Lecture 9: Depression Flashcards
What is depression?
Depression is a normal reaction to grievous loss e.g. loss of a loved one, loss of self-esteem or loss of health – everyone experiences this feeling – CLINICAL DEPRESSION=/ NORMAL DEPRESSION
Some individuals’ tendency towards depression is out of proportion… these individuals repeatedly fall into despair, experience anhedonia (loss of the capacity to experience pleasure) often for no apparent reason
Can be so extreme fail to meet essential daily requirements (job, maintain social contacts eat, personal hygiene, sleep disturbance, suicide) = clinical depression/major depressive disorder
What is anhedonia?
Loss of the capacity to experience pleasure
What are affective disorders?
Mood disorders/ disorders of emotion
Depression is an affective disorder (any psychiatric disorder characterised by a disturbance of mood or emotion)
Major categories of affective disorders:
Mania
Mania: characterised by overconfidence, impulsivity, distractibility and high energy
Mild Mania: People are talkative, energetic, impulsive, positive and very confident, very effective at certain jobs, can be great fun to be with
Extreme Mania: Serious clinical problem, person awakens in state of unbridled enthusiasm with outflow of incessant chatter that careens nonstop from topic to topic, no task is too difficult, no goal is unattainable –> confidence and grandiosity coupled with high energy, distractibility and a leap before you look impulsiveness results in a continual series of disasters –> leaves behind trail of unfinished projects, unpaid bills and broken relationships
Major categories of affective disorders:
‘polar Disorders
(2 kinds)
2 main kinds:
- Bipolar Affective Disorder: Depressive patients who experience periods of mania, there is no sex difference in the incidence
- Unipolar Affective Disorder (Depression): Depressive patients who do not experience periods of mania
Depression often divided into 2 categories:
• Reactive Depression: Depression triggered by a negative experience (e.g. death of a friend, loss of a job)
• Endogenous Depression: Depression with no apparent cause
Depression categories
Depression often divided into 2 categories:
- Reactive Depression: Depression triggered by a negative experience (e.g. death of a friend, loss of a job)
- Endogenous Depression: Depression with no apparent cause
Causal Factors in Affective Disorders:
Genetic Factors
-Genetic factors contribute to differences among people in the development of affective disorders
Twin studies of affective disorders suggest a concordance rate of about 60% for identical twins and 15% for fraternal
- Concordance rate for bipolar disorders tend to be higher than those for unipolar disorders
- No particular gene has been linked to affective disorders
Causal Factors in Affective Disorders:
Stress
Stress has role in aetiology of depression, stressful experiences can trigger attacks in people already suffering from depression
Stress often increases susceptibility to PTSD rather than depression e.g. stress of a sexual assault
> Affective disorders caused by timing:
- SAD (Seasonal Affective Disorder) in which attacks of depression and lethargy typically recur every winter, attacks triggered by reduction in sunlight, light therapy effective in reducing symptoms
- Postpartum Depression: Intense sustained depression experienced by some women after they give birth, diagnosis requires depression for at least 1 month, usually lasts no longer than 3, occurs in about 10% of deliveries
Discovery of Antidepressant Drugs:
4 types of antidepressant drugs
4 major classes of drugs used in treatment of affective disorders:
- Monoamine oxidase inhibitors
- Tricyclic antidepressants
- Selective monoamine reuptake inhibitors
- Mood stabilisers
Discovery of Antidepressant Drugs:
- Monoamine oxidase inhibitors
Ipronizid (1957) – first antidepressant drug,
As a monoamine agonist it increases levels of monoamines (norepinephrine and serotonin) by inhibiting the activity of monoamine oxidase (MAO), the enzyme that breaks down monoamine neurotransmitters in the cytoplasm (cellular fluid) in the neuron
MAO inhibitors have several side effects, Cheese Effect: Cheese, wine and pickles are high in tyramine, potential elevator of blood pressure. Usually not a problem because tyramine is quickly metabolised by MAO. BUT people who take MAO inhibitors run risk of strokes caused by surges in blood pressure
Discovery of Antidepressant Drugs:
- Tricyclic antidepressants
Tricyclic – chemical structure has three rings of atoms
Imipramine initially thought to be an antischizophrenic drug
- Block reuptake of serotonin and norepinephrine thus increasing their levels in the brain, safer alternative to MAO inhibitors
Discovery of Antidepressant Drugs:
- Selective monoamine reuptake inhibitors
SSRI’s (1980’s) act as agonists (substances which initiate a physiological response when combined with a receptor) that exert agonistic effects by blocking the reuptake of serotonin from synapses e.g. Fluoxetine (Prozac)
Prozac’s structure, while a slight variation in structure of imipramine and other tricyclic antidepressants, is no more effective than imipramine in treating depression
SSRI’s are popular as they have few side effects and act against wide range of psychological disorders in addition to depression (lack of self-esteem, fear of failure, excessive sensitivity to criticism, inability to experience pleasure)
Increased suicide rate with SSRI’s – no evidence but received lots of media coverage
Selective norepinephrine reuptake inhibitors (SNRI’s) e.g. Reboxetine have proven to be as effective as SSRI’s in treatment of depression
- Wellbutrin and Effexor also used against depression, block reuptake of more than one monoamine neurotransmitter
Discovery of Antidepressant Drugs:
- Mood stabilisers
Often drugs acted against depression in bipolar patients by triggering bouts of mania
–> Led to development of mood stabiliser drugs - act against depression without increasing mania or act against mania without increasing depression
Mechanism by which they work is unknown, are also effective in treatment of epilepsy
- Lithium – first drug found to act as mood stabiliser, lithium salts can produce extreme nausea, inactivity can be mistaken for calmness instead of sickness, lithium on manic patients seemed to have calming effect (treat mania without increasing depression)
Effectiveness of Drugs in the Treatment of Affective Disorders:
Lithium and carbamazepine are best for treating mania (anti-epileptic drug)
Lamotrigine (anti-epileptic drug) best for treating depression
MAO inhibitors, tricyclic antidepressants, selective monoamine reuptake inhibitors have about the same rates of effectiveness –> 50% of clinically depressed patients improved however control group showed 25% rate of improvement therefore only 25% of the depressed group were helped by the antidepressants
Harder to treat bipolar affective disorder with antidepressants than unipolar affective disorder
Brain Pathology and Affective Disorders:
MRI studies of bipolar patients have shown;
- Reductions in overall brain size and in the size of many different brain structures e.g. amygdala, striatum, hippocampus or prefrontal cortex have been reported for bipolar patients, however pattern is inconsistent, *suggests not all patients diagnosed as having bipolar affective disorder by current criteria suffer from the same disorder
- Amygdala and Anterior cingulate cortex are found to be abnormal in many structural and functional brain-imaging studies of affective disorders, even the connections between the 2 structures are disturbed in patients
Theories of Depression:
2 theories
Depression and mania often occur in the same patients – in those with bipolar affective disorder – suggests that the mechanisms of the two are closely related
- Monoamine theory of depression
- Diathesis-stress model of depression
Theories of Depression:
- Monoamine theory of depression
Depression is associated with underactivity at serotonergic and noradrenergic synapses
Largely based on fact that monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin-reuptake inhibitors and selective norepinephrine-reuptake inhibitors are all agonists of serotonin, norepinephrine or both
Support provided by autopsy studies, norepinephrine and serotonin receptors have been found to be more numerous in the brains of deceased clinically depressed individuals who had not received pharmacological treatment, implicates deficit in monoamine release:
- When an insufficient amount of a neurotransmitter is released at a synapse, there are usually compensatory increases in the number of receptors for that neurotransmitter (process of up-regulation)
- ->Support for monoamine theory of depression is weak, lots of patients are treated for depression with monoamine agonist drugs but few patients benefit substantially from them
Theories of Depression:
- Diathesis-stress model of depression
Some people inherit a diathesis (a genetic susceptibility) which is incapable of initiating the disorder by itself
Central idea of diathesis-stress model is that if susceptible individuals are exposed to stress early in their life, their systems become permanently sensitised and they overreact to mild stressors for the rest of their lives
- Support is largely indirect, based on finding that depressed people tend to release more stress hormones e.g. depressed individuals synthesise more hypothalamic corticotropin-releasing hormone and release more adrenocorticotropic hormone from the anterior pituitary and more glucocorticoids from the adrenal cortex
Evidence not convincing, no evidence of excessive early stress in lives of the majority of depressed patients even those who have experienced early sexual abuse (which cannot be confirmed, based on recollections of patients) –> no evidence of excessive early stress in lives of most depressed patients
What is a diathesis?
A heritable genetic susceptibility
Treatment of Depression with Brain Stimulation:
Chronic brain stimulation through an implanted electrode has significant therapeutic effect in depressed patients who had repeatedly failed to respond to conventional treatments
Lozano and Colleagues (2008):
- Implanted tip of a stimulation electrode into an area of the white matter of the anterior cingulate gyrus just ventral to the anterior end of the corpus callosum
- stimulator implanted under the skin delivered continual pulses of electrical stimulation that could not be detected by the patients
Found:
- 60% showed substantial improvements
- 35% largely symptom free
- maintained for at least 1 year –> careful double blind-evaluation of the effectiveness of the procedure must be performed before it can be recommended for wider use
Antidepressant Effect of Sleep Deprivation and Exercise:
More than 50% of depressed patients display dramatic improvements after one night of sleep deprivation – goes against findings that sleep disturbances (increases or decreases in amount of sleep) are often associated with depression
- Little therapeutic value
- Exercise has a beneficial effect on depression, increases adult neurogenesis in the hippocampus – as do various antidepressants
- Can be said that depression is associated with reductions in neurogenesis in the adult hippocampus
What is neurogenesis?
The development of new neurons
