stress and mood disorders

stress response

suppression of the PNS and activation of the SNS

stress regulatiion

regulated via negative feedback through glucocorticoid receptors in the PVN, hippocampus and ACC

chronic stress and regulation

impairs the negatve feedback loop through damage to the hippocampus, leading to sustained cortisol levels and energy inefficiency

MDD

marked by persistent, debilitating symptoms like low mood, sleep disturbance and fatigue

MDD and HPA axis dysregulation

both high and low cortisol levels can induce depressive symptoms

treatments that reduce subgenual ACC activity

alleviates depressive symptoms

chronic stress and monoamines

depletes noradrenaline, serotonin and dopamine

SSRIs - lipophillic

block serotonin reuptake to increase synaptic availability

neurogenesis suppression

depression suppresses hippocampal neurogenesis

enhancement of neurogenesis

SSRIs and exercise enhance neurogenesis, necessary for antidepressant

3 brain features of MDD

1. hyperactive amygdala

2. impaired ACC

3. reduced striatum activity

where are glucocorticoids released from

adrenal cortex

where do glucocorticoids bind to

the PVN of the hypothalamus, hippocampus and ACC

what does the binding of glucocorticoids do

inhibits further release of CRH and ACTH which suppresses the HPA through negative feedback

subgenual ACC

implicated in mood regulation and depression

subgenual ACC activity and anti-depressants

its activity decreases in response to SSRIs

SNRIs

increases both serotonin and noradrenaline to improve mood and energy

tricyclics and monoamine oxidase inhibitors

inhibit reuptake and block enzyme monoamine oxidase

enzyme monoamine oxidase

breaks down monoamines

adrenal medulla

secretes hormones for fight-flight response

3 catecholamines

1. dopamine

2. adrenaline

3. noradrenaline

paraventricular nucleus (PVN)

cluster of neurons in the hypothalamus which maintain body stability in response to internal and external stressors

corticiotropin releasing factor (CRF)

produced by the PVN and initiates the stress response by stimulating ACTH release

adrenocorticotropic hormone (ACTH)

stimulates the adrenal cortex to produce and release cortisol

how does ketamine help relieve depressive symptoms

increases neural plasticity and synaptogenesis to reverse structural changes

2 structural brain changes in depression

1. shrinkage of neurons

2. reduced connectivity in mood-regulating regions

mineralocorticoid receptors (MR)

regulate stress responses by influencing electrolyte transport and gene expression

reserpine drug

a drug which depletes monoamines by blocking vesicle storage

effects of reserpine

lowers blood pressure and increases depressive symptoms

5-HIAA

marker of serotonin activity in cerebrospinal fluid

dentate gyrus

neurogenesis