Lecture 9: Depression

Question 1

What is depression?

Answer 1

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

Question 2

What is anhedonia?

Answer 2

Loss of the capacity to experience pleasure

Question 3

What are affective disorders?

Answer 3

Mood disorders/ disorders of emotion

Depression is an affective disorder (any psychiatric disorder characterised by a disturbance of mood or emotion)

Question 4

Major categories of affective disorders:

Mania

Answer 4

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

Question 5

Major categories of affective disorders:

‘polar Disorders

(2 kinds)

Answer 5

2 main kinds:

1. Bipolar Affective Disorder: Depressive patients who experience periods of mania, there is no sex difference in the incidence
2. 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

Question 6

Depression categories

Answer 6

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

Question 7

Causal Factors in Affective Disorders:

Genetic Factors

Answer 7

-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

Question 8

Causal Factors in Affective Disorders:

Stress

Answer 8

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

Question 9

Discovery of Antidepressant Drugs:

4 types of antidepressant drugs

Answer 9

4 major classes of drugs used in treatment of affective disorders:

1. Monoamine oxidase inhibitors
2. Tricyclic antidepressants
3. Selective monoamine reuptake inhibitors
4. Mood stabilisers

Question 10

Discovery of Antidepressant Drugs:

1. Monoamine oxidase inhibitors

Answer 10

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

Question 11

Discovery of Antidepressant Drugs:

2. Tricyclic antidepressants

Answer 11

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

Question 12

Discovery of Antidepressant Drugs:

3. Selective monoamine reuptake inhibitors

Answer 12

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

Question 13

Discovery of Antidepressant Drugs:

4. Mood stabilisers

Answer 13

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)

Question 14

Effectiveness of Drugs in the Treatment of Affective Disorders:

Answer 14

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

Question 15

Brain Pathology and Affective Disorders:

Answer 15

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

Question 16

Theories of Depression:

2 theories

Answer 16

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

1. Monoamine theory of depression
2. Diathesis-stress model of depression

Question 17

Theories of Depression:

1. Monoamine theory of depression

Answer 17

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

Question 18

Theories of Depression:

2. Diathesis-stress model of depression

Answer 18

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

Question 19

What is a diathesis?

Answer 19

A heritable genetic susceptibility

Question 20

Treatment of Depression with Brain Stimulation:

Answer 20

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

Question 21

Antidepressant Effect of Sleep Deprivation and Exercise:

Answer 21

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

Question 22

What is neurogenesis?

Answer 22

The development of new neurons