Depressive Disorders

Question 1

Anhedonia

Answer 1

Loss of the capacity to experience pleasure

Question 2

Clinical depression(also known as major depressive disorder)

Answer 2

When people for 2 weeks or longer experience deep depression often with no apparent reason.

Question 3

Depression is often divided into two categories

Answer 3

• Reactive depression –> depression triggered by an obvious negative experience
• Endogenous depression –> depression with no apparent cause

Question 4

Comorbid

Answer 4

The tendency for two health conditions to occur together in the same individual

Question 5

There are two subtypes of major depressive disorder whose cause is more apparent because of the timing of the episodes.

Answer 5

• Seasonal affective disorder (SAD) –> in which episodes of depression and lethargy typically re­cur during particular seasons—usually during the winter months.
• Peripartum depression –> the in­tense, sustained depression experienced by some women during pregnancy, after they give birth, or both. Although estimates vary, the disorder seems to be associated with about 19 percent of pregnancies.

Question 6

Two lines of evidence suggest that the episodes of SAD are triggered by the reduction in sunlight.

Answer 6

• Incidence of the disorder is higher in Alaska (9 percent) than in Florida (1 percent) where the winter days are lon­ger and brighter.
• Light therapy (e.g., exposure to 15-­30 minutes of very bright light each morning) is often effective in reducing the symptoms of SAD.

Question 7

Five major classes of drugs have been used for the treat­ment of depressive disorders

Answer 7

• Monoamine oxidase inhibitors,
• Tricyclic an­tidepressants,
• Selective monoamine-­reuptake inhibitors,
• Atypical antidepressants,
• NMDA-­receptor antagonists.

Question 8

Iproniazid

Answer 8

Iproniazid is a monoamine agonist; it increases the levels of monoamines (e.g., norepinephrine and serotonin) by inhibiting the activity of monoamine oxidase (MAO).

Question 9

MAO inhibitors dangerous side effect (cheese effect)

Answer 9

Foods such as cheese, wine, and pickles contain an amine called tyramine, which is a potent elevator of blood pres­sure. Normally, these foods have little effect on blood pres­sure because tyramine is rapidly metabolized in the liver by MAO. However, people who take MAO inhibitors and consume tyramine-­rich foods run the risk of stroke caused by surges in blood pressure.

Question 10

Monoamine oxidase

Answer 10

The enzyme that breaks down monoamine neurotransmit­ters in the cytoplasm (cellular fluid) of the neuron.

Question 11

Tricyclic antidepressants

Answer 11

So named because of their antidepressant action and because their chemical structures include three rings of atoms. Tricyclic antidepressants block the reuptake of both sero­tonin and norepinephrine, thus increasing their levels in the brain. They are a safer alternative to MAO inhibitors.

Question 12

Imipramine

Answer 12

The first tricyclic antidepres­sant, was initially thought to be an antipsychotic drug. However, when its effects on a mixed sample of psychiat­ric patients were assessed, it had no effect against schizo­phrenia but seemed to help some depressed patients.

Question 13

Selective serotonin-reuptake inhibitors (SSRIs)

Answer 13

• Are serotonin agonists that exert their ago­nistic effects by blocking the reuptake of serotonin from synapses.
• The success of the SSRIs spawned the introduction of a similar class of drugs, the selective norepinephrine-reuptake inhibitors (SNRIs). Have proven to be just as effective as the SSRIs in the treatment of depression.

Question 14

Fluoxetine (marketed as Prozac)

Answer 14

Was the first SSRI to be developed.

Question 15

Atypical antidepressants

Answer 15

• A new class of antidepressant medications emerged that is really just a catch­all class comprising drugs that have many different modes of action.

Question 16

Bupropion

Answer 16

Atypical antidepressant: Several effects on neurotransmission: It is a blocker of dopamine and norepinephrine reuptake, and it is also a blocker of nicotinic acetylcholine receptors.

Question 17

Dissociative hallucinogen ketamine

Answer 17

• Antagonizing the glutamate NMDA receptor on depressive disorders
• Even single low dose of ketamine rapidly reduces depres­sion, even in patients who had been experiencing a severe episode
• However, because ketamine has undesirable side effects, researchers are now in the process of trying to identify more selective NMDA-­receptor antagonists with fewer side effects.

Question 18

How effective are antidepres­sants?

Answer 18

• About 50% of clini­cally depressed patients improved. This rate seems quite good; however, control groups showed a 25 percent rate of improvement, so only 25 percent of depressed individuals were actually helped by the antidepressants.
• Antidepres­sants were not significantly better than placebo in treating patients with mild or moderate depression. Only the se­verely depressed seemed to benefit.

Question 19

What is observed in structural MRI studies of the brains of de­pressed patients?

Answer 19

• Consistent reduc­tions in gray matter volumes in the prefrontal cortex, hippocampus, amygdala, and cingu­late cortex.
• Atypical activ­ity in frontal, cingulate, and insular cortices as well as in the amygdala, thalamus, and striatum.
• Communication amongst these structures has been found to be atypical during a variety of cognitive states.

Question 20

Monoamine theory

Answer 20

Depres­sion is associated with underactivity at serotonergic and noradrenergic synapses.

Question 21

Up-regulation

Answer 21

When an insufficient amount of a neurotransmitter is released at a syn­apse, there is usually a compensatory increase in the number of receptors for that neurotransmitter.

Question 22

Two recent lines of evidence have challenged the monoamine theory of depression.

Answer 22

1. Monoamine agonists not effective in the treatment of most depressed patients. When effective, only slightly better than placebo.
2. Other neurotrans­mitters (e.g., GABA, glutamate, acetyl­choline) play a role in the development of depression.

Question 23

Neuroplasticity theory

Answer 23

Depression results from a decrease of neuroplastic processes in various brain structures (e.g., the hippocam­pus), which leads to neuron loss and other neural pathol­ogy.

Question 24

Support for the neuroplasticity theory of depression comes from two kinds of research

Answer 24

1. Research showing that stress and depression are associated with the disruption of various neuroplastic processes (e.g., a reduction in the synthesis of neurotrophins, a decrease in adult hippocam­pal neurogenesis).
2. Research show­ing that antidepressant treatments are associated with an enhancement of neuroplastic processes (e.g., an increase in the synthesis of neurotrophins, an increase in synaptogenesis, and an increase in adult hippocampal neuro­genesis)

Question 25

Biomarker

Answer 25

A biological state that is predictive of a particular disorder

Question 26

Brain­-derived neurotropic factor (BDNF)

Answer 26

• Interest to researchers because treatments that improve depression (both pharmacological and non-phar­macological) have been found to increase BDNF levels in those patients who show improvement.
• Decreased blood levels of BDNF might be a biomarker for depres­sion, increased blood levels of BDNF might be a biomarker for the successful treatment of depression
• Hypothesized that antidepressants increase BDNF levels, which in turn increase certain neuroplastic processes (e.g., increase adult hippocampal neurogenesis) that lead to the alleviation of depression.

Question 27

Where is the monoamine theory based on?

Answer 27

• Based on the fact that monoamine oxidase inhibitors, tricyclic anti­ depressants, selective serotonin­-reuptake inhibitors, and selective norepinephrine-­reuptake in­hibitors are all agonists of serotonin, norepinephrine, or both.
• Autopsy studies. Norepinephrine and serotonin receptors have been found to be more numerous in the brains of deceased depressed individuals who had not received pharmacological treatment.
  
  • -> up-regulation

Question 28

Repetitive transcranial magnetic stimulation (rTMS)

Answer 28

• Involves the noninvasive delivery of repetitive magnetic pulses at either high frequencies (e.g., five pulses per second) or low frequen­cies (e.g., less than one pulse per second) to specific cortical areas—usually the prefrontal cortex.
• High ­frequency rTMS and low­ frequency rTMS are believed to stimulate and inhibit, respec­tively, activity within those brain regions to which they are ap­plied.
• Meta­-analyses have shown reliable improvement of depressive symptoms after either low­ frequency or high-­frequency rTMS when compared with sham rTMS.

Question 29

Deep brain stimulation

Answer 29

Chronic brain stimula­tion through an implanted electrode –>

Lozano and colleagues (2008) implanted the tip of a stimulation elec­trode into an area of the white matter of the anterior cingulate gyrus in the medial prefrontal cortex. Electrode delivered continual pulses of electrical stimulation that could not be detected by the patients. The results were strikingly positive.

Question 30

Remarkable popularity of fluoxetine and other SSRIs is attributable to two things:

Answer 30

1. Have fewer side effects than tricyclics and MAO inhibitors
2. Act against a wide range of psychological disorders in ad­dition to depression.