Flashcards in Development, Memory and Addiction Deck (261)
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?
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?
What does ventricular enlargement at diagnosis of Schizophrenia indicate?
It is non-progressive
What is the DA hypothesis in Schizophrenia?
- 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?
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?
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?
Where are D2 receptors also present?
What receptor is Bromocriptine an agonist of?
What receptor is Raclopride an antagonist of?
What receptor are Raclopride and Haloperidol antagonists of?
What receptor is Quinpirole an agonist of?
What receptor is Clozapine an antagonist of?
What does subcortical DA hyperactivity result in?
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?
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?
What does Neuregulin do?
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?
How do typical antipsychotics work?
- Immediate blockaed
- Delay in onset of effect
What are the side effects of typical antipsychotics?
Muscle stiffness and cramps
What is the definition of an atypical (2nd gen.) antipsychotic?
1. Less likely to induce extrapyramidal symptoms
2. 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?
What are the side effects of most/all atypical antipsychotics?
- Weight gain
- Dyslipidaemia and Hypertension
What atypical antipsychotics can cause extrapyramidal symptoms at high doses?
What side effect can olanzapine have?
Increase PRL at high doses
How does an acute dystonic reaction present?
Within hours-days of initiation of antipsychotics
How are acute dystonic reactions treated?
What is tardive dyskinesia?
Repetitive, involuntary movements:
- Sticking tongue out
- Lip smacking
- Pursing lips
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?
What drugs have a high affinity for 5-HT2 receptors?
How is 5-HT2 receptors binding affected in Schizophrenia?
Blockade of what histamine receptor causes sedation?
How does histamine blockade affect appetite?
Why are newer anti-histamines not as sedative?
Do not cross BBB
What is histamine involved in?
Regulation of pituitary hormon secretion
Reducing nausea and vomiting
What serious side effect can Clozapine have?
How are the side effects of Clozapine monitored and prevented?
- 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?
How does Clozapine cause myocarditis?
IgE-mediated Type 1 sensitivity
How is myocarditis monitored/prevented while on Clozapine?
- 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?
During the first line treatment of Schizophrenia, if there is only partial improvement by what point should an alternative therapy be considered?
If there is remission of the first episode of Schizophrenia, how long should maintenance therapy be continued for?
If no response to the first line antipsychotic in Schizophrenia, what can be prescribed?
A different atypical antipsychotic
Chlorpromazine (or another typical low-potency antipsychotic)
What drug is used in treatment-resistant Schizophrenia? When is Schizophrenia deemed treatment-resistant?
Poor response to 2 antipsychotics (one of which must be an atypical antipsychotic)
How can aggression in hospital be predicted?
How can aggression in hospital be prevented?
How can aggression in hospital be treated?
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
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?
What is the first step of the Tayside Rapid Tranquilisation Policy?
Consider non-drug approaches:
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
PO Haloperidol 5mg
When can the third stage of the Tayside Rapid Tranquilisation Policy be initiated?
If PO therapy unsuccessful
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
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?
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):
How is the enduring pattern of behaviour changes in a Personality Disorder described?
What do the behaviour changes in a Personality Disorder lead to?
Clinically significant distress
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?
What kinds of personality disorders are classed as Cluster A; 'Odd and Eccentric' in DSM-V?
What kinds of personality disorders are classed as Cluster B; 'Dramatic, emotional, erratic' in DSM-V?
What kinds of personality disorders are classed as Cluster C; 'Anxious and fearful' in DSM-V?
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)
- 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
- Reluctance to delegate
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
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?
- Phenelzine also for hostility
What is the IQ range for a mild learning disability?
What is the IQ range for a moderate learning disability?
What is the IQ range for a severe learning disability?
What is the IQ range for a profound learning disability?
What is the IQ range for a borderline learning disability?
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?
Difficulties reading and writing
What do people with a moderate learning disability usually have problems with?
Slow comprehension and language
Delayed self-care and motor skills
What common comorbidities are seen in moderate learning disorders?
What are some prenatal aetiologies of learning disability?
What are some perinatal aetiologies of learning disability?
What are some postnatal aetiologies of learning disability?
What is the incidence of Down's Syndrome at maternal age 30?
What is the incidence of Down's Syndrome at maternal age 40?
What is the incidence of Down's Syndrome at maternal age 50?
What is the typical IQ range in Down's Syndrome?
What is Down's Syndrome associated with?
What is Patau Syndrome?
What is the incidence of Patau Syndrome?
How many Patau Syndrome patients survive 1 year?
What is Edward's Syndrome?
How does Cri du chat syndrome present and what causes it?
Profound/Severe learning disability
Chromosome 5p deletion
How does Angelman syndrome present and what causes it?
Paroxysms of laughter
Chromosome 15q(11-13) deletion:
- Maternally derived
How does Prader-Willi syndrome present and what causes it?
Chromosome 15q(11-13) deletion:
- Paternally derived
How does DiGeorge syndrome present and what causes it?
50% have learning diability
Chromosome 22q11.2 deletion
What else can DiGeorge syndrome be called?
What is Turner's syndrome?
What is Klinefelter's syndrome?
What is the incidence of Fragile X?
What causes Fragile x?
Faulty FMR1 gene
What genetic protein defect is a cause of severe learning disability?
What genetic carbohydrate defect is a cause of severe learning disability?
What genetic lipid metabolism defect is a cause of severe learning disability?
How is Tuberous Sclerosis inherited?
What does TSC1 code for?
On chromosome 9q34
What does TSC2 code for?
On chromosome 16p13.3
How is Lesch-Nyhan syndrome inherited?
What causes Lesch-Nyhan syndrome?
Mutations in HPRT1 gene:
- Codes for hypoxanthine-guanine phosphoribosyltransferase
Results in uric acid build up:
- Kidney problems
What else does Lesch-Nyhan syndrome result in?
Cognitive and behavioural disturbances:
- Including self-mutilation
What causes holoprosencephaly?
Prosencephalon (forebrain) fails to divide into two hemispheres
What prenatal maternal infections can cause learning disabilities?
What is Foetal Alcohol Spectrum Disorder associated with?
Mild learning disability
What perinatal infections are associated with learning disabilities?
What newborn complications (other than infections) can result in learning disabilities?
What is the Flynn Effect?
Average IQ in the US rises 3 points per decade:
- Therefore ~10 points per generation
What factors contribute to underdiagnosis of psychotic comorbidities in learning disability?
Compliance ('Talked out of' symptoms)
Eager to please
When might antipsychotics be used in the context of learning disability?
When might antidepressants be used in the context of learning disability?
When might anticonvulsants be used in the context of learning disability?
Bipolar affective disorder
When might stimulants be used in the context of learning disability?
When might opiate antagonists be used in the context of learning disability?
When might anti-libidinal drugs be used in the context of learning disability?
When might beta-blockers be used in the context of learning disability?
How does Schizophrenia present in learning disability?
3 times more common
Early onset (mean age 23)
Negative symptoms more common
Main presentation may be change in behaviour
How does Schizophrenia present in severe learning disability?
How common is bipolar affective disorder in learning disability?
How common is a depressive disorder in learning disability?
What anxiety disorder is more common in learning disability?
What anxiety disorder is less common in learning disability?
What is the M:F ratio of autism?
What are the triad of symptoms in autism?
Abnormal social interaction
Rigid/Restricted or repetitive behaviour, interests and activities
How many units of alcohol indicate higher risk drinking?
>35 units per week (regularly)
How many units of alcohol indicate increased risk drinking?
15-35 units per week
How many units of alcohol indicate low risk drinking?
=<14 units per week spread over >=3 days
What does the AUDIT tool aim to do?
Detect hazardous drinking
What does the CAGE tool aim to do?
Detect alcohol abuse and dependence
What does the TWEAK tool aim to do?
Screens for alcohol problems in pregnant women
What does the MAST tool aim to do?
Full version useful for psychiatric settings
What do the PAT and FAST tools aim to do?
What does GGT indicate?
Degree of liver injury
What does Carbohydrate Deficient Transferrin indicate?
Identifies men drinking >=5 units per day for >=1 years
What is FRAMES in regard to alcohol abuse?
Feedback - Review problems due to alcohol
Responsibility - Patient is responsible for change
Advice - Reduction/Abstinence
Menu - Provide options for change
Self efficacy - Encourage optimism for change
When should referral be considered in alcohol abuse?
Signs of moderate-severe alcoholism
Failure to benefit from structured brief advice and want more help
Signs of severe alcohol impairment or comorbidity
What are some specialist interventions for alcohol abuse?
What channels does alcohol inhibit? What does chronic use result in?
Excitatory NMDA-glutamate ion channels
Chronic use -> Receptor upregulation
What channels does alcohol potentiate? What does chronic use result in?
Inhibitory GABAa controlled ion channels
Chronic use -> Receptor downregulation
What does alcohol withdrawal result in?
Excess glutamate activity -> Nerve cell toxicity
When do alcohol withdrawal symptoms peak?
When does delirium tremens tend to occur?
Usually within 24 hours
How long does it take for alcohol withdrawal symptoms to resolve?
How can delirium tremens cause death?
What benzodiazepines are used in alcohol withdrawal and why?
How do BZDs work in alcohol withdrawal?
Cross tolerant with alcohol:
- At on GABAa
How long is the BZD dose reduced over in alcohol withdrawal?
How is BZD therapy guided in alcohol withdrawal?
Why can Thiamine be prescribed in alcohol withdrawal?
Prophylaxis against Wernick'e Encephalopathy
How is Thiamine given in alcohol withdrawal?
What is the first line drug for relapse prevention in alcohol abuse? How does it work?
- Reduces reward from alcohol
How does Disulfiram prevent alcohol abuse relapse?
Inhibits acetylaldehyde dehydrogenase:
- Acetylaldehyde accumulates if alcohol consumed
What symptoms does Disulfiram cause if alcohol is consumed?
Nausea and vomiting
How does Acamprosate work in preventing alcohol abuse relapse?
Acts centrally on glutamate and GABA systems
When is Acamprosate started?
As soon as detoxification finishes
When there is a relapse, what happens to acamprosate?
What are the side effects of acamprosate?
When would detoxification be used for opiate abuse?
Relatively stable socially
Detoxing TO something (not from something)
When is opiate blockade used for opiate abuse?
If an impulsive relapser
What drugs can be prescribed to assist with detoxification from opiate abuse?
Alpha-2 adrenergic agonists:
What adjunct drugs can be prescribed in detoxification from opiate abuse?
What are some opioid substitution therapies?
What effect does mephedrone have?
Inhibits reuptake of serotonin, NA and DA
Stimulant (Self-confidence, talkative)
Empathogenic (Intimacy, openness, dancing)
What is sympathetic toxidrome?
Acute toxic effects of amphetamine-type substances
What are the symptoms of serotonin syndreom?
What drugs can cause serotonin syndrome?
OTC cough medications
What is methiopropamine?
Structural analogue of methamphetamine
How does methipropamine work?
NA and DA reuptake inhibitor
What is CHING?
Cut with lidocaine
How does CHING work?
DA and NA reuptake inhibitor
What effects do synthetic cannabinoids have over cannabis?
Sympathemimetic effects (2-3x as likely)
What primary effect does ketamine have?
What is a ketamine bladder?
How does ketamine work?
NMDA receptor antagonist
How do we do urine toxicology?
20ml urine in white universal container
What does a urine immunoassay detect?
What CAGE score indicates the possibility of alcoholism?
>=2 Yes repsonses
What sensation does the mesolimbic pathway produce?
What does the mseolimbic pathway connect?
Ventral Tegmental Area to the Nucleus Accumbens
What does the mesolimbic pathway release?
DA into the Nucleus Accumbens -> Reward
What effect does DA have in the Nucleus Accumbens?
Involved in normal pleasurable experiences
What drugs increase DA release?
In fMRI studies, non-addict controls (gambling) had increased blood flow to striatum after winning. Addicts had a lower response. What does this suggest? What is the potential mechanism?
Tolerance to reward:
- Repeated DA release -> DA receptor downregulation
- Threshold for reward increased (during abstinence)
- Normal pleasurable experiences don't evoke reward
What are the initial stages of drug-taking driven by?
Reward (positive reinforcement)
What are the late stages of drug-taking driven by?
Becomes a thirst:
- Negative reinforcement
What happens to orbitofronal cortex activation in addicts when presented with drug cues? What does this correlate with?
- Correlates with self-reported drug cravings
- Changes persists into abstinence
What is the role of the prefrontal cortex in behaviour?
Helps intention-guided behaviour
Modulates powerful effects of reward system
Sets goals and focuses attention
Keep emotions and impulses under control:
- Long term goal achievment
How does an adolescents response to reward compare to an adults?
Strong stimulus reward
How does an adolescents prefrontal cortex control compare to a childs? What does this mean?
- Minimal judgement and impulse control
In terms of memory and habit forming, what parts of the brain are important in acquisition, consolidation and expression of drug stimulus learning?
What type of learning is the striatum responsible for?
What type of learning is the hippocampus responsible for?
What effects does stress have on DA release?
Increased release in neural reward pathway
What do the following parts of the brain belong to:
- Mamillary bodies
- Anterior thalamic nuclei
- Cingulate gyrus
- Enterohinal cortex
Circuit of Papex
What is the function of the right side of the amygdala?
What is the function of the left side of the amygdala?
Both pleasant and unpleasant emotions
What are the three stages of memory?
Encoding -> Storage -> Retrieval
In the multi-store model of memory, what commits a sensory memory to short-term memory?
In the multi-store model of memory, what commits a short-term memory to long-term memory?
In the multi-store model of memory, what recalls a long-term memory to short-term memory?
In the multi-store model of memory, what is recall?
The ability to recollect something from the short-term memory
How long does sensory memory last for?
How long does short-term memory last for?
What are the two types of long-term memory?
What are the two types of explicit memory?
Episodic (events, experiences)
Semantic (facts, concepts)
What is the type of implicit memory? What does it allow us to undertake?
What features need to be present to diagnose Alzheimer's?
1. Presence of dementia
2. Insidious onset and slow deterioration
3. Absence of clinical/investigation evidence of a biological cause
4. Absence of a sudden, apopleptic onset or of focal neurological damage early in illness
What biological causes may be differential diagnoses for Alzheimer's?
Vit B12 deficiency
Niacin (Vit B3) deficiency - ie. Pellagra
Normal pressure hydrocephalus
What is the neuropathology of Alzheimer's?
How can vascular dementia present?
Abrupt onset or stepwise deterioration in:
- Memory loss
- Intellectual impairment
- Focal neurological signs
How are insight and judgement affected in vascular dementia?
How can vascular dementia be confirmed?
What are associated features in vascular dementia?
What is the central feature of Lewy Body Dementia?
- Deficits in attention and executive functions
What are the core features in Lewy Body Dementia?
- Pronounced variations in attention and alertness
Complex visual hallucinations:
- Well formed
What are some suggestive features of Lewy Body Dementia?
REM sleep behaviour disorder (years before onset)
Severe neuroleptic sensitivity (50%)
Low DA transporter uptake in basal ganglia:
What are some supportive signs in Lewy Body Dementia?
Transint loss of consciousness
What indicates a probable diagnosis of Lewy Body Dementia?
Dementia PLUS >=2 core features
- 1 core features AND
- >=1 suggestive features
What indicates a possible diagnosis of Lewy Body Dementia?
Dementia PLUS 1 core feature
Dementia PLUS >=1 suggestive features
What are Lewy Bodies?
Alpha-synuclein proteins in cytoplasm of neurones
Where is DA lost in Lewy Body Dementia?
What other neurones are lost in Lewy Body Dementia?
What are the three types of Fronto-Temporal Dementia?
Progressive non-fluent aphasia
What are usually preserved in FTD?
What are Pick Bodies?
Tau-positive spherical cytoplasmic neuronal inclusions composed of straight filaments
What are Pick Cells?
Ballooned neurones with dissolution of chromatin
Apart from Pick's Disease, what else are Pick Bodies and Cells seen in?