Topic 9- psychiatric conditions Flashcards
What is schizophrenia?
Although there are records of Schizophrenia-like symptoms throughout history, medical records did not show clear cases until around between 1797 and 1809. The term Schizophrenia was not introduced until 1908 by Bleuler.
Chronic mental health condition affecting 0.5-1% of the population.
It is characterised by psychotic symptoms, emotional dysregulation and cognitive deficits.
Onset is typically later in women (~30 years) compared to men (15-25 years).
It also tends to be less severe in women, with less pronounced brain abnormalities and less resistant to treatment.
What are the positive symptoms of schizophrenia?
Positive Symptoms
Hallucinations
Delusions
Disordered thoughts
These are positive as they are seen as additional to normal functioning.
What are the negative symptoms of schizophrenia?
Negative Symptoms
Reduced speech (alogia) Social withdrawal (asociality) Lack of emotion Diminished ability to start and continue activities (avolition) Decreased ability to find pleasure in everyday activities (anhedonia) Negative Symptoms Reduced speech (alogia) Social withdrawal (asociality) Lack of emotion Diminished ability to start and continue activities (avolition) Decreased ability to find pleasure in everyday activities (anhedonia)
These are negative as they are a lack of normal functioning.
What are the cognitive deficit symptoms of schizophrenia?
Cognitive Deficits Memory Attention Planning Decision making
Explain the course of schizophrenia.
Schizophrenia starts much earlier than a formal diagnosis.
- Premorbid phase which is typically childhood
- Prodromal phase (brief positive symptoms and some functional decline) (Childhood/Adolescence)
- Psychotic phase (florid positive symptoms) (Adolescence/young adult)
- Stable phase (negative symptoms, cognitive/social deficits and functional decline)(Adolescence/young adult)
After the initial episode there are several possible courses for the condition:
8% will experience several psychotic episodes with functional impairment in between and no return to normality.
22% will experience one psychotic episode only and no further functional impairment.
35% will have several psychotic episodes with a return to normality in between.
38% will experience several psychotic episodes with increasing functional impairment in between and no return to normality.
Focus now is on identifying people before onset of symptoms – Clinically High Risk individuals can be identified and started on treatment early on. However, most of those identified as high risk will not develop schizophrenia which creates some problems with early treatment.
Explain the experience of schizophrenia.
The experience of schizophrenia can be very difficult for individuals and those around them.
Stigma
Increased family stress
Reduced employability
Reduced income
Difficulties obtaining
housing
Shame
Physical, verbal or
emotional abuse
Explain the impact of schizophrenia.
Having schizophrenia increases a person’s risk of:
- unemployment
- poverty
- homelessness
- incarceration
- recurrent hospitalisations
- high rates of comorbid medical illness and depression
- increased suicide attempts with a suicide completion rate of 5–10%
Overall life expectancy that is reduced by 1–3 decades.
Explain risk factors for schizophrenia.
A role for genes has been identified from family studies, adoption studies and twin studies:
Concordance rate for MZ twins = 48% and DZ = 17%, shows it is not entirely genetic.
Evidence indicates 70-80% heritable but no single gene
There are two options for genetic influence for a common disorder:
- Common variant – large number of common genetic variants each having a small effect which combine. They all have to come together to produce schizophrenia. Genes include those relating to the immune system, dopamine and glutamate.
- Rare variant – rare variant that has a big impact. Key gene identified so far is ‘Disrupted in Schizophrenia I’ or DISC1. This is linked to a scaffolding protein important in development, neurogenesis and synaptic function.
There are also environmental risk factors which are established in the literature:
Winter births – increase risk by 5%
Owning a cat in childhood – increase by 53%
Complications at birth – increase by 71%
Urban upbringing/location – increase by 85%
Infection during pregnancy – increase by 182%
These are not mutually exclusive. Also Adverse Childhood Experiences – risk will depend on severity but include things like: abuse, parental death.
Explain gross changes in the brain in schizophrenia.
CT scans have revealed some changes in gross anatomy of the brain:
Ventricles are around 15% larger in SZ, indicative of loss of tissue.
Both patients and relatives (without SZ) show loss of grey matter in the frontal and temporal cortex which indicates a genetic predisposition.
There are associated changes in brain functioning:
Reduced activity in the frontal lobes and this is thought to relate to negative and cognitive symptoms.
Ventricular changes correlates with poorer cognitive ability and drug responsiveness.
During hallucinations there are increases in activity in areas association with hearing.
Explain dopamine changes in the brain in schizophrenia.
The main theory of schizophrenia for many years has focused on dopamine – the Dopamine Hypothesis. This theory assumes that the symptoms of SZ are caused by altered levels of dopamine:
Drugs which block dopamine receptors (antagonists) can reduce psychotic symptoms.
Drugs which raise dopamine levels (e.g. amphetamine) can induce psychotic symptoms.
An increase in DA in the mesolimbic pathway is linked to positive symptoms.
However, a decrease in DA in the mesocortical pathway is linked to negative and cognitive symptoms.
This poses a challenge as it’s difficult to increase dopamine in one pathway and decrease it in another
Explain glutamate changes in the brain in schizophrenia.
Low glutamate cerebrospinal fluid in SZ patients
PCP or ketamine which are known to act on glutamate receptors produce SZ-like symptoms in healthy people and exacerbate SZ in patients
Post mortem changes in glutamate transmission have been found (it’s not always clear when the changes occurred and if they were part of the process of dying or a result of the treatment, which is a limitation of looking at post-mortem changes).
Genes associated with SZ can influence glutamate transmission
Reduced NMDA receptor binding in patients with SZ
Glutamate modulates DA and so they might work together to produce SZ sypmtoms
Explain serotonin changes in the brain in schizophrenia.
Modulates DA
Linked to negative symptoms
Newer antipsychotics act on 5HT
Explain acetylcholine changes in the brain in schizophrenia.
Rates of cigarette smoking in schizophrenia have been reported to be as high as 90% compared with 33% in the general population, leading to the hypothesis that nicotine is treating a fundamental problem in schizophrenia.
In schizophrenia, nicotine administration improves working memory and selective attention, whereas withdrawal exacerbates cognitive impairments.
Explain the NICE guidelines for treating schizophrenia.
These are split according to the stage of the condition.
Preventing psychosis:
- individual cognitive behavioural therapy (CBT) with or without family intervention.
interventions recommended in NICE guidance for people with any of the anxiety disorders, depression, emerging personality disorder or substance misuse.
Acute Psychotic Episode:
- Anti-psychotic medication, chosen by patient and clinician.
- Consideration of side effects.
- Avoid combined treatment.
- Social, psychological and educational support.
Promoting recovery:
- Offer clozapine to people with schizophrenia whose illness has not responded adequately to treatment despite the sequential use of adequate doses of at least 2 different antipsychotic drugs.
- Offer supported employment programmes to people with psychosis or schizophrenia who wish to find or return to work.
Explain the use of first generation antipsychotics in treating schizophrenia.
First developed in 1950s and include chlorpromazine and haloperidol.
Block ALL D2 receptors irrespective of location:
Reduces dopamine in the mesolimbic pathway which reduced positive symptoms. (+)
But also reduces dopamine in the nigrostriatal pathway giving extrapyramidal side effects and tardive dyskinesias (<50% of patients). (-)
Reduces dopamine in the mesocortical pathway making negative/cognitive symptoms worse. (-)
Decreases dopamine in the tuberoinfundibular pathway has the effect of altering prolactin which results in altered lactation, menstruation and bone density. (-)
However, you can treat the negative side effects with other drugs.
Explain using second generation antipsychotics to treat schizophrenia.
Block D2 receptors but with less affinity so less potent (less efficient) at these receptors. Some also act on serotonin receptors- the 5HT2A receptors – these are found on DA neurons.
Reduces dopamine in the mesolimbic pathway which reduced positive symptoms. (+)
Still reduces dopamine in the nigrostriatal pathway but this effect is cancelled out by actions at 5HT2A receptors, which increases DA so there are no extrapyramidal side effects (The dopamine receptors are still blocked but so are the serotonin ones which counters the action to reduce dopamine by increasing it.)
Another theory is SGA just unbind from D2 receptors quicker and so do not cause side effects.
5HT2A effects in mesocortical pathway can act to increase DA here so reducing negative/cognitive symptoms. (+)
Still decreases dopamine in the tuberoinfundibular pathway but these effects are cancelled out by actions at 5HT2A receptors so no side effects. (-)
First and second generation antipsychotics are pretty much equal in their efficiency in treating SZ.
What are the additional side effects of drug treatment for SZ?
A 1% risk of agranulocytosis (decrease in white blood cells), making frequent blood testing needed (clozapine only). This is why clozapine is not used unless a patient has failed to respond to two other antipsychotic medications first.
Most antipsychotics but especially the atypical ones increase the risk of developing the metabolic syndrome, which consists of obesity, high blood pressure, insulin resistance and elevated cholesterol.
Blockade of muscarinic acetylcholine receptors - constipation, dry mouth, blurred vision and drowsiness.
Blockade of histamine receptors, promoting weight gain and drowsiness along with decreased blood pressure due to blockade of a1 norepinephrine receptors.
What are mood (affective) disorders?
Central component of affective disorders is disordered feelings. Feelings are part of our everyday life and normally how we feel reflects what is happening to us. In pathological cases, feelings cannot be justified by what is happening to us. Mood disorders can range for severe depression to severe mania and a range of conditions in between.
Major Depressive Disorder:
Prevalence: 15%, Incidence: 1% Onset is normally early adulthood 15% attempt suicide 10% commit suicide More prevalent in females than males but only after 13 years of age May be continuous or come in episodes
Bipolar Disorder:
Prevalence: 1-1.5% (i.e. slightly higher than SZ)
Incidence: 4%
Age of onset is usually in late adolescence
30% attempt suicide
15% commit suicide
Equally prevalent in males and females
