psychosis Flashcards
main 4 symptoms of psychosis
delusions, disordered thoughts, hallucinations and catatonia
what causes schizophrenia
schizophrenia
bipolar disorder
illegal drugs
prescription drugs
PTSD
sleep deprivation
caffeine intoxication
Alzheimer’s disease
-part of other conditions- can have causes that are not directly related to an illness
normal experience with first episode of psychosis
First episode usually unexpected
cannot usually be immediately diagnosed with particular causal disorder
definitive diagnosis may come later
may be designated as having experienced ‘brief psychotic episode’
what is a ‘brief psychotic episode?
period of psychosis not caused by a mental health disorder
what are psychotic episodes frequently predicted by
prodromal phase
what is predromal phase? How long does it last?
changes in behaviour: irritability, difficulty concentrating, memory problems, anxiety, depression
can last months to years
why may there be a delay in treatment when acute phase begins?
person suffering doesn’t recognise they are ill? Friends/ relatives do not understand what’s happening?
what is the effect of delayed treatment
worse outcomes
what can help a person receive speed intervention?
If person has experiences psychosis because of an underlying mental health condition, they may recognise prodromal symptoms and receive speed intervention before their next episode
three types of symptoms of schizophrenia
cognitive, positive and negative
positive symptoms of schizophrenia
hallucinations, delusions, disorganised speech, disorganised behaviour or catatonia
symptoms that a person with schizophrenia has that a normal individual does not
negative symptoms of schizophrenia
loss of emotional response, anhedonia and apathy
symptoms that a person with schizophrenia lacks, that a normal person has
requirements for a schizophrenia diagnosis
two positive symptoms, or a positive and negative symptoms
must impact significantly
continuous signs of disturbance in behaviour for at least 6 months
not explained by something else
schizoaffective disorder
meets the criteria for schizophrenia and a major mood episode (mania or depression)
three types of schizoaffective disorder
bipolar type, depressive type and mixed
bipolar type schizoaffective disorder
manic and depressive episodes
depressive type schizoaffective disorder
depressive only
mixed schizoaffective disorder
manic and depressed simultaneously
epidemiology of schizophrenia
Around 1% of the population
Males 1.4x female (more frequent in males)
Strikes at an early age
Males: late teens
Females: late twenties
second female peak around the age of menopause
Highly disabling
no cure
suicide and schizophrenia
Much higher rate of suicide in schizophrenia than depression
5% of those suffering will take their own life
(double the rate of people with depression, while 10-15% of people with bipolar disorder type 1 commit suicide)
obesity and antipsychotics
Many antipsychotics can produce significant increases in BMI
-likely due to actions at H1 and 5HT receptors. Because obesity is associated with T2DM,
increased BMI is likely to be a major reason why the risk of diabetes is higher in people on antipsychotic drugs.
the negative symptoms of schizophrenia and the sedative effects of antipsychotics may also contribute to weight gain
antipsychotics and insulin resistance
can induce insulin-resistance independent of their effects on BMI:
this effect can occur with drugs that do not produce marked changes in appetite.
Antipsychotics are 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)
Antipsychotics and beta cells
direct effect on beta cells
can cause pancreatic beta cell dysfunction in several ways
acting on muscarinic dopamine, adrenergic and serotonergic receptors they can decrease insulin secretion
may also decrease cellular concentrations of ATP which would also decrease insulin secretion
may damage beta cells and induce apoptosis
mental health act 1983
allows for compulsory hospitalisation and treatments
gives power to medical professionals, social workers and the police
section 2 mental health act
28 day assessment and treatment order
section 2 mental health act
28 day assessment and treatment order
section 3 mental health act
6 month treatment order
can be renewed
usually have a pre-diagnosed mental health disorder that has worsened, therefore doctors are sure that keeping them for an extended time is of benefit
sectioning
approved mental health professional or nearest relative
must be seen by two doctors
-one must be a psychiatrist
-one has to know the patient
and an approved mental health professional
cannot refuse treatment (except ECT)
genetic factors of schizophrenia
1% in general population
8-10% if near relative affected
50% in twin studies (concordance rate)
–Probably influence of many “tendency” genes, which may have a small impact individually (unlikely to be due to a single schizophrenia gene). eg. DISC1 – disrupted in schizophrenia 1
–Many of these tendency genes may require an environmental impact too
gene disrupted in schizophrenia 1
DISC 1
Environmental factors
winter birth
substance abuse: cannabis, amphetamine
winter birth as an environmental for schizophrenia?
maternal exposure to viruses?
controversial risk factor, many think it is a myth
amphetamine as an environmental factor for schizophrenia
causes psychosis
can worsen the psychosis of someone who already have schizophrenia, or cause them to have a relapse
cannabis as an environmental factor of schizophrenia
heavy cannabis use can increase the risk of development about schizophrenia
why is it controversial that substance abuse may cause schizophrenia?
cause or effect? schizophrenics have a high risk for substance abuse
what does AKT1 code for?
kinase that inactivates enzyme glycogen synthase kinase
involved in signalling via dopamine D2 receptors
example that genetic factors may require some influence of the environment
increased risk of schizophrenia in those homozygous for mutant ATK 1 when they use cannabis everyday,
but not if they used cannabis at week ends or less, or never used cannabis
social factors influencing schizophrenia
difficult childhood conditions:
-discrimination
-dysfunctional families
-abuse/ trauma
epigenetic changes?
evidence schizophrenia may be a neurodevelopmental disorder
Age of onset (teenage/early adult)
-around time where the brain is changing quite a lot
Structural differences in the brain between schizophrenic and healthy individuals
evidence that schizophrenia is a neurodegenerative disorder
Progression of disease in many cases, particularly true if it is not treated early
Reductions in brain volume
Excitotoxicity? could be that glutamate is one of the major factors
T gondii
Risk factor suggested for schizophrenia and bipolar
Estimated that up to 30% of the world’s population is infected with T gondii
Once infected, impossible to get rid of
Migrates to tissues (brain) , where it forms cysts
Known to manipulate the behaviour of rodents to increase their chances of being eaten by cats (a necessary part of the parasite’s life cycle)
Has been suggested that it may also be able to influence human behaviour
original form of dopamine hypothesis of schizophrenia
due to hyperactivity of the mesolimbic pathway (VTA to ventral striatum)
unlikely to describe the root cause of schizophrenia but may be a ‘final common pathway’
what is a final common pathway
system on which several different causal factors converge on to produce the symptoms of a disease
evidence for the dopamine hypothesis
reserpine depletes dopamine, leads to improvement in positive symptoms
-hallucinations and delusions lessen
amphetamine releases dopamine, amphetamine can cause psychosis
L-DOPA and dopamine agonists can cause psychosis if given at high doses
altered dopaminergic activity (hyperactivity) in certain brain areas may play a role in schizophrenia
D1 like receptors
D1, D5
D2 like receptors
D2, D3, D4
correlation of therapeutic concentration of antipsychotics with the concentration needed to occupy 75% of D2 receptors
almost 1:1 relationship
indicates that activity at D2 receptors is important for antipsychotic activity
increased dopamine transmission in mesolimbic pathway
mesolimbic pathway involved in emotion, fear and motivation
important in positive symptoms
suggested importance of mesocortical pathway in schizophrenia
Decreased dopaminergic transmission in mesocortical pathway, important in negative symptoms
dopaminergic pathways seen as being important in side effects
tuberhypophyseal (HT/Pituitary) - hormone release from the pituitary
nigrostriatal - motor control. important in Parkinson’s disease
modern view of dopaminergic pathways
excess of dopaminergic activity in the nigrostriatal pathway going to the associative pathway
-explains positive symptoms
normal ore reduced DA activity in the mesolimbic pathway to ventral striatum
-cause of negative symptoms?
detail of associative striatum DA hypothesis of schizophrenia
Associative striatum (AS) involved in assigning salience to stimuli e.g. threat level
Excess noise in AS dopaminergic signalling
-increased salience assigned to unimportant stimuli
-May lead to the positive symptoms
Cognitive impairments
-hypodopaminergic cortical function
-possibly driven by striatal hyperdopaminergic signalling
Negative symptoms
-impaired reward based learning
-not able to assign importance to things should be important
–decreasing reward we get from those stimuli
–possibly leading to apathy and anhedonia
?driven by striatal hyperdopaminergic signalling
involvement of other receptors in schizophrenia (not dopamine)
NMDA receptor dysfunction
serotonin receptors
muscarinic receptors
NMDA receptor dysfunction? in schizophrenia
glutamate dysfunction may be the root cause
NMDA antagonists cause psychosis e.g. ketamine
suggests that positive allosteric modulators of glutamate receptors could be a new therapeutic approach - AMPAkines?
Serotonin receptors and schizophrenia
LSD causes psychosis
apathy and avolition in schizophrenia superficially similar to depression?
probably not the root cause, but 5HT receptor activity seems to give a better therapeutic profile
muscarinic receptors and schizophrenia
mAChR antagonists worsen negative + cognitive symptoms
Scopolamine (non-selective mAChR antagonist) can cause psychosis
? muscarinic agonists useful
but mAChR antagonist activity gives better side effect profile
-with antipsychtic drugs that don’t have activity at muscarinic receptors, you sometimes see very serious movement disorders as an unwanted effect- drugs that have muscarinic antagonistic activity seem to avoid this problem
may be useful to develop subtype selective allosteric modulators
-difficult to do as the sites of muscarinic receptors don’t differ much between receptor subtypes but may be possible to develop allosteric modulators of individual subtypes
-allosteric site on muscarinic receptors is much less conserved so it may be a viable therapeutic approach
antipsychotics : dirty drugs
dopamine D2 antagonists/ partial agonists
-actions at many different receptor types
-lack of selectivity = side effects
dirty nature may also give rise to therapeutic benefits
e.g. actions at 5HTR
common side effects of antipsychotics
extrapyramidal effects (esp in older)
galactorrhea
cognitive impairment
sedation
weight gain
anti-muscarinic effects
what are extrapyramidal effects? what causes them?
Movement disorders
dystonia: involuntary muscle contraction and spasms
tardive dyskinesia: face, body/ both make sudden irregular movements - can be permenant
probably interfering with the function of D2 receptors in the motor striatum
what is galactorrhea? what causes it?
inappropriate milk production in women who haven’t given birth
tuberohypophyseal D2 receptors inhibit prolactin release. When these are inhibited it causes hyperprolactinemia
what causes cognitive impairment (antipsychotics)
D2 inhibition in cortex?
effects at other receptors (anti-muscarinic effects probably produce cognitive impairment too
why do antipsychotics cause sedation?
Histamine H1 antagonism ?
why do antipsychotics cause weight gain?
H1 and 5HTR antagonism?
what are anti-muscarinic side effects?
dry mouth, blurred vision, memory problems (cog impairment), cardiac problems
