Psychotic Disorders

Question 1

Diagnostic criteria for schizophrenia

Answer 1

• Characteristics symptoms (2 for at least one month):
  
  • delusions
  • hallucinations
  • disorganized speech
  • grossly disorganized or catotonic behavior
  • negative symptoms such as affective flattening
• social/occupational dysfxn
• duration of symptoms for at least 6 months
• mood disorder isn’t major part of illness
• illness not due to medication/medical condition or substance abuse
• illness is not part of autism/developmental disorder

Question 2

Characteristics of Psychotic patients

Answer 2

• primary disorder in thinking

1. hallucinations = hear voices, experience other unreal sensations
2. paranoid delusions = influenced by unseen forces around them
3. persecutory delusions = tormented, harmed, followed, tricked or spied on
4. formal thought disorder = idiosyncratic association; disorganized speech or writing

Question 3

Characteristiscs of schizophrenia

Answer 3

• chronic, debilitating psychotic psychiatric disorder
• impacts 1% of people worldwide
• sx often begin in late adolescense or early adulthood
• positive sx: psychosis (delusions, hallucinations)
• negative sx: inability to pay attention, disorganized thoughts/speech, flattened affect, social withdrawal

Question 4

Genetic causes of schizophrenia

Answer 4

• heritable component established by epidemiology, twin studies, and adopted children from schizophrenic mothers
• polygenic disorder = several small genes associated w/increased risk

1. rare copy number variants of strong effect: on chromosomes 1q, 2p, 15q, 16p, 22q
   
   1. genes involved in neuronal development
2. Large scale genome wide association studies: small nucleuotide polymorphisms
3. linkage and candidate gene: key growth factors and regulators of neurodevelopment
4. family-based exome sequencing: higher incidence of de novo mutations

Question 5

Environmental causes of schizophrenia

Answer 5

• viruses
• malnutrition before birth
• birth complications
• other psychosocial factors

Question 6

Neurotransmiter theories of schizophrenia

Answer 6

• dopamine
• glutamate
• GABA

Question 7

Dopamine theory of schizophrenia

Answer 7

• disregulation of dopamine ==> psychosis
• mesolimbic system = VTA ==> nucleus accumbens
  
  • hyperactivity ==> positive sx of schizophrenia
• mesocortical system = dopamine neurons @ VTA (==>prefrontal cortex) & substantia nigra (==>basal ganglia)
  
  • hypoactivity ==> negative sx of schizophrenia

Question 8

Glutamate model of schizophrenia

Answer 8

• Glutamate can bind to dopaminergic neurons ==> regional hyperactivity and hypoactivity of dopamine release
• chronic NMDA antagonist administration ==> persistant elevation of DA release @ nucleus accumbens + decreased DA release @ prefrontal cortex

Question 9

Neural circuitry hypotheses of schizophrenia

Answer 9

• association cortex
• medial temporal lobe and hippocampus
• thalamus
• basal ganglia

Question 10

Association cortex role in schizophrenia

Answer 10

• association cortex = brain outside of primary sensory cortices
  
  • includes dorsal lateral prefrontal cortex (DLPFC) = executive fxn
• volume reduction of association cortex has been seen in schizophrenia
• cerebral blood flow and glucose metabolism are abnormal @ rest and during cognitive tasks
• hypofrontality observed in neuroimaging during working memory
• hyperactivity of DLPFC during task performance = indicator of prefrontal inefficiency

Question 11

Medial temporal lobe and hippocampus role in schizophrenia

Answer 11

• mild cortical atrophy @ medial temporal lobe
• abnormal alignment of neurons @ medial temporal lobe structures
• hippocampal dysfxn ==> dysfxn w/in its circuits (memory, emotion)
  
  • altered synaptic organization
  • fewer nonpyramidal cells
  • inreased metabolism/blood flow @ baseline
  • associated w/positive sx

Question 12

Role of thalamus in schizophrenia

Answer 12

• thalamus = gateway for all incoming sensory info
• proposals:
  
  1. decreased thalamic volume ==> decreased sensory-gating ==> increased stimulation at primary sensory cortices
  2. dysfxn @ dorsal medial nucleus ==> impairments of cortical association areas

Question 13

Role of basal ganglia in schizophrenia

Answer 13

• possible changes in volume of caudate nucleus/other basal ganglia nuclei

Question 14

First generation antipsychotics

Answer 14

• phenothizines
• thioxanthines
• butyrophenones

Question 15

First gen. antipsychotics: MOA & SE

Answer 15

• MOA: target dopamine D2 receptor
• SE:
  
  • parkinsonianism
  • tardive dyskinesia = choreoathetosis

Question 16

Second generation antipsychotics

Answer 16

• also called “atypical neuroleptics”
• Clozapine
• risperidone
• olanzapine
• quetiapine
• asenapine
• ziprasidone

Question 17

Second generation antipsychotics: MOA & SE

Answer 17

• ==> antipsychotic effects w/parkinsonian SEs
• MOA: blocks several receptor types (ACH, serotonin, NE, dopamine) but w/weaker dopaminergic action
• SE: enhanched appetite ==>
  
  • weight gain
  • hypercholesterolemia
  • diabetes