Hallucinogens, starvation, and magnets: A new cure for depression?

What do hallucinogens, starvation and magnets all have in common? No, they’re not the key ingredients for a wild and crazy weekend; they are all potential alternative treatments for depression that are being explored by researchers and clinicians alike.

Scientists have long known that the serotonin theory of depression is imperfect, yet few treatment options are available beyond the standard course of cognitive-behavioral therapy and selective serotonin reuptake inhibitors (SSRIs). In my new piece for Pacific Standard, I explore recent research that has emerged looking at some potential alternatives for depression that are rather… unconventional.

This includes giving people psilocybin, the active ingredient in so-called “magic” mushrooms, which also boosts serotonin levels and crucially taps into the amygdala, the brain’s major emotional center. Another possible avenue involves boosting ghrelin levels in the brain, a hunger hormone that may also play a role in protecting neurons from the destructive effects of stress, particularly in the hippocampus. Alternatively, using high-powered magnets, researchers and clinicians are able to activate certain key parts of the brain that can potentially lead to a suppression of other over-active emotional regions, turning down our feelings of anxiety or depression.

While none of these options is perfect, they do provide an encouraging new perspective, thinking outside the box to treat this condition that will afflict at least one in ten of us at some point in our lives.

You can check out the full story in Pacific Standard here.

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Amazing aging discoveries: It’s in the blood

In a candidate for coolest experiment of the year, scientists at Stanford University surgically created conjoined-twin mice of different age pairs to assess the impact of young versus old blood on the brain.

Published this month in Nature, researchers investigated the effect of proteins in the blood to encourage or inhibit neurogenesis (new cell growth in the brain), concentrating on the dentate gyrus of the hippocampus, a key area in memory consolidation and a region known to be susceptible to environmental and age-related changes in cellular growth and death. The hippocampus is strategically located in an area rich with blood vessels, making it an ideal region to look for the effects of aging blood on the brain.

First, looking at older mice, scientists identified a decrease in neurogenesis and synaptic plasticity, as well as behavioral learning and memory, confirming deficits commonly seen in aging populations.

Next, using a procedure called parabiosis, pairs of young and old mice were surgically attached to one another, enabling the sharing of blood, plasma, and proteins between the two through their newly conjoined cardiovascular systems. In the heterochronic condition (unions of young to old mice), significant differences in the levels of new neurons and progenitor cells (similar to stem cells) were seen in each of the pair members. Older heterochronic mice had significant increases in these levels as compared to their isochronic paired counterparts (unions of old to old mice), whereas the unlucky younger mice of the heterochronic pairs saw significant reductions in the number of these new cells compared with the young isochronic mice. Additionally, extracellular recordings were taken from the heterochronic pairs, and a decrease in long-term potentiation–an indicator of the cellular plasticity essential in learning and memory–was decreased in the young heterochronic mice but increased in the older ones, further indicating the deleterious effects of old blood on the brain.

To confirm that the aging effects seen were due to proteins in the blood of these animals, a  different set of young mice were injected with the plasma from either young or old animals. Again, young mice injected with the plasma from older mice saw decreases in the number of new cells in the dentate gyrus, indicating impairment in neurogenesis, whereas no differences were seen in the animals who were given younger blood. Behaviorally, these young blood recipients showed no changes in their learning and memory abilities, however, the mice who received the plasma from older mice now exhibited impairments in their fear conditioning and spatial learning behaviors similar to those seen in aging populations.

Finally, using a method known as a proteomics, researchers attempted to identify the individual proteins that might be causing these aging effects. They measured the levels of 66 individual proteins in the plasma taken from young and old mice and then compared them to the heterochronic pairs. In normal aging mice, 17 of these proteins were identified as being negatively correlated with neurogenesis, an increase in the proteins signifying a decrease in new cell generation. Increases in these specific protein levels across aging seem to inhibit neurogenesis, and 16 of these proteins were also found to be elevated in the young heterochronic paired mice. The team then narrowed down the field to one particular protein, CCL11, which is also known to have an age-related increase in humans. Scientists performed one last experiment to confirm the role of CCL11 in aging, injecting the protein into mice. This resulted in the anticipated increase in CCL11 levels in plasma, as well as a corresponding decrease in neurogenesis and new cells in the hippocampus.

The depth of this study, including the variety of different methods the researchers used, is one of the most impressive things about it, independent of the exciting discoveries they have made. Additionally, the idea of pinpointing a specific protein to stave off aging is one that keeps popping up in science, and the fact that CCL11 has been shown to have aging effects in humans as well as mice suggests that this might be a promising one to target. Or, on the flip side, we might see an unfortunate increase in geriatric vampire literature as a result of these findings. You never know.

A neural workout

Last week I wrote about some of the emotional benefits of regular moderate exercise. This week, several timely new articles have come out touting the cognitive advantages of even minimal daily activity.

Numerous studies have shown evidence of the neurological benefits of exercise, which can foster cell growth and new cell generation (known as neurogenesis). One region that seems to be particularly impacted is the hippocampus, an area known to be involved in memory consolidation. Prior studies in mice have shown that exercise can trigger neurogenesis in the hippocampus, and in humans exercise has been linked to better performance on memory assessments and spatial learning, as well as a decreased risk for dementia. While some of these benefits are believed to be due to the new proliferation of cells in the hippocampus and other associated regions of the brain, several studies published recently suggest that exercise may serve more as a protective factor against neurological decay than a booster of existing memory performance.

A study presented last week at the Alzheimer’s Association International Conference by doctors at the University of California, San Francisco used mathematical modeling to estimate risk factors for the development of Alzheimer’s disease, and they came up with seven critical variables: diabetes, hypertension, obesity, smoking, depression, low education, cognitive inactivity, and physical inactivity. The researchers predicted that these seven variables were to blame in nearly 50% of current Alzheimer’s diagnoses, and lack of exercise alone was attributed to over 20% of cases. In addition, the researchers predicted that reducing these risk factors could potentially stave off over one million future diagnoses. However, these numbers are estimations, and first author Dr. Deborah Barnes–as well as other lead researchers in the field–caution against using these statistics as hard goals and guidelines. Barnes notes that while these seven factors do increase the risk for Alzheimer’s, a causal relationship has not yet been established, and therefore simply changing one’s behavior in regards to one or all of the variables may not be enough to prevent the onset of the disease.

While the association between Alzheimer’s and exercise is still tentative, there is little doubt about the mental and physical benefits of daily activity. However, previous studies have largely focused on the advantages of moderate-to-high levels of exercise in humans and animals, such as the widely recommended guidelines of 30 minutes of exertion 5 days a week. But what about people who are unable to workout that much or that often? Fortunately, there is new evidence that the even minimal movement can offer cognitive benefits. In a longitudinal study investigating elderly adults aged 70 and up, those with the least amount of daily average energy expenditure had the greatest amounts of cognitive decline over a period of three years, whereas those who were the most active had significantly less cognitive impairment both during the three-year study period, as well as after a five-year follow-up. It seems that even small exertions like walking around the block, doing household chores, or even fidgeting–behaviors that often go unreported in other studies of physical activity–can help stave off the neural deterioration that commonly occurs as we progress into old age.

However, if you still can’t be bothered to get up and start moving, you can always resort to surgical implants and get one of these to improve your memory.