Depression: It’s Complicated
Written by wellsmithhealth
A study came out recently(1) that debunked the “serotonin hypothesis of depression.” This hypothesis argues that symptoms of depression are largely due to challenges around brain levels of serotonin, a feel-good neurotransmitter. Many psychiatrists and other healthcare professionals were either quick to attack the study or defend it. Others, including myself, had a more measured response to the study and were not too surprised by the findings. We are already keenly aware of the limitations of manipulating serotonin and other “monoamines” (a variety of brain neurotransmitters, including serotonin, which are the target of most currently available antidepressant medications) to notably improve a person’s mood beyond what a placebo would do. Yet we also recognize that these treatments can make a huge and often life-saving difference for many peopl
The main takeaway of the study, for me, was validation of something that should already be common knowledge. Depression is complicated. It’s unique. We will never find a silver bullet for treating everyone’s depression, just like we will never find one single cause of it.
That said, themes are certainly emerging in recent years as we have a better understanding of brain dysfunction. For example, chronic stress, inflammation, and insulin resistance are popular, inter-related topics in psychiatry (and more integrated interdisciplinary fields like “psychoneuroimmunology”), for good reason.
Indeed, a 2021 longitudinal study(2) found that if you develop insulin resistance (a condition where you have challenges controlling your blood sugar levels, often from chronically high stress), you double your risk of developing depression, even if you’ve never struggled with depression before. Another recent study showed that inflammation in your body (which can also arise from chronic stress) can actually lead to swelling of certain key brain regions involved in a range of psychiatric conditions(3). This is why I believe (and why I teach psychiatrists in training) that in addition to checking more standard “psychiatric screening labs” like thyroid markers and vitamin B12, all psychiatrists should be checking laboratory indicators of inflammation and insulin resistance in everyone struggling with symptoms of depression.
Going back to the “it’s complicated” theme, however, not all insulin resistant patients are depressed, and not all depressed patients are insulin resistant!
Many have healthy laboratory markers but are dealing with negative views of the world and of themselves in the aftermath of unresolved trauma or grief. In our current era of biological psychiatry, sometimes we can get so focused on finding abnormal laboratory results or abnormal brain findings that we can overlook the powerful impact of a human’s existential angst, for example. Or perhaps we are overlooking longstanding sleep challenges, whether it be from undiagnosed sleep apnea or from simply not prioritizing good sleep habits. If we don’t address these key aspects of our suffering, it can feel a lot like chasing our not-necessarily-inflamed tails!
The bottom line is that there should never be a one-size-fits-all approach to depression treatment.
This is why I practice integrative psychiatry, where we use personalized combinations of lifestyle interventions (and, when necessary, medications or targeted supplements) to get people feeling as well as possible, to live life to their fullest potential.
1. Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2022). The serotonin theory of depression: a systematic umbrella review of the evidence. Molecular psychiatry, 10.1038/s41380-022-01661-0. Advance online publication. https://doi-org.treadwell.idm.oclc.org/10.1038/s41380-022-01661-0
2. Watson, K. T., Simard, J. F., Henderson, V. W., Nutkiewicz, L., Lamers, F., Nasca, C., Rasgon, N., & Penninx, B. W. J. H. (2021). Incident Major Depressive Disorder Predicted by Three Measures of Insulin Resistance: A Dutch Cohort Study. The American journal of psychiatry, 178(10), 914–920. https://doi-org.treadwell.idm.oclc.org/10.1176/appi.ajp.2021.20101479
3. Kitzbichler, M. G., Aruldass, A. R., Barker, G. J., Wood, T. C., Dowell, N. G., Hurley, S. A., McLean, J., Correia, M., Clarke, C., Pointon, L., Cavanagh, J., Cowen, P., Pariante, C., Cercignani, M., Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium, Bullmore, E. T., & Harrison, N. A. (2021). Peripheral inflammation is associated with micro-structural and functional connectivity changes in depression-related brain networks. Molecular psychiatry, 26(12), 7346–7354. https://doi-org.treadwell.idm.oclc.org/10.1038/s41380-021-01272-1
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