How Could I Return to Ordinary Life After My Son Died?

Threshold

Source: AI generated

How could I return to ordinary life after my son died? My grief was overwhelming, spilling into every task and coloring every interaction. Condolences triggered fresh crying jags. I wondered how my eyes could produce so many tears.

Over time, however, my work began to draw me in again, demanding that I return to the scientific questions that had defined my career. The discipline of research began to reassert itself, requiring that I take on the necessary but unrelenting work of writing grant proposals and papers, the data analysis, the meetings with colleagues and team members. I settled into a routine, willing myself to ignore the images and memories of Bill.

Yet underlying these tasks was a persistent internal dialogue that haunted me. Why hadn’t I been able to save him? What biological mechanisms made him so relentlessly ill? Could more effective treatments have altered the outcome? Gradually, these questions redirected the focus of my work, one that I continue to pursue. Having long studied the neurobiology of major depression, I began to concentrate on developing new treatments for bipolar disorder, the illness that had claimed my son’s life.

The broad emphasis of my research, which focused on major depression, had always been about reasons for altered brain structure, dysfunctional connections in brain circuits, and how treatment might help reshape these abnormalities. These brain features are queried using neuroimaging studies and related to patient experience with extensive inventories of symptoms and history. How does the stress response alter the brain? The angst, dread, and despair of depression produce stress responses, and adrenal glands pump out stress hormones that then flood the brain. How does repeated exposure to stress and stress hormones carve its signature into gray-matter loss?

This mechanistic approach has involved multiple research groups over time and has generated results that pointed to the function of specific brain regions underpinning the psychopathology of depression. The degree of structural brain changes correlated with higher numbers of repeated depressive episodes, supporting the role of depressive episodes in producing damage. Further, numerous research studies of brain function have found neuropsychological changes in depression tied to regional brain activity and connectivity. Frontal cortex underactivity was tied to decreased regulatory control of emotions, which, in turn, leads to increased activation of brain regions with overactive emotional responses, especially overactive negative responses.

This line of inquiry helped inform the development of transcranial magnetic stimulation (TMS), now a standard treatment for major depression. The underlying idea was to develop a brain stimulation treatment using magnetic energy—transcranial magnetic stimulation (TMS) that could be targeted to a specific brain region—in the case of depression, targeting the underactive frontal cortex to boost its activity. Numerous studies have now shown that this stimulation reduces depressive symptoms.

Unfortunately, the usual TMS treatment takes six weeks to be effective. A newer form of TMS called accelerated intermittent theta burst stimulation (aiTBS) was developed to provide patients with more rapid treatment. Not only is aiTBS stimulation faster, but it is also more effective, with more patients who respond and who, on average, experience a larger change in depression symptoms. Multiple daily iTBS treatments (10 treatments are common) are given over the course of a day, for a total of five days, resulting in a large drop in depression symptoms at the end of this period.

For bipolar disorder, the question of how the illness is similar to or differs from major depression is critical to developing treatments. Can some of the same treatments used in major depression be effectively used in bipolar disorder? Could the same mechanisms be operative? Could a treatment that rapidly treats depressive symptoms in major depression also be effective in bipolar depression? I decided to implement an accelerated TMS protocol in a clinical trial in bipolar patients and was pleased with the outcome: Patients responded with a substantial and rapid improvement. Although larger confirmatory trials are needed, it was an exciting new development.

Addressing suicide in severely ill patients at the extreme end of the mood disorder spectrum is a critical unmet need for patients and their families—and a high priority for me and my research. The question here is, can treatment aimed at reducing depression also alleviate suicidal thoughts and intent, or is there a separate process leading to suicide that would then require a different approach? Currently, there is no consensus.

Recent studies have met with preliminary success: Ultra-accelerated TMS protocols can deliver a full course of depression treatment to suicidal patients in just a day or two, but this has, as yet, not been extensively tested. A rapid-acting drug, ketamine, has also shown promise in the acute treatment of suicide, but with variable effects on durability. Moreover, while psychedelic compounds can rapidly decrease depressive symptoms, no demonstrated anti-suicide effects have yet been found.

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I am always seeking to find more effective and intensive treatments that work more rapidly. Understanding whether these treatments have shared effects on brain circuitry or operate through different brain circuits will be critical. As we have come to understand brain functional abnormalities in terms of the relationship among brain circuits rather than resulting from dysfunction in only particular brain regions, we can predict how a particular circuit should be activated to impact symptoms. Combining stimulation with drug therapy may also further improve treatment outcomes.

At this moment, science stands at an extraordinary threshold, where emerging insights into brain circuit connectivity may transform our understanding and treatment of bipolar disorder. Real progress will depend on bold, innovative research and a deep grasp of how individual differences shape the most effective treatments. Current efforts are focused on refining these approaches by identifying optimal stimulation targets, integrating neuromodulation with drug therapy to augment the effect, and exploring newer modalities such as focused ultrasound stimulation and deep brain stimulation. My work in this area stems from both a scientific and personal commitment: to translate insights about brain circuitry into treatments that alleviate suffering and save lives. This mission is what draws me out of bed each morning and fuels my work every day: a commitment to keep my son’s memory close and to honor his life through the pursuit of knowledge that can heal others.