Schizophrenia Flashcards
How much of the population does schizophrenia affect?
→ 1%
What gender is affected more?
→ men are more affected
What are positive symptoms in schizophrenia?
→ increase in abnormal behaviour in addition to normal behaviour
What are negative symptoms in schizophrenia?
→ absence of normal behaviour
What are cognitive symptoms in schizophrenia?
→ problems with thought processes
What are examples of positive symptoms?
→ hallucinations
→ delusions
→ disorganised thought/speech
→ movement disorders
What are examples of negative symptoms?
→ social withdrawal → anhedonia → lack of motivation → poverty of speech → emotional flatness
What are examples of cognitive symptoms?
→ impaired working memory
→ impaired attention
→ impaired comprehension
How long must symptoms last for?
→ 6 months
If an identical twin has schizophrenia what is the likelihood of the other twin having it?
→ 50%
What are 3 candidate genes for schizophrenia?
→ COMT
→ DISC1
→ GRM3
What are 4 pregnancy complications that can lead to schizophrenia?
→ low birth weight
→ premature birth
→ asphyxia
→ influenza
What are the 4 types of stress that can contribute to schizophrenia?
→ moving country
→ bereavement
→ loss of job/home/relationship
→ physical/emotional/sexual abuse
What kind of drug use can contribute?
→ cannabis
→ amphetamine
→ cocaine
→ LSD
What is the evidence for the dopamine hypothesis for schizophrenia?
→ DA is only released in mesocortical and mesolimbic not nigrostriatal
→ D2 agonists produce stereotyped behavior
→ Reserpine depletes DA and controls +ve symptoms
→ antagonist of the D2 receptor has antipsychotic effects
→ Amphetamine increases DA release in schizophrenics which makes the disease worse
What is the evidence against the dopamine hypothesis?
→ No change in DA receptors in drug free patients
→ No change in CSF HVA concentration
What are the 3 structural differences in schizophrenic brains?
→ brain is slightly smaller
→ grey matter is reduced
→ enlarged ventricles and smaller hippocampus
What are the 6 reasons that contribute to the pathophysiology of schizophrenia?
→ Dopamine hypothesis → Brain structure differences → Hypofrontality → NMDA receptor hypofunction → Oxidative Stress
WHat is hypofrontality?
→ Reduced blood flow to the frontal cortex → reduced activity
What is the evidence for the glutamate hypothesis?
→ NMDA antagonists (PCP and ketamine) cause hallucinations and psychotic symptoms
→ Decreased glutamate receptor density in the prefrontal cortex
→ transgenic mice have decreased NMDA receptors and have decreased social interactions
What does NMDA hypofunction enhance and reduce?
→ enhances mesolimbic DAergic activity
→ reduces GABA striatal neuron activity
What are the effects of Glutamate and Dopamine on GABA receptors?
→ Glutamate - excitatory
→ dopamine - inhibitory
What does too little glutamate and too much dopamine cause in the brain?
→ uninhibited sensory input to limbic areas
What is the evidence of the effect of 5-HT on schizophrenia?
→ LSD - partial 5-HT agonist causes hallucinations
→ many antipsychotics antagonise 5-HT receptors
→ 5-HT activates DA pathways
What does 5-HT2A antagonism cause?
→ antipsychotic effect
→ reduce movement disorder side effects
What is the main current theory for schizophrenia?
→ over stimulation mesolimbic of D2 receptors
→ Hypoactivity of frontal cortical D1 receptors
→ reduced pre frontal glutaminergic activity
→ 5-HT involved
What are the two categories of antipsychotics?
→ typicals
→ atypicals
What do typicals do?
→ antagonise D2 receptors
What do atypicals do?
→ 5-HT2A agonists and D2 agonists
Why are atypicals better than typicals?
→ they produce fewer side effects and are more effective at treating the negative symptoms
→ typicals are only effective in treating positive symptoms
What are the effects of a D2 blockade on the nigrostriatal pathway?
→ Parkinsonian like symptoms
→ Dystonia
→ Akinesia
→ Tardive Dyskinesia
What are the endocrine effects of a D2 blockade?
→ Breast swelling
→ Lactation
→ Impotence
What are the effects of a D2 blockade on the mesocortical pathway?
→ Loss of motivation and reward pathways
→ sedation
What are the effects of a D2 blockade on mesolimbic pathway?
→ Decreased hallucination and treats positive symptoms
What other receptors do antipsychotics block other than D2?
→ Muscarinic
→ histamine
→ alpha adrenoceptos
→ 5-HT
What is the effect of an alpha adrenoceptor blockade?
→ Postural hypotension
→ nasal congestion
→ hypothermia
What is the effect of a muscarinic blockade?
→ Dry mouth
→ blurred vision
→ constipation
→ urinary retention
What is the effect of blocking H1 and 5-HT?
→ H1 - sedation
→ 5-HT weight gain + photosensitisation
What does prolactin do?
→ promotes milk production
What are two schizoaffective disorders?
→ schizophrenia
→ bipolar
What is the phase before the disease characterized by?
→ social isolation
→ interest in fringe cults
→ social withdrawal
What are the 4 phases of schizophrenia?
→ prodrome - late teens/early twenties mistaken for depression and anxiety
→ Active acute phase - onset of positive symptoms, differentiation between what is and isn’t real is difficult
→ remission - returning to normality
→ Relapse
What are the requirements for a schizophreniform disease?
→ positive symptoms for at least a month but under 6 months
What are the 4 kinds of auditory hallucinations?
→ voices talking about them in 3rd person
→ voicew talking to them
→ voices giving running commentary
→voiced echoing thoughts
What is a delusion?
→ a fixed belief not consistent with cultural norms
What are the two states of behavior that schizophrenics exhibit?
→ hyperactivity - destructiveness
→impulsive behavior - murder
What cognitive defects do schizophrenics have?
→Decreased responsiveness to emotional issues.
→Incongruous affect
→Expression of affect inappropriate to circumstances.
What are negative symptoms caused by?
→ decreased dopamine activity in the mesocortical system
→ decrease in D1
→ Decrease in glutamate (NMDA)
What are positive symptoms caused by?
→ Increased dopamine activity in the mesolimbic pathway
→ Increased D2
What is the mesolimbic pathway?
→ VTA to
→ nucleus accumbens
→ amygdala
→ hippocampus
What is the mesocortical pathway?
→ VTA to cortex
What is the tuberohypophyseal pathway?
→ dopamine in anterior pituitary inhibiting the release of prolactin
