Mood Disorders (part 1, 2 and 3) Flashcards
Describe the current diagnosis of a depressive illness
At least 2 of:
Depressed mood, anhedonia, anergia, fatigue, diminished activity
At least 3 of:
Reduced concentration, low self esteem and confidence, guilt and unworthiness, pessimism, ideas or acts of self harm, reduced sleep, anorexia
FOR 2 WEEKS (minimum)
Describe the clinical course of depression
Uncomplicated moderate episode; 4-6 months
54% recovered at 26 weeks
>85% have further episodes
4-10% die from suicide
Around 5-10% will eventually have a manic episode = bipolar
How is the severity of depression quantified?
Rating scales;
Beck Depression Inventory
17-item Hamilton
MADRS
Is CBT effective in depression?
Yes; but only mild illness
Not mod/severe as seen in secondary care
In terms of depression; what is a failed adequate trial?
Adequate trial of antidepressant:
Prescription of a specific antidepressant above a specific minimum dose for a minimum of 6 weeks with reasonable certainty of compliance
How is treatment resistance depression quantified?
Number of failed adequate trials of antidepressants
Rating scales used: MGH-S, ATHF
In terms of evolutionary concepts; what are the links with depressive illness?
To identify stimuli predicting appetitive or aversive consequences
Generate behavioural and physiological (autonomic and endocrine) responses, and social communications (emotions, cognition) in response to a stimuli
Coordinate and optimise responses and communications to maximise chances of survival
Describe the 5 main domains of established brain systems?
Negative valence; fear, anxiety, loss, non-reward
Positive valence; reward learning, valuation, habits
Cognitive; attention, memory, cognitive control
Social system; attachment, communication, perception self/ others
Arousal/ modulatory; circadian rhythm, sleep/wake cycle
Describe the neural circuits involved with the positive valence system (appetitive system)
Ascending dopaminergic; mesolimbic/cortical
Endogenous opioid system (mu)
Ventral striatum/ N. Acc
Dorsal striatum (movement)
Amygdala (conditioning/ learning)
Anterior cingulate (attention/ conflict/ response selection)
OFC (relative reward preference/ rule learning)
Describe the neural circuits involved with the negative valence system (aversive system)
Endogenous opioid (kappa) Ascending 5-HT NA/ CRF/ peptide transmitters Central nucleus of amygdala Hippocampus VA and medial hypothalamus PAG
Describe a depressive illness in terms of a disordered appetitive functioning
Difficulty identifiying rewarding stimuli
Reduced contact with previously rewarding stimuli
Increased contact with aversive stimuli
Overall reduction in behaviour
Move less, eat less, lose weight, decreased libido
Low mood
Describe a manic episode in terms of a disordered appetitive functioning
Previously neutral stimuli become rewarding
Increased exploration/ overall activity
Increased appetite for food, activity, sex etc
Intolerant of aversion/ boredom
Intolerant of frustration
Elated mood
Is there a link between anxiety and mood?
Yes; study has shown with an increased severity of mood disorder (MADRS) in MDD, OCD, BAD there is positive correlation with anxiety severity rating
Is there a link between cognitive impairment and MDD?
Yes
Unmedicated patients with depression; impaired in cognitive function (attention, executive function, visuospatial learning and memory)
Severity of depression correlated with impairment of learning and memory
Is the hippocampus implicated in MDD?
Yes
Study (sheline et al) showed a significant volume reduction in hippocampi between depressed subjects and matched controls (degree of reduction correlated with total duration of MDD)
ENIGMA data; robust reduction in hippocampal volume in MDD patients
Reduction in glial cells predominantly
Are the hippocampal neurons affected in MDD
Yes; stress and corticosteroids induce dendritic shrinkage
Repeated stress results in atrophy of the dendrites in the CA3 region of the hippocampus
Describe the role of the amygdala in MDD
fMRI and PET imaging studies have demonstrated an abnormally increased amygdala activity in depressive illness
Describe the role of ventral striatum/ N. Acc in MDD
Blunted striatal reward link activation = anhedonia
Abnormally increased hippocampal activity in MDD with aversive stimuli = negative valence system
Describe the role of the anterior cingulate and OFC in MDD
Brain regions assoc with emotional health are abnormally functional in MDD
Is it possible to diagnose depression with a brain scan?
Study using T1 weighted brain scans had a 90% accuracy in diagnosis of depression
Can MDD severity be predicted using a brain scan?
Yes;
Study determining if this was possible;
Increased BDI with predicted BDI using T1 weighted images was very accurate in determination of severity
What areas of the brain were utilised in the studies to determine severity and diagnosis of MDD using T1 weighted MRI images?
Hippocampus
Medial brain structures
Superior temporal gyrus
Describe the beliefs held about 5-HT and DA in the early 70s
Used using animal models
Dopamine at a tonic background level results in vigour with the phasic levels homing animals into the cues predictive of reward
5-HT has an inhibitory effect on behaviour and may have anxiolytic properties
5-HT neurons mediate the effects of punishment on behaviour
Describe Daeken and Graeff’s theory of 5-HT function and its link with depression
Dorsal Raphe Nucleus (DRN) neurones functioned in an opposite way to DA projections, being engaged by distal cues predictive of aversive reinforcers, functioning as a “stop” or negative reinforcement signal, guiding the animal away from threats (passive avoidance) and towards DA safety cues (active avoidance)
Linked with 5-HT2c function
Medial Raphe Nucleus (MRN) neurones mediate a disconnecting “unlearning” function during extinction or punishment of instrumental learning.
Linked to 5-HT1a agonists effects on impairment of learning and projections to the hippocampus.
MRN projections act to prevent consolidation of aversive memories allowing tolerance to chronic adversity (resiliance)