Schizophrenia & Psychosis Flashcards
1
Q
what is psychosis ?
A
a collection of symptoms which can form part of another disease
ranks as more diabling than blindness or paraplegia
2
Q
what are common traits of psychosis ?
A
- delusions
- disordered thoughts
- catatonia
- hallucinations
3
Q
what are some causes of psychosis ?
A
- Schizophrenia
- Bipolar
- AD
- PTSD
- sleep deprivation
etc.
4
Q
A
5
Q
What is usually not possible when someone first displays psychotic symptoms?
A
A definitive diagnosis of a particular causal disorder
Initial symptoms may lead to a designation of a ‘brief psychotic episode’ rather than a specific mental health disorder.
6
Q
What may be designated when someone experiences a period of psychosis without a specific causal disorder?
A
‘Brief psychotic episode’
This designation indicates that the psychosis is not attributed to disorders such as schizophrenia, bipolar disorder, or major depressive disorder.
7
Q
Describe the nature of a first episode of psychosis.
A
Usually unexpected
First episodes of psychosis can occur without prior indication or warning.
8
Q
What is the term used for the phase that often precedes psychotic episodes?
A
‘Prodromal’ phase
This phase may include various behavioral changes leading up to the onset of psychosis.
9
Q
What changes in behavior might occur during the prodromal phase?
A
- Irritability
- Difficulty concentrating
- Memory problems
- Anxiety and depression
These symptoms can last for months or even years before a psychotic episode occurs.
10
Q
How long can the prodromal phase last?
A
Months or sometimes years
The duration of the prodromal phase can vary significantly among individuals.
11
Q
What is a challenge in recognizing psychosis during a first episode?
A
Symptoms can occur in other mental health disorders such as depression, which can complicate the identification of psychosis as a warning sign.
12
Q
What is a common issue regarding the treatment of acute psychotic phases?
A
There is often a delay before treatment starts due to the person not recognizing their illness, and relatives or friends not understanding what is happening
13
Q
What has been shown to produce worse outcomes in psychosis treatment?
A
Delayed treatment
Timely intervention is crucial for better outcomes.
14
Q
What can help speed intervention during psychotic episodes and who does this apply to ?
A
- recognising prodromal symptoms
- if the person has experienced psychosis due to an underlying mental health condition like schizophrenia
15
Q
what are the two diagnostic criteria for schizophrenia and schizoaffective disorder ?
A
- DSM-5
- ICD-I0
16
Q
what are the groups of symptoms for schizophrenia that are empahsised in the DSM-5 ?
A
positive symptoms
and
negative symptoms
and
congitive problems
17
Q
what are positive symptoms and what are some examples from the DSM-5?
A
things normal people don’t experience
- hallucinations
- delusions
- disorganised speech
- disorganised behaviour or catatonia
18
Q
what are negative symptoms and what are some examples from the DSM-5 ?
A
behaviours or responses that people with schizophrenia lacks that a normal individual would have
- they have a loss of emotional response
- experience anhedonia
- can be apathetic
19
Q
what are the DSM-5 criteria for diagnosis of depression ?
A
- two of symptoms from either positive or negtive symptoms present for a month
- musct include one of either hallucinations, delusions or disorganised speech
- continuous signs of disturbance for at least 6 months
- not explained by something else
20
Q
what diagnostic criteria do we use in the UK for schizophrenia ?
A
ICD-10
similar criteria to DSM-5
21
Q
What is schizoaffective disorder ?
A
hybrind disorder of schizophrenia with a mood disorder e.g. MDD or bipolar
22
Q
how is schizoaffective disorder diagnosed ?
A
- has to meet criteria for schizophrenia AND
- also a major mood episode (mania or depression)
23
Q
what are the three types of schizoaffective disorder ?
A
- manic and depressive episodes: bipolar type
- depressive only: depressive type
- mixed (manic and depressed simultaneously)
24
Q
epidemiology of gender in schizophrenia
A
- 1.4x more frequent in males than females
- in males can occur in late teens
- in females often late twenties
a highly disabling condition that occurs early in life and there is no cure
25
do people with schizophrenia have split personalitites ?
no. this is a different disorder termed dissociateive personality disorder and is unrelated
26
are people with schizophrenia dangerous ?
a small minority are prone to violence, but most are only dangerous to themselves
## Footnote
high rate of suicide
27
is it true that people with schizophrenia will never recover ?
many schizophrenics will have partial or full recovery. many have the potential to live productive lives with medication
28
what are some symptoms associated with schizophrenia or schizoaffective disorder that psychiatrists may also look for to support the diagnosis?
- sleep problems
- anxiety
- cognitive problems
there are also neurological 'soft-signs' (subtle neurological deficits) such as motor problems and difficulty distinguishing right and left
## Footnote
**these are not in main diagnositc criteria**
29
what is the legislation that allows people to be detained in psychiatric hospitals against their will ?
The Mental Health Act 1983
## Footnote
term 'sectioning' comes from sections of the Act
30
what does The Mental Health Act 1983 allow for ?
compulsory hospitalization and treatment
31
when does the mental health act come into play ?
person must be a danger to themselves or others
32
who does the mental health act give power to ?
medical professionals, social workers, and police
33
what are the two most common parts of the mental health act that are used to detain people ?
section 2 and section 3
34
what is section 2 of the mental health act ?
a 28 day assessment and treatment order
35
what is section3 of the mental health act ?
6 month treatment order (can be renewed)
## Footnote
normally have a pre-diagnosed mental health disorder which has worsened
36
who can an application for sectioning be made by ?
- nearest relative or 'approved mental health professional' (AMHP)
- must be seen by two doctors (one must be a known psychiatrist) and AMHP
37
what are the exceptions for refusing sectioning ?
they cannot refuse unless exceptional circumstances like doing ECT instead
38
what are some risk factors for schizophrenia ?
- environmental and social factors (which can produce epigenetic changes)
- genetic factors
## Footnote
epigenetics e.g. trauma early in life can induce genetic changes in genes that may impact risk in later life
39
what is some evidence for genetic involvement of schizophrenia ?
- normal population rate is 1% risk, but increases to 8-10% if near relative affected
- 50% concordance rate in twin studies
40
what does a high concordance rate in twin studies suggest for the genetic involvement in schizophrenia ?
- probably many 'tendency genes' e.g. DISC1
- many of these tendency genes may require an environmental impact
41
what is the classic environmental factor for increased risk of schizophrenia ?
- winter birth: suggests reason is maternal exposure to viruses
## Footnote
might be a myth but is debated
42
what is another (common) environmental factor for increased risk of schizophrenia and what do we know about it?
substance abuse
- amphetamine can cause psychosis or worsen it for someone who already has psychosis
- heavy cannabis use can increase risk
- but schizophrenics have a high risk for substance abuse, so does this cause schizphrenia or is it an effect of their schizophrenia ?
43
what does AKT1 code for ?
codes for a kinase that inactivates glycogen synthase kinase
44
what is a potential target for glycogen synthase kinase ?
lithium salts in bipola disorder
45
what is glycogen synthase kinase involved in ?
signalling via dopamine D2 receptors
46
what did the different alleles for ATK1 reveal about environmental and genetic interactions as a risk factor for schizophrenia ?
- those with ATK1 (T/T): homozygous for wild type is did't matter is you never used cannabis, used at weekends or less, or used everyday, it did not increase the risk of schizophrenia
- those with ATK1 (C/T): heterozygous with a mutant and wild form saw no increased risk for schizophrenia no matter how much cannabis they used
- those with ATK1 (C/C): homozygous for mutant form has no problem if they didn't use cannabis or only used at the weekends or less, but heavy users had an increased risk of schizophrenia by 7 fold
## Footnote
shows how genetic factors may require certin environmental factors to have an impact
47
what are some social risk factors for schizophrenia ?
## Footnote
(enivornment)
- difficult childhood conditions: discrimination, dysfunctional families, abuse or trauma
- epigenetic change
48
what is debated about schizophrenia ?
whether it is a neurodevelopmental disorder or neurodegenerative disorder
49
what is some evidence supporting schizophrenia as a neurodevelopmental disorder ?
- age of onset (teenage/early adult) is when the brain i changing a lot
- you also see some structural difference in the brain of people with schizophrenia compared to people who don't (different wiring?)
50
what is evidence supporting schizophrenia as a neurodegenerative disease ?
- progression of disease in many cases, particullary if not treated early
- also some reductions in brain volume
- suggested excitotoxicity having a role (glutamate?)
51
what is a risk factor suggested for both scizophrenia and bipolar disorder ?
infection with the parasite Toxoplasma gondii
52
what is toxoplasma gondii ?
- organism has cats and other feilds as definitive hosts, but can use any warm blooded animal as a secondary host
- impossible to get rid of
- migrates into tissues and forms cysts, especially in the brain
## Footnote
around 30% of worlds population is infected
53
what does T gondii cause in rats ?
manipulates their behaviour and increases their chances of being eaten by cats
## Footnote
suggested it may also be able to influence human behaviour
54
what disorder is the dopamine hypothesis related to ?
schizophrenia
55
what is the dopamine hypothesis ?
schizophrenia was due to hyperactivity of the mesolimbic pathway (VTA to ventral striatum)
56
what do we think about the dopamine hypothesis as the cause of schizophrenia ?
unlikely to be root cause, but likely to be a common pathway through which several causal factors converge to produce symtpoms of the disease
57
what are 3 pieces for evidence for the dopamine hypothesis and what does this suggest?
- resperpine (antihypertensive agent) depletes dopamine, and improves positive symptoms of schizophrenia (e.g. hallucinations)
- amphetamine releases dopaminen, and this can cause psychosis, and this can be treeated with drugs that also treat schizophrenia
- L-DOPA and dopamine agonists cause psychosis at high doses
altered dopaminergic activity in certain brain areas may play a role in schizophrenia
## Footnote
(hyperactivity)
58
how are dopamine receptors divide ?
- 5 subtypes: D1-5
- D1 like: D1/5
- D2 like: D2/3/4
59
DOPAMINERGIC PATHWAY DIAGRAM
60
What are the 4 main dopaminergic pathways in the brain ?
- mesocortical
- nigrostriatal
- tubero-infundibular
- mesolimbic
61
what is the mesocortical pathway ?
from ventral tegmentum into cortex
62
what is the nigrostriatal pathway ?
substantia nigra into basal ganglia (striatum)
63
what is the tubero-infundibular pathway ?
hypothalamus into pituitary gland
64
what is the mesolimbic pathway ?
ventral tegmental area into ventral striatum (nucleus accumbens)
65
what was the traditional view point of where positive schizophrenia symptoms came from ?
- increased DA in mesolimbic pathway
- this area is involved in emotion, fear and motivation and so positive symptoms arise from this
66
what was the second traditional view of where negative schizophrenia symptoms came from ?
- decreased DA in mesocortical pathway
- involved in emotion, motivation and cogntive control, important in negative symptoms (lead to congitive problems)
67
what was the taditional view of involvement of the tuberhypopyseal and nigrostriatal pathways in schizophrenia ?
important in side effects
- tuberhypophyseal (HT/Pituitary) hormone release from pituitary
- nigrostriatal: motor control (parkinson's diease)
68
what is the cortical basal ganglia loop/circuit for parkinson's disease and what modulates it?
## Footnote
motor pathway
(motor) cortex -> stiratum -> globus pallidus -> thalamus -> back to cortex
- modulated by input from substantia nigra into striatum
69
what is the cortical-basal loop/circuit involved in reward and what modulates it?
## Footnote
emotion/motivation pathway
cortex -> ventral striatum (NA) -> globus pallidus -> thalamus -> back to cortex
- mesolimbic pathway from ventral tegmental area (VTA) modulates input in ventral striatum
70
what part of the cortical-basal ganglia circuit was thought to play a role in schizophrenia?
increased DA transmission from VTA which lead to positive symptoms
71
what is the associative/executive cortical-basal ganglai circuit/loop and what is it involved in?
cortex -> striatum -> glbus pallidus -> thalamus -> back into cortex
- input from substantia nigra also goes to associate striatum
- involved in learning, habituation, memory, motivation etc. might be important in schizophrenia
72
what is the substantia nigra striatal pathway inportant in ?
- motor function (motor loop)
- high level cogntive processors (executive/associate loop)
73
what is a more modern view of dompaniergic pathways and what does this suggest for schizophrenia?
- functional imaging shows no increased DA transmission in mesolimbic pathway (VTA->Striatum)
- instead the excess of dopaminergic activity is from nigrostriatal pathway that goes into associative striatum
most probable explanation for positive symptoms
74
what is the associative striatum (AS) involved in ?
assigning salience to stimuli e.g. threat level or how important it is
75
what is suggested about excess noise in associative striatum dopaminergic signalling as part of the DA hypothesis?
- can lead to increased salience assigned to unimportant stimuli (inappropriate importance)
- may lead to positive symptoms
76
what is suggested about cognitive impariments in the DA hypothesis ?
- due to hypodopaminergic cortical function
- potentially driven by excessive activity in AS (possibly driven by striatal hyperdopaminergic signalling)
77
what is suggested about the origin of negative symptoms of schizophrenia in the DA hypothesis ?
- may reflect impaired reward based learning
- noise from AS means it cannot provide the proper importance to stimuli
- driven by striatal hyperdopaminergic signalling
- this decreases reward we get from those stimuli which can lead to apathy and anhedonia
78
why does the dopamine hypothesis not give us a complete picture of schizophrenia ?
doesn't address the involvement of other receptor types
79
what are 3 lines of research concerning the involvement of receptors in schizophrenia ?
- NMDA receptor dysfunction / glutamatergic tansmission dysfunction
- serotonin receptors
- muscarinic receptors
80
what is suggested about NMDA receptor dysfunction in schizophrenia?
- glutamatergic transmission dysfunction
- NMDA antagonists cause psychosis e.g. ketamine
- so positive allosteric modulators of glutamate may be new theraputic approach e.g. AMPAkinase (enhance Glu transmission)
81
what is suggested about the involvement of serotonin receptors in schizophrenia ?
- LSD can cause psychosis (inc. serotonin)
- apathy/anhedonia in scz. similar to depression... supports involvement of serotonin
- not root cause, but 5HT activity in newer antipsychotics gives a better theraputic profile
82
what is suggested about the involvement of muscarinic receptors in schizophrenia ?
- mAChR antagonists worsen negative + cognitive symptoms of scz.
- scopolaime as a muscarnic antagonist can cause psychosis (dec. ACh)
- therefore muscarinic agonists useful ?
- but mAChR antagonist activity in drugs gives better side effect profile as antipsychotics that don't have this activity can lead to movement disorders
83
given what we know about the potential involvement of muscarinic receptor activity, what could be a potential target for treatment of schizophrenia ?
developing subtype selective allosteric modulators (of ACh)
## Footnote
difficult as ACh site doesn't differ much between receptor subtypes/ but allosteric site is less conserved
84
why are antipsychotics seen as dirty drugs ?
have effects at target site and also off target sites
85
what is the mechanism of antipsychotic drugs ?
nominally dopamine D2 antagonists/ partial agonist
- actions at other receptor types too
86
what is a limitation and benefit of antipsychotic drug actions at different receptor types ?
- lack of selectivity gives rise to side effects
- can also give rise to theraputic effects e.g. actions at 5HT receptors
87
what are common side effects of antipsychotics ?
- movement disorders
- glactorrhea
- cogntive impairment
- weight gain
- anti-muscarinic effects
88
what is common side effects of old antipsychotics ?
movement disorders or 'extrapyramidal' side effects
- dystonias (contractions) and tardive dyskinesia (jerking/writhing movements)
## Footnote
movement disorders can sometimes remain permenant even is antipsychotic is stopped
89
why do we get a side effect of movemment disorders from antipsychotics ?
intereference of dopamine D2 receptors in motor striatum
90
what is galactorrhea and what is it due to?
inappropriate milk production
- due to tuberhypophyseal D2 receptors that inhibit prolactin release, if we block there we get too much prolactin hence...
91
why is cogntive impairment a side effect of antipsychotics ?
these happen as a symptom due to hypodopaminergic transmission
- D2 inhibition in cortex may worsen this
## Footnote
may also be due to actions at muscarinic receptors
92
why do we see sedation with antipsychotics ?
- due to H1 antagonism
93
why might we see weight gain as a side effect of antipsychotics and what could this lead to?
H1 and 5HTR antagonism
- potential for diabetes, heart disease etc.
94
what can the anti-muscarinic effects of antipsychotics lead to ?
- dry mouth
- blurred vision
- memory problems
- cardiac problems
95
what is there an increased risk for when taking antipsychotics ?
diabetes
96
What is a known side-effect of several antipsychotics that can cause diabetes?
Hyperglycaemia
97
what is hyperglycaemia ?
a condition characterized by an excess of glucose in the bloodstream, which can lead to diabetes.
98
What is another major reason for the increased risk of diabetes in people taking antipsychotics?
Obesity
## Footnote
Obesity is closely linked to type 2 diabetes mellitus (T2DM).
99
How do antipsychotics contribute to weight gain?
Actions at H1 and 5HT receptors
## Footnote
These receptors are involved in appetite regulation and metabolic processes.
100
What negative symptom of schizophrenia may contribute to weight gain due to reduced exercise?
Avolition (lack of motivation)
## Footnote
Avolition is a lack of motivation or ability to initiate and persist in activities.
101
What phenomenon can antipsychotic drugs induce independent of BMI changes?
Insulin-resistance
## Footnote
Insulin-resistance can occur even with medications that do not significantly affect appetite.
102
What component of the insulin signalling cascade is inhibited by antipsychotic drugs that may cause insulin resistance?
Akt, which plays a critical role in the insulin signalling pathway, affecting glucose metabolism.
103
What is IRS-1 ?
Insulin receptor substrate 1, which is a key protein that mediates insulin signaling and its phosphorylation is important for insulin action
104
What is IRS-1 in the context of insulin resistance ?
antipsychotics can cause insulin resistance by decreasing the phophorylation of IRS-1, a target of the insulin receptor kinase activity
105
in summary, how are antipsychotics thought to cause insulin resistance ?
by inhibiting a component of the insulin signalling cascade, Akt, and by decreasing the phosphorylation of one of the targets of the insulin receptor kinase activity, insulin receptor substrate 1 (IRS-1)
106
How can antipsychotics affect pancreatic beta cells?
cause pancreatic beta cell dysfunction via action on muscarinic, dopaminergic, adrenergic and serotonergic receptors
- can induce apoptosis
## Footnote
which decreases insulin secretion
107
What effect can antipsychotics have on cellular concentrations of ATP?
Decrease, which could decrease insulin secretion
108
what are 3 things antipsychotics can affect ?
- obseity
- induce insulin resistance
- dysfunction of beta cells
109
how can antipsychotics affect obseity ?
- increase BMI
- due to actions at H1 and 5HT
110
why is increased obseity linked to increased risk of diabetes with antipsychotics ?
- obseity associated with T2DM
111
how can antipsychotics induce insulin-resistance, independent of their affects on BMI ?
- in drugs that do not affect appetite
- inhibit Akt
- decrease phosphorylation of IRS-1
112
What do the newest theories about the pathophysiology of schizophrenia hold ?
- cog symptoms due to reduced DA activity in mesocortical pathway
- negative symptoms due to recude DA activity in mesolimbic pathway
- positive symptoms from excess dopamine release in associate striatum
113
What do the newest theories about the pathophysiology of schizophrenia hold that the positive symptoms may be due to ?
Excess dopamine release in the associative striatum
114
what do the newest theories about the pathophysiology of schizophrenia hold that the cognitive symptoms may be due to ?
Reduced dopaminergic activity in the mesocortical pathway
115
what kind of schizophrenic symptom is paucity of speech ?
negative symptom
