Flashcards in SZ Deck (63):
- a chronic mental disorder with disturbances in thoughts, emotions and behaviour resulting in faulty perception, inappropriate actions and feeling
- often involves withdrawl from reality and personal relations into fantasy and delusion and a sense of mental fragmentation
what is SZ characterised with?
divorcement from the reality in the mind of the person (psychosis)
what is the prevalence of SZ?
- onset in the late teens or early 20s
- affects 1% of the population worldwide
anatomical changes are prevalent in SZ?
A. True B. False
B. False, changes may or may not be present
what are the positive symptoms of SZ?
3. ideas of reference
what are the negative symptoms of SZ?
1. cognitive deficits
4. social withdrawl
5. emotional blunting
6. extreme inattentiveness/lack of interest to interact with the environment
what are the cognitive deficits in SZ?
1. focus - difficulty in focusing or paying attention
2. executive functioning - is poor
3. memory - problems with working memory (reduced GABA in PFC, which is responsible for working memory)
- these symptoms are often subtle but cause great emotional stress
what are the features of SZ?
1. +ve symptom
2. -ve symptom
3. cognitive deficits
4. mood symptoms
5. disorganisation (of speech or behaviour)
what are the five main criteria according to the DSM-5 for the diagnosis of SZ?
3. disorganised speech
4. disorganised or catatonic behaviour
5. negative symptoms
- patient must have at least 2 symptoms for SZ
for how long must the disturbances persist to be diagnosed for SZ?
- continuous signs of disturbances must persist for 6 months
- during these 6 months, the patient must experience a month of active symptoms (or less if successfully treated)
- along with social/occupational deterioration over a significant amount of time
what are the seven factors affecting the prognosis of SZ?
1. age of onset (male - 20-28 yrs; female - 26-32yrs)
2. sex (diagnosed 1.4 times more in men than female)
3. pre-morbid function
4. family history of mood disorder
5. abrupt vs gradual onset
6. duration of untreated illness
7. substance abuse
in which cases and why are antipsychotic agents used?
- used in SZ, bipolar disorder, psychotic depression and drug induced psychosis
- they prevent SZ episodes instead of treating or curing them (administered life long)
what are the classification of antipsychotic drugs?
on the basis of what factors are typical or atypical drugs being chosen?
1. incidence of extrapyramidal side effects (less in atypical group)
2. efficacy in treatment resistant groups
3. efficiency against the negative symptoms
what is the action mechanism of typical and atypical anti-psychotics?
1. Typical - preferential blocking of D2 receptors > D1Rs in the mesolimbic pathway
2. Atypical (Clozapine) - non selective b/w D1 and D2; high affinity for D4
what are the adverse effects of anti-psychotics?
1. extrapyramidal motor disturbances
3. cardiac toxicity - hypotension due to alpha adrenergic blockade
what are the extrapyramidal motor disturbances as adverse effects in SZ?
1. Parkinson like symptoms (tremors/shakes)
2. neuroleptic malignant symptom
3. tardive dyskinesia - involuntary movement of face, tongue, muscles; appears after months/years of anti0-psychotic treatments
4. acute dystonia
what are the FOUR main dopaminergic pathways and their impact on symptoms?
1. mesolimbic pathway (MLP) = +ve symptoms
2. mesocortical pathway (MCP) = -ve symptoms
3. nigrostriatal pathway (NSP) = extrapyramidal effects, tardive dyskinesia
4. tuberoinfundibular pathway (TIP) = hyperprolactinemia
what is the role of MLP and the impact of D2 antagonist it?
1. detects rewarding stimuli, key reward circuit
2. activation tells individual to repeat the action - motivation, positive reinforcement
3. in SZ, increased dopamine in MLP = +ve symptoms
however, D2 antagonist reduces the +ve symptoms
what is the role of MCP and the impact of treatments on it?
1. important in emotions, motivation and executive functions
2. in SCZ, decreased dopamine in MCP = negative symptoms, treatments aim to increase dopamine in this pathway
what is the role of NSP and the impact of treatments on it?
1. involved in motor planning, dopaminergic neurons stimulate purposeful movement (contains 80% of the brain's dopamine)
2. in SCZ, D2 antagonist induce the extrapyramidal symptoms
what is the role of TIP and the impact of treatments on it?
1. involved in regulating blood prolactin levels
2. in SCZ, D2 antagonist cause an increase in blood prolactin levels
in which area or region of the brain are these pathways located?
1. MLP - nucleus accumbens (NAc) + ventral tegumental area (VTA)
2. MCP - VTA - pre-frontal cortex + ventromedial pre-frontal cortex
3. NSP - substantia nigra + striatum
4. TIP - project from tuberal region of hypothalamus to the medial eminence
what are the limitations of typical anti-psychotics?
1. 1/3 of patients with SZ fail to respond
2. limited efficacy against negative symptoms
3. high proportion of patients relapse
4. side effects and less compliance
5. anti-psychotic resistant - clozapine may be effective in some cases
what are the characteristics of the atypical drug: clozapine?
1. effective in treating some patients with psychosis that were unresponsive to standard neuroleptic drugs
2. blocks D4 receptor and have low affinity for D1 and D2 receptors
3. lacks many extrapyramidal side effects
4. more compliant
what are the adverse effects of atypical drug: clozapine?
1. need to monitor the granulocyte count due to higher incidence of agranulocytosis (bone marrow fails to make granulocytes)
2. increase in weight, blood glucose, lipids
3. risk of worsening diabetes
5. constipation (obstipation)
what is the main reason for relapse of SZ with anti-psychotics?
what are the evidence supporting the dopamine theory of SZ?
1. grater occupancy of D2 antagonists by anti-psychotics => greater dopaminergic stimulation
2. tyrosine hydroxylase (rate limiting enzyme involved in the synthesis of dopamine) is significantly increased in substantia nigra => more dopamine in midbrain
what is the evidence against the dopamine theory of SZ?
1. anti-psychotics are partially effective is 70% cases however, are ineffective for some patients
2. phencyclidine; NMDA antagonist > DA agonist => SZ symptoms in non-SZ subjects
3. atypical antipsychotics have low affinity for D2 receptors
what is the glutamate hypothesis for SZ?
the 'hypofucntion of NMDA receptors' prevents the glutamate to bind to the receptor thereby, increase excitotoxic glutamate levels which induce SZ symptoms
what is evidence supporting the glutamate hypothesis of SZ?
recreational use of single dose NMDA antagonist like phencyclidine (PCP) or ketamine produces "SZ like symptoms" in healthy individuals and exacerbates the pre-existing symptoms in SZ patients
what are the differences between glutamate and GABA?
1. Glutamate - major excitatory NT in CNS
GABA - major inhibitory NT in CNs
2. Glutamate - involved in neurogenesis and synaptogeneis
GABA - target of anti-anxiety and anti-convulsant drugs
3. Glutamate - excitotoxic
GABA - regulates sleep wake cycle
what is relationship between glutamate and SZ?
SZ patients have decreased glutamate concentration in PFC
what is the evidence for GABA involvement in SZ?
1. animal models and post-mortem samples suggest SZ is associated with GABA dysfunction
2. reduction in GABA-synthesising enzyme, GAD67 mRNA and protein
3. altered GABA neurotransmission in PFC of SZ subjects, PFC is involved in working memory thus reflecting the impaired memory seen in SZ
what is the role of GABA in a healthy and SZ individual?
act on glutamate and dopamine and carry inhibitory signals to keep activity at optimal levels since there is dysfunction of GABA, there is increased levels of glutamate and dopamine
what factors are responsible for
1. positive symptoms
2. negative symptoms
3. cognitive symptoms
1. positive symptoms - dopamine, Ach, inflammation
2. negative symptoms - 5-HT, glutamate, GABA
3. cognitive symptoms - 5-HT, glutamate, Ach
what is CBT?
cognitive behavioural therapy is a non-pharmacological treatment for SZ which seeks to change the pattern of thoughts and behaviour and thus impact the mood
what is the procedure in ECT?
electroconvulsive therapy is a procedure in which electric currents are passed though the brain, deliberately triggering a brief seizure
what are the two non-pharmaceutical treatments for SZ?
what is the impact of ECT on the brain and is used to treat which diseases?
ECT changes the brain chemistry which can immediately reverse the symptoms of mental illness. It is used to treat SZ, severe mania and catatonia
when is ECT used SZ?
it is used SZ when SZ is accompanied by psychosis, desire to commit suicide, hurt someone or refuse to eat
what are the drawbacks of early ECT treatment which resulted much stigma with its usage?
high doses of electricity were administered without anaesthesia resulting in
1. memory loss
2. fractured bones
3. other serious side effects
what are the rules for ECT procedure now?
a patient must take a muscle relaxant and is put under brief anaesthesia before ECT administration in order to not consciously feel the electrical impulses administered
how long does the ECT procedure take and after how long do the patients recover?
1. ECT lasts from 30-90 seconds
2. people recover after 5-15 mins and are able to go home
what are short term side effects of ECT?
3. memory loss
but these side effects typically clear soon
what are the seven structural and functional abnormalities in SZ?
1. reduced hippocampal volume
2. reduced basal ganglia volume
3. reduced gyrification (hypogyria; folds of the cerebral cortex)
4. atrophy of cortical layers
5. enlarged cerebral lateral ventricles
6. increase in cell packing density - reduced neuropil hypothesis
7. reduced gray matter and whole brain volume (~2%)
8. disrupted white matter
name three diagnostic tool used to observe the abnormalities in SZ?
1. structural MRI (reduced grey matter, disrupted white. matter)
2. functional MRI (cognitive deficits related frontotemporal system)
3. diffusion tensor imaging (DTI)
what is the hypofrontality hypothesis?
neuroleptic naive SZ patients show reduced activity in
1. right frontal lobe
2. left temporal lobe
3. left cerebellum
how is frontal lobe affected in SZ?
1. reduced activity in frontal lobe
what is the neurodevelopment hypothesis of SZ?
1. combined effects of genes and early brain lesion during pregnancy or birth increase the risk of SZ
2. the brain insults remain latent until critical periods of normal maturation and synaptic pruning
3. prodromal symptoms followed by disease onset in adulthood
what is the evidence regarding the the neurodevelopment hypothesis of SZ?
1. brain histopathology
2. periventricular bleeding in neonates brain when exposed to prematurity or hypoxia resulting in ventricular enlargement
3. SZ increased in late winter/spring
4. SZ risk increased for prenatal truths exposed to maternal infections
what is synaptic pruning?
process of eliminating unnecessary synapses during development
why is synaptic pruning essential?
for maintaining balance b/w E/I
explain the synaptic pruning process?
- spine density increases during infancy reaching peak before 9th birthday
- and then begins too fall away as pruning begin
- continues to fall gradually until the late 20s
state the environmental risk factors with examples for SZ?
1. social - urban-rural dwelling, migration
2. environmental - cannabis smoking, chemical pathogens, famine
3. familial - childhood trauma and adversity
4. neurodevelopment - advanced paternal age, seasonal birth, birth defects/obstetric complications, vitamin D, prenatal maternal infections
5. economic - developing vs developed country, socio-economic status
what is the impact of following for SZ onset?
1. seasonal birth effect
2. maternal nutrition
3. advanced paternal age
4. cannibis smoking
1. seasonal birth effect - people born in winter or early spring have higher probability (5%-8%) of developing SZ, possibly due to maternal infections or diet during that period in pregnancy
2. maternal nutrition - SZ risk increased by x2 for nutritionally deprived mothers (e.g. during dutch hunger winter)
3. advanced paternal age - increased risk of SZ in offspring born to older father (+45 years)
4. cannabis smoking - cannabis use by 15yr olds were 4x more likely to have SZ diagnosis at 26 yrs
what is the acute effects of cannabis on healthy and psychotic illness?
healthy - induce transient psychotic symptoms
psychotic illness - worsen the symptoms
how is the reproductive fitness affected in SZ?
reduced rate of reproduction
despite the reduce reproductive fitness in SZ, how there is high prevalence of SZ worldwide?
1. strong positive selection
2. new alleles generated through de novo mutations
what is the two-third hit theory in SZ?
the vulnerability of a gene with mutation is passed on to three stages
1. first hit - embryonic due to infection, nutrition, birth trauma resulting in neurodevelopment problems
2. second hit - young adult due to stress events resulting in +ve symptoms or psychosis
3. third hit - recurrence in the adult resulting in negative symptom
what are multifactorial disorders?
diseases that show familial clustering but do not conform to any recognised pattern of single gene inheritance
how are multifactorial diseases identified?
they are identified with additive effects of many genes at different loci together with the effect of environmental factors