schizophrenics or controls
  • Greater dopamine release in the Nucleus Accumbens
    (NAcc) of schizophrenics
  • More dopamine release more positive symptoms

24
Problems with typical antipsychotics
  • Dopamine is heavily involved in motor functions.
  • Long term treatment with antipsychotics (dopamine
    blockers) can cause movement (a.k.a
    extrapyramidal) side effects
  • Tardive dyskinesia occurs in about one third of
    patients treated with classical antipsychotics
  • grimacing, tongue protrusion, lip smacking, rapid
    limb/trunk movements symptoms continue after
    discontinuing medication.
  • Drugs that are more selective for dopamine vs
    other receptors usually cause the worst side
    effects
  • Antipsychotic drugs treat psychosis (delusions,
    hallucinations) Other negative symptoms rarely
    improve with typical antipsychotics

25
Problems with the DA hypothesis
  • Antipsychotics block dopamine receptors right
    away, yet drug treatment takes 2 weeks to reach
    full effect
  • If schizophrenia is merely an increase in
    dopamine, drugs should work right away
  • Not all schizophrenic patients respond to drugs
    that block dopamine receptors
  • If schizophrenia is merely an increase in
    dopamine, drugs should work for all patients
  • Dopamine blockers can alleviate psychosis, but do
    not treat negative symptoms.
  • If cognitive deficits are due to an increase in
    dopamine, these drugs should alleviate the
    symptoms

26
Problems with the Dopamine Hypothesis
  • 4) Some drugs that reduce symptoms do not block
    D2 receptors very well
  • Example Clozapine (atypical antipsychotic)
  • Not as effective at blocking D2 receptors as
    classical antipsychotics
  • Less likely to produce motor side effects
  • Has a much higher affinity to other receptors,
    like serotonin (5 HT)
  • Can improve negative symptoms
  • (possibly via 5 HT blockade)
  • If positive and negative symptoms are merely due
    to overstimulation of D2 receptors, atypical
    antipsychotics shouldnt work very well
  • Problems some patients have an adverse blood
    reaction to clozapine not all patients can take
    it safely

27
  • 5) Drugs that increase dopamine release can
    improve performance on cognitive tasks
  • Study Schizophrenics and controls tested on a
    working memory task (dependent on PFC function)
  • Given either placebo or low dose of amphetamine
    (dose dopamine release, but not psychotic
    symptoms)
  • Under placebo, schizophrenics performed worse
    than controls
  • Amphetamine, improved performance in
    schizophrenics, up to control levels

Errors
  • If schizophrenia is just an increase in dopamine,
    then why should a drug that increases dopamine
    release
  • 1) not affect psychosis (even at low doses)
  • 2) improve cognitive functions?

28
The Glutamate hypothesis
  • Abuse of phencyclidine (PCP, angeldust) or
    ketamine (Special K) can cause psychotic symptoms
    and cognitive deficits resembling schizophrenia
  • Long lasting effects can persist after drug use
    has stopped
  • Can also cause degeneration of PFC neurons
  • These drugs block NMDA subtype of glutamate
    receptors
  • Block the ion channel glutamate cannot activate
    receptor
  • Glutamate hypothesis Schizophrenia is caused by
    decreased glutamate transmission
  • Neurons in PFC/hippocampus use glutamate as a
    transmitter
  • Degeneration of these neurons in schizophrenia
    disrupts their function, less glutamate released
    in these areas

29
The Glutamate hypothesis
Working memory performance
Dopamine levels
  • Rat/primate studies show that repeated PCP
  • 1) decreases dopamine release in PFC
  • 2) causes cognitive deficits on PFC-dependent
    tasks
  • These effects persist weeks after drug treatment
    has stopped
  • Schizophrenics show decrease dopamine activity in
    PFC
  • This model encompasses both positive and negative
    symptoms of the disorder
  • Recent finding these drugs are also potent D2
    receptor agonists (stimulate the receptors)
  • Negative symptoms decreased glutamate/dopamine
    transmission in PFC
  • Positive symptoms increased D2 receptor
    stimulation in NAcc

30
Neural Circuitry Implicated in Schizophrenia
Cognitive functions impaired in schizophrenia
(decreased glutamate, dopamine?)
PFC projects back to VTA
Increased dopamine release in schizophrenia
related to psychotic symptoms
Nucleus Accumbens
VTA sends dopamine input to PFC and accumbens
  • This connectivity suggests that prefrontal cortex
    can modulate dopamine release in the NAcc

31
A New Hypothesis
PFC
Nucleus Accumbens
  • 1) Decreased PFC dopamine/glutamate reduces
    activity, (negative symptoms)
  • 2) Decreased PFC activation reduces inhibition of
    dopamine system
  • 3) Release from this inhibition leads to
    increased dopamine transmission in NAcc (positive
    symptoms)
Write a Comment
User Comments (0)
About PowerShow.com