DEPRESSION: HOW KETAMINE CAN HELP (YALE MEDICINE)

Depression is one of the most common and most debilitating mental health disorders, affecting some 17 million adults in the US. It also continues to be a misunderstood, often hard-to-treat illness. Researchers have worked for decades to better understand the neurobiology underpinning depression.

For patients with severe, treatment-resistant depression, spending months or even years searching for good treatments can be totally disabling. The prevailing hypothesis for years was that depression was regulated by the neurotransmitter’s serotonin and norepinephrine.

Eventually, data began to suggest that maybe something much larger and more global was involved in the brain to account for depression, which led researchers to begin working with glutamate and GABA, the most abundant neurotransmitters in the brain. These chemicals are involved in neuroplasticity – the brain’s ability to adapt to change and protect itself against stressful events.

Neuroplasticity is a physical thing, too: it manifests itself “in terms of synapses, how these neurons are actually touching each other and communicating with each other,” explains Gerard Sanacora, PhD, MD, Director of the Yale Depression Research Program. “And we know that in depression, the number and strength of these interconnections decreases,” says Rachel Katz, MD, a professor of Clinical Psychiatry at Yale.

Ketamine – originally developed and still used as an anesthetic – works on those two neurotransmitters and was discovered to have rapid antidepressant effects. Some experience an improvement in symptoms in 24 hours or less. “We think that one of the things that Ketamine does, that helps to explain its antidepressant effects, is help the brain to regrow the synapses, the connections between nerve cells,” says John Krystal, MD, Chair of the Department of Psychiatry at Yale.

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MEDICINE: UNDERSTANDING ‘LONG COVID’ SYNDROME

The risk of COVID-19 has been largely communicated only in terms of deaths and hospital capacity, with recovery and survival conflated with each other. Around one in three people with symptomatic COVID-19 still experience symptoms 12 weeks after onset (1). Long Covid can be experienced by all age groups and not only those with acute severe disease. The debilitating symptoms are wide-ranging, multisystemic, and predominantly fluctuating or relapsing. There is still much to understand about Long Covid, but what is not well understood should not be ignored.

Long Covid is likely the first illness in history that has been defined by patients through social media platforms such as Twitter and Facebook. People with Long Covid formed a movement that demanded recognition of what was happening to them. During the first wave of the pandemic in 2020, online testimonials of prolonged symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were the only source of reassurance to others with a similar experience, including this author (2). In the absence of any guidance or recognition about the possibility of a persistent illness, peer support is all that people with Long Covid had. Many previously healthy and active people described persistent symptoms of the acute illness that fluctuated, with new symptoms appearing weeks later. In many countries, most nonhospitalized people did not have lab confirmation of SARS-CoV-2 infection owing to lack of access to community testing, so their symptoms remained without a diagnosis.

By summer 2020, thousands were joining social media support groups. A common theme started to emerge: lack of recognition by the medical profession. Patients, including doctors, with Long Covid were consulting their health care providers, and their symptoms were commonly minimized, dismissed, or labeled as anxiety (3). A narrative emerged of people struggling to make sense of their symptoms and forming their own groups to understand and research what was happening to them in an international citizen science movement (4). The testimonials of people living with Long Covid demonstrated themes of stigma and discrimination.

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