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Clinical depression is a health condition of depression with mental and physical components reaching criteria generally accepted by clinicians.

Although nearly any mood with some element of sadness may colloquially be termed a depression, clinical depression is more than just a temporary state of sadness. Symptoms lasting two weeks or longer in duration, and of a severity that they begin to interfere with daily living, can generally be said to constitute clinical depression. Using DSM-IV-TR terminology, someone with a major depressive disorder can, by definition, be said to be suffering from clinical depression.

Clinical depression affects about 16% of the population on at least one occasion in their lives. The mean age of onset, from a number of studies, is in the late 20s. About 2 times as many females as males report or receive treatment for clinical depression, though this imbalance is shrinking over the course of recent history; this difference seems to completely disappear after the age of 50 - 55, when most females have passed the end of menopause. Clinical depression is currently the leading cause of disability in the US as well as other countries, and is expected to become the second leading cause of disability worldwide (after heart disease) by the year 2020, according to the World Health Organization.

Signs and symptoms

It has been suggested that Depressive pseudodementia be merged into this article. (Discuss)

According to the DSM-IV-TR criteria for diagnosing a major depressive disorder (see also: DSM cautionary statement) one or both of the following two required elements need to be present:

• Depressed mood, or
• Loss of interest or pleasure.

It is sufficient to have either of these symptoms in conjunction with four of a list of other symptoms. These include:

• Feelings of overwhelming sadness or fear, or seeming inability to feel emotion.
• Marked decrease of interest in pleasurable activities.
• Changing appetite and marked weight gain or weight loss.
• Disturbed sleep patterns, either insomnia or sleeping more than normal.
• Changes in activity levels, restless or moving significantly slower than normal.
• Fatigue, both mental and physical.
• Feelings of guilt, helplessness, anxiety, and/or fear.
• Lowered self-esteem.
• Decreased ability to concentrate or make decisions.
• Thinking about death or suicide.

Depression in children is not as obvious as it is in adults; symptoms children demonstrate include:

• Loss of appetite.
• Sleep problems such as nightmares.
• Problems with behavior or grades at school where none existed before.
• Significant behavioral changes; becoming withdrawn, sulky, aggressive.

In older children and adolescents, an additional indicator may be the use of drugs or alcohol. Moreover, depressed adolescents are at risk for further destructive behaviours, such as eating disorders and self-harm.

One of the most widely used instruments for measuring depression severity is the Beck Depression Inventory, a 21 question multiple choice survey.

It is hard for people who have not experienced clinical depression, either personally or by regular exposure to people suffering it, to understand its emotional impact and severity, interpreting it instead as being similar to "having the blues" or "feeling down". As the list of symptoms above indicates, clinical depression is a syndrome of interlocking symptoms which goes far beyond sad or painful feelings. A variety of biological indicators, including measurement of neurotransmitter levels, have shown that there are significant changes in brain chemistry and an overall reduction in brain activity.

One consequence of a lack of understanding of its nature is that depressed individuals are often criticized by themselves and others for not making an effort to help themselves. However, the very nature of depression alters the way people think and react to situations to the point where they may become so pessimistic that they can do little or nothing about their condition.

Because of this profound and often overwhelmingly negative outlook, it is imperative that the depressed individual seek professional help. Untreated depression is typically characterized by progressively worsening episodes separated by plateaus of temporary stability or remission. If left untreated it will generally resolve within six months to two years although occasionally depression becomes chronic and lasts for many years or indefinitely. In many cases (but not all) treatment can shorten the period of distress to a matter of weeks.

While depressed, the person may damage themselves socially (e.g. the break up of relationships), occupationally (e.g. loss of a job), financially and physically. Treatment of depression can significantly reduce the incidence of this damage, including reducing the risk of suicide which is otherwise a common and tragic outcome. For all of these reasons, treatment of clinical depression is seen by many as very useful and at times life saving.

Some people can experience anhedonia for long periods of time before they discover it is a mental illness. The inability to feel pleasure can advance negativity already present in a depressed person's mental state.

Historical perspective

The modern idea of depression seems to be the same as the much older concept of melancholia. The name melancholia derives from 'black bile', one of the 'four humours' postulated by Hippocrates.

The Ebers papyrus (ca 1550 BC) contains a short description of clinical depression. Though full of incantations and foul applications meant to turn away disease-causing demons and other superstition, it also evidences a long tradition of empirical practice and observation.

Types of major depression

Major depression is also referred to as major depressive disorder or biochemical, clinical, endogenous, unipolar, or biological depression. It is characterized by a severely depressed mood that persists for at least two weeks. Episodes of depression may start suddenly or slowly and can occur several times through a person's life. Major depressive disorder may be categorized as "single episode" or "recurrent" depending on whether previous episodes have been experienced before.

Clinicians recognise several subtypes of major depression.

• Psychotic depression is accompanied by hallucinations or delusions.

• Melancholic depression (what used to be referred to as endogenous depression) is characterized by insomnia, poor appetite and weight loss, less responsive mood, and morning worsening.

• Atypical depression is characterized by "reversed vegetative symptoms" which include oversleeping, overeating, leaden paralysis, rejection sensitivity and temporary brightening of mood in response to positive events. It may overlap with anxiety and panic attacks. It is often more chronic than melancholic depression.

• Dysthymia is a long-term, mild depression that lasts for at least two years. By definition the symptoms are not as severe as in major depression, although those with dysthymia are highly likely to have superimposed major depressive episodes (known as "double depression"). It often begins in adolescence and spans several decades.

Major depression may also be referred to as unipolar affective disorder, a term which emphasizes its relatedness to bipolar disorder.

Unipolar vs bipolar disorder

Bipolar disorder is a cyclical illness in which moods fluctuate between mania (extreme happiness or giddiness and frantic activity) and clinical depression. Bipolar disorder has also been commonly called "manic depression", although this usage is now unpopular with psychiatrists, who have standardised on Kraepelin's usage of the term "manic depression" to describe the whole bipolar spectrum that includes both bipolar disorder and unipolar depression; they now usually use the term bipolar disorder. This then leaves the term unipolar depression which is used to differentiate it from bipolar disorder.

Causes of depression

No specific cause for depression has been identified, but there are a number of factors believed to be involved.

• Heredity The tendency to develop depression may be inherited; there is some evidence that this disorder may run in families.

• Physiology There may be changes or imbalances in chemicals which transmit information in the brain, called neurotransmitters. Many modern antidepressant drugs attempt to increase levels of certain neurotransmitters, like serotonin. While the causal relationship is unclear, it is known that antidepressant medications do relieve certain symptoms of depression. Seasonal affective disorder (SAD) is a type of depressive disorder that occurs in the winter when daylight hours are short. It is believed that the body's production of melatonin, which is produced at increased levels in the dark, plays a major part in the onset of SAD, and that many sufferers respond well to bright light therapy, also known as phototherapy. High levels of Omega-6 fatty acids in the brain have also been linked to depression.

• Psychological factors Low self-esteem and self-defeating or distorted thinking are connected with depression. While it is not clear which is the cause and which is the effect, it is known that sufferers who are able to make corrections to their thinking patterns can show improved mood and self-esteem. Psychological factors include the complex development of one's personality and how one has learned to cope with external environmental factors, such as stress.

• Early experiences Events such as the death of a parent, abandonment or rejection, neglect, chronic illness, and severe physical, psychological, or sexual abuse can also increase the likelihood of depression later in life. Post-traumatic stress disorder (PTSD) includes depression as one of its major symptoms.

• Life experiences Job loss, financial difficulties, long periods of unemployment, the loss of a spouse or other family member, or other traumatic events may trigger depression. Long-term stress, at home, work or school, can also be involved.

• Medical conditions Certain illnesses including hepatitis, mononucleosis, and hypothyroidism may contribute to depression, as may certain prescription drugs such as birth control pills and steroids.

• Alcohol and other drugs Alcohol can have a negative effect on mood, and misuse or abuse of alcohol, benzodiazepine-based tranquillizers and sleeping medications, or narcotics can all play a major role in the length and severity of depression. The link between cannabis abuse (as opposed to use) and depression is also widely documented.

• Postpartum depression About ten percent of new mothers experience some form of depression after childbirth. When it occurs, the onset is typically within three months after delivery, and it may last for several months. About two new mothers out of a thousand have depression so severe it includes hallucinations or delusions.

• Living with a depressed person Those living with someone suffering from depression experience increased anxiety, and life disruption, which increases the possibility of their also becoming depressed.

• Social Environment Evolutionary theory suggests that depression is a protective mechanism: if an individual is involved in a lengthy fight for dominance of a social group and is clearly losing, depression causes the individual to back down and accept the submissive role. In doing so, they are protected from unnecessary harm. In this way, depression maintains the social hierarchy.

• Other Evolutionary Theories Another evolutionary theory is that the cognitive response that produces modern day depression evolved as a mechanism that allows people to assess whether they are in pursuit of an unreachable goal. Still others claim that depression can be linked to perfectionism. People that accept satisfactory outcomes in lieu of "the best" outcome tend to lead happier lives.

Treatment

Treatment of depression varies broadly, and is different for each individual. Various types and combinations of treatments may have to be tried. There are two primary modes of treatment, typically employed in conjunction with one another, medication and psychotherapy. A third treatment, electroconvulsive therapy (ECT) may be used where chemical treatment fails. Other alternative treatments used for depression include exercise, and the use of vitamins, herbs, or other nutritional supplements.

The effectiveness of treatment often depends on factors such as the amount of optimism and hope the sufferer is able to maintain, the control s/he has over stressors, the severity of symptoms, the amount of time the sufferer has been depressed, the results of previous treatments, and the degree of support of family, friends, and significant others.

While treatment is generally effective there are some cases of where the condition fails to respond. Treatment resistant depression requires a full assessment which may lead to the addition of psychotherapy, higher medication doses, changes of medication or combination therapy, a trial of ECT or even a change in the diagnosis with subsequent treatment changes. Although this process helps many, some people continue with their symptoms unabated.

In emergency situations with suicidal persons, psychiatric hospitalization is used simply to keep the person safe until they cease being a danger to themselves. Another treatment program is partial hospitalization, in which the patient sleeps at home but spends the day, either five or seven days a week, in a psychiatric hospital setting in intense treatment. This treatment usually involves group therapy, individual therapy, psychopharmacology, and academics (in child and adolescent programs).

Medication

Medication which relieves the symptoms of depression has been available for several decades.

Tricyclic antidepressants are the oldest, and include such medications as amitriptyline and desipramine. They are used less commonly now, due to side-effects which may include increased heart rate, drowsiness, dry mouth, and memory impairment. Most importantly, they have a high potential to be lethal in moderate overdose. The reason why tricyclic antidepressants are still used is their high potency, especially in severe cases of clinical depression.

Monoamine oxidase inhibitors (MAOIs) may be used if other antidepressant medications are ineffective. Because there are undesirable interactions between this class of medication and certain foods and drugs, it is important that the user be aware of which ones to avoid. A new MAOI has recently been introduced. Moclobemide (Manerix), known as a reversible inhibitor of monoamine oxidase A (RIMA), follows a very specific chemical pathway and does not require a special diet.

Selective serotonin reuptake inhibitors (SSRIs) comprise the current standard family of antidepressants. It is thought that one cause of depression is that an inadequate amount of serotonin, a chemical which the brain uses to transmit signals between nerve cells, is produced. These drugs work by preventing the reabsorption of serotonin by the nerve cell, thus maintaining the levels the brain needs to function effectively. This family of drugs includes fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft) and nefazodone (Serzone). These antidepressants typically have fewer adverse side effects than the tricyclics or the MAOIs, though such effects as drowsiness, dry mouth, and decreased ability to function sexually may occur.

Selective norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor) and reboxetine (Edronax) and duloxetine (Cymbalta) are a newer form of anti-depressant which work by maintaining the level of noradrenaline in the brain at a constant level as well as acting upon serotonin. They typically have fewer side-effects than other types of anti-depressant although there may be a withdrawal syndrome on discontinuation which may require a tapering of the dose. SNRIs are thought to have a positive effect on concentration and motivation in particular.

S-adenosyl-methionine (SAM-e) is a derivative of the amino acid methionine that is found throughout the human body, where it acts as a methyl donor and participates in other biochemical reactions. It is available as a prescription antidepressant in Europe, and an over-the-counter dietary supplement in the United States. Clinical trials have shown SAM-e to be as effective as standard antidepressant medication, with many fewer side effects., Its mode of action is unknown.

Some antidepressants have been found to work more effectively in some patients when used in combination with another drug. Such "augmentor" drugs include tryptophan (Tryptan) and buspirone (Buspar).

Tranquillizers and sedatives, typically the benzodiazepines, may be prescribed to ease anxiety and promote sleep. Because of their high potential for addiction, these medications are intended only for short-term or occasional use. Medications are often employed not for their primary function, but to exploit what are normally side effects. Quetiapine fumarate (Seroquel) is designed primarily to treat schizophrenia and bipolar disorder, but a frequently-reported side-effect is somnolence. Hence, this non-addictive drug can be used in place of an addictive anti-anxiety agent such as clonazepam (Klonopin, Rivotril).

Antipsychotics such as risperidone (Risperdal) and olanzapine (Zyprexa) are prescribed as mood stabilizers and are also effective in treating anxiety. Antipsychotics (typical or atypical) may be also prescribed in an attempt to augment an antidepressant, to make antidepressant blood concentration higher, or to relieve psychotic or paranoid symptoms often accompanying clinical depression. However, they may have serious side effects, particularly at high doses, which may include blurred vision, muscle spasms, restlessness, tardive dyskinesia, and weight gain.

Lithium remains the standard treatment for bipolar disorder, but may also be effective for people with depression, particularly in preventing relapse. Lithium's potential side effects include thirst, tremors, light-headedness, and nausea or diarrhea. Some of the anticonvulsants such as carbamazepine (Tegretol), sodium valproate (Epilim), and lamotrigine (Lamictal) are also used as mood stabilisers, particularly in bipolar disorder.

Failure to take medication, or failure to take it as prescribed, is one of the major causes of relapse. Should one feel a change or discontinuation of medication is necessary, it is critical that this be done in consultation with a doctor.

Psychotherapy

In psychotherapy, or counselling, one receives assistance in understanding and resolving problems which may be contributing to depression. This may be done individually or with a group, and is conducted by health professionals such as psychiatrists, psychologists, social workers, or psychiatric nurses. It is important to enquire about both the therapist's training and approach; a very close bond often forms between practitioner and client, and it is important that the client feel understood by the clinician.

Counsellors can help a person make changes in thinking patterns, deal with relationship issues, detect and deal with relapses, and understand the factors that contribute to depression.

There are many therapeutic approaches, but all are aimed at improving an individual's personal and interpersonal functioning. Cognitive therapy, also known as Cognitive Behavior Therapy focuses on how people think about themselves and their relationship to the world. It works to counteract negative thought patterns and enhance self-esteem. Therapy can be used to help a person develop or improve interpersonal skills in order to allow them to communicate more effectively and reduce stress. Behavioral therapy is based on the assumption that behaviors are learned. This type of therapy attempts to teach individuals new and healthier types of behaviors. Supportive therapy encourages people to discuss their problems and provides them with emotional support. The focus is on sharing information, ideas, and strategies for coping with daily life. Family systems therapy helps people live together more harmoniously and undo patterns of destructive behavior.

Transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is currently under study as a possible treatment for depression. Initially designed as a tool for physiological studies of the brain, this technique shows promise as a means of alleviating depression. In this therapy, a powerful magnetic field is used to stimulate the left prefrontal cortex, an area of the brain which typically shows abnormal activity in depressed individuals. Studies currently show an efficacy similar to that of ECT, but with fewer side effects. No sedation is required, and the only reported side effects are a slight headache in some patients, and facial muscle contraction during treatment.

Electroconvulsive therapy

Electroconvulsive therapy, also known as electroshock therapy, shock therapy, or ECT employs short bursts of a carefully controlled current of electricity (this is fixed at 0.9 ampere in one typical machine) to induce an artificial epileptic seizure while the patient is under general anesthesia.

ECT has acquired a fearsome reputation from its use as a tool of repression in the former USSR, and its fictional depiction in films such as One Flew Over the Cuckoo's Nest, but when applied appropriately it is still a useful treatment where other means of treatment have failed, or where the use of drugs is unacceptable, such as in pregnancy. In a typical regimen of treatment, a patient receives three treatments per week over three or four weeks. Repeat sessions may be required. Short-term memory and long-term memory loss, lowering of intellectual ability, personality reconfiguration and headache may result from this treatment.

Other methods of treatment

Light Therapy

Bright light (both sunlight and artificial light) is shown to be effective in seasonal (winter) depression, and sometimes may be effective in other types of depression, especially atypical depression or depression with "seasonal phenotype" (overeating, oversleeping, weight gain, apathy). It is wise to recommend to any depressive patient to take as much sunlight as possible by walking at daytime, even if the patient suffers from depression which does not have seasonal pattern or "seasonal symptoms".

Important note: an antidepressant effect is caused by visible light stimulation of retina, not by ultra-violet, so it is not necessary (and may be even dangerous in some cases) to sunburn. It is enough just to walk at daytime or to take light therapy in a light cabin with a special powerful lamp.

Exercise

It is shown that physical activity and exercise helps depressive patients and promotes quicker and better relief from depression. It helps antidepressants and psychotherapy to work better and faster. But exercise itself, as the sole treatment, usually cannot (at least in severe, clinical cases of depression) be enough to relieve the depression. Moreover, in severe depression it is often very hard even to get out from the bed. What about any therapeutically significant amount of exercise or physical activity in that case? Nevertheless, it is recommended to keep regular physical activity when possible, even to force yourself to do so. Do not exercise until you are severely tired, exercise just a little bit, but regularly, if you are depressed.

Be safe, though, and consult your doctor before starting any exercise if you have cardiac or other general health problems.

Enemas and Colon Hydrotherapy

Severe clinical depression is often accompanied by constipation. From the other side, tricyclic antidepressants themselves tend to produce constipation as their side effect. It is shown that any laxative reduces the absorption of an antidepressant in the small intestine, thereby reducing its bioavailability and clinical efficacy. Warm water enemas, on the other hand, do not interfere with antidepressant absorption, and may themselves have a slight antidepressive effect, by increasing serotonin production in thick bowel wall and temporarily raising serotonin level in the bloodstream.

Magnetic Fields

Recent work in Poland has suggested that weak, variable magnetic fields may offer relief from depression in those that have been unresponsive to medication.

Old Methods

Insulin shock treatment is an old and currently mostly abandoned treatment of severe depressions, psychoses, catatonic states and other mental disorders. It consists of induction of hypoglycemic coma by intravenous infusion of insulin. The treatment is potentially unsafe and can be lethal in some cases (about 1% of patients undergoing insulin coma), even with proper monitoring. That was the main reason why it was abandoned from current medical practice. In contrast, ECT is considered to be very safe.

Nevertheless, insulin shock therapy is still officially used in Russia and some other countries, and can be administered to a very treatment-resistant patient under his written consent in many Western countries.

Atropinic shock therapy, also known as atropinic coma therapy, is an old and currently rarely used method. It consists of induction of atropinic coma by rapid intravenous infusion of atropine.

The atropinic shock treatment is considered relatively safe but the problem with its administration is that it requires prolonged coma (4-5 hours), careful monitoring and preparation, and it has many unpleasant side effects, like blurred vision due to atropine. Thus it is rarely used now. But it can be used under written consent in Western countries in some very treatment-resistant cases, and is still officially used in Russia and some other countries.

Relapse

Relapse is more likely if treatment has not resulted in the full remission of symptoms. In fact, current guidelines for antidepressant use recommend 4 to 6 months of continuation treatment following symptom resolution to prevent relapse of depression.

Strong anecdotal evidence exists to suggest that chronic disease is accompanied by relapes after prolongued treatment with antidepressants (Tachyphylaxis). Psychiatric texts suggest that physicians respond to this by increasing dosage, complementing the medication with a different class, or changing the medication class entirely. The reason for relapse in these cases is as poorly understood as the change in brain physiology induced by the medications themselves. Possible reasons may include ageing of the brain or worsening of the condition.

See also

• Beck Depression Inventory
• Cyclothymia
• Dysthymia
• Mania
• Bipolar disorder
• Seasonal affective disorder (SAD)
• List of people who have suffered from depression
• Stress
• Learned helplessness
• Wikibooks - Demystifying Depression

External links

• General Information
  • Depression Information from the US Institute of Mental Health
  • Depression: Clinical and Alternative Treatments
  • Dr. Ivan's depression central - Links to a plethora of information about depression and related disorders by biopsychiatrist Ivan Goldberg, MD.
  • Psych Central: Depression Information and Treatments
  • 100 FAQs about depression
  • Detailed information - Concerning Emil Kraepelin, who identified Manic Depression
  • A Buddhist View on Depression
  • Mental Health Matters: Depression
  • Symptoms of Clinical Depression (Major Depressive Disorder)
  • Internet Mental Health: Major Depressive Disorder
  • About.com: Depression Information
  • TrappedMinds.org - Depression and Mood Disorder Resources
  • McMan's Depression and Bipolar Web
  • DepressionAdvisor.com: Depression Information
  • clinical-depression.co.uk - A free online course that aims to equip people with all the knowledge required to understand, treat and ultimately overcome depression
• Online Support Groups
  • Secretworld - Mood Disorders and Depression Support
  • Moodgym - Training CBT for preventing depression
• Books and Publications
  • The Wave Riders - A book and newsletter with an alternative approach to Bipolar disorder and depression.
  • The Hamilton test - The Hamilton test for evalutating the degree of depression (pdf)
  • The MADRs test - The MADRs test for evaluating the degree of depression (pdf).
  • Against Depression Peter Kramer's exploration of cultural stereotypes of depression and artistic expression.
• Organizations
  • Depression Alliance website (UK charity)
  • "Philosophy And Depression," Philosophical Society.com
• Discussions
  • Psych Forums: Depression Forum
  • DepressioNet: board for depression sufferers.
• News
  • Omega-6 Levels in Brain Linked to Depression.
• Evolution and Depression
  • Randolph Nesse's homepage
  • Martin Seligman Seligman was the discoverer of learned helplessness in laboratory mice. He is also the developer of Positive Psychology.

Books

Books by psychologists/psychiatrists

• Beck, A. T., Rush, A. J., Shaw, B. F., Emery, G. (1987). Cognitive therapy of depression. New York: Guilford.
• Klein, D. F., & Wender, P. H. (1993). Understanding depression: A complete guide to its diagnosis and treatment. New York: Oxford University Press.
• Weissman, M. M., Markowitz, J. C., & Klerman, G. L. (2000). Comprehensive guide to interpersonal psychotherapy. New York: Basic Books.
• Sarbadhikari S. N. (2005).Ed, Depression and Dementia:Progress in Brain Research, Clinical Applications and Future Trends. Hauppauge, Nova Science Publishers. ISBN 1-59454-114-0

Books by persons suffering or having suffered from depression

• Wurtzel, E. (1997) Prozac Nation: Young and Depressed in America: A Memoir. Riverhead Books. ISBN 1573225126
• Lewinsohn, P. M., Munoz, R. F, Youngren, M. A., Zeiss, A. M. (1992). Control your depression. New York: Fireside/Simon&Schuster.
• Nesaule, Agate (1995). A Woman in Amber: Healing the Trauma of War and Exile New York: Penguin Books.

  ISBN 1-56947-046-4 (hc.); 0 14 02.6190 7 (pbk.)

• Rowe, Dorothy (2003). Depression: The way out of your prison. London: Brunner-Routledge.
• Sealey, Robert (2002). Finding Care for Depression, Mental Episodes & Brain Disorders, Toronto: Sear Publications www.searpubl.ca
• Smith, Jeffery (2001). Where the roots reach for water: A personal and natural history of melancholia. New York: North Point Press.
• Solomon, Andrew (2001). The noonday demon: An atlas of depression. New York: Scribner.
• Styron, William (1992). Darkness visible: A memoir of madness. New York: Vintage Books/Random House.
• Wolpert, Lewis (2001). Malignant sadness: The anatomy of depression. London: Faber and Faber.

References

Bland, R.C. (1997) Epidemiology of Affective Disorders: A Review. Can J Psychiatry, 42:367?377.

Roberto Delle Chiaie, Paolo Pancheri and Pierluigi Scapicchio. (2002). Efficacy and tolerability of oral and intramuscular S-adenosyl- L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr, 76 (5): 1172S-1176S

Mischoulon D, Fava M. (2002). Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr, 76 (5): 1158S-61S.

Keller, M.B. (2003) Past, Present, and Future Directions for Defining Optimal Treatment Outcome in Depression. JAMA, 289:3152-3160.

Murray, C.J.L., Lopez, A.D. 1997. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 349, 1498-1504

• Psychiatry
• Mood disorders