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: Mark.Haselgrove@nottingham.ac.uk