Case 8 - Schizophrenia Flashcards
What are the 3 functional divisions of the striatum?
- Sensorimotor (dorsal) = putamen
- Associative (mid) = globus pallidus
- Limbic (ventral) = Ventral Tegmental Area
Which brain regions are the main source of input to the 3 functional divisions of the striatum?
Motor areas of cortex > to sensorimotor
Dorsolateral prefrontal cortex > associative
Hippocampus and amygdala > limbic
What are the 4 dopamine system pathways?
Nigrostriatal
Mesolimbic
Mesocortical
Tuberoinfundibular
For the nigrostriatal pathway, where is dopamine released from/ to? What is the role of this pathway?
From substantia nigra pars compacta (SNc) to the striatum (caudate + putamen). Has 2 functional divisions:
- SNc -> sensorimotor (dorsal) striatum = involuntary motor control
- Snc -> associative (mid) striatum = cognition and emotion
For the mesolimbic pathway, where is dopamine released from/ to?
From ventral tegmental area to limbic regions in the midbrain, including the nucleus accumbens, amygdala, hippocampus and medial prefrontal cortex
What is the role of the mesolimbic pathway?
Associated with reward, motivation, affect and memory
For the mesocortical pathway, where is dopamine released from/ to? What is the role of this pathway?
From ventral tegmental area to the frontal cortex (particularly the dorsolateral prefrontal cortex)
Role: normal cognitive function, motivation and emotional response
For the tuberoinfundibular pathway, where is dopamine released from/ to? What is the role of this pathway?
From tuberal region of the hypothalamus to the median eminence (top of pituitary stalk)
Role: dopamine inhibits release of prolactin from the anterior pituitary
What dopamine abnormality is present in psychosis?
Increased dopamine presynaptic function in the nigrostriatal pathway, thought to be secondary to an abnormal glutamate or GABA system
Explain the 2 principal dopamine abnormalities present with schizophrenia
1: Excessive dopamine release in the striatum, via the nigrostriatal pathway (particularly associative branch) during acute psychotic episodes
2: Inadequate dopamine release in the frontal cortex (constant)
What symptoms is an increase in dopamine in the nigrostriatal pathway associated with? What is the relationship between DA and these symptoms?
Positive symptoms, and is positively correlated (i.e. higher excess dopamine = higher severity of symptoms)
What is associated with a better treatment response to antipsychotics?
Higher excess dopamine release in the nigrostriatal pathway (associative branch)
What symptoms is inadequate dopamine release in the frontal cortex associated with? What is the relationship between DA and these symptoms?
Deficits of cognitive function, i.e. working memory (less dopamine in the frontal cortex= worsened cognitive impairment)
Define schizophrenia
Severe mental disorder with distortions of thinking and perception, and affects that are inappropriate or blunted. Clear consciousness and intellectual capacity are usually maintained but cognitive deficits may evolve over time
What is a hypothesised explanation for negative symptoms?
Decreased dopamine release in the ventral striatum
What receptor is responsible for the altered release of dopamine in schizophrenia?
NMDA receptor - hypofunction
What is the glutamate-dopamine hypothesis for schizophrenia?
1: hypofunctional NMDA receptor = less glutamate release = less stimulation of GABA neurones
2: Low GABA doesnt adequately suppress cortico-brainstem glutamate outflow
3: Excessive glutamate stimulation of substantia nigra dopamine neurones = increased dopamine in associative and sensorimotor striatum
4: Excessive glutamate = stimulates GABA interneurone = increased GABA inhibits mesolimbic and mesocortical dopamine neurones in the VTA, so dopamine will be low in the VTA = negative symptoms
5: inhibition to dorsolateral prefrontal cortex = decreased cortical dopamine = cognitive deficit
What are positive symptoms (psychosis) of schizophrenia? Give examples
Positive = presence of experiences additional to what the person is usually like
- Delusions
- Hallucinations
- Thought disorders
Define delusion
A fixed, false belief, unshakeable by superior evidence to the contrary, and out of keeping with a person’s cultural norms.
Name the types of delusions that may be seen in schizophrenic patients
- Reference
- Persecution
- Control
- Bizarre and impossible
What is a reference delusion?
Believing everyday events have a strong personal coincidence/ refer to them, i.e. believing people are spying on them
What is a persecution delusion?
Believing others are out to harm or kill the patient
What is a control delusion?
Belief that their thoughts, beliefs, impulses and behaviour are under the control of other people or an external force
What type delusion may be present during mania of a patient with bipolar disorder?
Grandiose = belief that you have special powers, wealth or fame
What type delusion may present with depression?
Hypochondriacal or somatic: refer to one’s health or body, belief they have a disease or abnormality
What 2 types of delusion may be present in psychotic depression?
Nilhistic = belief they no longer exist, or part of their mind/ body is missing
Guilt = believing you’re worthy of punishment, usually from small acts in the past
What is a hallucination?
Abnormal sensory perception, internally generated, in the absence of an external stimuli
What are the potential types of hallucinations?
Any sensory modality:
- Visual
- Taste (gustation)
- Auditory
- Smell (olfactory)
- Somatosensory (tactile)
- Kinaesthetic (body position)
- Temperature
- Pressure
What type of hallucination is typically seen in schizophrenia?
Auditory
What is a thought disorder?
Breakdown of logical association between words, recognised when it is difficult/ impossible to follow a patient while talking. May be described as ‘derailment’ (i.e. train of thought coming off its track)
What term is used to describe thought disorder when it is completely unrecognisable?
World salad
What is the difference between a delusion and hallucination?
Delusion = abnormal belief (fixed, false)
Halucination = abnormal sensory perception
What is a negative symptom of schizophrenia?
Absence of capacities usually present, which disproportionately contribute to functional impairment and poor psychosocial outcomes in schizophrenia
Give some examples of negative symptoms of schizophrenia
- Anhedonia = inability to experience pleasure
- Poverty of speech (alogia) / reduced speech
- Flat or blunted affect (mood) and emotion
- Lack of motivation (avolition)
- Lack of desire to form relationships (asociallity) and/or social withdrawal
- Apathy
What can cognitive symptoms of schizophrenia affect?
Memory and executive functions, i.e. working memory, learning, planning, mental flexibility, impulse control
Other than positive, negative and cognitive symptoms of schizophrenia, what other symptoms may be apparent?
- Disorganised symptoms: incoherent speech, bizarre and unpredictable behaviour
- Excitement and agitation
What areas of the brain might be affected with visual hallucinations in schizophrenia?
Primary visual cortex (Brodmann’s area 17)
Cortical areas responsible for visual processing
Visual association areas (Brodmann’s areas 18 and 19) - more complex hallucinations
What areas of the brain might be affected with auditory hallucinations in schizophrenia? What neurotransmitters might be implicated with this?
Spontaneous activation of the auditory network in your brain, i.e. superior temporal gyrus, temporal lobe
= serotonin and dopamine imbalance
What symptoms are predominant with paranoid schizophrenia?
Positive symptoms are predominant (hallucinations and delusions), with unreasonable suspicion
What symptoms are predominant with disorganised (hebephrenic) schizophrenia? Give examples
Disorganised symptoms:
- Disorganised speech, e.g. word salad
- Disorganised behaviour, e.g. difficulty starting/ finishing a task, inappropriate social behaviour
- Flat or inappropriate affect, i.e. lack of eye contact, lack of facial expression
Why is catatonic schizophrenia now a rare subtype?
Occurs with untreated schizophrenia, so now we have early intervention and treatment it occurs less
What is catatonic schizophrenia characterised by?
Considerable increase or decrease in movement, i.e. largely immobile or excessive movements, echolalia (repeating what others say), echopraxia (mimicking other’s movement)
What is residual schizophrenia?
Happens after schizophrenia, i.e. left over symptoms, usually negative. Doesn’t experience delusions or hallucinations but symptoms to a lesser extent, i.e. odd beliefs
What is schizophreniform disorder?
Schizophrenia but only present for 1-6 months (for schizophrenia to be diagnosed has to be > 6 months)