Prozak (fluoxetine) is among the Selective Serotonin Reuptake Inhibitors (SSRIs), aka. second-generation antidepressants. As all SSRIs, Prozak blocks the reuptake transporter for serotonin, preventing it from being taken back to the axon terminal. Since this transporter is blocked, serotonin remains in the synaptic cleft for long periods, continuing to have its effect on the postsynaptic neuron. Although this effect takes place very quickly, depression symptoms take long periods to be alleviated. This phenomenon is not fully understood, but it’s interesting to note that Prozak increases the production of new neurons in the hippocampus – a limbic structure that is very vulnerable to stress-induced damage. Therefore, it is suspected that this renewal in the hippocampus is exactly the reason behind this antidepressant’s effect.

Symptoms of Major Depression

Feelings of helplessness and hopelessness; sadness; loss of interest and pleasure (from food and/ or sex) – anhedonia; may be accompanied by significant weight loss or gain (sometimes hyperphagia); insomnia or hypersomnia (middle of the night awakening, early morning awakening); fatigue, general loss of energy; having hard time concentrating. People with depressive symptoms are indecisive, have low self-esteem; pessimism; disturbance of body rhythms; suicidal tendencies are common.

Evidence for genetic predisposition for Depression

Although the impact of genes varies, depending on the type of depression, there is a correlation. Depression tends to run in families. That is why adopted children, resembling their real parents’ genes may have depression in spite of living in a cheerful, lively atmosphere. One is at risk of depression if one has close relatives who have had severe early-onset depression, especially if that relative is a female. However, no single gene has been identified to have a strong link with that mood disorder. So, obviously, depression depends on a combination of genes and environmental factors.

Are males or females more vulnerable to depression? What is the role of hormones?

Depression is much more common in women, in all cultures. For sure, hormonal changes can trigger an episode of depression, but this correlation does not necessarily imply causation, as some women are more vulnerable than others. Still, the reason why women suffer depression more often is not clearly identified.

What is the role of traumatic experiences for episodes of depression?

Stress is a typical trigger for an episode of depression, as it causes the release of cortisol that prepares the body for action and, in the long run, exhausts the body. A lot of women experience postpartum depression, after giving birth and some of them enter a more serious, long lasting depressed condition. However, giving birth itself does not cause depression as many of the women have already suffered previous onsets. Thus, traumatic experiences may trigger an episode of major depression, but do not cause the disorder.

What are the patterns of hemispheric dominance with happy moods in normal people? How do they differ from patterns in depressed people?

Happy mood is generally related with increased activity in the left prefrontal cortex. Depressed people, however, have decreased activity in that area, whereas it is increased in the right prefrontal cortex. Also, many people who have had damage to the left hemisphere become seriously depressed. Fewer become depressed after damage to the right hemisphere. And sometimes, people with right hemisphere damage become manic.

What is Borna disease? What evidence links it to depression?

Borna disease was first noticed in European farm animals. It affects behavior, causing frantic activity or inactivity. In severe cases, the disease can be fatal. As many other viruses, Borna disease can be passed between humans and other species. However, the effect is different in humans. In an experiment/ survey, in all 12 cases of people with Borna disease, those same people had either major depression or bipolar disorder.

What are 3 groups of antidepressants? How does each of them exerts its effects?

Tricyclics prevent the presynaptic neuron from reabsorbing catecholamines or serotonin after they have been released. Thus, the neurotransmitters remain in the synaptic cleft longer, continuing to stimulate the postsynaptic cell. They inhibit the reuptake of NE and dopamine. However, tricyclic also block certain receptor which may lead to side effect.

Selective serotonin reuptake inhibitor (SSRIs) block the reuptake of serotonin by the presynaptic terminal (in a way, those are similar to tricyclics). SSRIs have little and only mild side effects. Still, sometimes, they may cause nervousness and, thus, are not recommended for people suffering anxiety.

Monoamine oxidase inhibitors (MAOIs) block the enzyme monoamine oxidase, which has the function to metabolize catacholamines and serotonin into an inactive form. O, when this enzyme I blocked, the amount of those neurotransmitters in the presynaptic terminal and the cleft increases. However, MAOIs tend to affect blood pressure, which can be very dangerous and, in general, are very dangerous in the long run, although they tend to work within a few days.

Why does Prozac/ fluoxetine preferred over tricyclics and the monoamine oxidase inhibitors?

It almost no side effects (sometimes mild nausea, headache, or nervousness, very rarely people react with having Serotonin fever). Also, there is almost no risk of over dosage. In addition, it takes only within 2 – 4 weeks to work and, in the short term, causes loss of weight, which is, generally desired by people.

What are atypical antidepressants? For whom are they used?

This is a miscallaneous group of drugs that have the antidepressant effect, but very little side effects. They are being prescribed to people who did not respond to the other drugs. Some atypical antidepressants are bupropion (inhibiting the reuptake of DA and sometime NE, but not 5HT), venlafaxin (mostly inhibit the reuptake of serotonin, and lightly of DA and NE).

How effective is St. John’s wort? Which class of antidepressants produces similar effect? What is one potential problem?

St. John’ wort is an herb that works like the selective serotonin reuptake inhibitors. However, it efficacy I not yet accurately determined, a different studies how different results (some suggest it is more effective that SSRIs, some claim it is equal to them, others that it is not effective at all). One potential dangerous side effect is that St. John’s wort increases the production of the liver enzyme that breaks don toxins, also medicines. Thus, it decreases the effectiveness of many medicines that may be vital. Another problem is, that it is cheaper that drugs and can be taken without prescription, which hides risk of inappropriate use and dosage.

Explain the problem of time course effects on neurotransmitters and depressive symptoms. What are some delayed effects of antidepressants?

Antidepressant drugs, in general, have delayed effects that limit the excitation of the postsynaptic cell, decreasing the sensitivity or the receptors on the postsynaptic cell. They also affect autoreceptors (the negative feedback receptors on the presynaptic terminals). Also, Prozac, for example, causes gain of weight hen used for a long time.

What neurotrophin is produced as a result of repeated use of antidepressants? In which brain areas is it produced?

Brain-derived neurotrophic factor is produced that aid the growth, survival and connections between the neurons. The cerebral cortex and the hippocampus.

How is electroconvulsive therapy (ECT) applied today? How is this an improvement over practices in the 1950s?

In the 1950, ECT was widely used without patients’ consent, being tried on many people in mental hospitals. Today, however, ECT is used only with informed consent for patients who do not respond to other antidepressant drugs. During ECT, the patient is under general anesthesia, with muscles being blocked. Thus, the process is not painful and the risk of injury is minimized. A common side effect is that the patient has a loss of memory for that particular time hen ECT has taken place.

For which two groups of patient is ECT most often used?

ECT is used with people ho do not respond to other antidepressant drugs and with people ho have severe depression and suicidal tendencies, who need fast results and betterments (may be the difference between life and death).

What are the advantages and disadvantages of ECT?

Advantage is that it is the most effective treatment available nowadays and gives very fast results. Some disadvantages are that it may cause prolonged convulsion that can be fatal. Also, ECT should be applied over long periods of time and, as people lose memory of that time, it may, eventually, cause amnesia. Often, the case is that, after ECT treatment, patients enter another episode of depression within 6 months.

What are the effects of ECT on neurotransmitter receptors? What newer treatment is similar to ECT?

ECT stimulates the production of additional dopamine (types D1 and D2 receptors) and decreases the number of norepinephrine receptors.

How does the onset of REM sleep differ in depressed people, compared in non-depressed? How may this be related to body temperature cycles?

People with mood disorders also suffer some disorder of the biological rhythms. Depressed people have troubles sleeping and people who have sleep problems are more likely to get depressed, so it is a two way street. After going to sleep, most non-depressed people enter REM sleep after about 80-90 minutes and the amount of REM sleep is increased in the second half of the night. Depressed people, however, enter REM phase of sleep after about 45 minutes after going to bed. Also, the have trouble staying asleep and feel drowsy the next day.

What change in sleeping schedules has been found to alleviate depression? How long do the benefits last?

Surprisingly, sleep deprivation improves the condition of depressed people, relieving the symptoms of the disorder. Yet, this is not a solution as sleep deprivation is dangerous in the long run. Both antidepressant drugs and sleep deprivation decrease the amount of REM sleep. So, there is something about that stage of sleep that may be a hidden cure for depression, but researchers are not certain yet.