neuroscience and psychological disorders: the depressed brain

Question 1

what are the five main types of antidepressant

Answer 1

MAOIs Monoamine oxidase inhibitors

Trucyclics

SSRIs (Selective serotonin reuptake inhibitors)

SNRIs (serontonin and noradrenaline reuptake inhibitors)

NASSAS (noradrenaline and specific serotoninergic antidepressants)

Question 2

how do SSRIs function

Answer 2

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

Question 3

what are antidepressants used for

Answer 3

moderate to severe depressive illness, severe anxiety and panic attacks, OCD, chronic pain, eating disorders, PTSD

Question 4

how well do antidepressants work

Answer 4

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)

Question 5

what is the serotonin hypothesis

Answer 5

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

Question 6

how have antidepressants been criticised

Answer 6

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

Question 7

what happens when tryptophan is depleted

Answer 7

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

Question 8

who is the relapse in low mood induced by tryptophan depletion more likely for

Answer 8

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

Question 9

how does roboxotine affect emotion-processing in faces (Harmer et al., 2009)

Answer 9

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

Question 10

how does serotonin affect emotion-processing

Answer 10

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

Question 11

what is the role of the amygdala

Answer 11

threat detection
directing attention to emotionally salient/ ambiguous stimuli to engage further processing
emotional learning

Question 12

what is the relationship with the amygdala and depression

Answer 12

at rest there is hyperactivation
this correlates with symptom severity
tends to return to normal after successful antidepressant treatment

Question 13

what functional data is there for hyper activation of the amygdala (Sheline et al., 2001)

Answer 13

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

Question 14

what are the different functions of the right and left amygdalas

Answer 14

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

Question 15

what is the effect of a single dose of SSRI in healthy volunteers (Murphy et al., 2009)

Answer 15

reduces amygdala responses to fearful faces

Question 16

what is the role of the hippocampus in depression

Answer 16

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

Question 17

what is the role of PFC in depression

Answer 17

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

Question 18

PFC asymmetric in depression

Answer 18

left side: approach behaviour

right: withdrawal, inhibition of action

right activation enhanced so relative support for withdrawal

Question 19

how is the dorsolateral PFC implicated in depression

Answer 19

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

Question 20

how is the ventral/orbital PFC implicated in depression

Answer 20

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

Question 21

how is the subgenual anterior cingulate cortex implicated in depression

Answer 21

reduced volume in major depressive disorder

higher activation at rest

Question 22

correlations of disorders and sgACC

Answer 22

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

Question 23

how does deep brain stimulation help with depression

Answer 23

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

Question 24

what support is there for deep brain stimulation for treatment resistant depression

Answer 24

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)?