Depression

Question 1

What is Psychiatry?

Answer 1

• Branch of medicine, diagnosis & treatment of disorders that affect the mind or psyche
• Disorder of thought, moods and fears considered outside the reach of neuroscience
• Now hope that neuroscience will help identify causes and treatment of mental illnesses (Anxiety, scz, depression)

Question 2

What do you think of mental illness and the brain?

Answer 2

• Human behaviour is the product of the brains activity
• The brain is the product of genetics and environment
• Experience
• Genetic make-up and experience can interact, making a person more or less susceptible to future experience

Question 3

Give some facts about mental illnesses

Answer 3

• In 2020, estimated about 971 mil ppl living with mental or behavioural disorders
• 1 in 4 British adults experience at least one diagnosable mental health problem in any year
• Depression affects 1 in 5 older people living in the community
• More than 70% of prison population has two or more mental health disorders

Question 4

Describe the characteristics of affective disoders

Answer 4

• Disorders of mood rather than thought/cognition
• Most common is depression
• Major cause of premature death and disability

Question 5

List the 2 different types of depression

Answer 5

• Unipolar Depression
• Bipolar depression

Question 6

Describe unipolar depression

Answer 6

• Mood swings in one direction
• Most common depressive illness
• 75% cases REACTIVE (induced by environmental factors)
• 25% cases are ENDOGENOUS (genes)

Question 7

Describe Bipolar depression

Answer 7

• Oscillation between depression and mania
• Mania: Excessive exuberance, enthusiasm, self confidence
• Type 1: More mania episodes with or without depression
• Type 2: Hypomania and always episodes of major depression (0.6%)
• Onset usually in adult life
• Strong hereditary tendency (no genes found yet)

Question 8

What is the criteria for being diagnosed with depression?

Answer 8

• Depressed mood most of the day, nearly everyday
• Markedly diminished interest or pleasure in all, or almost all activities most of the day
• Significant weight loss when not dieting or weight gain or decrease/increase in appetite nearly everyday
• A slowing down of thought and a reduction of physical movement
• Fatigue or loss of energy nearly everyday
• Feelings of worthlessness or excessive or inappropriate guilt nearly everyday
• Dimished ability to think or concentrate or indecisiveness

Question 9

What is required in order to be diagnosed with depression?

Answer 9

• 5 or more of the following symptoms have to be present during the same 2 week period and represent a change from the previous functioning
• Atleast one of the symptoms being a depressive mood or loss of interest

Question 10

What can the symptoms of depression be split into?

Answer 10

• Emotional symptoms
• Biological symptoms

Question 11

List some biological symptoms of depression

Answer 11

• Loss of appetite
• Loss of sleep
• Loss of libido
• Reduced activity

Question 12

List some Emotional symptoms of depression

Answer 12

• Apathy, Negativity
• Low self esteem, feeling guilty
• Loss of motivation
• Indecisiveness

Question 13

What are the other medical conditions that can coincide with depression (Co-morbidity)?

Answer 13

• Terminal illness
• Chronic illness
• Thyroid dysfunction
• Stroke
• Drug abuse
• Parkinson’s disease
• Anxiety

Question 14

What is the monoamine theory of depression?
Discuss evidences for the theory

Answer 14

Evidence for
- Overall reduced activity of central noradrenergic and/or serotonergic systems
- Reserpine depletes brain of NA and 5 HT induces depression
- Main antidepressants drugs (amines) in brain

Question 15

What is the monoamine theory of depression?
Discuss evidences against the theory

Answer 15

• Difficult to show deficits in the brain (NA) & (5-HT) and functioning results from CSF, plasma in depressed individuals respond better to one AD than another
• Most antidepressant drugs take several weeks for therapeutic effect but ã in amines acute
• Some antidepressants weak/no effect on amine uptake/ no increase in 5HT or NA but antidepressants
• Cocaine blocks amine uptake but has no antidepressant effect
• Decrease in 5HT in dipolar linked to aggression rather than depression

Question 16

What is the neuron doctrine theory of depression?

Answer 16

• NAergic & 5HT neurons input to hypothalamus
• Hypothalamus releases corticotropin releasing hormone
• CRH acts on pituitary, release of adrenocorticotrophic hormone
• Cortisol release from adrenal cortex in response to ACTH in blood

Question 17

What is the evidence for the neuron doctrine theory of depression?*

Answer 17

• There is evidence of hyperactivity of HPA in depressed patients
• Corticol plasma in depressed patients
• [CRH] I’m the cerebrospinal fluid
• There is clear evidence that genes and environment can contribute to this hyperactivity and as such could offer an explanation for how genes x environment interaction can predispose ppl to mental health conditions

Question 18

Describe the neuroendocrine in more detail

Answer 18

• ‘d hippocampal feedback in depression
• ’d glucocorticoid receptors (cortisol receptors) in hippocampus
• Glucocorticoid receptor gene expression regulated by early experience
• Tactile stimulation just after birth activates 5-HT pathways to hippocampus
• 5-HT triggers long-lasting  in expression of glucocorticoid receptor gene
•  in glucocorticoid receptors in hippocampus
• SSRIs  glucocorticoid receptors in the hippocampus

Question 19

Describe the neuroplasticity & neurogenesis theory of depression

Answer 19

• Evidence of neuronal loss and  neuronal activity in hippocampus and prefrontal cortex (decision making centres)
• Antidepressants and electroconvulsive therapy (ECT) promote neurogenesis in these regions
• 5-HT promotes neurogenesis during development (BDNF)
• Increase in Glutamate in Cx of depressed people (NMDA antagonists potential for depression treatment e.g. ketamine)

Question 20

Describe the brain activity in depressed patients

Answer 20

Depressed patients tend to have lower levels of activity’s in all areas of the brain

Question 21

List and describe the different types of treatments for Depression

Answer 21

• Cognitive behavioural therapy (CBT): Based on helping depressed individuals to recognise and change their negative cognitive processes and thus improve their mood & their counterproductive behaviours
• Pharmacotherapy: Assumes that depression is multi factorial but that interpersonal difficulties play a central role in maintaining depressive symptoms

Question 22

List some pharmacological treatment

Answer 22

• Tricyclic antidepressants
• Monoamine oxidase inhibitors
• Selective serotonin reuptake inhibitors

Question 23

Describe the use of SSRI’s

Answer 23

• NICE recommends SSRI’s for the pharmacological treatment of depression
• Selectively inhibit the reuptake of serotonin in the synapse
• Because they’re more selective in the molecules to which they bind, they do not bind to receptors on other classes of neurons

Question 24

List some long term neurochemical antidepressants

Answer 24

• Monoamine Oxidase inhibitors (MAOIs)
• Tricyclic Antidepressant Drugs (TCAs)
• Selective Serotonin Re-uptake Inhibitors (SSRIs)
• Other mixed 5HT/NA reuptake inhibitors (SNRIs)
• NA reuptake inhibitors
• Monoamine receptor antagonists
• Downregulation a2, 5HT1A, b1, b2, 5HT2A, 5HT3

Question 25

Describe the mechanism of action of MAOI’s

Answer 25

- Inhibition of MAO A correlates with anti depressive activity - MAO-A 5-HT > Na - MAOIs rapidly increase [5HT] > [Na] > [DA] - Increase in Na -> increased Euphoria -> increase motor activity

Question 26

Describe MAO I

Answer 26

- Associated with food and drug interactions - Tyramine acts as indirect sympathomimetic and increase Na release - Excess Na destroyed by MAO, if blocked then Na will accumulate - Na accumulation increases headaches, intracranial haemorrhage-> elevation in BP -> severe hypertension - MAOI’s not specific, reduce metabolism of opioid analgesics and alcohol

Question 27

Describe Reversible MAOI’s (RIMA)

Answer 27

- One example is moclobemide - Accumulation of NA displaces the RIMA allowing degradation of excess NA - RIMAs sager and selective RIMAs better tolerated

Question 28

What is a side effect of MAOI’s?

Answer 28

- MAO is inhibited in the gut - Dietry amines such as tyramine can get into the circulation - Foods include cheese,yoghurt,meat,wine,yeast products - All contain high concentrations of tyramine - Tyramine acts as an indirect sympathomimetic displacing noradrenaline from vesicles

Question 29

Describe the mechanism of action of Tricyclic antidepressants

Answer 29

- Main therapeutic affects are: Na reuptake inhibitor, 5HT reuptake inhibitor - Initially increase [NA] & [5HT] in synaptic cleft - Chronic treatment down regulation of (B1) & 5HT2 - ⍺2, 5-HT1A/1D (autoR) - Also affect mACh, HR, 5HTR