Lecture 3 - Unipolar depression Flashcards
What is an emotion and how is it different from a feeling?
Complex reaction pattern used by an individual to deal with a personally significant matter
Emotion involves feeling but differs from feeling in having an overt or implicit engagement with the world i.e., emotion has an object
What is a feeling and does it interact with the world?
A self-contained phenomenal experience: subjective, evaluative, and independent of the sensations, thoughts, or images evoking them. Typically evaluated as pleasant or unpleasant.
- Feelings are purely mental, whereas emotions are designed to engage with the world i.e., feelings do not have an object. And do not interact with the world.
What is affect?
Any experience of feeling or emotion
Ranging from suffering to elation, simplest to the most complex sensations of feeling, most normal to the most pathological emotional reactions.
Often described in terms of positive affect or negative affect, both mood and emotion are affective states.
What is mood? How does this differ from emotion?
A disposition to respond emotionally in a particular way that may last for hours, days, or even weeks, perhaps at a low level and without the person knowing what prompted the state.
- Moods differ from emotions in lacking an object.
What is the first DSM criteria for a depressive episode?
A. In a 2-week period, 5 or more of symptoms below present almost every day for most of the day (must include 1 or 2):
1) Depressed mood
2) Diminished interest/ pleasure in activities (anhedonia)
3) Weight loss/gain, appetite change
4) Insomnia/ hypersomnia
5) Psychomotor agitation/retardation
6) Fatigue/loss of energy
7) Worthlessness/ excessive guilt
8) Can’t think/ concentrate, indecisive
9) Recurrent thoughts of death or suicide
What is the second criteria for a depressive episode?
B. Symptoms cause clinically significant distress/major functional impairment
- Varies from person to person, could be:
- Unable to take care of their basic needs (wash, dress, cook)
- Managing to go to work but really struggling to do so and having to work harder than average to keep on top of this
What is the third criteria for a depressive episode?
C. Episode not caused by physiological effects of substance or medical condition
What two criteria have to be met for a depressive episode tom then be diagnosed as major depressive disorder?
MDD - also need these criteria:
D. Disturbance not better explained by schizophrenic-spectrum disorder
E. Complete absence of manic/ hypomanic episodes / cyclothymic disorder
What do the following MDD diagnostic specifiers involve? Anxious distress, mixed features, melancholic features, atypical features
Anxious distress: tense, restless, sense of dread
Mixed features: mania / hypomania
Melancholic features: despondency, worse in a.m.
Atypical features: mood reactivity, increased appetite
What do the following MDD diagnostic specifiers involve? Psychotic features, catatonia, peripartum onset, seasonal pattern
Psychotic features: delusions/ hallucinations; mood (in)congruent
Catatonia: lack of movement / speech
Peripartum onset: started in pregnancy / <4 weeks after birth
Seasonal pattern: regular annual trend in episodes & recovery
What do diagnostic specifiers do?
If symptoms have a lot in common with another mental health condition, they help with prognosis and treatment approaches
What are the criteria for persistent depressive disorder?
MDD symptoms for ≥2 years
Any break from symptoms ≤2 months
Mild to moderate severity - only need 3 symptoms not 5 (this may not reflect reality of severity though), still linked to MDD and people with PDD usually have at least one episode of MDD
What is premenstrual dysphoric disorder?
Symptoms present 7 days before menstruation
Remit in the week following
When is the onset and diagnosis period of disruptive mood dysregulation disorder?
Onset before 10 years
Must be <18 & >6 years at diagnosis
How does disruptive mood dysregulation disorder present in children?
Negative affect looks different - irritability and angry outbursts as children have not developed abilities to manage and talk about sad emotions
≥3 times per week temper outbursts
Mood between outbursts persistently irritable
Symptoms present for ≥ 12 months
What cognitive functions decrease in MDD and what cognitive biases occur?
Decrease in processing speed, attention, executive function, learning, and memory
Distorted information processing and (or) focus moving away from positive stimuli and toward negative stimuli (especially affective stimuli) - better memory for negative
Abnormal responses to negative feedback and decision making
Do cognitive impairments in MDD remain during symptom remission? What do recurrent episodes increase the risk of?
They can
Recurrent episodes increase risk of progressive function loss
What are the three aspects of Beck’s negative triad?
Negative thoughts about the self, the environment and the future
Early life experiences lead to dysfunctional beliefs about the world which later on triggers irrational automatic negative thoughts
What % of people with MDD experience symptoms for over 2 years, and what this lead to a diagnosis of?
10-20% of people with MDD experience symptoms for ≥2 years, leading to a diagnosis of persistent depressive disorder
What is remit, relapse and recurrence in MDD?
Most people’s symptoms remit (definition: gone for ≥2 months)
If they reappear in a short period of time, this is relapse
Recurrence is when symptoms remit for a longer time, then return i.e., onset of a new episode of depression
What % of people with MDD experience recurrence?
40-50%
What makes recurrence more likely?
If the number of previous episodes increases and if other mental health conditions present
What are residual symptoms of MDD?
Residual symptoms - even when someone remits, still have fatigue problems with sleep and cognitive function persist
Do depressive disorders have significantly higher disability adjusted life years than most other mental health conditions?
Yes
DALYS represent total worldwide number of years of otherwise healthy life lost or profoundly impacted by a health condition
When are there more disability adjusted life years (DALYS) in depressive disorders? What is the most common age of onset of a first major depressive episode?
Burden of depressive disorders is biggest during early adulthood - most DALYS years
Most common age of onset of first major depressive episode = 10-21
What % of the global population have MDD?
Affects around 6% of the global population.
What are age, gender and race risks for MDD?
- Young adulthood
- Identify as a woman
- Identify as transgender
- Belong to specific ethnic groups, although the specific groups vary between countries & regions
How much more likely are women to have MDD than men at ages 15 and 25?
3x more likely to be diagnosed than men at 15, 2x at 25
What could gender differences in MDD diagnosis be due to?
Could be due to fewer men getting diagnosis because less of them help-seek
What is the odds ratio for MDD diagnosis based on gender?
Odds ratio = likelihood of diagnosis in women compared to likelihood of diagnosis in men
What risk factor is the strongest predictor of effect size for symptom severity?
Age
What are four likely explanations for gender differences in incidence of depression?
- Different patterns of risk factors
- Gender discrimination
- Differential exposure to childhood or adult adversities
- Biologically different stress responses
What life events are women or men more likely to experience depression as a result of?
Women more likely to experience depression after interpersonal struggles - relationship issues or lack of social support, men more with roles related to success
What is the HPA axis?
Hypothalamus
- > corticotropin releasing hormone (CRH)
Anterior Pituitary
- > adrenocorticotropic hormone (ACTH)
Adrenal Cortex
- > cortisol (CORT)
ANS - sympathetic branch of ANS, fight or flight response, adrenal medulla - adrenaline
Rapid rise in cortisol that tails off quickly as stressor terminates
Correct regulation of cortisol important
How are cortisol levels different between females and males?
Females have higher levels of cortisol
The adrenal gland (produces cortisol) is larger in females than males
Thus, females have an increased response to fear and stress
Is there heterogeneity in the presentation of depression?
Yes - varying causes and subtypes
What is the role of the stress response in depression?
Stress may lead to depression via dysregulation of our normal stress response
Chronic stress disrupts negative feedback loops for cortisol - cascade of biological effects that cause depressive symptoms that depression can feed back into.
Stress response becomes hyperactive
e.g. Hyperactivity in HPA axis can damage brain areas involved in emotion regulation: hippocampus, PFC, amygdala -> damage to these areas damages HPA axis more e.g. hippocampus related to hypothalamus which affects cortisol
Caudate nucleus - What does this do and is its volume smaller in MDD?
Motivation, emotion processing, memory
Smaller
- 3.5%
Thalamus - What does this do and is its volume bigger or smaller in MDD?
Body’s relay station - communicates with cortex. Attention and memory, connected to limbic system.
Smaller
- 6.7%
Putamen - What does this do and is its volume bigger or smaller in MDD?
Motivation, emotional processing, reward and learning
Smaller
- 4.1%
Globus Pallidus - What does this do and is its volume bigger or smaller in MDD?
Relays info to thalamus, modulates cognitive and limbic pathways
Smaller
- 4.5%
Hippocampus - What does this do and is its volume bigger or smaller in MDD?
Memory formation and retrieval
Emotion regulation and HPA axis
Smaller
- 5.5%
Frontal lobe - What does this do and is its volume bigger or smaller in MDD?
Attention and behavioural control
Smaller
- 3.8%
Orbitofrontal cortex - What does this do and is its volume bigger or smaller in MDD?
Learning and decision-making, emotion and reward
Smaller
- 7.5%
Gyrus rectus - What does this do and is its volume bigger or smaller in MDD?
Higher cognitive functions like personality or social function and expression of emotion
Smaller
- 15.5%
What is the affective-salience circuit in MDD?
Amygdala is hyper-activated & hyper-connected with areas including dorsal ACC & insula. Might reflect increased salience of negative info.
Limbic regions associated with processing and regulating emotion and negative evaluation - circuit is hyper-activated in depression
What is the default mode network in MDD?
This network is typically most active at rest
Hyperconnectivity correlates with higher levels of self-directed thoughts (e.g., rumination) - over-processing self-referential negative experience
What is the fronto-parietal (cognitive control) circuit in MDD?
Hypoconnectivity (reduced) of this circuit may reflect difficulties in goal-directed tasks.
Impaired top-down control of negative thoughts and emotions
Under- activity is observed at rest & for negative but not positive stimuli
Are brain circuit functional differences in MDD consistent across all people?
No
Variable findings - these brain networks have been detected to be different in different groups with very heterogeneous clinical presentations
More replication needed
Does the brain communicate with the CNS, stress response system (HPA axis), the ANS and the immune system?
Yes
What biological effect do psychological stressors cause?
Repeated HPA axis response
What does repeated HPA axis response over time cause?
- Diminished feedback inhibition capacity (i.e. can’t be switched off or turned down)
- Chronically elevated cortisol and CRH (corticotropin releasing hormone)
What can cause chronically elevated levels of inflammatory mediators (e.g. cytokines)?
Chronically elevated cortisol and CRH
A combination of stress response & immune activation affects the central nervous system in MDD - what is affected?
Alters neural plasticity, connectivity, & neurotransmission.
May exacerbate tissue loss.
What does altered neural plasticity, connectivity, & neurotransmission in the brain as a result of stress response and immune activation explain in MDD?
May explain structural and functional brain differences seen in MDD
Does chronic stress lead to chronic inflammation?
Yes
What behaviours linked to stress can cause inflammation and subsequently MDD?
Alcohol use, smoking, poor diet & physical inactivity
What is the two-way relationship between stress-linked behaviours and MDD?
Stress-linked behaviours (e.g. smoking) cause inflammation and thus MDD
These behaviours can be exacerbated by MDD as well
Are our current stressors primarily social?
Yes
What is the continuous cycle between stress and inflammation?
Prolonged stress alters the adaptive innate immune system response and prolongs inflammation. Our bodies are not equipped to deal with these.
Inflammation itself perpetuates cognitive-affective-behavioural changes that themselves perpetuate stress.
What is a bidirectional relationship in MDD?
By bidirectional, we mean that the factor raises the likelihood of an MDD diagnosis and MDD diagnosis can increase the severity of the factor as well.
e.g. MDD diagnosis and lack of social support
How do early life events affect immune and stress reponses?
Altered immune response develops in response to adverse early life events: a proinflammatory phenotype, shaped by the developing organism’s exposure to social-environmental threat.
What is the dose-response effect?
Childhood adversity linked to subsequent exaggerated cognitive, emotional, & biological stress responses
What are causes of early systemic inflammation that predispose inflammatory responses across the life course?
Childhood obesity, diet, & low physical activity
What are socioeconomic causes of elevated immune and stress responses?
Disadvantaged children face more stressors.
Inflammatory response over-calibrated - linked to depression
What negative life events might preced the onset of MDD?
Bereavement, divorce, chronic/life-threatening illness, discrimination, loss of employment, violence, displacement etc.
How do genetic risk factors for MDD interact with environmental risk factors?
For example, alleles may differentially amplify the effects of stressful life events
What is the social drift hypothesis in MDD?
People with mental illness, especially those with a chronic course, may experience deteriorating functioning
Clinical features can contribute to downward socio-economic spiral
Can lead to work and family problems (so-called ‘social drift’), which raises the likelihood of further socioeconomic disadvantage
Compounded by systemic stigma, discrimination & marginalisation based on mental health status AND socioeconomic disadvantage: occurs with many MHCs.
What is the heritability of MDD? Is it polygenic?
35%
Yes
Does heritability of depression vary according to different subtypes of depression?
Yes
How much more likely are MZ twins to develop depression than DZ twins?
2x more
What presentations of depression is heritability higher for?
Heritability higher for more severe, early onset, or recurrent depression.
What do diathesis stress models for MDD suggest?
Suggest that stress can precipitate the development of MDD in individuals who have a pre-existing vulnerability to depression
What does the gene 5-HTTLPR do?
Serotonin transporter gene
Is there a significant interaction between stress and 5-HTTLPR genotype?
No
What is the stepped care approach to depression treatment?
Match treatment to presentation
e.g. for mild depression the immediate treatment would not be medication, instead you would start with assessment, referral, psychoeducation, active monitoring and support
How do selective serotonin reuptake inhibitors (SSRIs) work? (e.g. fluoxetine)
Block reuptake of serotonin so it remains in the synaptic cleft for longer
How do tricyclic / tetracyclic antidepressants (e.g. amitriptyline) work?
Block reuptake of serotonin and norepinephrine so they remain in the synaptic cleft for longer
How do monoamine oxidase inhibitors work?
An enzyme called monoamine oxidase is involved in removing norepinephrine, serotonin and dopamine from the brain: MAOIs stop this happening. Block enzyme responsible for clearing away monoamine
What do all anti-depressant medications essentially do?
Increase monoamine
How effective are anti-depressant drugs?
In a large and recent systematic review and meta-synthesis of antidepressant effectiveness, all 21 varieties examined (SSRI and TCA) performed better than placebo.
Effect sizes of drugs tend to be quite small - some people do not respond at all
What do monoamine hypotheses of anti-depressant drugs focus on?
Hypothetical deficiencies of/ insensitivity to serotonin (5-HT), noradrenaline, & dopamine
Is rapid change to serotonin concentration in the brain consistent with the delayed onset of symptoms relief in SSRIs?
No, and not everyone experiences relief
Does lowering serotonin (5-HT) concentration in brain of people without MDD induce depression?
No
What is a negative side-effect of long term antidepressant treatment?
Long-term antidepressant treatment actually downregulates total 5-HT concentration in the brain
Is there evidence of problems with monoamine receptor dysfunction in the brains of people with MDD?
No - depression is not due to a simple monoamine deficiency
Are neurotransmitter concentration and receptor insensitivity theories completely accepted explanations of depression?
No - it is more complex
What does the delay in symptom relief when antidepressant drugs are started suggest?
New neurons need to grow (neurogenesis) in key areas of the brain (e.g., hippocampus) in response to antidepressants, for some people.
How does chronic stress substantially alter neuronal circuits in the brain?
Includes disruption of intracellular signalling and the number and function of synapses
How might antidepressants help reverse changes to neuronal circuits in the brain caused by chronic stress?
Antidepressants may help reverse some of these changes by increasing neural plasticity – this happens via BDNF (brain derived neurotrophic factor)
What is the interaction between thought, emotion and behaviour in the CBT model?
Thought - what we think affects how we act and feel
Emotion - what we feel affects how we think and do
Behaviour - what we do affects how we think and feel
These are all reciprocally deterministic
What does CBT for depression aim to do?
CBT helps us recognise the relationships between thoughts, behaviours and emotions in our lives, making changes to thoughts and behaviours to enhance emotional experiences/ symptoms
Individual’s capacity to change - breaking down problems to cope with them better
What does CBT for MDD involve?
Cognitive–behavioural therapy helps patient identify negative, distorted thinking patterns that contribute to depression.
CBT for MDD consists of how many sessions for how long?
16-20 sessions over 3 to 4 months
What is homework in CBT for MDD?
Opportunity to practice skills for testing and challenging negative thoughts
What does behavioural activation in CBT for MDD do?
Behavioural activation helps patient increase positive activities that provide a sense of pleasure or mastery. Systematically, processes used to avoid activities are tested and reduced.
What is collaborative empiricism in CBT for MDD?
Collaborative empiricism means that the patient and the therapist become co- investigators both in ascertaining the goals for treatment and investigating the patient’s thoughts.
e.g., thought records: Identifying and challenging negative automatic thoughts
e.g., behavioural experiments pragmatically testing predictions about consequences behaviour
Is CBT more effective than doing nothing/usual care or pill placebo/medication alone? (for MDD)
CBT (overall) more effective than doing nothing (placebo) for MDD
Effect size (Hedge’s g) moderate to large
Also more effective than usual care or pill placebo with smaller effect sizes.
CBT marginally more effective than medication alone for MDD
What is interpersonal psychotherapy for depression?
Psychological problems understood as responses to current difficulties in day-to-day interactions with others
Focus on attachments, grief, role transitions, interpersonal disputes and deficits.
IPT aims to improve interpersonal functioning, well-being and through helping individuals effectively communicate, resolve interpersonal crises, help patients effectively utilise social support
How many sessions are usual for interpersonal psychotherapy for depression?
12-16
Is interpersonal psychotherapy an effective treatment?
Effectively reduces depressive symptoms in comparison to placebo, and in combination with antidepressants (Cuijpers et al, 2011)
For what symptom level of depression does NICE recommend physical activity programmes for?
Mild to moderate symptoms
Useful in increasing social engagement and decreasing somatic complaints
When would couples therapy be used for depression treatment? How many sessions are typical over 5-6 months?
(15 to 20 sessions over 5 to 6 months)
Useful when the person has a regular partner and where relationship may contribute to development/maintenance of depressive symptoms
How many sessions of counselling are typically done over 8 to 12 weeks?
6-10
How many sessions of psychodynamic counselling are typically done over 4-6 months?
16-20
Is there a strong evidence base for counselling and psychodynamic therapy?
No
Are cognitive behavioural therapy and second-generation antidepressants equally cost effective across the course of 5 years?
Yes
