neuroscience and psychological disorders: the depressed brain Flashcards
what are the five main types of antidepressant
MAOIs Monoamine oxidase inhibitors
Trucyclics
SSRIs (Selective serotonin reuptake inhibitors)
SNRIs (serontonin and noradrenaline reuptake inhibitors)
NASSAS (noradrenaline and specific serotoninergic antidepressants)
how do SSRIs function
SSRIs downregulate SERT receptors reapsorotion of serotonin into the pre-synaptic nerve endings once it has been released
this increases the concentration of serotonin in the synaptic cleft
what are antidepressants used for
moderate to severe depressive illness, severe anxiety and panic attacks, OCD, chronic pain, eating disorders, PTSD
how well do antidepressants work
after 3 months of treatment 50-65% improved compared to 25-30% if given placebo
effectiveness (clinically significant difference) increases relative to placebo with increasing initial severity of the depression (Kirsch et al., 2008 meta analysis)
what is the serotonin hypothesis
antidepressants typically work by acting on 5-HT systems
depression is caused by a serotonin imbalance or deficiency in the brain
abnormalities of serotonin regulation are implicated in the aetiology for depression
how have antidepressants been criticised
typically work by acting on 5-HT but don’t work straitht away, don’t work for everyone
also work for a variety of other disorders so are non-specific
reducing serotonin can cause transient recurrance of depression symptoms
what happens when tryptophan is depleted
tryptophan is necessary for the synthesis of 5-HT
because amino acides compete for entry across the blood brain barrier, giving participants a drink containing amino acids but no tryptophan, central TRP and 5-HT decrease (confirmed by reduced plasma TRP and 5-HT in brain )
no robust mood effects in healthy volunteers
who is the relapse in low mood induced by tryptophan depletion more likely for
particiapnts who are female, SSRI treated, who had recurrent previous episodes of depression or who had reported being previously suicidal
thus reducing serotonin can cause transient recurrance of depression symptoms in some vulnerable individuals
how does roboxotine affect emotion-processing in faces (Harmer et al., 2009)
comparing healthy participants who have been given a placebo and depressed patients who have been given placebo
and depressed patients with placebo or roboxetine
investigates recognition of happiness
depressed patients less likely to recognise happiness than comparison subjects
on roboxotine however there are much higher rates of recognition of happiness
how does serotonin affect emotion-processing
acute tryptophan depletion sometimes increases depression-congruent cognition
e.g impaired recognition of happy facial expressions, reduced reward sensitivity, enhanced punishment predictions (cools et al., 2007)
but sometimes it does the opposite
increased positive motivational biases, reduced recognition of fear in healthy volunteers
what is the role of the amygdala
threat detection
directing attention to emotionally salient/ ambiguous stimuli to engage further processing
emotional learning
what is the relationship with the amygdala and depression
at rest there is hyperactivation
this correlates with symptom severity
tends to return to normal after successful antidepressant treatment
what functional data is there for hyper activation of the amygdala (Sheline et al., 2001)
depressed and nondepressed participants were shown one face briefly (weren’t aware they were seeing it - fearful, happy, neutral )
immediately masked with a second face
higher activation in left amygdala for fearful and neutral faces in depressed participants
what are the different functions of the right and left amygdalas
right: automatically activated by emotinal stimuli - role in dynamic emotion stimulus and detection
left: specifc sustained stimulus evaluation
bias in evaluating incoming information in depression which resolves with successful treatment
what is the effect of a single dose of SSRI in healthy volunteers (Murphy et al., 2009)
reduces amygdala responses to fearful faces
what is the role of the hippocampus in depression
potentially involved in memory impairment
structurally reduced volume
high level of cortisol inducing neuronal loss
impariment in creation of new pathways: neurogenesis
seem to be restored with antidepressant medication
what is the role of PFC in depression
maintains representation of goals and means to achieve them (EF)
emotion processing: top-down regulation and control of emotional responses
frequent reports of abnormal activation in dperession
PFC asymmetric in depression
left side: approach behaviour
right: withdrawal, inhibition of action
right activation enhanced so relative support for withdrawal
how is the dorsolateral PFC implicated in depression
maintains or manipulates informatoin in WM
emotion regulation (inhibitory control over the amygdala via other PFC regions)
at rest there is reduced activation in depressed patients
in non emotional WM tasks when performance is matched to controls there is increased activation (although findings are mixed)
but there is reduced activation for executive control during emotional processing (links to increased amygdala activation)
resolved after sucesssful treatment
how is the ventral/orbital PFC implicated in depression
representation of reward and punishment
using reward and punishment to guide behaviour
subjective hedonic processing (orbitogrontal)
at rest: increased activityin left ventrolateral PFC
possibly increased during tasks involving reward punishment processing
how is the subgenual anterior cingulate cortex implicated in depression
reduced volume in major depressive disorder
higher activation at rest
correlations of disorders and sgACC
Transient sadness in
healthy controls
increases sgACC
activation
Fluoxetine treatment for Parkinson’s related MDD decreases sgACC activation
MDD patients with lower sgACC activation are more likely to respond to CBT treatment
Fluoxetine treatment for
MDD decreases sgACC
activation
Placebo treatment for
MDD decreases
sgACC activation
Social phobia patients who respond to CBT / SSRI show reduced sgACC activity compared to nonresponders
how does deep brain stimulation help with depression
electrode inserted in ACC
one month after stimulation, 2/6 have responded
two months 5/6
near remission
Before DBS: increased sgACC compared to controls After DBS: decreases in sgACC in treatment responders
what support is there for deep brain stimulation for treatment resistant depression
2014 meta-analysis
• After approx. 13 sessions, 29.3% and 18.6% of subjects
receiving HF-rTMS were classified as responders and
remitters, respectively (compared with 10.4% and 5% of those
receiving sham rTMS).
Berlim et al., 2014, J of Affective Disorders
• Mechanism of action remains unclear
• “silences” stimulated neurons?
• modulates network activity/neurotransmission at distal sites?
• induces long-term synaptic changes (plasticity)?
• “sensitizes” brain to effects of other treatments (ADMs)?
