stress and mood

Stress response

Some aspects of the response to many stressful conditions are shared eg being attacked, attacking someone, hunger, cold, overheating

Stress and PNS/CNS

Stress stimulates SNS

stress in

What do pre-ganglionic neurons of the SNS stimulate?

The adrenal medulla to release adrenaline and noradrenaline into blood stream

Adrenal cortex

Makes and releases cortisol

Amygdala (telencephalon)

Central nucleus of amygdala (in response to homeostatic challenges). Medial nucleus of amygdala (in response to psychogenic challenges). Amygdala activates SNS and HPA axis.

Subgenual Anterior Cingulate Cortex

Indirect activation

Activation of stress response

Activation of amygdala and subgenual anterior cingulate cortex activates the SNS and HPA axis

HPA axis

ACTH and Cortisol peaks shortly then goes down

HPA negative feedback

Need to bring it back down as body can’t handle the stress response for a long time. Direct negative feedback of cortisol on the PVN via glucocorticoid receptors

HPA negative feedback - hippocampus

Indirect inhibition. Contains many MR and GR. intermediate-term feedback, returns psychogenic stress response back to baseline

HPA negative feedback - Dorsal Anterior Cingulate Cortex

Indirect inhibition, GR receptors, early and intermediate-term feedback

Major depressive disorder symptoms

Depressed, sleeping problems, lethargy, change in appetite. Had to be persistent and not easily explained by outside factors. Twice as common in women

Brain features of MDD

Depletion of noradrenaline from locus coeruleus

depletion of serotonin from raphe nuclei

Depletion of dopamine from ventral tegmental area to nucleus accumbens and prefrontal cortex

MDD and HPA axis

Dysregulated HPA axis. Both pathological increases and decreases in cortisol can lead to depressive symptoms

Chronic stress positive feedback

Amygdala stimulates HPA axis, glucocorticoids activate the locus coeruleus. LC has noradrenergic projections which activate the amygdala

Chronic stress reduces negative feedback

Repeated stimulation by glucocorticoids reduced the sensitivity of receptors in the hippocampus.

Chronically high glucocorticoids also damage hippocampal neurons, leading to further reduction of negative feedback in long term

MDD and sleep

REM entered too early, REM deprivation has long term effects. Many anti-depressant suppress REM

Role of monoamine in depression

Reserpine (monoamine antagonist) induces depression. Lower levels of 5-HIAA in cerebrospinal fluid

SSRIs

All very lipophilic, only work after several weeks. First 2 weeks is adaption of auto-receptors. Initially, SSRIs increase 5HT levels in synapse by blocking reuptake channels. Autoreceptors respond to this and reduce 5HT through negative feedback.

Ketamine

Dissociative anaesthetic and analgesic.

Ketamine short term effects

Low doses - lightness and euphoria, disconnection from thoughts and world

High doses - mind/body disconnect, hallucinations

Ketamine physiological action

NMDA-R antagonist

Ketamine as antidepressant

New synapse formation in anterior Cingular cortex, course of several doses per week for a few weeks.

Doesn’t last more than a few months

Ketamine long term effects

Memory/Cognitive problems, bladder and kidney damage, abdominal cramps

Ketamine addictiveness

Physical - tolerance build up, withdrawal symptoms include psychotic features

Psychological - less known but NMDA-R antagonists can influence dopamine release in nucleus accumbens

Anxiety disorders

Extreme worry, fear and chronic stress. Often do morbid with depression. To be a disorder, has to last more than 6 months. Twice as common in women

Benzodiazepines

Sedatives and anxiolytics eg Valium, Xanax. Lipid solubility varies

Benzodiazepines clinical use

Sleeping pills (against insomnia)

Anxiolytic (against anxiety)

Recovery from withdrawal

Anticonvulsant

Short term effects

Sleepiness, reduction of anxiety, anterograde amnesia, mental confusion, muscle relaxation

Benzodiazepines physiological action

Facilitation of GABA-A receptors (increases inhibitory processes)

Benzodiazepines long term effects

Mental confusion

Dementia

Learning problems

Benzodiazepines addictiveness

Physical - withdrawal (anxiety, insomnia, agitation)

Physiological - GABA-A receptors in ventral receptors in ventral tegmental area and nucleus accumbens

Autonomic nervous system

Controls involuntary functions and responds to stress

Sympathetic nervous system

Triggers flight - fight response during stress

Parasympathetic nervous system

Restores body to calm state after stress by slowing down bodily functions

Adrenaline

Prepares body to respond to threat by increasing heart rate

Noradrenaline

Involved in arousal and alertness during stress

Adrenal medulla

Inner part of the adrenals goand that release adrenaline and noradrenaline during stress

Catecholamines

Group of stress related hormones including adrenaline, noradrenaline and dopamine

Paraventricular nucleus

Hypothalamic region that helps regulate stress response through hormone release

Glucocorticoids

Stress hormones (cortisol) that help body manage energy use and immune function

Adrenals cortex

Outer part of adrenal gland that produces glucocorticoids in response to stress

Corticotropin releasing factor

Hormone released by hypothalamus that initiates stress hormone cascade

Adrenocorticotropic hormone (ACTH)

Hormone from pituitary gland that stimulates cortisol release from adrenal cortex

Anterior pituitary gland

Releases ACTH during stress to activate the adrenal cortex

glucocorticoids receptors

Bind cortisol and help regulate the stress response by providing negative feedback

Mineralocorticoid receptors

Bing corticosteroid and help maintain baseline stress hormone levels

5-HIAA

Metabolite of serotonin, measured to assess serotonin function

Cerebrospinal fluid

Surround brain and spinal cord, measure brain chemical levels

Autoreceptors

Regulate NT release by providing feedback to neuron