Lecture 4 - Depression Flashcards
Name some of the main symptoms for major depression according to the DSM-IV diagnostic criteria.
Depressed mood Irritability Low self-esteem Feelings of hopelessness, worthlessness and guilt Decreased concentration Decreased appetite Weight loss or weight gain Insomnia or hypersomnia Low energy, fatigue Decreased interest in pleasurable stimuli Recurrent thoughts of death and suicide
What percentage of the UK population experience depression in any one year?
Between 8% and 12%
What is the monoamine theory of depression?
5HT1A receptors (sub-type of serotonin receptor) mediate mood, anxiety and temperature Therefore, a decrease in serotonin in the system leads to dysregulation of the above factors.
What is one piece of evidence for the monoamine theory of depression?
Young et al., (1985) found higher levels of symptoms of depression in normal males given a tryptophan-free diet, compared to those given a balanced or excess tryptophan mixture.
What is the first line of treatment for depression?
SSRIs, selective serotonin reuptake inhibitors - drugs which block serotonin reuptake, and noradrenaline.
This reuptake blocking would leave greater amounts of extracellular serotonin, enabling more to bind to receptors and allow regulation of mood, anxiety, etc.
What is the function of noradrenaline?
Noradrenaline increases blood pressure by narrowing blood vessels and by affecting the heart directly. It also increases levels of glucose and immune cells (i.e. T cells)
What is social adaptation?
The ability of an individual to adapt their behaviour to make it appropriate for the social situation they find themselves in.
What is social support?
People who are emotionally close to the individual and provide understanding, encouragement and generally positive feedback.
What percentage of depressed patients remit following citalopram treatment?
33% remitted following 14 weeks of citalopram treatment
What are other methods of treatment for depression?
- CBT
- ECT
- TMS
- DBS
What percentage of the risk for depression is genetic?
40%-50%, which is at least as heritable as type II diabetes, hypertension and asthma.
What did Kendler et al., (2001) find about major depression as a progressive illness, and using previous episodes to predict risk?
The more the previous depressive episodes, the greater the odds ratio (risk) of depression onset.
The more the previous depressivesodes, the lower the likelihood that recent stressful life events is the cause of the depression (suggests that the later episodes are set off by previous/early episodes, rather than directly from life stressors)
What did Kendler et al., (2001) find about major depression as a progressive illness, and using previous episodes to predict risk?
The more the previous depressive episodes, the greater the odds ratio (risk) of depression onset.
The more the previous depressisodes, the lower the likelihood that recent stressful life events is the cause of the depression (suggests that the later episodes are set off by previous/early episodes, rather than directly from life stressors)
Which areas have been consistently implicated in mood disorders since work in patients with secondary mood disturbances resulting from acquired brain injuries?
Frontal lobes and basal ganglia - greater incidence of depression following strokes which damaged the PFC or basal ganglia, especially the left side of the brain. Also associated with rare cases of secondary mania (sub-category of bipolar that is caused by trauma or physical illness).
(Clark, Chamberlain and Sahakian, 2009).
Why might lesions to frontal lobes and the basal ganglia be implicated in depression?
Potential difficulty for regions of the PFC to be able to regulate responses of the amygdala to negative or positive feedback.
Basal ganglia may be implicated due to dopaminergic abnormalities…?
Which other neurological conditions are associated with elevated levels of depression?
PD and HD - conditions affecting the basal ganglia. Increases support for the implication of the basal ganglia in underlying mechanisms of depression.
How is executive control affected in mood disorders, specifically in major depressive disorder (MDD)?
Executive control is diminished in unmedicated cases of MDD, and are exaggerated in bipolar depression.
Functional imaging evidence finds that dorsal and lateral PFC is dysregulated in depressed patients performing executive tasks (e.g. stroop/WM task), with PFC hypoactivity on tasks where performance was impaired.
On tasks where performance was no different to controls, PFC activation was greater, suggesting that cortical efficiency is lower in depressed patients.
(Clark, Chamberlain and Sahakian, 2009)
How is memory affected in mood disorders, specifically in major depressive disorder (MDD)?
Mnemonic impairment is predictive of functional outcome, and correlates with the extent of chronicity of the depression - Gorwood et al., (2008) found a 2/3% decline in delayed paragraph recall with each depressive episode, up to the 4th (i.e. memory worsens with each episode)
Reduced hippocampal volume is the most robust neuropathological finding in MDD. No differences in volume between controls and untreated first-episode cases of MDD but large reductions in patients who had experienced multiple episodes (MacQueen et al., 2003).
Reduction in volume may occur due to the vulnerability of the hippocampus to hypoxic effects. Depressive episodes are associated with increased cortisol levels, which seem to cause the hippocampus to resemble an aged brain (Sapolsky et al., 1985).
(Clark, Chamberlain and Sahakian, 2009)
How is affective processing bias affected in mood disorders, specifically in major depressive disorder (MDD)?
Depressed patients are impaired at recognising happy facial expressions (Lembke & Ketter, 2002)
Depressed patients respond more rapidly to sad word targets, compared to happy word targets, on the affective go/no-go task, and compared to healthy controls (Murphy et al., 1999).
Depressed patients showed increased subgenual cingulate responses to sad targets, and a distinct response to sad distractors in the right OFC (Elliott et al., 2002).
Increased amygdala response in MDD patient groups, in response to negative emotional faces (Fales et al., 2008)
(Clark, Chamberlain and Sahakian, 2009)
How does the positivity of memory recall differ in depressed patients?
Patients with depression have an increased tendency to recall negative autobiographical memories. When they do recall positive memories, they are lacking in detail (Brittlebank et al., 1993).
How might connectivity be relevant in depression?
Connectivity between the amygdala and multiple PFC sites may be affected in depressive states.
Negative correlation between amygdala and ventrolateral PFC activity in controls, when performing an emotional reappraisal task. In MDD patients, there was either no correlation, or the correlation was positive
(Chen et al., 2008) in Clarke, Chamberlain and Sahakian, 2009).
What is one of the few pieces of causal evidence that reduced serotonin function is linked to depression?
Smith et al. (1997) - finding that acute tryptophan depletion in remitted MDD patients causes a temporary relapse of low mood.
How is feedback sensitivity affected, specifically exaggerated responses to negative responses, in mood disorders, specifically in major depressive disorder (MDD)?
Depressed patients have exaggerated responses to negative responses during lab testing:
Elliot et al., (1997) found that depressed patients who responded incorrectly on a given trial of a working memory task would be disproportionally likely to fail the following trial.
Reduced top down control of the amygdala due to hypoactivity of the PFC and a failure to decrease amygdala activity in response to misleading negative feedback (Tavares et al., 2008).
How is feedback sensitivity affected, specifically numbed responses to positive feedback, in mood disorders, specifically in major depressive disorder (MDD)?
Anhedonic symptoms:
Reductions in ventral striatal activity in MDD in response to happy facial expressions and positive words (Surguladze et al., 2005).
MDD patients showed decreased ventral striatal activity in response to correct feedback, and reduced ACC activity in response to incorrect feedback, suggesting a deficient/lacking positive reinforcement/recognition of success, and an attenuated use of negative feedback to improve task performance (Steele et al., 2007).
