Neurobiology of Psychotic Disorders

Question 1

Describe the onset and prevalence of schizophrenia.

Answer 1

Onset: Men - 15-25, women - 20-30

Prevalence: up to 1% of population

Question 2

In the UK, schizophrenia costs 11.8 billion pounds a year, which equates to what percentage of total mental health expenditure?

Answer 2

70%

Question 3

According to DSM-IV, what criteria are required for classification of schizophrenia?

Answer 3

Two or more of the following present for a significant period of time:

• Delusions
• Hallucinations (paranoid)
• Disorganised speech, emotional blunting and meaningless behaviour
• Grossly disorganised or catatonic behaviour (abnormality of posture)
• Negative symptoms (affective flattening; predominant negative symptoms)

Question 4

Name 6 generalised symptoms of schizophrenia.

Answer 4

1. Abnormal ideas
2. Abnormal perception
3. Motor, volitional and behavioural disorders
4. Formal thought disorder
5. Emotional disorders
6. Psychophysiological changes

Question 5

Describe the effects of schizophrenia on cognition.

Answer 5

• Anxiety and depression
• Premature dementia more likely
• Cognitive deficits are resistant to antipsychotics

Question 6

What is a functional hallucination?

Answer 6

Perception experienced without a stimulus

Question 7

What is the most common manifestation of functional hallucination in schizophrenia?

Answer 7

Auditory - patient hears:

• Voices talking about them in 3rd person
• Voices talking to them
• Voices giving a running commentary
• Voices echoing their thoughts

Patients may engage in dialogue with the voices or obey their commands

Question 8

What is a delusion?

Answer 8

A fixed and unshakable belief that is not consistent with cultural and social norms

Often paranoid or persecutory

Passivity of thoughts and actions

Question 9

Give examples of motor, volitional and behavioural disorders seen in schizophrenia.

Answer 9

Peculiar forms of motility, stupor, mutism, stereotypy, mannerism, negativism, spontaneous automatism, impulsivity:

–Stereotypies: purposeless, repetitive acts

–Bizarre postures, strange mannerisms

–Altered facial expression – grimacing

–State of catatonia – motionless, mute, expressionless, uncomfortable or contorted postures

–State of catalepsy – waxy flexible

–Bouts of extreme hyperactivity (destructiveness; walk around naked)

–Impulsive behaviour – violent acts; murder w/o reason

Question 10

What is formal thought disorder?

Answer 10

A disorder of conceptual thinking, reflected in speech that is difficult to understand and rapid shifts from one subject to another. New words are invented - neologisms.

• Disturbances in thinking > unintelligible speech
• Derailment of speech
• Loosening of associations - failure to follow train of thought to its conclusion
• Poverty of speech - fails to convey sense/info - manifests as distorted or illogical speech

Question 11

What is the likelihood that a dizygotic and monozygotic twin will develop schizophrenia if the other twin gets it?

Answer 11

Dizygotic: 14%

Monozygotic: 50%

Hereditary - risk is positively correlated with degree of genetic relatedness

Question 12

Schizophrenia is mainly associated with which 2 genes?

Answer 12

1. Neurogulin-1 gene - NMDA, synaptic development and plasticity. Underexpressing mice show the disease.
2. COMT gene - COMT enzyme breaks down neurotransmitters. High COMT > low dopamine > higher risk of schizophrenia.

Question 13

Name a neurodevelopmental disorder associated with schizophrenia.

Answer 13

Frontal hypofusion

Question 14

Name 3 environmental factors that may predispose to schizophrenia.

Answer 14

• Increased incidence in people born in winter months (December-May?)
• Viral epidemics - development in utero
• Obstetric complications (oxygen deprivation)

Question 15

Describe the deficits of neuronal matter seen in schizophrenia.

Answer 15

• Smaller brains
• Larger ventricles, particularly in medial temporal lobe and left hemisphere

Question 16

PET ligand scans appear to show schizophrenics having increased D₂ receptors in what brain region?

Answer 16

Nucleus accumbens

Question 17

Electroencephalogram abnormality is reported in 80% of schizophrenics in which 2 related brain regions?

Answer 17

Thalamus and basal ganglia

Alterations present, but changes are non-specific

Question 18

Schizophrenia features dysfunction in prefrontal circuits. For example, schizophrenics perform worse than control in the Wisconsin card test. What is the hypothesised explanation for this?

Answer 18

Hypofrontality - less blood flow to prefrontal cortex

Question 19

Describe the pathological changes in the cortex and hippocampus in schizophrenia.

Answer 19

• Abnormal clustering of neurons in cortex
• Small cell bodies and reduced axodendritic tree of pyramidal neurons in cortex and hippocampus

Question 20

What are the ‘positive’ and ‘negative’ symptoms of schizophrenia and what are the consequences of damage to the prefrontal cortex?

Answer 20

Positive:

• Delusions
• Hallucinations
• Thought disorder

Negative:

• Social withdrawal
• Lack of motivation
• Flattened emotional affect
• Under-activity

Question 21

Circuits connecting which 3 brain structures become dysfunctional in schizophrenia? What system do these structures belong to?

Answer 21

1. Hippocampus - learning and memory
2. Amygdala - emotional stress and learning
3. Anterior cingulate cortex - affect, selective attention and social interactions

These structures are part of the corticolimbic system, which also includes the dorsolateral prefrontal cortex - this deals with motivation and executive function.