What is depression?

A feeling, a state of being or a made up medical condition?


It is natural to experience mood swings. It becomes a problem when the sadness persists for weeks or months and prevents you from  doing your job, study, or prevent you from looking after yourself. It can last for weeks or a lifetime.

People tend to disagree on the validity of depression as a medical condition as they understand it as an experience of  feeling sad  that most of us are familiar with. Hence it could be a state of being “depressed”, a very private human experience that emerges in reaction to personal circumstances. It is worth remembering its distinction from “normal reactive sadness” usually called grief. For instance, loss of a loved one might cause a spell of sadness for most of us. But generally people are able to adapt to this quickly and are able to get on with their lives. Similarly relationship break ups, business losses and bankruptcy can occur to anyone but people are able to cope with these extreme situations without much dysfunction. Normally, they are not expected to last for weeks or months and restrict your emotional repertoire.

Clinical depression represents a pathological state of mind compared to normal sadness. Scientists have identified multiple pathological pathways which culminate in development of depression. Moreover, early treatment can prevent brain damage due to depression (Hippocampal volume loss). Hence it is vital to diagnose and treat depression without delay.

One might hear people asking a depressed person to snap out of it or to shake it off. However, this may not work for those with clinical depression. If neglected, the situation may begin to deteriorate rapidly with a risk of completed suicide.  This is a matter of professional care and hence one should contact their GP or psychiatrist (mental health Doctor) at the earliest.

How to identify Clinical depression/Major Depression

The experience of depression may vary depending on a person’s cultural background, personality, gender, upbringing, societal and family expectations etc. However, generally most people would feel a persistent sadness from which they can’t easily snap out of, they feel lethargic, they feel a general lack of motivation, poor self worth and a sense of lack purpose or meaning in life . This may be associated with changes in appetite and sleep. Some people are acutely aware of their emotional state whereas some others describe it as a physical symptom such as physical weakness, loss of appetite or pain symptoms. Some may seek help early but a large majority often wait till their symptoms get very severe.

Sometimes a suicidal note or an act could trigger a consultation, whilst others might seek help for their academic decline, break up of relationships or loss of their job due to ongoing depression.

Ask yourself whether you are experiencing:

  • Sadness or anxiety
  • Poor motivation and energy
  • Inability to focus and complete tasks
  • Changes in sleep or appetite
  • Low self worth/pessimism/suicidal ideas

If the answer is yes, it is worth considering a psychiatric consultation.

Who gets depression?

Although anyone can get depression, some individuals might be more prone to depression than others. On average more than 1 in 5 people will have depression sometime in their life and it can affect people of all ages. Women are about twice as likely as men to get depression.

Depression can occur on its own or occur along with a wide range of physical and mental illness including stroke, heart attack, cancer, autoimmune/inflammatory diseases, schizophrenia, OCD or even physiological states such as pregnancy or after a delivery of a child.

Depression can run in families and the contribution of genes to the development of  depressive illness is estimated to be 30% , the rest 70% are due to factors such as childhood adversity, sexual abuse, trauma, lack of social support, marital problems etc. These results suggest that there is a huge potential for the prevention of major depression by means of psychosocial interventions.

As we know, stress plays a big part in our emotional state. While men and women are, in general, equally sensitive to stressful life events, their responses depend upon the type of stressor. Specifically, men are more likely to have depressive episodes following divorce, separation, and work difficulties, whereas women are more sensitive to events in their proximal social network, such as relationship difficulties, serious illness, or death.

Although we know that genes play a part in the etio-pathology of depression, discovering the specific genes responsible for  clinical depression was not that straight forward. Moreover, no specific gene-environment interactions between candidate genes and potential environmental factors could be proven in larger studies. It is known that depression could be a heterogenous condition which can occur to people with many different temperamental traits. Furthermore, more than one neuronal circuitry our neuro-chemical could be involved in its causation. Hence we propose the inverted iceberg hypothesis to explain this complex phenomena. This is described elsewhere on our website.

How does brain produce depression?

Our emotion is an evolutionary gift that nature has given us. Although other mammals are also able to express emotions, humans are different as they able to modify raw emotions by virtue of  a more developed brain(neocortex). This also comes with its pitfalls, our ability for abstraction and symbolic representation might also lead us to misrepresent our competence, conceal motivations or express emotions triggered by past experiences than based on current circumstances.

Why does this happen to us but not other animals?. This is because broadly there are two brain centres for regulation of emotion, one  the Limbic system- the primitive seat of emotion and the frontal cortex , the more advanced and rational part of the brain which makes us humans. Our sensations, movements and emotions flow through nerves which are packed closely together connecting these centres.

From your own experience you might have noticed that some events or goals are more emotionally relevant to you than the others. Yet your responses may vary or even can be contradictory. Why would this happen?

Certain brain regions such as Amygdala, Anterior Cingulate cortex (parts of limbic system) together with the pre-frontal cortex (PFC) determine the significance of these stimuli. Whilst the left cortex might ask you to seek out the emotional stimuli , the right cortex might activate avoidance. You may be able to relate it to a date night situation where you contemplate whether or not to approach a person you feel attracted to. If you have had prior negative social experiences, the seat of emotional memory-hippocampus would remember it. Hippocampus will then create a fear response by activating amygdala and pituitary adrenal axis. Moreover, this might also activate the adrenergic centres of the brain causing a flight or fight response. The subsequent neuro-chemical cascade would also reduce your attention span, your ability to think rationally and to act logically. As explained above, it can cause sensory and motor symptoms commonly known as “dissociation” as these centres are closely packed together. Once you had such a negative experience, your brain would remember it ,code it and store it mainly via hippocampus and process it later via the Pre-frontal cortex. When you think about another date night, this might trigger a fear response via the activation of  a centre called bed nucleus of stria terminals (BNST), which we call anticipatory anxiety.

What is the role of chemicals in causing depression?

Monoamine systems are implicated in the causation of depression as they seem to regulate a wide range of emotions. They are also intricately linked and counter-balance each other.

Serotonin (5 HT) is an important regulator of sleep, appetite, body temperature and libido. Hence it is vital for our survival, goal directed activity and behavioural regulation. Interestingly serotonin is sensitive to stress and seasonal changes.

Nor adrenaline on the other hand is involved in alertness and emotional memory. Chronic adrenergic surge (chronic stress) can cause a state of learned helplessness. This can also lead to a state of low energy, attentional deficits and anhedonia.

Finally, Dopamine is vital in maintaining the emotional tone, motivation, goal directed activity and attention span. It is closely linked to motor behaviour. Some people may have experienced patterns of behaviour where they needed immediate gratification, couldn’t persist on their goals and were easily bored if  activities providing high levels of stimulation were not immediately available. They might “self medicate” with stimulants such as Amphetamines and cocaine to boost the dopamine levels in their brain.

Glutamate is an excitatory neurotransmitter which works with high cortisol levels to cause brain damage in chronic stress or depression. Drug that block glutamate such as Ketamine or Esketamine is known to produce quick relief from depressive symptoms.

Is depression curable?

Major depression can have more than one type of course or outcome. It can resolve by itself  in some cases and in one-third of  those with a current episode of depression may not have another episode in their life at all. Hence the decision to treat depends on the clinical factors and patient choices. The goal of treatment is to get people back to their normal lives at the earliest and prevent  unwanted consequences such as loss of job, relationship etc.

Those who had an acute episode with no past history or family history might only require a course of anti-depressant lasting for 6-12 months. The depressive symptoms might resolve within the first 6-8 weeks, the rest of the treatment is considered as the continuation phase, aimed at preventing a relapse. People who have more adverse prognostic factors might need a longer duration of treatment or multiple trials of anti-depressants. However, failure or lack of tolerance to one anti-depressant does not mean that another anti-depressant may not work. This fact has been proven by the STAR D trials. Moreover, those who partially responded to initial treatment but did not achieve full symptom resolution, continued to improve in the continuation phase of treatment. Studies show that those who are treated with a combination of anti-depressant and psychotherapy had a better outcome than those who were treated with either of them alone. Although 1 in 4 people with major depression may be resistant to anti-depressant treatment, newer treatment  modalities such as repetitive trans-cranial magnetic stimulation (rTMS) and esketamine might improve this outlook.