Development, Memory and Addiction Flashcards
What brain structural changes in Schizphrenia result in a poorer prognosis?
Reduced frontal lobe volume
Reduced frontal lobe grey matter
Increased lateral ventricle volume
Where are there consistent reductions in brain structure in Schizophrenia?
Temporal cortex (esp. Superior Temporal Gyrus) Medial temporal lobe (esp. Hippocampus)
What is the neuropil composed of?
Mostly unmyelinated axons, dendrites and glial cells processes
What does neuropil form?
Synaptically dense region with a relatively low number of cell bodies:
- eg. Neocortex and olfactory bulb
When are grey matter abnormalities present in Schizophrenia?
Early
How can brain white matter be investigated?
Diffusion tensor imagine
What do higher numbers in fractional anisotropy indicate?
Healthy white matter tracts
What do higher numbers in mean diffusivity indicate?
Less healthy white matter tracts
Children showing impairment in what areas during infancy are more likely to develop Schizophrenia?
Behaviour
Motor development
Intellect
What does ventricular enlargement at diagnosis of Schizophrenia indicate?
It is non-progressive
What is the DA hypothesis in Schizophrenia?
Drugs which:
- Release DA (eg. Amphetamine) OR
- D2 receptor agonists (eg. Apopmorphine)
…both produce psychosis
According to the DA hypothesis, what effect does Amphetamine have on Schizophrenia?
Worsens it
According to the DA hypothesis, what effect do D2 receptor antagonists have in Schizophrenia?
Treat the symptoms
What DA pathways are overactive and may be related to Schizophrenia?
Tuberinfundibular (PRL release)
Mesolimbic/Cortical (Motivation and reward)
Nigrostriatal (Extrapyramidal motor system)
What do D1 family DA receptors (D1 and D5) do?
Stimulate cAMP
What do D2 family DA receptors (D2, D3 and D4) do?
Inhibit adenylyl cyclase
Inhibit voltage-gated calcium channels
Open potassium channels
What are the most abundant DA receptors?
D1
Where are D2 receptors also present?
Pituitary
What receptor is Bromocriptine an agonist of?
D2
What receptor is Raclopride an antagonist of?
D3
What receptor are Raclopride and Haloperidol antagonists of?
D2
What receptor is Quinpirole an agonist of?
D3
What receptor is Clozapine an antagonist of?
D4
What does subcortical DA hyperactivity result in?
Psychosis
What does mesocortical DA hypoactivity result in?
Negative and cognitive symptoms
What is the glutamatergic hypothesis?
Altered NMDA receptor subunit expression
What drug, which can cause psychosis, is explained by the glutamatergic hypothesis?
Ketamine
What is the serotonergic hypothesis?
Serotonin 2A binding potential in frontal cortex slightly small (by 16.3%) in schizophrenic patients
What gene alterations are indicated in psychosis?
Neuregulin
Dysbindin
DISC-1
What does Neuregulin do?
Signalling protein
Mediates cell-cell interactions and plays critical roles in growth and development
What does Dysbindin do?
Essential for adaptive neural plasticity
What does DISC-1 do?
Involved in neuritic outgrowth and cortical development via interactions with other proteins
What are some examples of typical (1st gen.) antipsychotics?
Chlorpromazine Thioridazine Fluphenazine Haloperidol Zuclopentixol
How do typical antipsychotics work?
D2 inhibition:
- Immediate blockaed
- Delay in onset of effect
What are the side effects of typical antipsychotics?
Dry mouth Muscle stiffness and cramps Tremor Extrapyramidal signs: - Akathisia - Parkinsonism - Dystonia
What is the definition of an atypical (2nd gen.) antipsychotic?
- Less likely to induce extrapyramidal symptoms
- High 5-HT2a:D2 ratio
(3. Better efficacy against negative symptoms)
(4. Effective if atypicals don’t work)
What are some examples of atypical antipsychotics?
Olanzapine Risperidone Quetiapine Clozapine Aripiprazole Amilsupride
What are the side effects of most/all atypical antipsychotics?
Mostly metabolic: - Weight gain - Hyperglycaemia - Dyslipidaemia and Hypertension Sexual dysfunction
What atypical antipsychotics can cause extrapyramidal symptoms at high doses?
Olanzapine
Risperidone
Amilsupride
What side effect can olanzapine have?
Increase PRL at high doses
How does an acute dystonic reaction present?
Muscle spasms
Within hours-days of initiation of antipsychotics
How are acute dystonic reactions treated?
Ach antagonists:
- Prochlorperazine
- Procyclidine
- Orhphenadine
What is tardive dyskinesia?
Repetitive, involuntary movements:
- Grimacing
- Sticking tongue out
- Lip smacking
- Pursing lips
- Blinking
How long does tardive dyskinesia take to develop?
Years to develop
What effect does stopping medications have on tardive dyskinesia?
It often continues
What do drugs with a high affinity for 5-HT2 receptors cause?
Hallucinations
Thought disturbance
What drugs have a high affinity for 5-HT2 receptors?
Hallucinogenic indoleamines
Phenylethylamines
How is 5-HT2 receptors binding affected in Schizophrenia?
Reduced
Blockade of what histamine receptor causes sedation?
H1
How does histamine blockade affect appetite?
Increases it
Why are newer anti-histamines not as sedative?
Do not cross BBB
What is histamine involved in?
Appetite
Pain perception
Regulation of pituitary hormon secretion
Reducing nausea and vomiting
What serious side effect can Clozapine have?
Agranulocytosis
How are the side effects of Clozapine monitored and prevented?
FBC:
- Weekly for first 6 months
- Fortnightly for next 6 months
- Every 4 weeks thereafter
- For 1 months after cessation
If a patient has a sore throat while on Clozapine, what must be done?
FBC!!
How does Clozapine cause myocarditis?
IgE-mediated Type 1 sensitivity OR Cytokine release OR Hypercatecholaminaemia
How is myocarditis monitored/prevented while on Clozapine?
Regular ECGs:
- May show nonspecific ST segment changes
What is the first line treatment of Schizophrenia?
An atypical antipsychotic (risperidone or olanzapine):
- Continue for 2 weeks
During the first line treatment of Schizophrenia, if there is no improvement by what point should an alternative therapy be considered?
4 weeks
During the first line treatment of Schizophrenia, if there is only partial improvement by what point should an alternative therapy be considered?
8 weeks
If there is remission of the first episode of Schizophrenia, how long should maintenance therapy be continued for?
> =18 months
If no response to the first line antipsychotic in Schizophrenia, what can be prescribed?
A different atypical antipsychotic
OR
Chlorpromazine (or another typical low-potency antipsychotic)
What drug is used in treatment-resistant Schizophrenia? When is Schizophrenia deemed treatment-resistant?
Clozapine
Poor response to 2 antipsychotics (one of which must be an atypical antipsychotic)
How can aggression in hospital be predicted?
Body language
How can aggression in hospital be prevented?
De-escalation
Observations
Room layout
How can aggression in hospital be treated?
Restraint
Seclusion
Rapid tranquilisation
How is a person who has or appears to have a mental disorder defined under section 329 of the Mental Health Act (Scotland)?
Any mental illness
Personality disorder
Learning disability
Who can approve a short-term detention or a CTO under the Mental Health Act?
Approved medical practitioner:
- Register practitioner who is either a member/fellow of the Royal College of Psychiatrists OR have 4 yers of continuous psychiatric experience and are sponsored by a local medical director
What is the only treatment authorised under Emergency Detention?
Emergency treatment
What is the first step of the Tayside Rapid Tranquilisation Policy?
Consider non-drug approaches:
- Distraction
- Seclusion
- Conversation
For the second step of the Tayside Rapid Tranquilisation Policy, what drug can be used if any of the following are met:
- Unknown PMHx or DHx
- Heart disease
- No Hx of typical antipsychotics
- Current illicit drug use
PO Lorazepam 1-2mg
For the second step of the Tayside Rapid Tranquilisation Policy, what drugs can be used if there is a confirmed history of significant typical antipsychotic exposure?
PO Lorazepam 1-2mg
AND/OR
PO Haloperidol 5mg
When can the third stage of the Tayside Rapid Tranquilisation Policy be initiated?
If PO therapy unsuccessful
OR
Effect required within 30 minutes
For the third step of the Tayside Rapid Tranquilisation Policy, what drug can be used if any of the following are met:
- Unknown PMHx or DHx
- Heart disease
- No Hx of typical antipsychotics
- Current illicit drug use
IM Lorazepam 1-2mg:
- Mixed 1:1 in water or NaCl
For the third step of the Tayside Rapid Tranquilisation Policy, what drugs can be used if there is a confirmed history of significant typical antipsychotic exposure?
IM Lorazepam 1-2mg: - Mixed 1:1 in water or NaCl AND/OR IM Haloperidol 5mg: - Not in same syringe as Lorazepam
What monitoring is required in IM Haloperidol is used in the Tayside Rapid Tranquilisation Policy? How frequently and for how long?
Respiratory rate
Pulse rate
BP
Every 5-10 minutes for 1 hour
When can the fourth step of the Tayside Rapid Tranquilisation Policy be initiated? What is the fourth step?
After waiting 30 minutes, another IM injection can be given
If this fails, get senior help
How can inner experience and behaviours deviating from the expectations of the individuals be manifested in the diagnosis of a Personality Disorder?
Cognition (perceiving/interpreting self and others) Affectivity (of emotional response): - Range - Intensity - Lability - Appropriateness Interpersonal functioning Impulse control
How is the enduring pattern of behaviour changes in a Personality Disorder described?
Inflexible
Pervasive
What do the behaviour changes in a Personality Disorder lead to?
Clinically significant distress
OR
Impairment in social/occupational/other functioning
What personality disorder is characterised by feelings of excessive doubt and caution, preoccupation with lists/rules, perfectionism, excessive scrupulousness, pedantry, stubbornness and unreasonable insistence that others submit to their way of doing things?
Anankastic (F60.5)
What kinds of personality disorders are classed as Cluster A; ‘Odd and Eccentric’ in DSM-V?
Paranoid
Schizoid
Schizotypical
What kinds of personality disorders are classed as Cluster B; ‘Dramatic, emotional, erratic’ in DSM-V?
Antisocial
Borderline
Histrionic
Narcissistic
What kinds of personality disorders are classed as Cluster C; ‘Anxious and fearful’ in DSM-V?
Avoidant
Dependent
Obsessive-Compulsive
What personality disorder is characterised by distrust and suspicion of others. It begins in early adulthood and presents with >=4 of the following:
- Suspecting others of exploiting/harming them
- Preoccupied with unjustified doubts of others loyalty
- Reluctance to confide in others
- Reads hidden meanings from benign remarks
- Persistently bears grudges
- Feels attacked and quickly reacts angrily
- Recurrent suspicions regarding partner’s fidelity
Paranoid personality disorder
What personality disorder is characterised by detachment from social relationships, restricted range of emotional expression, beginning in early adulthood and presents with >=4 of the following:
- Doesn’t desire/enjoy close relationships
- Chooses solitary activities
- Little interest in sex
- Takes pleasure in few/no activities
- Lacks close friends
- Appears indifferent to praise/criticism
- Emotional detachment or flat affect
Schizoid personality disorder
What personality disorder is characterised by disregard for and violation of the rights of others, occurs since around 15 years of age and is present with >=3 of the following:
- Failure to conform to social norms (forensic Hx)
- Deceitfulness
- Impulsivity
- Aggressiveness
- Reckless disregard for safety of self/others
- Consistent irresponsibility (ccupations/finances)
- Lack of remorse
Antisocial personality disorder
What personality disorder is characterised by instability of interpersonal relationships, self-image and affects, marked impulsivitiy, beginning by early adulthood and presenting with >=5 of the following:
- Frantic efforts to avoid abandonment
- Unstable/Intense interpersonal relationships
- Identity disturbance
- Impulsivity in two areas (sex, spending, substance abuse, reckless driving, binge eating)
- Recurrent DSH/suicidal ideation
- Marked reactivity of affect
- Chronic feelings of emptiness
- Inappropriate, intense anger
- Transient, stress-related paranoid ideation or severe dissociation
Borderline personality disorder
What personality disorder is characterised by social inhibition and feeling inadequate, beginning in early adulthood and presenting with >=4 of the following:
- Avoiding occupational activities
- Unwilling to socialise unless knowing you’ll be liked
- Restraint with intimacy
- Preoccupation with being rejected
- Inhibited in new social situations
- Views self as socially inept or inferior
- Unusually resistant to engage in new activities
Avoidant personality disorder
What personality disorder is characterised by excessive need to be taken care of, beginning in early adulthood and presenting with >=5 of the following:
- Needs excessive advice for everyday decisions
- Needs others to assume responsibility
- Difficulty expressing disagreement
- Difficulty being independent
- Goes to excessive lengths to obtain support
- Feels helpless when alone
- Urgently seeks another relationship for support
- Unrealistically preoccupied with fears of being left to take care of themselves
Dependent personality disorder
What personality disorder is characterised by a preoccupation with orderliness, perfectionism and interpersonal control at the expense of flexibility and openness. It begins in early adulthood and presents with >=4 of the following:
- Preoccupied with rules, lists etc
- Perfectionism affecting task completion
- Excessively devoted to work
- Inflexible about morality/ethics/values
- Hoarding
- Reluctance to delegate
- Frugal
- Stubborn
Obsessive-Compulsive personality disorder
What is the most common personality disorder?
Obsessive-Compulsive personality disorder (1.9% prevalence)
How is avoidant PD treated?
Social skills training
Antidepressants
How is borderline PD treated?
Dialectical Behavioural Therapy
‘Mentalism’ (Interpret own actions as meaningful)
Medication is usually for comorbidities
Borderline PD is over-represented in atypical depression, what drugs may help?
MAOIs:
- Phenelzine also for hostility
What is the IQ range for a mild learning disability?
50-69
What is the IQ range for a moderate learning disability?
35-49
What is the IQ range for a severe learning disability?
20-34
What is the IQ range for a profound learning disability?
<20
What is the IQ range for a borderline learning disability?
> =70 (-84)
What is the most commonly used psychometric assessment scale?
Wechsler Adult Intelligent Scale
What are O’Brien’s Principles?
Essentially that those with learning disabilities continue to grow and are worthy of all the dignity and rights of any citizen
What do people with a mild learning disability usually have problems with?
Delayed speech
Difficulties reading and writing
What do people with a moderate learning disability usually have problems with?
Slow comprehension and language
Limited achievements
Delayed self-care and motor skills