Week 2 Flashcards
What are some of the physiological symptoms of anxiety?
Sweating, hot flushes or cold chills
Trembling/shaking
Muscle tension or aches and pains
Numbness or tingling
Feeling dizzy, unsteady, faint or light headed
Dry mouth
Feeling of choking
Difficulty swallowing
Difficulty breathing
Palpitations/pounding heart and accelerated heart rate
Chest pain or discomfort
Nausea or abdominal distress
What are some of the cognitive symptoms of anxiety?
Fear of losing control, “going crazy” or dying
Feeling keyed up, on edge or mentally tense
Difficulty in concentrating
Feeling that objects are unreal - derealisation
Feeling that the self is distant or “not really there” - depersonalisation
Hypervigilance
Racing thoughts
Meta-worry (worrying about everything)
Health anxiety
Beliefs about the importance of worry
Preference for order and routine
What are some of the behavioural symptoms of anxiety?
Avoidance of certain situations
Exaggerated response to minor surprises or being startled
Difficulty in getting to sleep due to worry
Excessive use of alcohol/drugs
Restlessness and inability to relax
Persistent irritability
Seek reassurance from family/GP
Checking behaviours
Which part of the brain acts as the emotional filter for assessing whether sensory material via the thalamus requires a stress or fear response?
What hormone is released?
The amygdala
Cortisol is released from the adrenal glands
What is the effect of cortisol on the stress response?
Acute stress leads to dose-dependent release of catecholamines and cortisol, causing an increase in cortisol levels
Cortisol acts to mediate and shut down the stress response
Name some types of anxiety disorders
Generalised Anxiety Disorder (GAD)
Panic disorder
Agoraphobia
Social phobia
Specific phobia
OCD
Define ‘Generalised Anxiety Disorder’
GAD is generalised and persistent but not restricted to/predominating in any particular environmental circumstance
Dominant symptoms are variable but include…
- persistent nervousness
- trembling
- muscular tensions
- sweating
- lightheadedness and dizziness
- palpitations
What are the markers of severity for GAD that have to be satisfied?
- long-lasting (most days, for at least 6 months)
- not controllable
- causing significant distress/impairment of function
How might someone with suspected GAD present in a clinic?
Restlessness/feeling on edge
Being easily fatigued
Difficulty concentrating or mind going blank
Irritability
Muscle Tension
Sleep disturbance
Typically between age 20-40 with a chronic, fluctuating course
GAD - treatment
CBT
SSRIs/SNRIs
Pregabalin
Benzodiazepines (short term only)
Define “Panic Disorder”
Recurrent attacks of severe anxiety (panic) which aren’t restricted to any particular situation/set of circumstances, meaning that they are unpredictable
Primary symptoms are similar to those seen in other anxiety disorders
There is often also a secondary fear of dying, losing control or going mad
May occur with or without agoraphobia (50-67% of cases)
Not due to direct effects of a substance/medication, and not better accounted for by another mental disorder
How might a panic attack be triggered?
By infusions of lactate (by-product of muscular activity)
Can also be triggered by re-breathing air due to increased amounts of CO2
What are the 3 broad categories of phobia?
Agoraphobia
Social phobia
Specific phobia
When do phobias typically develop?
Agoraphobia - 50% by 20, 75% by early 30s
Social and specific - 80% by early adolescence
How might someone with agoraphobia avoid anxiety?
Get others to do their shopping for them, or do it online
Drink alcohol to overcome
Go shopping/go out at night when it’s quieter
Define “specific phobia”
Marked and persistent fear that is excessive or unreasonable, cued by the presence or anticipation of a specific object or situation
The person suffering recognises the fact that their fear is excessive/unreasonable
Exposure to the stimulus almost invariably invokes an immediate anxiety response, and normal functioning is impaired
How are specific phobias treated?
Behavioral therapy - graded exposure/systematic desensitisation
SSRIs/SNRIs if required
Define “social phobia/social anxiety disorder (SAD)”
Persistent fear of one or more social/performance situations in which the person is exposed to unfamiliar people or possible scrutiny
The individual fears that they will act in a way that will be embarrasing or humiliating - more than just being shy
Common symptoms - blushing/shaking, fear of vomiting, urgency or fear of micturation/defaecation
Which area of the brain shows increased activity in social phobia?
Increased bilateral activation of the amygdala and increased rCBF (regional cerebral blood flow) to the amygdala
Social phobias/SAD - treatment
CBT
SSRIs/SNRIs
Benzodiazepines (short term only)
Define “obsessive compulsive disorder”
Recurrent obsessional thoughts and/or actions. Must be present for most days for at least 2 weeks AND be a source of distress/interference with activities
Obsessional thoughts
- ideas, impulses or images entering the mind in a stereotyped way
- recognised as the patient’s own thoughts, but unpleasant, resisted and ego-dystonic
Compulsive acts
- repeated rituals or stereotyped behaviours
- not enjoyable or functional, recognised as ‘pointless’
Name some of the drugs used to treat anxiety
Barbiturates (not recommended)
Benzodiazepines (in the short term)
Antidepressants (SSRIs/SNRIs)
Buspirone
Pregabalin
Beta-blockers (propranolol)
What are some of the pharmacological effects of benzodiazepines?
Reduced anxiety and aggression
Hypnosis/sedation
Muscle relaxation
Anticonvulsant effect
Anterograde amnesia
What are some of the clinical uses for benzodiazepines?
Acute treatment of anxiety disorders
Hypnosis
Alcohol withdrawal
Mania
Delirium
Rapid tranquilisation
Premedication before surgery or during minor procedures
Status epilepticus
How do benzodiazepines reduce anxiety?
Increase the effectiveness (affinity) of GABA at GABA-A receptors
This allows for more influx of chloride ions, which hyperpolarises membranes and results in inhibition of postsynaptic potential
Can also produce mild muslce relaxation due to action on GABA receptors in spinal cord, cerebellum and brain stem
What are some of the problems associated with benzodiazepines?
Fairly safe in overdose, as by themselves they are unlikely to cause respiratory depression
May cause paradoxical aggression
Can cause anterograde amnesia, impaired coordination and sedation
Can lead to tolerance and dependence - addiction
May show withdrawal symptoms
How is OCD managed?
CBT including response prevention (confronting the anxiety-provoking stimulus and not performing the associated ritual)
SSRIs (fluoxetine, sertraline, citalopram, escitalopram, paroxetine)/TCAs (clomipramine)
What are some of the cautions to be aware of regarding benzodiazepine use?
Rapid action and well-tolerated but dependence can develop in as little as 3 weeks, so use no more than 2 weeks
Can cause sedation/psychomotor impairment
Problems with discontinuation/withdrawal
Alcohol interaction
Can worsen co-morbid depression
What is the difference between Type 1 Trauma and Type 2 Trauma (with regards to PTSD)?
Which holds the greater risk for development of PTSD?
Type 1 - single, unexpected incident
Type 2 - could be repetitive, ongoing, betrayal of trust, developmental etc.
Type 2 holds a x3 risk for developing PTSD
Cortisol levels are high/low in PTSD
Cortisol levels are low
The Mental Health Act is about treating _____
The Adults with Incapacity Act is about treating _____
MHA - about treating a mental disorder (18+ year olds). People may be physically restrained by physical components of disease cannot be treated under this act
AwIA - about treating a physical disorder (16+ year olds) in someone with a mental disorder or inability to communicate. Cannot use force
What are the differences between an Emergency Detention and a Shortened Detention?
ED - lasts 72 hours from admission, can be done by any qualified doctor but needs MHO approval as well. Can only assess the patient
SD - can be done at home, needs go ahead from an approved medical practitioner (section 22), psychiatrist, ST4 and above, and lasts for 28 days. Can both assess and treat
What is the average reduction in lifespan for the following disorders..
- BPD
- Schizophrenia
- Drug and Alcohol abuse
- Recurrent depression
BPD - 9-20 years
Schizophrenia - 10-20 years
Drug and Alcohol abuse - 9-24 years
Recurrent depression - 7-11 years
What are some of the side effects of Lithium?
LITHIUM
LT - low thyroid
I - diabetes Insipidus
H - heart
UM - unwanted movements
What does rapid cessation of benzodiazepines cause? How does this present and what is the mechanism?
Withdrawal symptoms
Presents with confusion, toxic psychosis, convulsions, insomnia, subjective anxiety, loss of appetite and body weight, tremor, perspiration etc.
Mechanism: neuroadaptation of GABA response. Chronic treatment with BZDs causes a reduced response to GABA, and withdrawal may result in symptoms due to decreased density of BZD receptors
How should someone be withdrawn from benzodiazepines?
- switch patient to equivalent dose of diazepam/chlordiazepoxide, preferably taken at night
- reduce dose every 2-3 weeks
- reduce dose further, in even smaller steps if necessary
- stop altogether
What antidepressants can be used to treat anxiety disorders?
SSRIs - panic disorders, OCD, PTSD, phobias, GAD
Tricyclics - 2nd line for panic disorders, OCD
Venlafaxine (SNRI) - GAD
Moclobemide (MAO inhibitor)- social anxiety disorder
Name some benzodiazepines
Midazolam
Lorazepam
Oxazepam
Temazepam
Diazepam
Chlordiazepoxide
What are the 2 major amino acids in the brain? What do they do?
Glutamine - major excitatory neurotransmitter in the brain
GABA (and Glycine in the spinal cord) - major inhibitory neurotransmitter in the brain
What are the 5 major monoamines in the brain?
Which ones are catecholamines?
Serotonin
Histamine
Dopamine (a catecholamine)
Adrenaline (a catecholamine)
Noradrenaline (a catecholamine)
How is GABA involved in feelings of anxiety?
GABA is used to control feelings of fear and anxiety
In stress, excitatory signals fire rapidly and are sent from the amygdala to other areas of the brain. This causes feelings of fear/anxiety
Inhibitory interneurones in the amygdala release GABA which binds to postsynpatic GABA receptors and inhibits the excitatory signals, reducing these feelings - GABA has a calming, tranquilizing effect
How do SSRIs affect anxiety a) acutely and b) chronically?
a) acutely, SSRIs are angiogenic
b) chronically, SSRIs are anxiolytic
Mechanism is not fully understood
Other than benzodiazepines and antidepressants, what other drugs can be used to treat anxiety?
Pregabalin (calcium channel blocker and GABA enhancer) - only used if patient is unresponsive to other treatments
Beta-blockers e.g. Propranolol - best for treatment of somatic symptoms e.g. tremor, palpitations etc.
Buspirone (5-HT1A receptor partial agonist, works antagonistically on D2, D3, D4 receptors as well as partially agonistically on Alpha1) - suppresses serotonergic activity while noradrenergic and dopaminergic activity is enhanced
Patient presents with GAD - what is the series of management options?
- psychoeducation
- Self help/education groups
- CBT or drug treatment (SSRIs)
- SNRIs
- Pregabalin
- Combination of CBT and drug treatment
Patient presents with Social Anxiety - what is the series of management options?
- CBT
- SSRI (escitalopram or sertraline) - review after 12 weeks
- SSRI plus CBT
- alternative SSRI or SNRI (venlafaxine)
- MAOI (moclobemide)
Patient presents with Panic Disorder - what is the series of management options?
- self help
- CBT or SSRI if long-standing/no benefit from CBT
- Tricyclics (clomipramine, desipramine, imipramine, lofepramine) - continue for 6 months
Patient presents with PTSD - what is the series of management options?
- If mild and <4 weeks from trauma - watchful waiting
- Within 3 months - trauma focused CBT and hypnotic medication if sleep disturbances
- More than 3 months after trauma - trauma focused CBT or EMDR (eye movement desenitisation and reprocessing)
- Drug treatment (limited evidence) - paroxetine (SSRI) or mirtazepine (MAOI)
Patient presents with OCD - what is the series of management options?
- low intensity psychological interventions - CBT, self help groups etc.
- more intensive psychological intervention or SSRI
- consider an increased SSRI dose after 4-6 weeks if indicated
- SSRI plus CBT & ERP
- Clomipramine (TCA)
- augmentation with antipsychotic, or clomipramine plus citalopram
What is the definition of a functional disorder?
Physical symptoms which after investigation are not fully explained by a physical disease process or injury
Symptoms are real, and not imagined
What are dissociation/conversion disorders?
Give some examples
“Partial loss of the normal integration between memories, awareness of identity, immediate sensations and control of bodily movements”
- Dissociative amnesia
- Dissociative fugue
- Dissociative stupor
- Trance and possession disorders
- Dissociative disorders of movement and sensation (motor, sensory and/or convulsions)
What are somatoform disorders?
Repeated presentation of physical symptoms and persistent requests for investigations, in spite of negative findings and reassurances
Usually resist attempts to discuss psychological basis, “attention-seeking behaviour”
Symptoms can be multiple, recurrent and frequently changing
What diagnosis would fit the following picture…
Patient presents with collapsing weakness, no changes in reflexes, dragging walk, power is better on bed than when walking
Functional weakness
(or Malingering)
What is non-epileptic attack attack disorder? How can it be differentiated from epilepsy?
Tonic-clonic fitting in someone without epilepsy (although 10% of sufferers also have epilepsy!)
More common in women and is commonly seen as a comorbidity with depression, anxiety and PTSD. 90% of sufferers report previous traumatic experiences, especially in childhood (e.g. abuse, neglect)
Requires EEG monitoring to differentiate from epilepsy
Give some examples of common functional disorders
IBS
Chronic Fatigue Syndrome, Fibromyalgia, ME
Chronic Regional Pain Syndrome
Hypochondriasis
Give some examples of conditions that present similarly to functional disorders by are not functional disorders
Factitious disorders (previously called Munchausen’s Syndrome) - feigning illness, disease or psychological trauma to draw attention, sympathy or reassurance
Malingering - feigning illness for secondary gain
By what mechanism is Huntington’s Disease inherited?
What are the chances that an affected person’s child will also have the condition?
What genetic sequence is seen in HD?
Autosomal dominant
Child risk - 50%
Genetic sequence - CAG repeats encoding polyglutamine, causing neuronal loss
What is the genetic phenomenon in which each generation develops a genetic disease at an earlier age called?
Anticipation
Huntington’s Disease can cause Psychiatric, Motor and Cognitive symptoms.
What are some of the Psychiatric symptoms?
- Depression and anxiety
- Compulsions
- Suicidal ideas
- Aggression
- Blunted affect
- Psychosis
Huntington’s Disease can cause Psychiatric, Motor and Cognitive symptoms.
What are some of the Motor symptoms?
- Choreiform movements
- Writhing movements
- Gait disturbances
- Problems chewing, swallowing, speaking
- Rigidity
Huntington’s Disease can cause Psychiatric, Motor and Cognitive symptoms.
What are some of the Cognitive symptoms?
- Decline in executive functions
- Short and long term memory deficits
Which mutations are associated with Early Onset Familial Alzheimer’s Disease?
How many cases of Alzheimer’s do these account for?
PSEN1, PSEN2 and APP are associated with EOFAD
Early onset familial disease accounts for 2% of Alzheimer’s cases
How do Mania and Hypomania differ?
Hypomania is a less intense version of Mania
Energy levels will be higher than normal but not to the extent of Mania, and there will be an absence of psychotic symptoms
Crucially, there is no distinct functional impairment in people with Hypomania and they may not require hospitalisation
What factors in a patient’s personal history may predispose them to developing schizophrenia later in life?
2nd trimester viral illness
Obstetric problems - pre-eclampsia, foetal hypoxia, emergency C section
Risk increased by 50% by childhood viral CNS infection
Substance abuse - cannabis, amphetamines, cocaine
How will a brain CT of a patient with Schizophrenia appear?
Reduced frontal lobe volume
Reduced frontal lobe grey matter
Enlarged lateral ventricles
What are some of the anatomical changes seen in the brain of someone with Schizophrenia?
Reduction in the volume of grey matter. NB - these changes are present early in the disease and are likely pre-morbid
- temporal cortex (especially the superior temporal gyrus)
- medial temporal lobe (especially the hippocampus)
- possibly also the orbitofrontal cortex, parietal cortex and basal ganglia
What two measures are most often reported when performing diffusion tensor imaging (DTI) to assess white matter health in patients with schizophrenia?
What do high levels of each indicate?
Fractional anisotropy (FA) - higher numbers indicate healthy white matter tracts
Mean diffusivity (MD) - higher numbers indicate less healthy white matter tracts
Which neurotransmitter has been implicated in the pathophysiology of Schizophrenia?
As a result, which medications are used to treat Schizophrenia?
Dopamine - it is assumed that schizophrenia is related to overactivity of dopamine pathways in the brain
Dopamine receptor antagonists are therefore used to treat the symptoms of schizophrenia (atypical antipsychotics such as quetiapine, risperidone or olanzapine, typical antipsychotics like haloperidol, antiemetics like metoclopramide or domperidone, TCAs etc.)
What are the following dopaminergic pathways associated with?
- Nigrostriatal
- Tuberoinfundibular
- Mesolimbic/Cortical
Nigrostriatal - extrapyramidal motor system
Tuberoinfundibular - control of prolactin release (dopamine is inhibitory to prolactin)
Mesolimbic/Cortical - motivation and reward systems
What are the effects of a) amphetamines and b) antipsychotics on the dopamine synapse?
a) amphetamines - extra release of dopamine vesicles into synapse
b) antipsychotics - blocks D2 receptor family on postsynaptic receptors
Dopamine receptor subtypes can be classified into two families: D1 and D2
Which receptors are a part of each subtype, and what are the functions?
D1 receptor family (D1 and D5) - stimulates cAMP
D2 receptor family (D2, D3, D4) - inhibits adenylyl cyclase, inhibits voltage gated Ca2+ channels and opens K+ channels
What gene alterations have been identified in the development of Schizophrenia?
Neuregulin - signaling protein that mediates cell-cell interacitons and plays critical roles in the growth and development of multiple organ systems
Dysbindin - essential for adaptive neural plasticity
DISC-1 - involved in neurite outgrowth and cortical development through its interaction with other proteins
Name some typical antipsychotics
What is important to remember about the dose of these drugs?
Haloperidol (high potency), Chlorpromazine (low potency), Fluphenazine
Important to remember that the dose of the drug correlates with the degree of D2 receptor blockade i.e. giving a higher dose of the drug will produce a greater effect
Associated with extrapyramidal side effects
Name some atypical antipsychotics
Olanzapine, Quetiapine, Risperidone, Clozapine
Which dopaminergic pathway is associated with the development of EPSEs?
The nigrostriatal pathway
What are some of the EPSEs?
Acute dystonic reaction - painful involuntary spasms
Parkinsonism
Akathisia - mental and/or motor restlessness
Tardive dyskinesia - typically affects face and mouth e.g. tongue rolling, lip smacking. Results from long term use
What other important endocrine side effect could occur as a result of antipsychotic use?
How might this present clinically?
Hyperprolactinaemia - inhibition of dopamine allows prolactin levels to rise
May present with sexual dysfunction
What is the major negative side effect associated with atypical antipsychotics? How does it present?
Metabolic syndrome as a result of serotonin blockade
Cluster of conditions that increase risk of heart disease, stroke and T2DM
Includes hypertension, raised blood glucose, raised triglycerides, excess body fat etc.
Which neurotransmitter is mainly affected by Olanzapine?
What are some of the potential effects caused by blockade of this neurotransmitter?
Olanzapine - histamine blockade
Could cause sedation and increased appetite
Which neurotransmitters are largely affected by typical antipsychotics?
How about atypicals?
Typicals - dopamine
Atypicals - have a greater degree of affinity for serotonin (5-HT)
Which medication is best used in treatment-resistant Schizophrenia?
What is the main potential side effect? How is this checked for?
Clozapine (atypical)
Major side effects is agranulocytosis
Clozapine use requires monthly blood tests (even though agranulocytosis is unlikely to occur outside of the initial beginnings of treatment) - weekly tests for the first 6 months, fortnightly for the next 6 months then every 4 weeks thereafter (including for one month after cessation)
