Schizophrenia and Affective Disorders C81BIO – Semester 2, Lecture 3 Dr. Mark Haselgrove
Mar 28, 2015
Schizophrenia and Affective Disorders
C81BIO – Semester 2, Lecture 3
Dr. Mark Haselgrove
Overview of the lecture
(1)SchizophreniaProperties of Schizophrenia
Heritability of Schizophrenia
Pharmacology of Schizophrenia : Dopamine hypothesis
Brain abnormalities in schizophrenia
(2) Affective DisordersProperties of Affective Disorders
Heritability of Affective Disorders
Pharmacological treatment: Monoamine hypothesis
Depression and sleep deprivation
(1) Schizophrenia
Properties of Schizophrenia
Afflicts approx 1% of the worlds population (66 million people)
Term coined by Bleuler (1911) “Split mind” – A break with reality
(1) Schizophrenia
Heritability of Schizophrenia
Relation % Developing Schizophrenia
Child of two Sx Parents
MZ twins
Parents
Siblings
Children
Husband/Wife
General Population
46%
48%
6%
9%
13%
2%
1%
About 10% probability
Genetic & environmentalcontribution
EnvironmentalContribution?
(1) Schizophrenia
Pharmacology of Schizophrenia: The dopamine hypothesis
Over-activity of dopamine neurons → Positive symptoms
Chlorpromazine (a dopamine antagonist) – Diminishes positive symptoms
Dopamine agonists (e.g. amphetamine) – Induce positive effects
More dopamine release inschizophrenics than controls
(1) Schizophrenia
Pharmacology of Schizophrenia: The dopamine hypothesis
Why do dopamine agonists induce positive symptoms?
Ventral tegmental area
Amygdala
Nucleus accumbens
Dopamine
Dopamine
- Activity of Dopamine neurons in the accumbens strongly reinforce behaviour
- Snyder (1974) Schizophrenics report elation at the start of a schizophrenic episode
- Fibiger (1991) Paranoid delusions caused by activity in Amygdala(Amygdala is involved with learning emotional responses)
(1) Schizophrenia
Brain abnormalities in Schizophrenia
Schizophrenics with negative and cognitive symptomsexhibit neurological damage
(1) Schizophrenia
Brain abnormalities in Schizophrenia
What causes the brain damage?
Viral infection during the 2nd trimester of pregnancy
(1) Schizophrenia
Brain abnormalities in Schizophrenia
Discordance in MZ twins – A pre-natal environmental effect?
Davis et al (1995) monochorionic concordance = 60% dichorionic concordance = 10.7%
(2) Affective Disorders
Properties of Affective disorders
Bipolar disorder – Alternating periods of mania and depression 1% of the population afflicted at some point in their life Equally frequent in men and women
Unipolar disorder – Depression without mania 2 or 3 three times more likely in women than men
Some cases of mania without depression – but rare
Depression – low energy levels, anhedonia, loss of appetite for food and sex, sleeping problems, constipation!
Mania – euphoria, delusional, poor attention span, lack of sleep, self important
(2) Affective Disorders
Heritability
Rosenthal (1971) – 10 times more likely to suffer from affective disorders if a close relative also does
Gershon et al. (1976) MZ concordance = 69%DZ concordance = 13 %
Price (1968) Concordance is the same whether twins are raised apart or together
(2) Affective Disorders
Pharmacological treatment
MOA (monoamine oxidase): enzyme that destroys Monoamines in PoSN - Serotonin, Dopamine, Norepinephrine
Drug Action Notes
Iproniazid Inhibits MOA (thus ↑ Serotonin, dopamine & norepinepherine
Discovered as a side effect of TB treatment
Unpleasant side effects
Tricyclic antidepressants
Agonists of just Serotonin & norepinepherine
Inhibits reuptake of neurotransmitter by terminal buttons
SSRIs (e.g. prozac)
Agonists of just Serotonin
Inhibits reuptake of just 5HT
(2) Affective Disorders
Pharmacological treatment: Monoamine Hypothesis -
Depression caused by low activity on Monoamine neurons
Dopamine agonists do not relieve depression
……. Serotonin and norepinepherine?
Reserpine (used to treat high blood pressure): side effect = depression(Sachar & Baron, 1979)
Reserpine = monoamine antagonist.
(2) Affective Disorders
Pharmacological treatment
Lithium (Lithium Carbonate): Used to treat mania
- Why it works is not fully understood – Possibly stabilises serotonin release
Side effects: diuresis, hand tremors, weight gain, thirst
(2) Affective Disorders
Depression and sleep deprivation
Vogel et al. (1975, 1990):Preventing REM sleep actsas an antidepressant
Scherschlicht et al (1982):Examined effects of 20 antidepressantsAll reduced REM sleepMost increased slow-wave sleep
Reading
Pinel, J. P.J. (2011) Biopsychology, Pearson. Chapter 18
Carlson, N. R. (2010) Physiology of Behavior, Allyn & Bacon. Chapter 16
Kalat, J. W. (2011) Biological Psychology, Thompson. Chapter 15
Next Time: Eating and Eating Disorders
Email: [email protected]