Suicide and schizophrenia

Question 1

What happens in the fight or flight stage of the stress response?

Answer 1

Sympathetic stimulation of the CORE of adrenal glands (medulla)
Norepinephrine and adrenaline released –> effects like raised heart and breathing rate etc
Preparing body for action

Question 2

What happens in the central stress response system?

Answer 2

Stimulation of anterior pituitary by CRH released by hypothalamus
Pituitary releases ACTH which drives adrenal CORTEX to release ADRENAL STEROIDS such as cortisol
Cortisol has effects that help body deal with stress e.g. mobilising glucose for energy
When cortisol gets too high hypothalamus responds to negative feedback and turns stress response off

Question 3

What is Cushing’s syndrome and how is this related to depression?

Answer 3

High circulating levels of glucocorticoids such as cortisol
Individuals more prone to depression - suggests that the HPA axis implicated in depression, supported by fact that many suicide victims show very high circulating levels of cortisol

Question 4

What is hypothesised about depression and the HPA axis and how can we test this?

Answer 4

ACTH released in excessive amounts by anterior pituitary
Use dexamethasone suppression test - reveals whether there is a tendency to release excess cortisol
Dexamethasone fools hypothalamus (when given late at night) into believing there is a high level of cortisol and thus early morning cortisol is suppressed the next day
In individuals with depression, this effect doesn’t occur

Question 5

What are the main risk factors for suicide?

Answer 5

Depression and other psychiatric disorders (bipolar is particularly bad)
History of previous attempts
Family history
Stressful life events
Bullying

Question 6

What is the demographic pattern of suicide?

Answer 6

Although depression is more common in females, suicide is more common in males

Question 7

How do stress and early life adversity contribute to development of depression etc that then contribute to suicide risk?

Answer 7

CRF is found in high levels in brains of suicide victims
ELA and stress cause SUSTAINED ELEVATION of CRF, causing long term damage to brain pathways (neuroadaptation) which then increases susceptibility to depression (impairs hippocampal serotonergic neurotransmission)
In individuals with ELA the HPA axis is overactive - when activated during development it becomes permanently unstable, hyperstimulated and vulnerable.
We don’t see the same negative feedback via binding of cortisol to glucocorticoid receptors (may be due to downregulation of the receptors in the hippocampus) - ELA leads to heightened stress responsiveness as effects of hypothalamus not being dampened

Question 8

What is early life stress associated with?

Answer 8

Diverse range of psychiatric consequences:
INTERNALISING BEHAVIOURS - anxiety, depression, somatic complaints, inhibition
EXTERNALISING BEHAVIOURS - aggression, delinquency, increased activity levels, sexual behaviour problems

Question 9

What is the link between serotonin and suicidal behaviour?

Answer 9

Those who choose more violent methods have lower levels of serotonin, and similarly decreased levels found in other impulsive behaviours and poor impulse control
Alcohol lowers serotonin at same brain sites as seen in depressed patients - it is a disinhibitor that further increases impulsivity and risk of suicide in depressed people
One third of adolescent suicide victims were intoxicated at time of death

Question 10

What is suicidal behaviour regulated by?

Answer 10

DISTAL (predisposing) factors - family history of suicide, genetics, early life adversity and associated epigenetic changes –> long term effects on gene function/expression
DEVELOPMENTAL (mediating) factors (may directly result from gene changes as consequence of predisposing factors or may be associated with factors such as chronic substance use –> accentuate traits linked with suicidality) - specifically family disposition and ELA can shape behavioural and emotional traits such as impulsive-aggressive behaviour and anxiety traits which increase risk of ACTING ON suicidal ideation
PROXIMAL (precipitating) factors - Genetic and epigenetic factors lead to acute substance abuse and depressive psychopathology (leading to hopelessness and cognitive distortions, also influenced by life events) –> behavioural disinhibition from substance use, and suicidal ideation –> increased suicide risk
(go back to diagram!!!)

Question 11

What are the main brain changes we can actually see in the brains of people who have attempted suicide?

Answer 11

Increased caudate volume (part of basal ganglia linked to initiating movement and aggression) in more violent attempts - this increased volume is also seen in violent offenders, aggression in schizophrenics

Reduced volume of left dorsomedial prefrontal cortex in individuals with family history of suicide - plays role in social cognition and decision making, aggression, impulsivity and response inhibition, all processes relevant to suicidal behaviour

Question 12

What does “split” in the sense of schizophrenia actually mean?

Answer 12

They are split off from reality and can’t distinguish between what is real and what isn’t

Question 13

What are the key positive symptoms of schizophrenia?

Answer 13

Symptoms which are additions to consciousness:
Delusions - bizarre and false beliefs, can be paranoid or grandiose
Psychosis - can’t tell whats real and what isnt
Hallucinations - unreal perceptions, most commonly auditory
Disorganised speech and dissociative thinking

Question 14

What are the main negative symptoms of schizophrenia?

Answer 14

Decreases in functionality:
Flattened affect
Alogia - poverty of speech
Avolition - severe lack of initiative to accomplish purposeful tasks
Catatonia - immobility and “waxy” flexibility, also involves mutism

Question 15

What is paranoid schizophrenia characterised by?

Answer 15

Unreasonable suspicion and primarily positive symptoms; patient is preoccupied with at least one delusion (usually persecutory) or experiences frequent auditory hallucinations; negative symptoms are not present/less prominent

Question 16

What is meant by disorganised/hebephrenic schizophrenia?

Answer 16

Predominantly disorganised symptoms - all of the following must be present for this diagnosis:
Disorganised speech
Disorganised behaviour e.g. difficulty starting/finishing a task, or acting inappropriately in social situations
Flat/inappropriate affect e.g. poor eye contact, lack of facial expressions

Question 17

What is catatonic schizophrenia?

Answer 17

Now considered a rare subtype because believed to largely result from untreated schizophrenia
Characterised by considerable increase/decrease in movement, with at least 2 of the following symptoms:
Largely immobile with rigid posture and resistant to attempts at movement
Excessive and seemingly purposeless movement including echolalia (repeating others) and echopraxia (mimicking movements of others)
Peculiarities in voluntary movement e.g. bizarre posture, grimacing or stereotypic movements such as hand waving or nail biting

Question 18

What is meant by undifferentiated schizophrenia?

Answer 18

For people who don’t fit into the previous 3 categories - experience significant symptoms but they are not predominantly positive, disorganised or movement disordered

Question 19

What does residual schizophrenia mean?

Answer 19

Describes a patient not currently experiencing prominent symptoms but are experiencing at least two to a lesser extent, or continue to only experience the negative symptoms such as social withdrawal, attentional deficits and apathy
Different from the RESIDUAL PHASE of schizophrenia which occurs in medicated patients who continue experiencing negative symptoms when positive symptoms treated by antipsychotics i.e. no longer reporting hallucinations or delusions
During this residual phase, a patient may or may not be categorised in the residual subtype

Question 20

Why are the 5 subtypes of schizophrenia not included in the DSM-5?

Answer 20

Not clinically helpful as symptoms change so often from one subtype to another and patients present with overlapping subtype symptoms, blurring distinctions among the subtypes and decreasing their validity

Question 21

What is thought about positive and negative symptoms of schizophrenia?

Answer 21

They are thought to arise from different neural abnormalities because they respond differently to drug treatments

Question 22

What is the evidence of genetic causes of schizophrenia?

Answer 22

Adoption studies - don’t confuse hereditary and environmental factors unlike family studies; biological parents of adoptees with the condition are far more likely to have suffered from the disorder
Twice the concordance in monozygotic twins as in dizygotic - however even in identical twins the concordance is only around 50% so genes aren’t the only cause

Question 23

What are the environmental/developmental influences?

Answer 23

Early experiences of physiological distress or trauma
Family stress and poor social interactions
Infections/viruses at early age - include prenatal e.g. influenza in first trimester makes schizophrenia 7 times more likely
Stress of city living - earlier move into city, higher risk

Question 24

What is the dopamine theory of schizophrenia?

Answer 24

Disorder may be caused by overactive dopamine system - either excessive dopamine release or excessive receptors
Supported by fact that many effective antipsychotics work by blocking dopamine receptors

Question 25

How do amphetamine abusers provide supportive evidence for dopamine theory?

Answer 25

Those who reach a high tolerance level and take very high levels of amphetamine to achieve their high develop symptoms of paranoia and persecutory delusions with auditory hallucinations (i.e. positive symptoms) - amphetamine psychosis
Amphetamine also exacerbates symptoms in patients with schizophrenia, and it turns out that amphetamine promotes release of dopamine and prolongs its action by blocking reuptake

Question 26

Why has dopamine theory been criticised and what is an alternative suggestion?

Answer 26

Some people don’t respond to dopamine antagonists at all, so chemistry has to be more complex than simply hyperactive dopamine synapses
Under-activation of glutamate receptors (NMDA-type), a more pervasive NT

Question 27

What 6 key brain areas are affected by schizophrenia?

Answer 27

Basal ganglia - involved in integrating sensory info, abnormal functioning leads to paranoia and hallucinations (blocking dopamine receptors here leads to motor side effects)
Frontal lobe - difficulty planning actions and organising thoughts
Limbic system - agitation and emotional disturbance
Auditory system - overactivity of speech (Wernicke) area can create auditory hallucinations
Occipital lobe - difficulties interpreting complex images, recognising motion and reading facial emotions
Hippocampus - learning and memory function both impaired

Question 28

What is the most consistent and significant anatomical change in the brains of individuals with schizophrenia?

Answer 28

Enlarged cerebral ventricles, especially LATERAL
Extent of enlargement predicts responsiveness to antipsychotics, with more enlargement = poorer response
Enlargement at expense of brain tissue, including areas of amygdala and hippocampus

Question 29

What was the first drug used for schizophrenia?

Answer 29

Chlorpromazine - originally developed as an anaesthetic but found to reduce positive symptoms

Question 30

What are “typical” neuroleptics?

Answer 30

D2 receptor antagonists e.g. HALOPERIDOL
Can produce extrapyramidal symptoms such as Parkinsonism due to the blockage of dopamine action in basal ganglia - parkinsons results from loss of dopaminergic neurons in substantia nigra, while antipsychotics block the D2 receptors here

Question 31

What is tardive dyskinesia?

Answer 31

repetitive and involuntary movements often involving parts of the face, with uncontrolled tongue movements being particularly prominent
Potentially the result of chronic blocking of dopamine receptors, resulting in compensatory receptor-site super-sensitivity (see similar hyperkinetic movement after long-term L-dopa use in parkinsons)

Question 32

What are “atypical” neuroleptics?

Answer 32

Designed to reduce the motor side effects - don’t have the selectively high affinity for dopamine receptors so don’t bind as strongly, but they do feature high affinity for other receptor types - clozapine, for example, selectively blocks serotonin receptors
See more metabolic side effects with these drugs such as weight gain