mental health (spring) Flashcards
define mental health
a state of well-being in which every individual realizes his or her own potential, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to her or his community.
define health
Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity
what is psychosis
Syndrome (a set of symptoms). includes:
- Delusions
- Hallucinations
- Disorganized speech
- Disorganized behaviour
- Gross distortion of reality
It is the defining set of symptoms of:
- schizophrenia
- substance-induced psychotic disorders
- schizophreniform disorder
- schizoaffective disorder
- delusional disorder
- brief psychotic disorder
- psychotic disorder due to a general medical condition
It may or may not be associated to:
- mania
- depression cognitive disorders
- Alzheimer’s dementia
how is genetics liked to Schizophrenia?
Schizophrenia tends to run in families, but no single gene is thought to be responsible.
It’s more likely that different combinations of genes make people more vulnerable to the condition.
Evidence that the disorder is partly inherited comes from studies of twins. Identical twins share the same genes.
In identical twins, if a twin develops schizophrenia, the other twin has a 1 in 2 chance of developing it, too. This is true even if they’re raised separately.
In non-identical twins, who have different genetic make-ups, when a twin develops schizophrenia, the other only has a 1 in 8 chance of developing the condition.
While this is higher than in the general population, where the chance is about 1 in 100, it suggests genes are not the only factor influencing the development of schizophrenia.
what are positive and negative symptoms?
give the positive and negative symptoms of schizophrenia
Positive: disinhibited behaviours/thoughts
Negative: inhibited/withdrawn behaviours/thoughts.
Some can be either positive or negative or have aspects of both.
(Diagnosis and classification of symptoms is solely psychiatric. There are no objective biochemical, metabolic or clinical signs.)
Symptom types:
- Thought disorder (+/-)
- Abnormal beliefs/delusions (+)
- Abnormal experiences (+)
- Mood disorder (+/-)
- Motor alterations (+/-)
- Changes in social function (-)
positive symptoms:
- delusions
- hallucinations
- distortions or exaggerations in language and communication
- disorganised speech
- disorganised behaviour
- catatonic behaviour
- agitation
negative symptoms:
- apathy
- anhedonia
- cognitive blunting
- neuroleptic dysphoria
match each symptom to hypothetically malfunctioning brain circuits
give genetic and environmental factors for Schizophrenia
Inherited genetic factors
- Increased risk in families if one family member affected
- In twins: Dizygotic(fraternal) 17%; Monozygotic (identical) 48%
- Identification of susceptibility genes e.g. Neuregulin 1
Environmental factors
- Birth complications, viral infection, inner cities, immigration, drug misuse
what is the Neurodevelopmental model for Schizophrenia?
Early environmental insult and/or genetic factors lead to changes in brain development with later environmental factors contributing to risk
what is the pharmacological dilemma of using dopamine to treat schizophrenia?
the mesolimbic Dopamine pathway overactivation can lead to schizophrenia positive symptoms exacerbation,
While antagonising the mesocortical dopamine pathway can worsen negative symptoms
what leads to positive symptoms in Schizophrenia?
Blockade of NMDA-R may prevent Glu-mediated excitation. NMDA-R hypofunction leads to Schizophrenia positive symptoms
NMDA-R hypofunction in psychosis might
be a consequence of…?
an autoimmune disorder
what causes reduced dopamine secretion?
Increased cortical serotoninergic tone, can lead to reduced dopamine secretion, downstream
Negative symptoms of schizophrenia on observation?
Negative symptoms of schizophrenia on questioning?
explain the diagram…
Acute psychotic episode typically alerts HCPs and allows patient to enter healthcare system for treatment
Symptoms tend to be initially mild but negative before showing increased positive dominance that steadily trails off into largely negative symptoms in the chronic phase.
give Prognostic signs for isolated episodes of and Prognostic signs for persistent (chronic) schizophrenia
Prognostic signs for isolated episodes include:
- No family history
- Stable premorbid personality
- Acute onset
- Emotional responses preserved
- Early diagnosis and treatment
Prognostic signs for persistent (chronic) schizophrenia include:
- Family history
- Disturbed premorbid personality
- Difficulty forming relationships early in life
- Poor social adjustment/disrupted domestic life
- Insidious onset
- Loss of initiative and drive
- Delayed diagnosis and treatment
non pharmacological treatments for schizophrenia
Control acute attacks (prevent harm to self and others)
Resolve contributory social and domestic factors
Rehabilitate the patient. (attacks of psychosis have consequential effects on mood, emotion etc)
Begin long-term maintenance therapy if necessary.
give examples of Antipsychotic (neuroleptic) drugs
moa?
what are they used to treat?
haloperidol, chlorpromazine (1st Generation)
D2 antagonists
Generally only treat positive symptoms
- Onset slow
- Depot formulation for secondary care – concordance/compliance
Dopamine hypothesis with conventional antipsychotics…
what effect does reducing mesolimbic dopamine hyperactivity have?
reduces positive symptoms but leads to exacerbated negative symptoms because it also reduces mesocortical dopaminergic tone.
side-effects associated with anti-psychotic use?
Extrapyramidal symptoms- Manifest as movement disorders
D2 antagonist: prolactinaemia
M1 antagonism: constipation, blurred vision, dry mouth, drowsiness
what is the Therapeutic index for conventional and atypical antipsychotic drugs?
conventional: Narrow therapeutic range
atypical: better therapeutic profile
serotonin hypothesis and atypical antipsychotics…
What effect does reducing mesolimbic dopamine hyperactivity have?
reduces positive symptoms
The 5HT2A antagonism leads to increased DA tone in Nigro-striatal pathways, reducing EPS side-effects
Blocking Serotonin receptors in the cortex, leads to increased dopamine secretion downstream also reducing EPS and prolactinaemia
describe Binding properties of atypical antipsychotics
Clozapine, olanzapine, and asenapine all bind relatively weakly to the 5HT1B receptor, while quetiapine and asenapine bind to the 5HT1D receptor.
Risperidone, paliperidone, ziprasidone, and iloperidone all have some affinity for the 5HT1B and 5HT1D receptors. In particular, ziprasidone binds more potently to the 5HT1B receptor than to the D2 receptor. Lurasidone does not bind to 5HT1B/D.
Aripiprazole and brexpiprazole each bind weakly to the 5HT1B receptor; aripiprazole also binds to the 5HT1D receptor; cariprazine does not bind to 5HT1B/D.
Atypical antipsychotic side effects
People with schizophrenia smoke more.
D2 Antagonists lead to weight gain, diabetes, increased smoking (lowered dopamine neurotransmission in NAc) etc.
People with schizophrenia develop metabolic syndrome, especially with atypical new medication (Serotonin antagonism). In the old times people treated with haloperidol were skinny and stiff (parkinsonism).
what makes an antipsychotic atypical?
D2 partial agonist actions…
Reducing mesolimbic dopamine hyperactivity reduces positive symptoms: es Aripiprazol
The partial agonism towards D2 in the mesocortical pathway, also reduces the negative symptoms
drugs for Schizophrenia
Anti-psychotics
- Typical (1st generation)
- Atypical (2nd generation)
Typical
- Developed in the 1950s and classified by chemical structure chlorpromazine
- Butyrophenones, phenothiazines or thioxanthenes (see BNF)
Atypical
- Selective (e.g. D2) dopamine antagonists
- Some with 5HT antagonist effects (subtype specific - 5HT2A, C and 5HT1A)
- Dopamine partial agonists
Treatment tailored to individual patient’s response and tolerance
fill in the table…
complete the table…
Schizophrenia treatment side-effects. what side effects are related to dopamine blockade?
Motor (extrapyramidal side effects (EPS))
- Acute dystonia (involuntary motor movement)
- Akathisia (innner perception of an inability to ‘sit still’)
- Parkinsonian
- Tardive dyskinesia (writhing movements of tongue and facial muscles)
Hyperprolactinaemia (high blood prolactin levels)
- >580 mIU/L women; >450 mIU/L men
Neuroleptic malignant syndrome
- Skeletal muscle spasticity
- Dysfunctional hypothalamic thermal regulation
Side effects typically related to side-effects arising from drug interactions with other (non-dopaminergic) systems
Anti-cholinergic
Anti-histaminic
Anti-adrenergic
Weight gain
Diabetic symptoms in African-Carribean populations
complete the table
what are the multifunctional actions of quetiapine?
25mg- hypnotic
300mg- antidepressant
800mg - antipsychotic
how long are treatments maintained for after an acute attack?
why does sustained treatment have disavantages?
12-24 months
Poor side effect profiles
what is cannabis psychosis?
Psychosis is a symptom in schizophrenia
Acute use (‘one joint’) may be enough to induce a short-term psychotic episode
- anxiety, depression, paranoid ideas, illusions, hallucinations, delusional beliefs (‘wanted’ and ‘unwanted’ effects).
This may be ameliorated by CBD
list Illicit and Prescription drugs considered to pose a potentially greater risk in schizophrenia
Illicit:
- Amphetamines
- Cocaine
- MDMA
- PCP
- Magic mushrooms
- Alcohol
- Mescaline, psylocybin, LSD
- Khat
- Solvents
Prescription:
- α-adrenoceptor blockers
- Antibiotics
- Anticholinergics
- Antiepileptics
- Antihistamines
- Antimalarials (mefloquine)
- Digoxin
- Dopaminergics
- H2 receptor antagonists
- Retinoids
- SSRIs (e.g. Prozac)
