W11 - Depression Flashcards
(35 cards)
What is Psychiatry?
Psychiatry
– Branch of medicine, diagnosis & treatment of
disorders that affect the mind or psyche
– Disorder of thoughts, moods and fears
considered outside reach of neuroscience
– Now hope that neuroscience will help identify
causes and treatment of mental illness
* Anxiety, depression, schizophrenia
What happens with mental illness?
- Human behaviour
– Product of brain activity - Brain
– Product of genetics and environment
– Experience (trauma / disease)
– Genetic make-up and experience can interact,
making a person more or less susceptible to
future experience
What are some facts about mental illnesses?
- In 2020, of the estimated 971 million people worldwide living with mental or behavioral
disorders, including drug or alcohol dependent, schizophrenia, and depression
(WHO,2020) - 1 in 4 British adults experience at least one diagnosable mental health problem in any
one year (The Office for National Statistics Psychiatric Morbidity report) - One in ten children between the ages of one and 15 has a mental health disorder (The
Office for National Statistics Mental Health in children and young people in Great Britai ) - Depression affect 1 in 5 older people living in the community
- More than 70% of the prison population has two or more mental health disorders (Social
Exclusion Unit quoting Psychiatric Morbidity Among Prisoners In England And Wales)
What is happening with antidepressants?
Millions of prescriptions for SSRIs are written up in the UK each year, but a major study says they’re no better than placebo.
What now for the citizens of Prozac Nation?
-Around 65 million prescriptions of antidepressants given in the UK every year.
What are the types of depression?
- Characteristics of Affective Disorders
– Disorders of mood rather than thought / cognition
– Most common is depression
– Major cause of premature death and disability - 1) Unipolar Depression
– Mood swings in one direction
– Most common depressive illness
– 75% cases REACTIVE (induced by environmental factors)
– 25% cases ENDOGENOUS (genetic) - 2) Bipolar Depression
– Oscillation between depression and mania
– Mania: excessive exuberance, enthusiasm, self confidence, impulsive actions, aggression, irritability, delusions of grandiose
– Type I: More mania episodes with or without depression (1%pop)
– Type II:Hypomania and always episodes of major depression (0.6%)
– Onset usually in adult life
– Strong hereditary tendency (no genes found yet)
What is a major depressive episode? What are some characteristics?
DSM V - Major Depressive Episode
Five (or more) of the following symptoms have been present during the same 2-week
period and represent a change from previous functioning; at least one of the symptoms
is either (1) depressed mood or (2) loss of interest or pleasure.
*Note: Do note include symptoms that are clearly due to a general medical condition, or
mood-incongruent delusions or hallucinations.
1) Depressed mood most of the day, nearly every day (in children irritable mood)
2) Markedly diminished interest or pleasure in all, or almost all, activities most of the
day, nearly every day.
3) Significant weight loss when not dieting or weight gain, or decrease or increase in
appetite nearly every day.
4) A slowing down of thought and a reduction of physical movement (observable by
others, not merely subjective feelings of restlessness or being slowed down).
5) Fatigue or loss of energy nearly every day.
6) Feelings of worthlessness or excessive or inappropriate guilt nearly every day.
7) Diminished ability to think or concentrate, or indecisiveness, nearly every day.
8)Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.
What is the symptomology: ICD-10?
- Emotional symptoms (Q)
– Apathy, pessimism, negativity
– Low self esteem, feeling guilty
– Loss of motivation
– Indecisiveness - Biological symptoms (Q)
– Reduced activity
– Loss of libido
– Sleep disturbance
– Loss of appetite
What is Co-morbidity?
General medical conditions in which you often find depression
* Terminal illness
* Chronic illness (e.g. chronic pain)
* Thyroid dysfunction
* Neurological disease
* Stroke
* Drug abuse
* Parkinson’s disease
* anxiety
What is a major theory of depression?
Monoamine Theory (Schildkraut, 1965)
* Evidence For
– Overall reduced activity of central noradrenergic and / or serotonergic systems
– Reserpine depletes brain of NA and 5-HT
induces depression
– Main antidepressant drugs increased [amines] in brain (Q devise drugs to treat depression)
What is evidence against the monoamine theory?
- Evidence Against
– Difficult to show deficits in 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 increase in amines acute (secondary adaptive changes more important)
– Some antidepressants weak / no effect on amine uptake (e.g trazodone)/no increase in 5HT and NA but antidepressants!
– Cocaine blocks amine uptake but has no antidepressant effect
– Decrease in 5HT in dipolar linked to aggression rather than depression
What is the neuroendocrine theory?
NAergic & 5-HT neurons input to
hypothalamus
*Hypothalamus releases corticotropin-
releasing hormone (CRH)
*CRH acts on pituitary – release of
adrenocorticotrophic hormone (ACTH)
*Cortisol release from adrenal cortex in
response to increase ACTH in blood - in time this may increase the basal levels of cortisol.
Neuroendocrine
– CRH – behavioural effects mimic some depression symptoms
– Evidence of hyperactivity of HPA in depressed patients
* increased [cortisol]plama in depressed patients
* increased [CRH] in 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 people to mental health conditions (diathesis)
What is the underlying mechanism for children being predisposed to depression? How do genetics interact with the environment?
The HPA axis is regulated by the amygdala and the hippocampus.
Amygdala -> activates HPA = increase cortisol
Hippocampus -> suppress HPA = decreased cortisol
*Decreased’d hippocampal feedback in depression
*Decreased’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 increased in
expression of glucocorticoid
receptor gene
*increased in glucocorticoid receptors in hippocampus
*SSRIs increased glucocorticoid receptors in the hippocampus
In rats, pups neglected by mother, has lower levels of glucocorticoid receptors. This means HPA would not be able to activate hippocampus.
What is the neuroplasticity and neurogenesis theory of depression?
- Neuroplasticity & Neurogenesis
– Evidence of neuronal loss and decreased 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). (Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory.)
– Increase in Glutamate in Cx of depressed people (NMDA antagonists potential for depression treatment e.g. ketamine)
What is the monoamine theory of depression?
Monoamine main theory of depression but needs to be extended
– Due to imbalances between NT (Monoamines, DA, Ach, CRF, CORT ect) producing long term alterations in gene expression, growth factors and NT (upregulation 5HT, NA receptors, HPA
hyperfunction and some neuronal loss)
What is brain atrophy in depression?
In fMRIs, there seem to be a loss of neurones in the hippocampus associated in depression.
What are possible treatments for depression?
Cognitive Behavioural Therapy
- Breaks the cycle of negative thoughts, behaviours and emotions. This is also psychosocial support.
Pharmacotherapy
What are psychological treatments for depression?
- Cognitive Behavioural Therapy: based on helping depressed individuals to recognise and change their negative cognitive processes and thus improve their mood and their counterproductive behaviours
- Interpersonal Therapy: assumes that depression is multi-factorial but that interpersonal difficulties play a central role in maintaining depressive symptoms
What are possible Pharmacological treatments for depression?
- Tricyclic antidepressants
- Monoamine oxidase inhibitors
- Selective serotonin reuptake inhibitors
- NICE recommends SSRIs for the pharmacological treatment
of depression - Selectively inhibit the reuptake of serotonin in the synapse - less side effects.
- Because they are more selective in the molecules to which
they bind, they do not bind to receptors on other classes of
neurons (fewer side effects)
What are the long term neurochemical effects of AD?
- 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 (a2, 5HT2c, 5HT3)
- Downregulation a2, 5HT1A, b1, b2, 5HT2A, 5HT3
What do MAOIs do?
*MAOI s increase [NA/5-HT]cytoplasm
*increase [NA/5-HT]cytoplasm increase leakage of amine
*increase [NA/5-HT] in synaptic cleft
The neurones contain serotonin, which is released, acts on receptors. The excess of Noradrenaline will go inside the neurones via the noradrenaline transporters. These are broken down via Monoamine oxidase enzyme. Action of NA is terminated.
Same thing with serotonin. Excess of serotonin outside will enters the neurone via 5-HT transporters, which will get broken down via MAO enzyme.
Depression caused by low levels of NA and 5-HT.
Antidepressants can fix this:
-Block Monoamines - without it, the NA and 5-HT will accumulate and release into the synaptic cleft.
What are the effects of MAOIs?
- Inhibition of MAO A correlates with AD activity
- MAO-A 5-HT > NA
- MAOIs rapidly increase [5-HT] > [NA] > [DA]
- Increase NA=>Incr euphoria=>Incr motor activity
- Early drugs e.g. phenelzine & isocarboxazid,
irreversible and nonselective (Q. Why problem?) - Downregulation of post and presynaptic autoreceptors. a2, 5HT1A, b1, b2, 5HT2A, 5HT3
How are MAO inhabitors a problem?
*Associated with food and drug interactions–
-Tyramine (in cheese and wine) acts as indirect sympathomimetic and increase NA release
– Excess NA destroyed by MAO – if blocked NA will accumulate
– NA accumulation (Increase headache, intracranial haemorrhage => elevation in BP => severe hypertension)
– MAOIs not specific – reduce metabolism of opioid analgesics and alcohol
After the case with cheese and wine etc, how did they make MAO-I reversible?
Reversible MAOIs (RIMA) e.g. moclobemide
– Accumulation of NA displaces the RIMA allowing
degradation of excess NA
– RIMAs safer and selective RIMAs (e.g moclobemide) better tolerated (no major side effects)
What is the Treatment: MAOIs Cheese Effect?
MAO in gut is inhibited
Dietary amines e.g. 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
