Psychosis and Schizophrenia Flashcards
What are positive psychotic symptoms?
Hallucinations
Delusions
Disorganised Speech
What are negative psychotic symptoms?
Anhedonia
Anergia
Apathy
Avolition
What are cognitive psychotic symptoms?
Cognitive Impairment
Poor Memory
Processing Speed
What is the prevalence of schizophrenia?
(1)
(2)
(3)
It affects over 20 million individuals world wide (1)
Ranked within top 10 of the most debilitating disorders in Global Burden of Disease Review (2)
Economic burden estimated to amount to £3.7 billion by 2026 (3)
What is psychosis?
An episode where on is detached from reality
What is schizophrenia?
A mental illness that impacts though processes, emotions, and behaviour
What are the symptoms of psychosis?
Sleep deprivation
Substance Use
Mental illness
Other conditions
What are the signs of psychosis?
Hallucinations
Delusions
Agitation
Disorganised thought and behaviour
How are you diagnosed with schizophrenia?
Must have experience at least 2 symptoms for 2 months, with one of the symptoms being:
- Delusions
- Hallucinations
- Disorganised speech
What are the symptoms of schizophrenia?
Delusions
Hallucinations
Disorganised speech
Catatonic behaviour
Negative symptoms
- Lessened emotional expression
How is schizophrenia manifested?
Initial elevation in risk due to elevated genetic susceptibility
- Il-6
- MHC
- IRF3
Exposure to peripheral and central stressors elicit maladaptive responses to stress in immune cells
What is the evidence of inflammation in schizophrenia and first episode psychosis- peripheral?
Upthegrove, Manaznares-Teson and Barnes et al
- Significant elevation in IL-1b, sIL-2r, IL-6, TNF-a
Dunleavy et al
- Significant elevation in IL-6, IL-12, IL-17, IFN-y
What is the evidence of inflammation in schizophrenia and first episode psychosis- central?
Catts et al
- Increased expression of astrocyte markers
- SCZ iPSC-derived astrocytes, day 80, 50x magnification
- SCZ Astrocytes exacerbated response to inflammatory stress
- Significant increase in intracellular IL-6/IL-8 accumulation
What is the importance of interventions at a first episode psychosis?
Early intervention in psychosis is both clinically effective and cost effective (6)
Limit experiences with server and debilitating symptom subtypes
Pathology still in its infancy
- Can change trajectory of illness to prevent long-term prognosis
Early intervention facilitates better:
- Symptomatic and functional outcomes
- Physiological outcomes
- Chances of optimum recovery
- Lifespan
What is the incidence rate of a first episode of psychosis being experienced in individuals?
31.7 per 100,000 in England
What is a “first episode” of psychosis?
First signs of an individual “losing contact with reality”
Symptoms that interfere with an individual’s daily life
First 5 years since symptom onset
How does antipsychotic drugs solve the problem?
Effectively reduce positive symptoms experienced in FEP/SCZ
Reduces hallucinations, delusions and anxiety
Operates via D2 dopamine receptor blockade
Regulated dopaminergic transmission
How does antipsychotic drugs cause problems?
Alvarez-Jimenez et al. 2009
Fails to ameliorate negative symptoms and cognitive deficits
33% SCZ cohorts do not respond
Can induce further extrapyramidal symptoms
Poor motivation, emotional numbing
Weight gain
What antipsychotic drugs cause weight gain over a 10-12 week trial?
Alvarez-Jimenez et al. 2009
Olanzapine
- 7.1-9.2kg 1
Risperidone
- 4.0-5.6kg
Haloperidol
- 2.6-3.8kg
What antipsychotic drugs cause weight gain over a >9month trial?
Alvarez-Jimenez et al. 2009
Olanzapine
- 15kg
Risperidone
- 8.9kg
Haloperidol
- 9.7kg
What are the adverse effects of antipsychotic drugs?
Sedation
Substantial Weight Gain
Dyslipidaemia (Cholesterol)
Impaired Glucose Tolerance
Hypertension (Blood Pressure)
Inflammatory Abnormalities
Cardiovascular disease
Metabolic syndrome
What are mortalities rate like from antipsychotic drugs in schizophrenia?
Saha et al. 2007
Risk factors accumulate to significantly elevated risk of mortality
Largely driven by metS/CVD
2.5x elevated risk of premature mortality
How does regular exercise influence T-Cell subsets? (Schizophrenia)
Shaw et al. 2018
Growth factors and a Phenotype shift to Th2
causes an increased release of Anti-Inflammatory Cytokines and Myokines
This then results in Treg upregulation
How does the inflammatory state influence T-Cell subsets? (Schizophrenia)
Shaw et al. 2018
Th1 expression causes release of Proinflammatory Cytokine Release (Inflammation)
This then causes ROS production= cell damage
What are the physiological benefits of using regular exercise? (Anti Inflammatory Mechanisms)
Offset AP induced Weigh Gain
Prevents MetS/CVD (insulin, gluc.)
Reduce premature mortality risk
Often, HRmax >60%= physiological change
What are the mechanistic benefits of using regular exercise? (Anti Inflammatory Mechanisms)
Regular exercise training induces upregulations in peripheral anti-inflammatory processes
Facilitates upregulation in cytokines and growth factors that can pass BBB to elicit neuroprotective effects
What are the mechanistic benefits of using regular exercise on biomarkers= increases? (Anti Inflammatory Mechanisms)
IL-6
Il-10
s-TNFR
IL-1ra
Treg
BDNF/IGF
GSH
What are the mechanistic benefits of using regular exercise on biomarkers= decreases? (Anti Inflammatory Mechanisms)
IL-6 (Adipose)
TNF
Th1 (IFN-y)
TLR exp.
Oxidative Stress
Adipose
What positive effects has exercise been reported to show in the brain and CNS?
Increased grey matter volume
Improved cognitive function (5)
- Working memory
- Social Cognition
- Attention
Influences neurogenesis and synaptic potentiation
Downregulates cerebral cytokines to reduce neuroinflammation
Delays onset of degenerative disease (7)
What research is missing in this field?
No study has assessed the effects of regular exercise on inflammatory biomarkers in FEP
What is FEP?
First-episode psychosis
