Depression: In search of the Biology behind it

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Dr. Juni Banerjee, Neucrad Health June 29, 2020

Worldwide statistical data shows that more than 264 million people suffer from ‘Depressive Disorder’ or ‘Depression’ irrespective of their age, success, fame or financial status. Inspite of its prevalence, depression still remains a matter of shame and myth in our society. Current Covid-19 pandemic and home quarantine situations have once again enforced humankind to properly comprehend the biological causes and therapeutic interventions for depression.

Depression is not about any one biological factor being too low or too high. As a matter of fact, any single reason cannot actually capture the complexity behind Depression. While considering the biological triggers, onset of depression may involve various interconnected factors like genetic vulnerabilities, chemical imbalances in brain, stressful events in various stages of life, medical condition, intake of certain drugs etc. Interestingly, numerous ongoing nerve communications and biochemical reactions make up the dynamic system responsible for our mood, perceptions, sense of pleasure and responses to various situations. With this level of biological complexity, we must clearly understand how two people might have similar symptoms of depression but different underpinning problems from the inside, and therefore may require entirely different treatments.

What follows right now is an overview of the current understanding of the major biological factors believed to play key role in depression.

Unfolding the Biology of Depression:

I. Genes and Depression:

Investigators have found that children, siblings and parents of people suffering from severe depression have an increased risk of depression by 1.5-3% over members of general population. Henceforth, one of the basic goals of in neuroscience field is to delineate how heredity makes some people more vulnerable to depression. Interestingly, research works have indicated that depression is unlikely a cause of a single gene but rather small effects of several genes. Certain group of genes e.g. DRD4, SLC6A3, SLC6A4, TPH2 have been already found that can be differentiated in depressed and non-depressed persons, cementing genetically vulnerability as a key factor for depression and future therapeutic interventions.

II. Neurotransmitters and depression:

Importantly, the communication of our brain functions are handled by the nerve cells and their chemical messengers called ‘Neurotransmitters (NT)’. Scientists have found the connection of following NTs with depression:

1. Serotonin helps to regulate our sleep, appetite, sexual behavior, mood and inhibition of pain. Current research suggested decreased productions of serotonin in people with depression and suicide risks.
2. Dopamine not only influences motivation but is involved in perception and proper functioning of our brain’s reward system . Low dopamine levels may in part explain depressed people lacking sense of pleasure.
3. Norepinephrine helps our bodies to recognize and respond to stressful situations. Researchers suggest that people vulnerable to depression usually have a poor norepinephrinergic system for handling the effects of stress proficiently.
4. Glutamate has been implicated in depression as well. It acts as an excitatory neurotransmitter which has been found to smooth out the highs of mania and lows of depression in the long term.
5. Gamma-aminobutyric acid (GABA) is an amino acid that acts as an inhibitory neurotransmitter. Scientific works have showed that it helps to suppress anxiety and plays an important role in depression.

Importantly, apart from the NTs, the over-sensitiveness or insensitiveness of their specific receptors also has major role in affecting mood and influencing depression.

III. Brain and Depression:

Following areas of the brain majorly regulates mood and influences depression as proved by Positron Emission Tomography (PET), Single-Photon Emission Computed Tomography (SPECT) mapping and Functional magnetic resonance imaging (fMRI) scans:

• Amygdale: A part of the limbic system that is associated with our emotions such as anger, pleasure, sorrow, fear and sexual arousal. Its activity has been found to be higher in a sad or clinically depressed person.
• Thalamus: The thalamus receives most sensory information and relays it to appropriate part of the cerebral cortex in order to achieve high-level functions viz. speech, behavioral reactions, movement, thinking, and learning. Research evidence shows that significant reduction of thalamic volume and changes in shape of the left thalamus responsible for Major Depressive Disorder (MDD) in patients.
• Hippocampus: The hippocampus, also part of the limbic system has a central role in processing long-term memory and recollection. Research works on hippocampus revealed smaller size of hippocampus and lesser neuron productions in depressed people.

IV. Hormones and Depression:

Stress has its own physiological consequences (e.g. heart beating, muscles tensing, breathing fast and sweating) known as stress response. Body usually returns to normal if the stress is short-lived. However, for a long-lasting stress, hormonal system gets affected and so the mental health.

• Adrenocorticotropic hormone (ACTH): In response to stress, Hypothalamic-pituitary-adrenal (HPA) axis governing a cascade of hormonal activities secretes corticotropin-releasing hormone (CRH). CRH further stimulates the production of adrenocorticotropic hormone (ACTH) that in turn prompts the release of cortisol from the adrenal glands. Cortisol ultimately helps deciding the “fight or flight” response towards the initial stress. Scientific investigations have shown that in depressed people (ref: Journal of the American Medical Association) cortisol is produced in excess.
• Thyroid hormone imbalances are another of the best-known culprits of depression. An excess of thyroid hormone (hyperthyroidism) can trigger manic symptoms. On the other hand, hypothyroidism, a condition in which your body produces too little thyroid hormone, often leads to exhaustion and depression.

V. Pathophysiology and Depression:

Medical illnesses like degenerative neurological conditions (multiple sclerosis, Parkinson’s disease, Alzheimer’s disease and Huntington’s disease), cardiovascular diseases, nutritional deficiencies (e.g. lack of vitamin B12), immune system diseases (e.g. lupus), viral infections (e.g. HIV), cancer, and erectile dysfunction in men are being considered root of up to 10-15% of all depressions. In certain people, medications and drugs may lead to depression e.g. Barbiturates and Opiods (morphine).

In order to break the myths surrounding depression and pave ways for better evaluations, counseling and anti-depressant drug therapies, more research on the biological basis of mental health, mood swings, anxiety and depression is the need of the hour.

References:

1. https://www.who.int/news-room/fact-sheets/detail/depression
2. https://www.verywellmind.com/common-causes-of-depression-1066772
3. https://www.ncbi.nlm.nih.gov/books/NBK215119/
4. Shadrina M, Bondarenko EA, Slominsky PA. Genetics Factors in Major Depression Disease. Front Psychiatry. 2018;9:334. Published 2018 Jul 23. doi:10.3389/fpsyt.2018.00334
5. Pandya M, Altinay M, Malone DA Jr, Anand A. Where in the brain is depression?. Curr Psychiatry Rep. 2012;14(6):634-642. doi:10.1007/s11920-012-0322-7
6. Nutt DJ. Relationship of neurotransmitters to the symptoms of major depressive disorder. J Clin Psychiatry. 2008;69 Suppl E1:4-7.
7. Brigitta B. Pathophysiology of depression and mechanisms of treatment. Dialogues Clin Neurosci. 2002;4(1):7-20.

Author Profile:

Dr. Juni Banerjeeঃ

Dr. Juni Banerjee is a former Assistant Professor in the Department of Neuropsychology & Neuroscience at Amity University, Delhi. She has PhD degree in Cancer Biology (Jadavpur University) and Postdoctoral Research experience in Electrophysiology from Dept. of Physiology, School of Medicine, University of Pennsylvania. Recently, the author has been involved in Scientific Teaching, Writings and Research awareness programs.