Feeling depressed? You may blame your genes

Major depression often develops into a chronic illness which is highly prevalent and is a major component of disease burden all around the globe.

Life is never a bed of roses for us as the light and darkness are intertwined . We dwell through many happy and sad phases of life. But our emotions, although in a peak , don’t last for long.

If darkness keeps prevailing in our minds, we remain morose, and if  someone experiences persistent and intense feelings of sadness for long periods of time, then they may be suspected of having major depressive disorder (MDD).

MDD is the clinical case of depression that keeps impacting our mood and behavior, causing disturbances in  regular physical habits like appetite and sleep. The people keep loosing interest in the activities which they used to love doing and it starts affecting their regular activities too. Gradually they start loosing interest in life.

As the people start distancing themselves, often they do not get opportunity or seek  medical attention. But psychotherapy, medications and other supportive methods may help in effective treatment and management of the conditions.

Depression is a major killer

Major depression often develops into a  chronic illness which is highly  prevalent and is a major component of disease burden all around the globe. Depressive disorders were cited as the second leading cause of years lived with disability in 2010 in Canada and the United States. A similar pattern is seen globally as well. MDD is one of the most common mental disorders in the United States. In 2015, nearly 7 percent of Americans above 18  years of age had an episode of MDD.

When depression-related deaths due to suicide and stroke are considered, depression has the third highest global burden of disease. it is predicted to be the leading cause of disease burden by 2030, and it is already the leading cause of debilitation in women worldwide.

Diagnosis of MDD

The Diagnostic and Statistical Manual of Mental Disorders (DSM) published by The American Psychiatric Association recommends that one must have at least five of the following symptoms experienced at least once a day for a period of more than two weeks to be considered as a patient of MDD:

  • Feeling sad or irritable most times of the day
  • Lack of  interest in most activities  once enjoyed
  • Sudden lose or gain in weight or a persistent change in appetite.
  • Either trouble falling asleep or wish to sleep more than usual.
  • Experiencing feelings of restlessness.
  • Feeling of unusual tiredness and lack of energy.
  • A profound feeling of  worthlessness or guilt, often about things that wouldn’t normally make him feel that way.
  • Difficulty in concentrating, thinking, or making decisions.
  • Thoughts about harming himself or committing suicide.

Causes of major depressive disorder

Depression is a much complex disease and so is its etiology. Its easy to blame past incidences of life that torments one which may include physical, sexual or emotional abuse and conflicts with family members. Only a few of us may be aware that there could be other conditions leading one to a depressive state which include certain medications (drugs like isotretinoin used for treating acne; corticosteroids used for treating allergy , asthma etc; statins for lowering cholesterol), and certain diseases like hypothyroidism. The social and family environment where we live  and grow up are also to blame where too many choices of products in life and urge to cope up with a fast paced lifestyle, lack of emotional support from peers, substance abuse and several other reasons may lead one going into a state of depression. But there is much more beyond that. Why should a 4 year old child face MDD?

There must be some other hidden parameters that  may cause this mental illness. With the unravelling of newer technologies and advances in big data analytics in recent days, many complex scenarios can now be simulated and analyzed. We have more precise view of a persons genetic makeup and this could be contrasted with the population data. These are helping the scientists to unravel further secrets behind depression.

Biological and anatomical factors responsible for MDD :

Around the globe, Males and females have a significant difference in total cases reported . In every region of the globe and different  socio-economic conditions women suffer more from depression than men.  The periodic hormonal changes; more emotion focussed ruminative lifestyle; family, social roles and culture related influences make the women more predisposed to mental depression. But some researchers suggest that actually there is not much difference in prevalence of depression between males and females. The general tendency of a depressed female to seek help more often than a male counterpart probably leads to the differences in diagnosed patient counts. Thus a deeper level of biology may actually play its roles in causing depression.

Role of altered brain structure:

For a long time researchers have suggested that there may be distinguished brain structures that may make one more susceptible to depression. These include specific brain regions, pathways between specific regions, which may play a collective role, but these have inconclusive evidences. But it is seen for certain that in several MDD patients, the hippocampus region of the brain appears to be smaller than the people who never experienced depression. This region is known to produce serotonin,  chemical causing neurotransmission between different region of brain and processing of emotions. It is not known yet whether depression susceptible people are born with smaller hippocampus or depression is caused by reduced secretion of serotonin later on in life.

Does depression run in the families?

Ah yes. It is sometimes observed that a in generations of a family a consistent history of depression may be found. Children, siblings, and parents of patients with severe depression also show a higher probability to suffer from depression in many cases than  family members within  general population. Weissman observed that 59.2% of the grandchildren of an MDD patient also show psychiatric disorders. Then the key factor for causing clinical grade depression might be lurking somewhere in a defective gene. Such genetic defects may also pass onto next generations making the children susceptible as well. Identification of these risk groups could help combating the disorder even before it sets in.

The researchers had been investigating this issue for a while but met with partial success as many gene products seemed to show minor differences in interaction with the environment and those rather might be collectively contributing to clinical level manifestation of the disorder than causing a single gene disorder as happens with many genetic diseases.

Investigation on genetic basis of depression:

Twin studies are very good options for geneticists to check if some variable genetic factor makes one more susceptible to a condition compared to general population as they share very similar genes. Twin studies on depression showed that there is a tendency of specific people to suffer from MDD. Over the last decade investigations were conducted by several institutions. The most remarkable ones included study on 5303 Han Chinese women ; a meta-analysis study on nearly 161500 individuals and an analysis of nearly 76000 cases of self-reported major depression by CONVERGE Consortium. In these studies respectively 2 and 15 genetic positions (loci) could be identified in their genes , which seemed to be highly responsible for depression. But these genetic factors may have a minuscule effect on depression, which were also similarly exerted by other cases like illnesses including psychiatric disorders.Thus the exact enumeration of genetic effect on clinical grade depression remained unattainable.

The recent advances in next generation sequencing technology has enabled us to sequence individual genomes in high details  at a very low cost and thus making personalized genomics and medicine a reality. We are now able to obtain high resolution sequences of genomes of many individuals and undertake very large-scale , big data enriched genome-wide association studies for a large population.Very large sample sizes help to filter out the subtle differences and attribute the to a particular disease condition.

A breakthrough Study identifies several genes responsible for MDD

A game-changing study was conducted over nearly half a million people and interesting results came out to uncover new genes responsible for depression. There were a huge array of researchers from all over the globe and the proceedings were published in April ,2018 in Nature Genetics. The study, done on a large population of clinical, population and volunteer individuals (cohorts) and multiple lines of evidences, for the first time provided a distinct relationship of genes with clinical MDD. There were 135,458 MDD patients and their genes were contrasted with 344,901 healthy individuals. They identified 9.6 million Single Nucleotide Polymorphisms (SNPs) and validated statistically to prove association with depression. A single instance of SNP refers to a deviation of a nucleotide (DNA base) in a particular position. Given the fact that there are nearly 3.3 billion nucleotide bases in our chromosomes in a particular cell, its truly a finding a needle in a colossal haystack scenario.

The team could identify 44 genetic loci out of which 14 were indicated in previous studies and 30 are novel in nature. The researchers then investigated on the function of the genes and found that those have diverse functions including connectivity between nerve cells, development of structures of nerve cells and differentiation of neuron types in central nervous system. Several genes here were found to be responsible for causing autism and schizophrenia as well. This also throws light to the question as to why autistic individuals and patients with bipolar disorders often exhibit clinically high levels of depression.

The scientists tried to correlate the function of these genes with 221 psychiatric disorders, medical diseases, and human traits. The gene defects were highly correlated with the cases where one experiences depression. The interesting point to note here is that many psychiatric disorders which start at childhood or adulthood and are distinct from MDD also are affected by same genes. This shows that the genes play a very complex concert in maintaining our mental balance of joy and sorrows and bit of difference may cause havoc and change our lives. These diseases include lack of appetite, insomnia, tiredness, daytime sleepiness, Anxiety disorders and much more. Thus the symptoms of these diseases manifesting in particular individuals add up to the depression and make it severe. The scientists also noted that individuals genetically predisposed to be obese, having higher hereditary chances of coronary artery disease and Squamous cell lung cancer are also more susceptible to MDD.

“We are stepping into an exciting time of detection. We are able to identify the causes of diseases and pinpoint them to genetic defects and it presents us with better opportunities to offer personalized medicine to people.” said Christ Pavlatos, CEO and Co-founder of PatientMD. The genetic results also match with brain anatomy specific for patients with MDD.

“This is going to change the course of our approach to MDD”, adds Pavlatos. “In coming years probably we would be able to detect propensity of an individual or a family in general to clinical grade depression much in advance and offer medication and other protective measures so that it never attacks the person in his lifetime, saving precious lives”