Psychological disorders Flashcards
What criteria are there for abnormality in psychological disorders?
- Statistical infrequency
- Unexpectedness of response - e.g. anorexia starves themselves
- Norms violation
- Causing personal distress
- Disabling
Flawed in isolation, useful taken together.
Advantages and disadvantages of classifying mental disorder?
Advantages:
- Helps determine clinical features
- Systematises diagnosis
- Shared understandings
Disadvantages:
- Can lead to stigma
- Pigeon holing - everyone is different and so you are just grouping people together even though they may not be exactly the same
- Natural vs constructed categories (I guess these are constructed?)
The different models for mental disorder?
Biological Behavioural Cognitive Psychodynamic Social
What is the biological model, what are the advantages and disadvantages?
Central tenet: Psychological disorder is a consequence of physical changes in brain and/or body
Advantages:
- Research into the role of heritability
- Role of Neurotransmitters
- Efficacy of some biological treatments
Problems:
- Passive patient
- Problem is situated with the persons body
- A biological treatment does not necessarily mean a biological cause
- Relapse
What is the behavioural model?
Symptoms and behaviour constitute the main features of mental disorder
The origin and persistence of the behavioural symptom can be understood through the science of learning theory
The application of learning theory removes maladaptive behavioural symptoms and in doing so removes the disorder.
The three types of learning theory in the behavioural model?
Classical conditioning - learning through association
Operant conditioning - Learning through consequences
Modelling - learning through copying
Benefits and problems with the behavioural model?
Advantages:
- Scientific
- Has Clear concepts
- Provides effective treatment (anxiety disorders in particular.
Problems
- Symptom substitution ie being scared of spiders may present in other ways and it may not tackle this as is not tackling cause.,
- Therapies crude and mechanistic e.g. flooding
- Offers poor explanation
Central tenets of the cognitive model?
Peoples view of the world is determined by their thinking (cognition)
Cognition influences symptoms, behaviour and attitudes.
Impaired cognition creates mental disorder
Significant changes in mental disorder requires significant changes in cognition
Benefits and problems in the cognitive model?
Benefits:
- Clear concepts
- Scientific
- Effective treatment options (particularly in combination with behavioural
Problems:
- Poor explanatory model
- Changed thinking does not necessarily mean changed behaviour (which came first the behaviour or the thinking)
- It is individualistic.
Central features of the psychodynamic model?
- The focus is the pattern of feelings
- We are unaware of many influential feelings
- Important feelings manifest in emotional reactions to the therapist - this is known as transference. The therapists reactions to the patient are equally important, know as counter transference.
- Troubling feelings and emotions are a part of the human condition, it is the imbalance of these negatives (against positives?) that causes mental disorder.
- Unconscious feelings are important in all relationships and can manifest themselves in symbols such as dreams.
- Emphasis on childhood experiences.
Benefits and problems with the psychodynamic model?
Benefits:
- Enduring contribution (endured for a long time, however not in academic psychology so much)
- Can be effective
Problems:
- Based on anecdotal evidence
- Findings based on small group of middle class viennese
- BIG influence of therapist - inserting own ideas etc.
- Can give insight into problems but this does not neccessarily fix them.
Central tenets of the social model?
Mental disorder is often triggered by life events, that appear independent of the disorder
Social forces such as class, occupational status and social role are precepitants of mental disorder
People with Mental disorder often become and remain disordered because of societal influences
Benefits and problems with the social model?
Benefit:
- Draws attention to the role of society and traumatic events
Problems:
- Is it the job of mental health professional to fight societal ills?
What are the central tenets of the integrated model of mental disorder?
We each have several layers of functioning, when mental disorder develops it can affect on or more levels.
At different times in the course of mental illness the predominant level of disorder may change
Each model links specifically to one level of functioning
Successful treatment involves matching the level of disturbance with the appropriate model
What is the stress-vulnerability model?
A predisposition towards mental illness is truggered by life stressors
This predisposition could be at a biological, cognitive and/or emotional level.
Major depressive disorder signs symptoms and diagnosis?
Emotional: sadness or emotional numbing, may include anxiety, anger and/or agitation
Cognitive: Negative view of self, guilt and self-blame, belief that the future is hopeless
Motivational: Have trouble getting started, physical inertia, difficulty making decisions
Somatic: Loss of appetite, sleep disturbance, fatigue, loss of libido and hypochondriasis (hypochondria)
At least 5 symptoms nearly everyday for at least 2 weeks and must include daily depressed mood for most of teh day and/or daily diminished pleasure in activities (anhedonia) - may have psychotic features
What is persistent depressive disorder (briefly)?
Milder chronic depression for at least 2 years without 2 months remission.
What is the aetiology of the behavioural model’s approach to depression?
Learned helplessness
- Failure to learn that responding can be successful as it has not been successful in the past.
EVIDENCE: Hiroto (1974) respondents stop trying to stop a loud noise if previous attempts are unsuccessful.
Reduced rewards:
- Negative spiral of social rewards ie. you feel bad, and people find it harder to be around you so you feel worse etc. Constantino (2012)
Behavioural approach to treatment of depression?
Operant conditioning:
- Challenge people’s preconceptions, learn through consequence
Classical conditioning:
- Learn a new non-depressive association to personal depressive stimuli. e.g. get up and do something enjoyable, eat chocolate
What is the aetiology of the cognitive models approach to depression?
Attributional reformation of learned helplessness:
- The expectation of negative events that one can do nothing about causes depression.
Depressive attributions for negative events are:
- Internal (inherent personal failing)
- Stable (persist over time)
- Global (persist in different situations)
Cognitive approach to treatment of depression? Typical scheme?
Typically used with behavioural elements
CBT:
- Cognitive elements correct dysfunctional thinking
- Behavioural elements aim to reinforce and reality test
Typically:
Eduction phase: Teach the relationship between cognition, emotion and behaviour
Behavioural activation and pleasant event scheduling: Increases engagement and activity
Cognitive rehearsal: Develop and practice cognitive/behavioural coping strategies
behavioural hypothesis testing: test the validity of negative assumptions (conditioning)
Evaluation of the cognitive approach to depression? (3)
Is negative cognition the cause or result of depression:
- High interpersonal stress regardless of negative cognition can predict depression as much as high negative cognitions Carter and Garber (2011)
Are negative cognitions necessarily pathological:
- Depressed people have less illusion of control than non-depressed people Moore and Fresco (2012)
Therapeutic success:
- roughly similar to pharmacological approaches
The aetiology of the psychodynamic model for depression?
It is a defence mounted by the ego against intrapsychic conflict Freud (1917):
- A reaction to loss and subsequent regression to oral stage of dependency theory
- unconscious anger turned upon the self
Modern assumptions:
- Rooted in early losses
- Wound reactivation by recent trauma
- Regression to sense of helplessness
- Ambivalent feelings are a central unconscious conflict
- Overly seek self-esteem from others, the dependency can cause depression
Psychodynamic approach to treatment of depressive disorders?
Traditional psychoanalysis:
- Uncover childhood roots of depression
- Explore the ambivalent feelings (conflicting feelings) towards ‘lost object’ through free association, dream analysis and analysis of resistance and transference.
Interpersonal psychotherapy:
- Focuses more on present problems than past problems
- Focuses more on how depression is used in relationships
- Identify core problem and discuss solutions
Evaluation of the psychodynamic approach to depression?
Some depressed people are highly dependent, supports.
Poor parenting is a risk factor for depression - consistent with attachment theory
Therapeutic success with depression, cognitive therapy and IPT (integrated psychological therapy) are all effective treatments for acute major depression, no consensus on the best.
Social approach to aetiology of depressive disorders?
R/Fs:
- Recent life event
- For women: Unsupportive spousal relationship, no job outside home, 3 or more young children, no religion, loss of mother <11 yrs
Treatment of depression according to the social model? and evaluation of it?
Interpersonal psychotherapy
Couples/marital therapy
Evaluation:
Draws attention to social and societal factors, Cannot predict who can actually become depressed.
Types of anxiety disorders (in this course?)
GAD
Panic disorder
Phobias: Specific, agoraphobia, SAD
OCD
What is diffuse anxiety, what conditions have this and what are there diagnostic factors?
Diffuse anxiety: Anxiety surrounding no specific object or situation, yet still feeling anxious
GAD: Chronic uncontrollable worry >3months, 2 or more activities or events, restlessness/muscle tension, significant distress or impairment
PD: Suddenly repeatedly overwhelmed with brief attacks of terror, >1 month of persistent concerns about attacks and/or significant maladaptive change in behaviour.
Social approach to GAD? Aetiology, Treatment and evaluation.
Aetiology: Societal pressure
Evidence: More likely following natural disaster, more likely on low income, higher in run-down communities.
Treatment: Support system and social change (social policy), international aid, civil rights, egalitarianism (all are equal).
Evaluation: why do some develop and some do not under similar social pressure - can’t all be down to social factors
Behavioural Aetiology approach to anxiety disorders?
Avoidance conditioning formulation:
- Learned through classical conditioning
Maintained through operant conditioning
Modelling
Behavioural approach to treatment of anxiety disorders?
Exposure:
Systematic desensitisation Flooding Modelling SAD: Social skill training, relaxation and exposure Virtual reality exposure treatment OCD: Ritual/response prevention
Behavioural approach to anxiety disorders evaluation?
Benefits:
- Effective treatments - particularly for OCD and SAD
Problems:
- Non-traumatic phobias - non-pathological phobias (realistic)
- not a very good explanatory model
Cognitive aetiology approach to panic disorders?
Catastrophic misinterpretation of bodily stimuli
Trigger:
- perceived threat - Apprehension - Bodily sensations - Interpretation of sensations as catastrophic - (loop back)
Cognitive approach to treatment of panic disorders?
CBT:
Reinterpret frightening sensations as not impending doom but from stress
- Mimic the start of an attack by hyperventilating
- Make link between behaviour and sensations
- Relaxation and social support
Evaluation of cognitive approach to panic disorders?
Benefit:
- Better model for understanding diffuse anxiety disorder
- Useful in combination with other models: CBT
Problems:
- Usefulness on own depends on the disorder itself
- Behavioural can be more cost-effective.
Psychodynamic approach to OCD, aetiology?
The type of disorder depends on:
- Psychosexual stage the pt is fixated at
- Defence mechanisms used to protect id (not truly successful
e.g. OCD:
- Fixation at anal stage
- Reaction to formation of id impulses
- Obtrusive thoughts linked to unconscious id wishes
Psychodynamic approach to treatment of OCD?
Insight into the unconscious conflict through interpretations of dreams, associations and transference.
Evaluation of psychodynamic model and it’s approach to OCD?
Benefits:
- case study basis of success
- Neuroimaging may support the idea that sexual and aggressive impulses reduce processing speed in OCD
Problems:
- Little evidence of effectiveness in OCD.
Signs and symptoms of schizophrenia?
Positive symptoms: delusions, heightened perception/hallucinations, disorganised speech/thought disorder.
Negative symptoms: Behavioural deficits, avolition, alogia (poverty of speech), anhedonia
Psychomotor: Catatonia (usually associated with with a delusion - think something awful will happen if they move)
What is psychosis?
Loss of touch with reality
What is loosened associations in schizophrenia?
‘word salad’ lose associations between words:
Fruitful becomes: wine-year or apple, saurkraut.
Schizophrenia diagnosis?
First rule out mood, organic or substance induced disorder
Presence of disorder for at least 6 months
Two or more of following for 1 month:
- One core positive symptom.
- Another psychomotor or negative symptom.
Decline in self-care occupational functioning and/or social functioning.
Prevalence of schizophrenia?
1/250
Percentage of voice-hearing in public and student population?
<8% in public
<40% in student population
Aetiological approach to schizophrenia in the cognitive model
Cognitive deficits approach:
- Impairments in perception, memory and attention make it hard to cope with environmental stress
Cognitive biases:
- Traumatic events in childhood affect the way one interprets info later in life:
Verbal hallucinations may be due to:
- Difficulty distinguishing internal thoughts from external voices
- Beliefs and explanations affect distress level
Delusions:
- Normal resistance to change
- Normal bias towards confirmatory evidence
- Normal thinking errors e.g. jumping to conclusions
Evidence for the existence of persecutory thoughts in everyday life?
Virtual reality study (Freeman & Garety 2004)
10 - 25% of the population experience persecutory thoughts (think that harm has occured or is going to occur)
Explanations for delusions?
As an attempt to explain experience:
- Ambiguous social information
- Coincidences
- Negative, irritating, stressful events (leading to vulnerability & anxiety)
- Importance of internal feelings (heightened state of arousal, feelings of significance, depersonalisation)
- Reasoning processes (reduced data gathering, externalising attributional biases, theory of mind difficulties (understand that mental states can be due to oneself and that others have separate, beliefs desires and perspectives different from ones own.))
Cognitive-behavioural approach to treatment of schizophrenia?
Token economy programmes:
- Operant conditioning to reduce presentation of symptoms.
Social skills training:
- Role playing
- Modelling
- Positive reinforcement
Reattributional therapy
- Questioning of where voices are coming from
- Explore alternative beliefs about explanations to reduce stress
- test reality of unusual beliefs and their supporting evidence
- Develop coping strategies
ACT:
- Accept troubling thoughts rather than judging or trying to change them
- Become detached observers of hallucinations
Evaluation of cognitive-behavioural approach to schizophrenia?
Usually used in conjunction with medication
Token economy programmes, and social skills are relatively successful, but may not last or generalise.
CBT is not always available however hospitalisation reduced by 50% when CBT is used.
Psychodynamic approach to schizophrenia in terms of aetiology and treatment?
Freud - Regression to pre-ego stage, with efforts to reestablish control.
Fromm-Reichmann - Schizophrenogenic mothers, statements of love but only with constraints
Jung - Dreams being brought to life
Treatment aims to increase insight:
- Interpret the covert meaning behind the symptoms
- Explore past experiences & seek connections with the present
- Intensive in time and emotion
Evaluation of psychodynamic approach to schizophrenia?
Freud felt SZ pts were unsuitable for psychoanalysis
Little evidence for schizophrenogenic families - (Willick 2001)
Treatment may expose pts to memories and insights they are unable to deal with.
Insight may mean agreeing to stigmatisation and dubious diagnosis.
Meta analysis suggests comparable improvement rates of schizophrenia with psychoanalysis compared to CBT.
Social approach to SZ in terms of aetiology and treatment?
Acceptance of a mental illness is associated with low mood and low self-esteem.
Sociogenic hypothesis - something about being on the lowest rung of the ladder
vs
Social selection theory - people fall to lower rungs because of their condition (evidence supports this)
Treatment, (rehabilitation) - focus on improved real-world functioning
- Milieu therapy (group stay for long periods), therapeutic communities and community care
- Family intervention - can be efficacious
- Occupational therapy
EValuation of the social approach to SZ
Draws attention to cultural differences, research has suggested black people are more likely than white people to receive a diagnosis of SZ even if expereinces are described as the same.
Vocational recovery and success are viable outcomes for those diagnosed with SZ spectrum disorders
Community care shows promise but is too often poorly resourced and co-ordinated.
What is the stress-vulnerability model of schizophrenia?
Vulnerability will result in the development of problems only when environmental stresses are present, prime environmental suspects are: (1) urban upbringing and (2) migration due to:
- Disintegration of family networks
- Social fragmentation - people think they are abnormal
Two forms of tissue pathology?
Organic pathology - a structural/morphological abnormality, sometimes observable to the naked eye
Functional pathology - functional or physiological abnormality detectable with biological/pharmacological techniques.
Contemporary view on the nature vs nurture argument, (interactionism) ?
Nonsensical argument, the two extensively interact, Tyrer and Steinberg have said that models should be complimentary and not oppositional.
Interactionism states that biological and environmental factors alone or in combination can cause mental dysfunction (each can also protect against each other).
The features of the first developed drugs for mental disorder as opposed to pre-medication treatment?
Selective and therapeutic actions
Immediate impact on quality of life for patients and public attitudes to mental illness
The two hypotheses of modern neuroscience?
The brain hypothesis: The brain is the source of all thoughts feelings and behaviour
The Neurone hypothesis: The neurone is the basic unit of structure and function in the nervous system.
Methods of signalling in neurones?
Within the neurone - electrical action potentials
Synaptic, neurotransmitters between nerve cells
What is the resting membrane potential? How is it maintained?
- 70mv
- Maintained through selective permeability of neuronal membranes, permeable to Cl- and K+ and the Na/K transporter
At rest, high concentration of Cl- Na+ beyond cell
And A-, K+ within the cell
Process of depolarization within a cell?
- Na+ channels open - Na+ enters cell at threshold potential (-55mv)
- Membrane potential is raised (-10mv), K+ begins to leave the cell (through channels).
- The Na+ causes the membrane potential to rise to 40mv (membrane potential ) - the sodium channels at this point become refactory and no more Na+ enters the cell
- the K+ continues to leave causing the potential to fall
- K+ channels close, Na+ channels reset, however the extra K+
- Hyperpolarisation is caused by the excess leaving of K+, the hyperpolarization inactivated Na+ channels so another action potential cannot start.
- Resting potential returns when the K+ resets back to normal levels.
What is a synapse and what are the three types of synaptic connections?
The minute gap between neurones in which an electrical signal is transmitted chemically.
Axo-somatic: axon to cell body
Axo-dendritic: axon to dendrite
Axo-axonic: axon to axon
Steps is synaptic transmission of action potentials?
- The arrival of an action potential to the presynaptic terminal opens Ca++ channels in the nerve membrane ( a bit further up.
- the influx of calcium causes neurotransmitter to be released through vesicular exocytosis from the presynaptic terminal into the synapse
- Neurotransmitters bind to receptors on post-synaptic membrane
- This causes a post-synaptic potential (EPSP or IPSP)
What happens in an IPSP and an EPSP? In reality what happens?
EPSP - small influx of Na+ ions causing partial depolarisation
IPSP - Small influx of Cl- or efflux of K+
Through ionophores. (ion channels). In reality there are lots of IPSPs and EPSPs affecting neurones and the event of depolarisation depends on the net effect of these potentials
In order for effective and discrete (distinct separate transmissions) communication between neurones, there must be mechanisms, what are these?
Mechanisms to prevent further release:
- Inhibitory autoreceptors
Inactivate released neurotransmitters after use:
- Enzymatic degradation
- Active reuptake (into presynaptic)
Mechanism of inhibitory autoreceptors, locations?
Inhibits the release of further neurotransmitter, either on presynaptic terminal or on cell body. Activated by it’s own neurotransmitter.
6 Criteria necessary to be classified as a neurotransmitter?
Present in nerve terminals, along with its precursors and enzymes
Nerve stimulation must cause it’s release
Exogenous application should mimic effect
Specific receptors present, interaction with a receptor must produce an EPSP or IPSP
What are substances recognised by a receptor called?
Ligands
Characteristics of receptors
Protein molecules selectively bind to them
Transduce PSPs
Two types of receptors?
Ion-channel linked receptors e.g. acetyl choline
G-protein linked receptors e.g. noradrenaline
Steps of neurotransmitter life cycle (action)?
Synthesis Axonal transport Storage in vesicles Release into synapse Interaction with presynaptic autoreceptors Interaction with post-synaptic receptors inactivation
How do psychoactive drugs bring about effect?
All work by altering chemical communication, act on one or more step in the neurotransmitter life cycle
Types of psychiatric classification system?
Symptomatology - weakest
Pathology
Aetiology - Strongest
Mutually exclusive or jointly exhaustive
Is the DSM & ICD all exhaustive in terms of psychiatric classification? What does this mean for researchers?
Mostly based on symptomatology and therefore not too impressive - many category overlaps and omissions.
Can lead to unreliable diagnoses and uncertainty in sample homogeneity.
How can you measure human psychiatric biochemistry (two ways) problems with each?
Direct - Biopsy, neuro-imagery and post-mortem studies. Problems include prior drug treatment, uncertain or separate causes of death.
Indirect - CSF, blood and urine. Problems include risk to patient and relies on assumption.
What different biochemical tests can be used in psychiatric conditions? Problems
Chemical assays (transmitters, hormones, enzymes and metabolites)
Receptor binding assays (density and affinity assays)
Results are only correlational?
What kind of studies use selective pharmacology?
Testing predictions:
- fMRI, look for changes in receptors
- Endocrine challenges
- Pharmacological induction studies
- Clinical trials of novel therapeutic agents in patient populations
Best use of pharmacological treatment in psychiatric disorders?
In combination. Pharmacology can allow for the correct conditions under which psychological therapies can be applied.
Psychopharmacology is rarely curative but can lead to amelioration of distressing symptoms.
Brief summary of the monoamine theory of depression? How was it first established? How did this change?
Depression is caused by a deficit in NA and/or 5-HT in the brain.
Reserpine found to induce depression, and found to have effects depleting stores of NA and 5-HT (due to vesicular leakage.
Revised later: Leonard (1980):
It can’t just be synaptic increases of neurotransmitter:
- Delayed therapeutic response, despite immediate neurochemical effect
- Cocaine blocks reuptake, but not clinically effective antidepressant
- Atypicals effect receptors
Receptor adaptation causes depression
Synthesis and degradation of NA?
Tyrosine
Dopa
Dopamine
NA
(metabolised by enzymes = MHPG)
Synthesis and degradation of 5-HT?
Tryptophan
5-Hydroxytryptamine (5-HT)
(metabolised by enzymes = 5-HIAA)
Evidence regarding degradation products and the monoamine theory of depression?
Lower levels of MHPG and 5-HIAA in depression in blood urine and CSF. 5-HT particularly pronounced in suicidal depression.
Mann (2003)
First generation antidepressants? examples? Mechanism?
MAOIs e.g. iproniazid, blocks degradation of MAOs
TCAs e.g. imipramine, blocks reuptake.
Evidence for 2 biochemical subtypes of depression?
Van Praag (1977)
Identified two groups, A and B.
A is normal in terms of NA
B is low in NA
Amitriptyline is selective for 5-HT
Desipramine is selective for NA
Amitriptyline is effective on group A and not B
Desipramine is effective on group B and not A
Why is there the so called ‘cheese’ reaction to MAOIs?
Tyramine is metabolised by MAO, cheese (and others) contain tyramine and when there is less MAO there can be an extreme hypertensive reaction due to hypertensive properties of tyramine (pressor amine)
problems with first generation antidepressants?
Adverse reactions e.g. cheese reaction
30% of pts are treatment resistant
3-4 week therapeutic delay
predictions based on biochemical subtypes.
Second generation antidepressants, examples, mechanism?
NA reuptake inhibitors (NARI) e.g. maprotiline
5-HT reuptake inhibitors SSRI - fluoxetine
MAO-A (brain MAO subtype) inhibitors e.g. moclobemide
SNRIs e.g. venlafaxine
Atypical monoamine antidepressants
Clinical evidence regarding two subtypes of depression?
NARI and SSRI have similar efficacy clinically and so the evidence for subtypes is little.
Recent evidence regarding the therapeutic delay of antidepressant treatment?
Harmer et al (2009):
The difference in therapeutic delay is due to criterion differences, i.e. measuring some change may occur after a week but more may be seen at 3/4 weeks.
What specifically is the cause of depression in reference to 5-HT? How does this relate to the therapeutic delay in depression treatment (pharmacologically)?
What is this for NA?
Inhibitory 5-HT1a autoreceptors initially become hypersensitive, causing a lack of 5HT release from presynaptic terminal and therefore the hyper-sensitising the post synaptic 5-HT2a receptors. This adaptation is not good enough to return to pre-depression levels of neurone activation.
So when given pharmacological treatment it can initially worsen symptoms due to activation of 5-HT1a autoreceptors, and the therapeutic delay is due to the normalisation of the hypersensitive autoreceptors and 5HT2a receptors.
The exact same for NA, however inhibitory autorecetors are α-2 and receptors are β receptors
What is the endocrine stress response mediated by the HPA? Feedback control?
CRF (from hypothalamus)
ACTH from pituitary
Cortisol release from adrenal glands
Cortisol causes stress and other responses.
Inhibitory negative feedback control is mediated by GR receptors in hypothalamus/hippocampus. Inhibits further CRF and ACTH release.
How does the feedback control mechanism fail in chronic stress? (endocrine stress response)
The GR inhibitory receptors are constantly flooded with cortisol and so themselves desensitise, causing a failure in the system leading to hypercortisolaemia which has been associated with brain pathology:
- lower levels of 5-HT, and NA and changes in their receptors
- organic brain atrophy - temporal lobe seen in MDD
What evidence is there regarding dopamine and depression?
Would make sense for dopamine to be associated with depression as some of the main symptoms are to do with reward/pleasure i.e. anhedonia, and dopamine primarily regulates this.
New antidepressants may target NA, 5HT and Dopamine in way of triple therapy.
Recent evidence regarding pharmacological treatment of depression and it’s specific symptoms?
Della Pasqua et al., (2010):
- too much attention paid to global depression scales and not enough on specific symptoms, as different transmitters may cause different symptoms.
Korte et al., (2015)
- Specific symptoms can be treated with specific treatment regimes according to the neurotransmitters effected (see image)
Gene-environmeantal approach to depression (stress diathesis)
Capsi et al 2003
MDD linked to deficient 5HT levels and possibly malfunctioning 5HT transporter
The gene for the transporter exists in several forms - short and long;
Individuals with short allele along with child abuse are prone to react to stress with depression (and suicidal ideation)
What has the work of caps et al (2003) stimulated in terms of new research ?
Polymorphisms in the 5-HTT gene moderate:
- The impact of early childhood trauma on susceptibility to depression
- Treatment outcome following depression
What may 5HTT polymorphisms be affecting?
Fox et al (2009):
- variations associated with cognitive bias. Short may selectively process negative emotion and vice versa.
Harmer (2008)
- Lab studies (non-depressed) suggest low 5HT will cause increased negative cognitive bias and vice versa
Harmer et al., (2009)
- antidepressants increase positive cognition bias much earlier than improvement in mood.
Research regarding ketamine and depression?
Many confirmatory studies that ketamine is effective in treatment resistant depression.
Rapid effect, 25-85% after 24hrs,
Brief, mild adverse effects
Does not work on monoamine system
Primary use for ECT?
Severe depression (1% of psychiatric pts receive it), used when:
- Failure to respond to antidepressant drugs
- Cannot tolerate pharmacological side effects
- Cannot wait for drugs to take effect (3-4 weeks)
Process of ECT?
Thorough physical and psychiatric examination
Counselling on ECT and likely side effects
No food prior to treatment
Premedication (anaesthesia, anticholinergic, muscle blocker)
Shock applied bitemporally (bite block and ventilation provided)
Tonic seizure followed by clonic movements
Pt self reports of ECT experience?
80% say no worse than visit to dentist, 50% say better
80-98% would have again if depression reoccured
S/Es of ECT?
Memory loss:
- memory acquired shortly before ECT may be lost forever, however 3-6 months later, no deficits
- may be both anterograde and retrograde
- Evidence that memory loss is a feature of depression
Animal research suggests ECT causes no structural changes to the brain
Deaths from ECT are very rare 0.006% (much greater risk in drug therapy)
Evidence for the efficacy of ECT?
UK ECT review group (2003):
- ECT most effective treatment for treatment resistant depression eg.
(Wechsler et al 1965) - retrospective
MRC (1965) clinical trial ECT more effective
No more very recent evidence due to unethical testing
Generally about 70% effective
Relapse rates for ECT?
Methods to tackle this?
Similar to traditional drug therapy (50% within 2-3 months)
Maintenance ECT, Maintenance drug therapy
Or combine ECT and drug therapy continuation (gagne 2000)
Mechanism of ECT action?
Alters key receptors α2, β, 5-HT1a, 5HT2a.
Stimulates neurogenesis and synaptogenesis
Are convulsions necessary to ECT?
Carletti and Bini (1938) - yes - sub convulsive therapy is not effective
Research e.g. Gregory et al., (1985) regarding sham ECT vs ECT suggest that real ECT is much more effective (although sham had some effectiveness)
Dukart et al (2014) ECT findings?
Observed specific local brain volume changes following ECT, associated with depression (and correlate with symptom severity)
What is Trans Cranial Magnetic stimulation? (TMS)
TMS - magnetic field to induce electrical field
research suggests equal to or more than 50% reduction in depression scores, rapid onset and better side effect profile than ECT and drugs. e.g. Berlin et al (2013)
What two types of anxiety are there?
Adaptive anxiety - normal anxiety that constitute a proportional reaction to danger - protect you from the world
Maladaptive anxiety - pathological - exaggerated and/or inappropriate to context.
Normal treatment for anxiety?
Rationale for drug treatment?
A mix of psychotherapy, social support, re-education and drug therapy.
Drug treatments are there to facilitate the patient for other therapies.
Symptomatology of GAD and PD?
GAD: diffuse, non-specific anxiety - external focus
PD: Spontaneous response to specific stimulus. strongly exaggerated autonomic, emotional and cognitive symptoms
What are the three major biochemical theories behind anxiety?
5HT hyperactivity
NA hyperactivity
GABA under activity
Mechanism of BDZ action?
Bind to GABA receptors at a specific BDZ binding site
Use of BDZ? Problems?
Good for treatment of GAD, - fast onset
Not very useful in other disorders
S/Es of sedation muscle relaxation and cognitive impairment
Normal dose physical dependence
Withdrawal symptoms of BDZ?
Anxiety, tension, agitation, irritability, and others
How to avoid withdrawal symptoms of BDZ?
Careful prescription
Only short term treatment
Tapering dose withdrawal
Treatment of PD?
Does not respond to BDZ unless given at high sedating dose
Responds very well to antidepressants
Non-BDZ, novel treatment of GAD?
Pregabalin
Buspirone
Mechanism of action of Buspirone?
As effective as diazepam for GAD
Works via the 5HT system. Reduces 5HT release in forebrain, acts on 5HT1a autoreceptors.
Buspirone problems?
Several weeks of therapeutic delay - not effective for pts who have been on BDZ
Unpopular (mostly for the delay, can cause compliance issues)
Alternative options for treatment at the BDZ receptor?
Partial agonists (BDZ are full agonists) like imidazenil were expected to have anxiolytic properties without side-effects, confirmed in early trials, but recent trials have been less successful.
Recent advances regarding the GABAa receptor? Structure of receptor?
There are 5 subunits in the receptor, different arrangements in different areas of the brain.
In rats: (Mohler 2012)
- inactivated α1-subunits produced resistance to sedative and cognitive effects of BDZ
- Inactivated α2-subunits produced resistance to anxiolytic effects of BDZ
- race to produce a2 specific binding drugs.
Current trends in the prescription of antidepressants for different mental disorders?
Antidepressants found to be useful in many conditions:
TCAs in GAD
SSRIs effective is all: GAD, PD, SAD and PTSD.
What did Sramek et al (2002) conclude about treatment for anxiety disorder?
BDZ should only be used in short-term treatment.
SSRIs (and buspirone) should be used for longer-term treatment.
Recent trends regarding classification of anxiety and depressive disorders?
They are a lot more blurred than previously thought,
Shorter and Tyrer (2003) question the validity of the separation all the way back to the 1930s
Goodwin and Gordon (2002) GAD is a major risk factor for MDD; successful treatment of GAD significantly lowers the risk of MDD.
What does recent research suggest in terms of polymorphisms in the 5-HTT gene and anxiety?
Polymorphisms (different forms) of 5-HTT predict:
- Stein et al (2006): SSRI response in anxiety disorders
- Anxiety reactivity in daily life Gunthert et al., (2007)
What is the MZ concordance percentage for schizophrenia, therefore how strong is the genetic influence?
65-80% genetic, strongly genetic
Symptoms of Schizophrenia?
Positive:
- Delusions
- Hallucinations
- Thought disorder
- Extreme emotions
Negative:
- Flattened effect
- Poverty of speech
- Social withdrawal
- Avolition
- Anhedonia
Cognitive symptoms (deficits in attention and WM)
What are positive (type 1) and negative symptoms of schizophrenia also referred to? How did Tim Crow refer to the symptoms?
Positive = functional
Negative = organic
Tim Crow (1982) suggested they are part of the same disease and not two syndromes. He also suggested the prevalence of different symptoms changes throughout the course of the illness.
Different biological theories regarding schizophrenia?
Dopamine dysfunction
Glutamate dysfunction
Neuroinflammation
Evidence for dopamine theory of schizophrenia?
Chlorpromazine (used to treat schizophrenia) induces parkinsonian symptoms (know to be caused by lack of dopamine)
Medication known to increase dopamine (L-dopa, amphetamine and cocaine, all known to induce psychotic reactions)
Dopamine synthesis enzymes more active in Schizophrenia. Howes et al., (2013)
Increased dopamine release during psychotic episodes. McGuire (2008)
Increased D2 receptors in Scz McGuire et al (2008)
Specific area of lack of dopamine according to dopamine theory of schizophrenia?
Mesolimbic dopamine system.
Two subgroups of schizophrenia related to D2 receptor density?
High density subgroup (230% increase above normal)
Low density group (25% above normal)
Related to disease severity
Dopamine receptor type clusters?
D1-Like (D1 and D5) D2 Like (D2, 3 and 4)
How do the positive and negative symptoms of schizophrenia respond to D2 antagonists?
Type 1 (positive) responds well
Type 2 does not respond - may be made worse
Problems with current schizophrenia medication?
Side effects:
- Motor symptoms, weight gain, postural hypotension, anticholinergic
Delayed (2-3week) response
30% of pts are drug non-responders (particularly those with negative symptoms)
What is unique about Clozapine as an antipsychotic?
Has an atypical profile (is an atypical): low parkinsonian symptoms, more effective against negative symptoms
(lower) affinity to D2 well as:
- High affinity to D4
- High affinity to 5HT2 receptors
- High affinity for α2
Possible mechanisms for atypical antipsychotics?
Action at D4: Seeman & Van Tol (1994)
Action at 5-HT2 (postsynaptic serotonin) - positive results seen when 5-HT receptor antagonists are used in combo with D2 receptor antagonist - (Reynolds 1992)
same as above but with GABA α2 receptors - Nutt (1994)
Brain regions that correspond to the different effects of antipsychotics?
Prefrontal - negative symptoms
Limbic - Positive symptoms
Striatum - motor symptoms
Possible explanation of the worsening of negative symptoms with typical antipsychotic symptoms?
D1 receptors are reduced in schizophrenia in the frontal lobe (vs increased D2 receptors in mesolimbic system)
Typical antipsychotics may worsen symptoms by blocking D1 receptors as well as D2.
Antipsychotics with D1 agonist and D2 antagonist effects are effective with low side-effects
Glutamate theory in schizophrenia?
Glutamate acts at NMDA receptors
NMDA receptors are deficient in frontal cortex in negative schizophrenia.
NMDA antagonists induce both positive and negative symptoms
Negative schizophrenia may relate to dysfunction of glutamate systems in frontal cortex and/or abnormality of interaction with dopamine system
Summary of current neurotransmitter theories in positive and negative schizophrenia?
Positive schizophrenia is associated with D2 overactivity in mesolimbic system. Effectively treated with typical antipsychotics
Negative schizophrenia is associated with disturbed frontal lobe function and frontal-limbic interactions, related to altered D1, 5-HT2 and glutamate receptors. It is more effectively treated with atypical antipsychotics.
Current knowledge contributing to neuro-inflammatory theory of schizophrenia?
S is widely considered a neurodevelopment disorder (rather than a neurodegenerative disorder).
Neurodevelopment is now known to occur long after birth and it involves not only cell growth but also death (known as pruning)
Excessive pruning may cause incorrect ‘wiring’ of the brain, leading to S.
- S known to have strong genetic link and MHC (cell surface receptor presented to WBCs) gene is one likely contender.
MHC genes also encodes for C4 complement component (system that aids in immunity - also called MHC class III proteins)
C4 also tags synapses for pruning.
It is known that the C4A variant of complement is strongly associated with
Overall it seems that over-expression of the immune system e.g. C4 would perhaps lead to erroneous over-excessive pruning which may lead to S in later life
