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THE SEROTONIN THEORY OF DEPRESSION

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 DEPRESSION

Depression, that is major depressive disorder (MDD), is a calamity for individuals and society. If we have not experienced it ourselves, we all know someone who has been struck by this disease. Twenty percent of women and 15 per cent of men suffer at least one episode in their lifetime. In the USA, the lifetime prevalence in the general population is estimated at 16.2 per cent.

MDD is characterized by two or more weeks of depressed mood or diminished interest, associated with symptoms such as disturbed sleep, decrease in appetite and libido, psychomotor changes, reduced concentration, excessive guilt and suicidal thoughts or attempts. It is insidious and often recurrent. Although depressive episodes can be treated well with antidepressant medication, structured forms of psychotherapy or a combination of these, the rate of recurrence is high, with each episode raising the probability of a new one by 16 per cent. MDD is the second leading cause of disability worldwide, in the age category of 15–44 years for both sexes combined, surpassed only by ischaemic heart disease.



THE 5-HYDROXYTRYPTAMINE HYPOTHESIS

Depression has too long been considered an illness of the soul. Currently, it is viewed as a disorder of the brain. This shift in paradigm began more than 50 years ago, soon after the biogenic amines, notably noradrenaline and serotonin (5-hydroxytryptamine, 5-HT), were discovered as brain transmitters. The monoamine hypothesis of depression was proposed by Schildkraut, referring essentially to catecholamines. Then, Coppen emphasized the possible role of 5-HT. In its original formulation, the 5-HT hypothesis postulated a deficit in 5-HT as a primary cause, reversed by antidepressants, which would restore normal function in depressed patients. Indeed, a variety of functional deficits of 5-HT neurotransmission in brain circuits known to regulate emotions, whether primary or secondary, have consistently been associated with aspects of the pathophysiology of MDD, as suggested by post-mortem and genetic, neurochemical, neuroimaging and pharmacological studies. More recently, reports that high-risk relatives of MDD patients are more sensitive to 5-HT challenge procedures, such as depletion of tryptophan/5-HT, and evidence that altered serotonergic function is still present in MDD patients in remission, suggest that altered or low 5-HT may represent a risk factor and trait diathesis increasing vulnerability to MDD.

The modelling of a mental disorder exclusively based on the dysregulation of a particular neurotransmitter system is obviously simplistic and open to criticism. Yet, it has provided an impetus for much of the subsequent research. Over the years, the 5-HT hypothesis of depression has been refined, to take into account new knowledge and several apparent inconsistencies, including: that a transient lowering of central nervous system 5-HT achieved experimentally in healthy controls devoid of risk for mood disorders has only modest effects on mood, if any; that not all patients benefit from drugs enhancing serotonergic neurotransmission; and that several drugs apparently devoid of major effects on serotonergic neurotransmission are effective to improve mood.


THE SEROTONIN THEORY--A PRIMER

The serotonin theory of depression originated in the 1960s. It focuses on the activation levels of the neurotransmitter serotonin within the central nervous system (CNS): At its core, this theory suggests that lower levels of active serotonin within the CNS cause the appearance of depressive symptoms.

The theory further specified that it is the lack of 5-HT serotonin receptors that causes lower levels of active serotonin, resulting in depression (for this reason, this theory is also sometimes called “the 5-HT hypothesis of depression”).

The serotonin theory of depression proceeded with another hypothesis from the 1950s, called “the monoamine theory of depression,” which claims depression was the result of the monoamine oxidase enzyme breaking down an array of neurotransmitters, including serotonin, norepinephrine, and dopamine. The serotonin theory of depression eventually overtook the monoamine theory in terms of widespread acceptance among researchers and other members of the mental health community.

BUILDING ON THE SEROTONIN DEPRESSION THEORY THROUGH SSRI'S

The earlier monoamine theory led to the introduction of first-generation antidepressants to the general public during the 1950s. This class of medication blocks the activity of the monoamine oxidase enzyme, thereby raising the activation levels of all affected neurotransmitters.Though first-generation antidepressants were found to be effective, side effects such as high blood pressure caused a decline in their popularity. These days, they are mainly prescribed for treatment-resistant depression and not as a first-line treatment.In the 1980s, a new form of antidepressant was made available, which was based on the serotonin theory of depression. Selective serotonin reuptake inhibitors, or SSRIs, are second-generation antidepressants that specifically target serotonin: By keeping the neurotransmitter active for longer periods of time, SSRIs manage to extend its effect on the CNS. The focus on serotonin provided by SSRIs was found to alleviate symptoms of depression. Additionally, SSRI side effects were found to be much more tolerable than first-generation antidepressants, making it easier for patients to continue taking them.As a result of their combined high efficacy and tolerability, the FDA has cited SSRIs as a first-line treatment for depression, with SSRIs continuing to be widely prescribed by psychiatrists for this condition.


REQUIREMENT OF FURTHER RESEARCH

The serotonin theory for depression, along with the above-mentioned depression-serotonin study, have raised a great deal of discussion over the role serotonin actually plays in the appearance of depression. The answer, it seems, was partially there all along, in the form of depression efficacy rates.

In 2006, a study funded by the National Institute of Mental Health (NIMH), found that only a third of participants with depression achieved full symptom remission on an SSRI medication — despite the fact that SSRIs are generally considered fairly effective.

Rather than detract from SSRI efficacy, the results of this (also much-touted) study underscores that depression has never been fully understood through a neurological lens. It is not merely caused by the lack of sufficient serotonin, nor is it purely a physiological disorder. Depression is, and always has been, a condition of the mind, rooted in deeply painful emotion, and understood through our own experiences of it.

For this reason, is it unsurprising that depression cases tend to respond well to psychotherapy treatment, particularly psychodynamic therapy. Such treatments allow both patient and therapist to approach the experiences, mental processes, and outlook that have all shaped the patient’s well-being, both in relation to any depressive symptoms they may have, and beyond.

As depression continues to receive attention in research and the field, it is important to remember that this disorder can emerge through a multitude of influential aspects of one’s life. As a result, treating depression necessitates an open mind, and a willingness for exploring the different options now available.





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