Neurodevelopmental and Mood disorders Flashcards
What is synaptic pruning?
The process by which extra neurons and synaptic connections are eliminated in order to increase the efficiency of neural transmissions.
What is major depressive disorder?
Persistent feelings of sadness and despair and a loss of interest in previous sources of pleasure.
What is bipolar disorder?
Experience of both depressed and manic periods.
What percentage of the population does bipolar disorder affect?
Just over 1% of the population.
What is the peak age of onset of bipolar disorder?
Between 20 and 40 years.
What are the symptoms of mania?
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.
How long must a manic episode last for diagnosis?
At least 1 week.
What percentage of manic patients have psychotic symptoms?
50%
What are psychotic symptoms?
Delusions or hallucinations.
What is the prevalence of major depressive disorder?
8%
What is the median duration of a major depressive episode?
About 5 months.
What percentage of people who experience one episode of depression will have recurrent episodes?
75-95%
Is depression more common in men or women?
Prevalence is twice as high in women as men.
What are the symptoms of major depressive disorder?
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
What are the genetic factors for depression?
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.
When can stress lead to anxiety phenotype?
Childhood stress interacts with a gene mutation to lead to anxiety phenotype.
Stress in adolescents does not have this effect.
Which polymorphism in 5-HTT promoter gene is associated with depression and anxiety?
44bp deletion (short allele)
What is the link between schizophrenia and synaptic pruning?
It is linked to excessive synaptic pruning.
What is the incidence of schizophrenia?
1-1.5%
What is the usual age of onset of schizophrenia?
Adolescence/young adulthood
What are the clinical features of schizophrenia?
Delusions, hallucinations, disorganised speech, deterioration of adaptive behaviour
What is the heritability of schizophrenia?
48%
Abnormalities on which chromosomes are linked to schizophrenia?
5, 8, 11, 13, 22
What are the five most commonly studied risk genes in schizophrenia?
NRG1 DISC-1 Dysbindin COMT RGS4
What are the pre/perinatal risk factors for schizophrenia?
Obstetric complications
Winter birth
Maternal influenza
Maternal malnutrition
What are the postnatal risk factors for schizophrenia?
Early childhood CNS infection Epilepsy Learning disability Delayed milestones Poor childhood peer relationships Early cannabis use Stressful life events
What are the social risk factors for schizophrenia?
Urban birth
Migrant status
Low social class
What does the DISC1 gene affect?
Neurodevelopment, neurite architecture, neuronal migration, intracellular transport and synaptic transmission
Have you gone back to the lectures and studied the behavioural mouse models?
Go and do it.
What does the neuregulin-1 gene affect in schizophrenia?
Myelination Heart development Neurotransmission Neuronal migration Axonal guidance Synaptic plasticity Inflammation
Have you done the further reading?
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
What are the positive symptoms of schizophrenia?
Hallucinations
Delusions
Disorder of logical thought
What are the negative symptoms of schizophrenia?
Sustained depression Anhedonia (inability to feel pleasure) Avolition (lack of drive) Slow thought/speech/actions Alogia (inability to speak) Lack of recognition of illness
What are the cognitive deficits found in schizophrenia?
Difficulties in learning and planning
Lack of flexibility.
What are the typical antipsychotics used to treat schizophrenia?
Chlorpromazine
Haloperidol
Sulpiride
Perphenazine
What are the atypical antipsychotics used to treat schizophrenia?
Clozapine Olanzapine Quetiapine Ziprasidone Aripiprazole
What are current antipsychotic drugs for the treatment of schizophrenia blocking?
D2 Dopamine receptors
In the treatment of schizophrenia which symptoms do most antipsychotics target?
Positive symptoms
What is the DA theory of schizophrenia supported by?
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.
What are the problems with the DA theory of schizophrenia?
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.
What are the side effects of anti-psychotic drugs?
PD-like akinesia Endocrine dysfunction Postural hypotension Sedation Dry mouth Weight gain
Which receptors do clozapine have a particularly high affinity for?
D4 Dopamine receptors
What has PET imaging found is going on in the schizophrenic brain?
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.
What is the pathology of schizophrenia?
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.
What did administration of PCP or ketamine to volunteers lead to?
Elevated scores on : Positive symptoms Negative symptoms Cognitive symptoms Hostility factors
What does PCP target in the body?
It is an NMDA receptor antagonist.
What was noticeable about long term PCP addicts?
They had symptoms indistinguishable from schizophrenia.
Which theory has study of PCP led to?
Glutamate hypofunction may underly psychosis.
What does MRS imaging show with relation to glutamate in schizophrenia?
Reduced prefrontal cortex glutamate.
What are the conclusions on glutamatergic drugs for antipsychotic therapy?
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.
