Neurodevelopmental and Mood disorders

Question 1

What is synaptic pruning?

Answer 1

The process by which extra neurons and synaptic connections are eliminated in order to increase the efficiency of neural transmissions.

Question 2

What is major depressive disorder?

Answer 2

Persistent feelings of sadness and despair and a loss of interest in previous sources of pleasure.

Question 3

What is bipolar disorder?

Answer 3

Experience of both depressed and manic periods.

Question 4

What percentage of the population does bipolar disorder affect?

Answer 4

Just over 1% of the population.

Question 5

What is the peak age of onset of bipolar disorder?

Answer 5

Between 20 and 40 years.

Question 6

What are the symptoms of mania?

Answer 6

Elation, euphoria, extreme sociability, impatience, racing thoughts, flight of ideas, impulsive behaviour, over-talkative, self confident, delusions of grandeur, hyperactive, unable to sleep or eat, increased libido.

Question 7

How long must a manic episode last for diagnosis?

Answer 7

At least 1 week.

Question 8

What percentage of manic patients have psychotic symptoms?

Answer 8

50%

Question 9

What are psychotic symptoms?

Answer 9

Delusions or hallucinations.

Question 10

What is the prevalence of major depressive disorder?

Answer 10

8%

Question 11

What is the median duration of a major depressive episode?

Answer 11

About 5 months.

Question 12

What percentage of people who experience one episode of depression will have recurrent episodes?

Answer 12

75-95%

Question 13

Is depression more common in men or women?

Answer 13

Prevalence is twice as high in women as men.

Question 14

What are the symptoms of major depressive disorder?

Answer 14

5+ symptoms over 2 weeks:
Depressed mood and/or diminished interest
Weight loss
Insomnia or hypersomnia
Psychomotor agitation or retardation
Loss of energy - fatigue
Worthlessness or guilt
Inability to concentrate or indecisiveness
Thoughts of death or suicide

Question 15

What are the genetic factors for depression?

Answer 15

Serotonin transporter promoter variant 5-HTTLPR
5-HTT target of SSRIs
S-short and L-long form of promoter: the L form has higher promoter activity.
Both are quite common in caucasians.

Question 16

When can stress lead to anxiety phenotype?

Answer 16

Childhood stress interacts with a gene mutation to lead to anxiety phenotype.
Stress in adolescents does not have this effect.

Question 17

Which polymorphism in 5-HTT promoter gene is associated with depression and anxiety?

Answer 17

44bp deletion (short allele)

Question 18

What is the link between schizophrenia and synaptic pruning?

Answer 18

It is linked to excessive synaptic pruning.

Question 19

What is the incidence of schizophrenia?

Answer 19

1-1.5%

Question 20

What is the usual age of onset of schizophrenia?

Answer 20

Adolescence/young adulthood

Question 21

What are the clinical features of schizophrenia?

Answer 21

Delusions, hallucinations, disorganised speech, deterioration of adaptive behaviour

Question 22

What is the heritability of schizophrenia?

Answer 22

48%

Question 23

Abnormalities on which chromosomes are linked to schizophrenia?

Answer 23

5, 8, 11, 13, 22

Question 24

What are the five most commonly studied risk genes in schizophrenia?

Answer 24

NRG1
DISC-1
Dysbindin
COMT
RGS4

Question 25

What are the pre/perinatal risk factors for schizophrenia?

Answer 25

Obstetric complications Winter birth Maternal influenza Maternal malnutrition

Question 26

What are the postnatal risk factors for schizophrenia?

Answer 26

``` Early childhood CNS infection Epilepsy Learning disability Delayed milestones Poor childhood peer relationships Early cannabis use Stressful life events ```

Question 27

What are the social risk factors for schizophrenia?

Answer 27

Urban birth Migrant status Low social class

Question 28

What does the DISC1 gene affect?

Answer 28

Neurodevelopment, neurite architecture, neuronal migration, intracellular transport and synaptic transmission

Question 29

Have you gone back to the lectures and studied the behavioural mouse models?

Answer 29

Go and do it.

Question 30

What does the neuregulin-1 gene affect in schizophrenia?

Answer 30

``` Myelination Heart development Neurotransmission Neuronal migration Axonal guidance Synaptic plasticity Inflammation ```

Question 31

Have you done the further reading?

Answer 31

Lin et. al. Better understanding of mechanisms of schizophrenia and bipolar disorder: From human gene expression profiles to mouse models. Neurobiology of Disease, 45(1); 48-56

Question 32

What are the positive symptoms of schizophrenia?

Answer 32

Hallucinations Delusions Disorder of logical thought

Question 33

What are the negative symptoms of schizophrenia?

Answer 33

``` Sustained depression Anhedonia (inability to feel pleasure) Avolition (lack of drive) Slow thought/speech/actions Alogia (inability to speak) Lack of recognition of illness ```

Question 34

What are the cognitive deficits found in schizophrenia?

Answer 34

Difficulties in learning and planning | Lack of flexibility.

Question 35

What are the typical antipsychotics used to treat schizophrenia?

Answer 35

Chlorpromazine Haloperidol Sulpiride Perphenazine

Question 36

What are the atypical antipsychotics used to treat schizophrenia?

Answer 36

``` Clozapine Olanzapine Quetiapine Ziprasidone Aripiprazole ```

Question 37

What are current antipsychotic drugs for the treatment of schizophrenia blocking?

Answer 37

D2 Dopamine receptors

Question 38

In the treatment of schizophrenia which symptoms do most antipsychotics target?

Answer 38

Positive symptoms

Question 39

What is the DA theory of schizophrenia supported by?

Answer 39

Observation that DA-R agonism can cause hallucinations. Observation that amphetamine and cocaine can exacerbate psychosis in patients. Some evidence of altered DA-Rs and DA turnover in the CNS of schizophrenic patients.

Question 40

What are the problems with the DA theory of schizophrenia?

Answer 40

D2 receptor blockade is immediate, but therapeutic benefit takes weeks to appear. Some patients do not respond, despite D2 receptor blockade. Changes in DA metabolites (HVA, DOPAC), observed in brains of schizophrenic patients, may reflect years of antipsychotic medication, rather than an underlying cause of the disease. These drugs tend to be much more effective against the positive symptoms than the negative symptoms.

Question 41

What are the side effects of anti-psychotic drugs?

Answer 41

``` PD-like akinesia Endocrine dysfunction Postural hypotension Sedation Dry mouth Weight gain ```

Question 42

Which receptors do clozapine have a particularly high affinity for?

Answer 42

D4 Dopamine receptors

Question 43

What has PET imaging found is going on in the schizophrenic brain?

Answer 43

Hypofunction in prefrontal cortex - not restored by current drugs Hypofunction in temporal cortex and thalamus Hyperfunction in temporal cortex and thalamus during hallucinations - restored by current drugs.

Question 44

What is the pathology of schizophrenia?

Answer 44

Gene/environment effects lead to altered function in corticolimbothalamic circuit. Impaired development of prefrontal/hippocampal chandelier cells. Chandelier cells unusual, in that NMDA receptors contribute to basal levels of activation. NMDA-receptor antagonists mimic dysfunctionin schizophrenia by reducing glutamatergic synaptic activation of cells.

Question 45

What did administration of PCP or ketamine to volunteers lead to?

Answer 45

``` Elevated scores on : Positive symptoms Negative symptoms Cognitive symptoms Hostility factors ```

Question 46

What does PCP target in the body?

Answer 46

It is an NMDA receptor antagonist.

Question 47

What was noticeable about long term PCP addicts?

Answer 47

They had symptoms indistinguishable from schizophrenia.

Question 48

Which theory has study of PCP led to?

Answer 48

Glutamate hypofunction may underly psychosis.

Question 49

What does MRS imaging show with relation to glutamate in schizophrenia?

Answer 49

Reduced prefrontal cortex glutamate.

Question 50

What are the conclusions on glutamatergic drugs for antipsychotic therapy?

Answer 50

Glutamatergic drugs appear to make no difference when added to existing treatment. Glycine and D-serine may somewhat improve negative symptoms when added to regular antipsychotic medication, but the results are not fully consistent and data are too few. Many participants in the trials were treatment resistant.