NEURO: Depression Flashcards
(40 cards)
Neurology
Psychiatry
What are psychiatric conditions caused by?
branch of medicine, diagnosis & treatment of nervous system disorders (e.g. MS, paralysis)
branch of medicine, diagnosis & treatment of disorders that affect the mind (or psyche)
an imbalance in neurotransmitters/chemical changes in the brain
What is depression?
There are multiple ways to define it:
DEPRESSIVE DISORDER: a low state marked by significant levels of sadness, lack of energy, low self-worth, guilt or related syndromes
MAJOR DEPRESSIVE DISORDER: severe pattern of depression that is disabling and is not caused by factors such as drugs or a general medical condition
DYSTHYMIC DISORDER (DYSTHYMIA): similar to major depressive disorder but less severe/disabling and more long-lasting (chronic)
What type of disorder is depression?
Treatments of depression
affective (mood) disorder
Non-pharmacological Treatment
-e.g. cognitive behavioural therapy
Pharmacotherapy
-antidepressants
Types of depression
Unipolar Depression: · Mood swings in one direction · Most common depressive illness · 75% cases REACTIVE (induced by environmental factors) · 25% cases ENDOGENOUS (genetic)
Bipolar Depression:
· Oscillation between depression and mania
· Mania: excessive exuberance, enthusiasm, self-confidence, impulsive actions, aggression, irritability, delusions of grandiose
· Less common
· Onset usually in adult life
· Strong hereditary tendency (no genes found yet)
Diagnosing depression
Diagnosis is difficult
- Wide variety of symptoms that patients can report
- Difficult to know when a normal fluctuation in mood becomes depression
- No single objective test to establish diagnosis
The diagnosis of depression is based on the interview with the patient, and if these patients are exhibiting 5 of the following symptoms during the same 2 week period. At least one of the symptoms is either:
- Depressed mood
- Loss of interest or pleasure
What are some symptoms of depression?
EMOTIONAL SYMPTOMS (Q):
- negativity
- low self-esteem
- loss of motivation
- indecisiveness
BIOLOGICAL SYMPTOMS (Q):
- reduced activity
- loss of libido
- sleep disturbance
- loss of appetite
Who gets depression?
GENDER:
- depression affects around twice as many females as males
- lifetime prevalence of major depression: 10-25 % for women, 5-12 % for men
AGE:
- 1st episode of depression is usually late adolescence or early adulthood
- age of onset has been decreasing in recent years
- is life now more stressful?
- are we just diagnosing more people with depression?
Suicide
- Suicidal thoughts are common among depressed patients
- 20% of depressed individuals will attempt suicide
- 10% of severe depressives will commit suicide
Co-morbidity
- depression is often comorbid with other psychiatric conditions (e.g. withdrawal from drugs of abuse)
Co-morbidity of Depression
Depression has co-morbidity with many other conditions:
- terminal illness
- chronic illness (e.g. chronic pain)
- thyroid dysfunction (hypothyroidism)
- neurological disease
- stroke
- drug abuse
- Parkinson’s disease
- Anxiety
Depression and anxiety are often co-morbid.
>Manifest more severe symptoms
>Less responsive to treatment
>Higher risk of suicide
Causes of depression
Genetic Predisposition
Environmental Factors
- loss
- social isolation
- environmental stressors
Monoamine Theory of Depression
Evidence supporting monoamine theory of depression
According to the monoamine theory of depression, depression is caused by low levels of noradrenaline and serotonin (5-HT) in the brain.
- Reserpine (depletes noradrenaline and serotonin from brain) induces depression when injected into mouse brain
Evidence against monoamine theory of depression
- Difficult to show deficits and functioning of noradrenaline and serotonin in the brain
- Most antidepressant drugs take several weeks for therapeutic effect but increase in monoamines is acute (secondary adaptive changes more important)
- Some antidepressants are weak/no effect on monoamine uptake (e.g. trazodone), with no increase in serotonin and noradrenaline
- Cocaine blocks monoamine uptake but has no antidepressant effect
- Decrease in serotonin in bipolar linked to aggression rather than depression
Neuroendocrine theory of depression
According to the neuroendocrine theory of depression, depression is caused due to a hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA axis).
What activates the HPA axis?
stressful stimuli:
- noradrenergic and serotonergic neurones input to the hypothalamus
- hypothalamus release corticotropin-releasing hormone (CRH)
- CRH acts on pituitary- release of adrenocorticotrophic hormone (ACTH)
- cortisol release from the adrenal cortex in response to an increase in ACTH in blood
Evidence to suggest the neuroendocrine theory of depression is correct
- CRH has behavioural effects which mimic depression symptoms
- Increased cortisol in plasma in depressed patients
- Increased CRH in CSF
HPA axis in depression
If you suffer from depression, the HPA axis is hyperactive. Therefore, the basal cortisol levels will be higher.
There is also reduced hippocampal feedback in depressed patients, evidently by:
- Reduced hippocampal glucocorticoid (cortisol) receptors
What causes the hyperactivity of the HPA axis?
genes and environment
What can cause depression?
GENETIC PREDISPOSITION?
- General population: 3.2%
- First degree relatives of patients: 20%
- Monozygotic twins: 40-50%
ENVIRONMENTAL FACTORS?
- Loss
- Environmental stressors
- Social isolation
Amygdala and HPA Axis
Activation of the amygdala induces the activation of the HPA axis to induce cortisol release.
*hyperactivity of amygdala causes increased HPA activity and an increase in cortisol, causing depression.
Hippocampus and HPA Axis
· Glucocorticoid receptors in the hippocampus detect increased cortisol levels. Activation of these receptors sends a signal to the HPA axis to inhibit CRH neurones in the hypothalamus, and therefore inhibit cortisol release.
*hypo-activity of the hippocampus causes increased activity of the HPA axis, and subsequently an increase in cortisol (check with Vanessa)
Glucocorticoid receptor gene expression
Regulated by early sensory experience:
· Tactile stimulation (e.g. hugging babies) just after birth activates 5-HT (serotonergic) pathways to the hippocampus.
· 5-HT triggers long-lasting increase in expression of glucocorticoid receptor gene
· Increase in glucocorticoid receptors in the hippocampus.
· Glucocorticoid receptors negatively regulate cortisol release by inhibiting CRH neurones in the hypothalamus
· Increased inhibition of HPA axis, decreasing cortisol
· Decreased cortisol means babies don’t get stressed (because increased cortisol causes depression)
Environmental stressor which affects glucocorticoid receptor expression
- Trauma at an early developmental age will reduce glucocorticoid receptor expression, reducing levels of glucocorticoid receptors in the hippocampus.
- This results in decreased hippocampal feedback, less activation of the hippocampus, and as a result less inhibition of the HPA axis (less inhibition of CRH neurones).
- HPA axis, therefore, increases levels of cortisol, which causes detrimental gene transcription response and subsequently causes mental health conditions later in life
How does trauma decrease glucocorticoid receptors?
via epigenetic modulations
-environment and genetics are therefore interacting to cause depression
Effect of SSRIs on glucocorticoid receptors
SSRIs increase glucocorticoid receptors in the hippocampus, and therefore SSRIs reduce depression by enhancing the inhibition of the HPA axis by the hippocampus.
What is the neuroplasticity & neurogenesis theory of depression?
Depression is caused by neuronal apoptosis (excitotoxicity) and decreased neuronal activity in the hippocampus and prefrontal cortex (decision-making centres)
Neurones are killed by the excess release of glutamate, which causes excitotoxicity and cell death, resulting in depression.
*evidence showed there is less neuronal loss with antidepressant drugs
