UCSF Health physicians have successfully treated a patient with severe depression by tapping into the specific brain circuit involved in depressive brain patterns and resetting them using the equivalent of a pacemaker for the brain.
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.
First this week, Contributing Correspondent Cathleen O’Grady talks with host Sarah Crespi about controversy surrounding the use of Botox injections to alleviate depression by suppressing frowning.
Next, researcher Stephen Zhang, a postdoctoral fellow at the Beth Israel Deaconess Medical Center, discusses his Science Advances paper on what turns on the fruit fly sex drive. Finally, we are excited to kick off a six-part series of monthly interviews with authors of books that highlight the many intersections between race and science and scientists. This week, guest host and journalist Angela Saini talks with Keith Wailoo, professor of history and public affairs at Princeton University, who helped select the topics about the books we will be covering and how they were selected.
For many people, depression turns out to be one of the most disabling illnesses that we have in society. Despite the treatments that we have available, many people are not responding that well. It’s a disorder that can be very disabling in society. It’s also a disorder that has medical consequences. By understand the neurobiology of depression we hope to be able more to find the right treatment for the patient suffering from this disease. The current standard of care for the treatment of depression is based on what we call the monoamine deficiency hypothesis. Essentially, presuming that one of three neurotransmitters in the brain is deficient or underactive. But the reality is, there are more than 100 neurotransmitters in the brain. And billions of connections between neurons. So we know that that’s a limited hypothesis. Neurotransmitters can be thought of as the chemical messengers within the brain, it’s what helps one cell in the brain communicate with another, to pass that message along from one brain region to another. For decades, we thought that the primary pathology, the primary cause of depression was some abnormality in these neurotransmitters, specifically serotonin or norepinephrine. However, norepinephrine and serotonin did not seem to be able to account for this cause, or to cause the symptoms of depression in people who had major depression. Instead, the chemical messengers between the nerve cells in the higher centers of the brain, which include glutamate and GABA, were possibilities as alternative causes for the symptoms of depression. When you’re exposed to severe and chronic stress like people experience when they have depression, you lose some of the connections between the nerve cells. The communication in these circuits becomes inefficient and noisy, we think that the loss of these synaptic connections contributes to the biology of depression. There are clear differences between a healthy brain and a depressed brain. And the exciting thing is, when you treat that depression effectively, the brain goes back to looking like a healthy brain, both at the cellular level and at a global scale. It’s critical to understand the neurobiology of depression and how the brain plays a role in that for two main reasons. One, it helps us understand how the disease develops and progresses, and we can start to target treatments based on that. We are in a new era of psychiatry. This is a paradigm shift, away from a model of monoaminergic deficiency to a fuller understanding of the brain as a complex neurochemical organ. All of the research is driven by the imperative to alleviate human suffering. Depression is one of the most substantial contributors to human suffering. The opportunity to make even a tiny dent in that is an incredible opportunity.SHOW LESS
The number of older people, including those living with dementia, is rising, as younger age mortality declines. However, the age-specific incidence of dementia has fallen in many countries, probably because of improvements in education, nutrition, health care, and lifestyle changes.
Overall, a growing body of evidence supports the nine potentially modifiable risk factors for dementia modelled by the 2017 Lancet Commission on dementia prevention, intervention, and care: less education, hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes, and low social contact.
We now add three more risk factors for dementia with newer, convincing evidence. These factors are excessive alcohol consumption, traumatic brain injury, and air pollution. We have completed new reviews and meta-analyses and incorporated these into an updated 12 risk factor life-course model of dementia prevention. Together the 12 modifiable risk factors account for around 40% of worldwide dementias, which consequently could theoretically be prevented or delayed.
The potential for prevention is high and might be higher in low-income and middle-income countries (LMIC) where more dementias occur. Our new life-course model and evidence synthesis has paramount worldwide policy implications. It is never too early and never too late in the life course for dementia prevention. Early-life (younger than 45 years) risks, such as less education, affect cognitive reserve; midlife (45–65 years), and later-life (older than 65 years) risk factors influence reserve and triggering of neuropathological developments.
Culture, poverty, and inequality are key drivers of the need for change. Individuals who are most deprived need these changes the most and will derive the highest benefit.
“We are learning that tactics to avoid dementia begin early and continue throughout life, so it’s never too early or too late to take action,” says commission member and AAIC presenter Lon Schneider, MD, co-director of the USC Alzheimer Disease Research Center‘s clinical core and professor of psychiatry and the behavioral sciences and neurology at the Keck School of Medicine of USC.
LOS ANGELES — Modifying 12 risk factors over a lifetime could delay or prevent 40% of dementia cases, according to an updated report by the Lancet Commission on dementia prevention, intervention and care presented at the Alzheimer’s Association International Conference (AAIC 2020).
Twenty-eight world-leading dementia experts added three new risk factors in the new report — excessive alcohol intake and head injury in mid-life and air pollution in later life. These are in addition to nine factors previously identified by the commission in 2017: less education early in life; mid-life hearing loss, hypertension and obesity; and smoking, depression, social isolation, physical inactivity and diabetes later in life (65 and up).
Schneider and commission members recommend that policymakers and individuals adopt the following interventions:
- Aim to maintain systolic blood pressure of 130 mm Hg or less from the age of 40.
- Encourage use of hearing aids for hearing loss and reduce hearing loss by protecting ears from high noise levels.
- Reduce exposure to air pollution and second-hand tobacco smoke.
- Prevent head injury (particularly by targeting high-risk occupations).
- Limit alcohol intake to no more than 21 units per week (one unit of alcohol equals 10 ml or 8 g pure alcohol).
- Stop smoking and support others to stop smoking.
- Provide all children with primary and secondary education.
- Lead an active life into mid-life and possibly later life.
- Reduce obesity and the linked condition of diabetes.
‘Journal of Neurology, Neurosurgery & Psychiatry” (July 10, 2020):
We tested the hypothesis that apathy, but not depression, is associated with dementia in patients with SVD. We found that higher baseline apathy, as well as increasing apathy over time, were associated with an increased dementia risk. In contrast, neither baseline depression or change in depression was associated with dementia. The relationship between apathy and dementia remained after controlling for other well-established risk factors including age, education and cognition. Finally, adding apathy to models predicting dementia improved model fit. These results suggest that apathy may be a prodromal symptom of dementia in patients with SVD.
Cerebral small vessel disease (SVD) is the leading vascular cause of dementia and plays a major role in cognitive decline and mortality.1 2 SVD affects the small vessels of the brain, leading to damage in the subcortical grey and white matter.1 The resulting clinical presentation includes cognitive and neuropsychiatric symptoms.1
Apathy is a reduction in goal-directed behaviour, which is a common neuropsychiatric symptom in SVD.3 Importantly, apathy is dissociable from depression,3 4 another symptom in SVD for which low mood is a predominant manifestation.5 Although there is some symptomatic overlap between the two,6 research using diffusion imaging reported that apathy, but not depression, was associated with white matter network damage in SVD.3 Many of the white matter pathways underlying apathy overlap with those related to cognitive impairment, and accordingly apathy, rather than depression, has been associated with cognitive deficits in SVD.7 These results suggest that apathy and cognitive impairment are symptomatic of prodromal dementia in SVD.