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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An unconventional treatment for depression: Sleep deprivation

I watched a good ‘psychological thriller’ the other night – Side Effects by Steven Soderbergh – that centers on a woman’s debilitating depression and critiques the pharmaceutical industry’s untoward influence over clinicians (it turns into a plot-twisty crime thriller, but that’s beside the point). The film got me thinking about our reliance on psychotropic medications to treat psychological distress, and how helpless we are when these pills don’t work.

I’ve written before on the over-medicalization of psychiatric disorders and the pharmaceutical industry’s role in this controversy, but this time the topic got me thinking about possible alternative treatments for depression, other than cognitive-behavioral therapy or mood-altering medications.

One innovative method for treating depression that has received attention is sleep deprivation. Acute sleep deprivation has been touted as having a 60% success rate in immediate relief from depression; however, this effect is temporary, only lasting until you finally do nod off.

At first this might seem surprising, after all, think about how cranky and irritable you feel after a poor night of sleep. But complete deprivation (i.e. missing an entire night’s sleep, or more than 12 hours) can actually have the opposite effect. Remember that loopy, giggly, hysterical feeling you used to get staying up all night at a sleepover, or at 5am in the library while studying for exams? It is believed that this phenomenon is at least partially caused by an alteration in activation and connectivity in our frontal cortex, potentially offsetting the harmful effects chronic depression can have on this area.

It is still relatively unknown how or why exactly this works though. A recent study from Tuft’s University attempted to answer this question by testing sleep deprivation and its efficacy as an anti-depressant in depressed mice. First, researchers confirmed that depressed animals who were sleep-deprived for 12 hours displayed significantly less depressive symptoms than control depressed mice. Then, for the first time, they were able to link this effect to the activation of a certain type of brain cell, astrocytes, that release a particular protein, adenosine.

Adenosine is important in sleep regulation, and its absence has also been implicated in a greater risk for depression. Adenosine release is increased the longer you’re awake (to a point), making you feel less aroused and more tired, and acting as part of your normal sleep-wake cycle. A beneficial side effect of its release now also appears to be an alleviation of depressive symptoms. However, after 72 hours of sleep deprivation there was no change in adenosine levels, as the astrocyte cells had largely shut down by this point. Thus, there was no effect of more extreme sleep deprivation on feelings of depression. Also, as soon as you do catch up on some zzz’s your adenosine levels return to normal and the anti-depressant effects disappear.

Adenosine’s effect on depression potentially works by altering the electrical signals in your brain, causing an immediate change in mood and behavior. Other fast-acting, unconventional treatments for depression, like deep brain stimulation and electro-shock therapy, are thought to work in a similar manner, impacting the brain’s electrical currents. These treatments also last much longer, suggesting that there may be a way to channel adenosine’s electrical effect into a longer-term solution.

I should be clear that I am in no way against using psychotropic medication to treat psychiatric disorders; in fact, in many instances these pills are absolutely essential. But in cases where these medications don’t work, or where their Side Effects are too severe (seriously, go see the movie!), it is important to have well-researched alternatives to the standard course of treatment. Also, it’s always nice to know how to get a good natural high every now and then, if you can stay up that long.

(Originally posted on Mind Read)

A Thanksgiving ode to tryptophan

My favorite holiday is on Thursday. And while I can’t be at home in the States to celebrate, being an ex-pat at Thanksgiving does have its perks, as I get to attend multiple alternate feasts over the weekend. That means twice the stuffing, twice the cranberries, twice the turkey, twice the tryptophan.

Yes, tryptophan. That infamous amino acid we use to justify dozing off during our aunt’s vacation slideshow after the big meal. Tryptophan is an essential amino acid, a protein precursor that the body uses to build various chemical structures. This includes serotonin, one of the primary neurotransmitters in the brain that is involved in everything from decision-making to depression. Serotonin is also a precursor to melatonin, which is important in sleep and wakefulness and is where the tryptophan-tiredness link comes in. However, despite the popular neuro-myth, turkey is actually no higher in tryptophan concentration than other types of poultry. Numerous different plant and animal proteins provide us with our daily doses of tryptophan, with sunflower seeds, egg whites and soy beans having some of the highest concentrations of the amino acid. In fact, turkey comes in at a measly 10th on the list of tryptophan sources.

Instead, the relation between eating and sleeping seems to be more dependent on the amount of food consumed, rather than the type we eat. Insulin is released after every meal, particularly ones high in carbohydrates, and the more carbs consumed, the more insulin is produced. This increase then changes the chemical levels in our bloodstream, affecting the re-uptake and release of various amino acids. Ultimately these changes result in greater amounts of tryptophan crossing the blood-brain-barrier and being taken up into the brain. There the tryptophan is converted to serotonin, some of which is also metabolized into melatonin, causing our postprandial nap.

Tryptophan’s influence on serotonin levels doesn’t just affect sleep cycles. The link between depression and low serotonin levels is well established, and tryptophan supplements have been suggested as less invasive treatments for the disorder. Unfortunately these studies have been mostly unsuccessful to date, as mild modifications of tryptophan seem to have little to no effect on mood in most individuals. However, it is possible that people with low endogenous levels of tryptophan due to specific genetic profiles may be more susceptible to the chemical’s effect on mood, and current research is still ongoing in the matter.

So regardless of whether it’s turkey, stuffing or sweet potatoes you prefer, remember to load up your plate during Thanksgiving to get those happy drowsy effects later. It may just help you feel a little bit calmer, and prevent some of the Black Friday mayhem the next day.

Pursuing happiness

In honor of the 4th of July and in the spirit of the Declaration of Independence, The Atlantic published a nice piece on the “Pursuit of Happiness” this week, specifically on how our community and environment can shape our mood and mindset, and how local governments are initiating public service projects to aid in our psychological well-being. However, a study published in the Journal of Human Genetics last month by behavioral economists at the London School of Economics suggests that it is not external factors but rather our genes and neurotransmitters (most notably serotonin) that determine how happy we are.

Serotonin has been linked to happiness and empathy, and a depletion of it is often seen in patients with depression. Many common antidepressants work by elevating levels of serotonin in the brain, including SSRIs (selective serotonin reuptake inhibitors), the most commonly prescribed medication for depression, which prevents the retraction of serotonin back into the cell after it has been released. This recycling of serotonin occurs naturally in the brain, with neurotransmitter transporters binding to the chemical in the synapse, taking the serotonin back up into the cell, and enabling it to be released again. The serotonin transporter gene 5-HTT is involved in the expression of the proteins that form these transporters and has two different forms it can take, a long or a short version. The long allele of 5-HTT results in more transporters being expressed, however, paradoxically, researchers have recently discovered that individuals who carry two long versions of the gene are significantly more likely to report higher levels of subjective well-being than those who inherited two short versions of the allele. In the study by Dr. Jan-Emmanuel De Neve, 69% of those with the long versions rated themselves as either satisfied or very satisfied with their lives, as opposed to only 38% of people with the short versions. While this is contradictory to the theory behind SSRIs, which prevent the recycling of the neurochemical and thus enable higher levels of serotonin to be present in the synapses, the greater number of transporters in the long allele population permits faster turn-over, facilitating greater release and higher, more stable levels in the brain.

On the other end of the spectrum, individuals with short alleles are known to have decreased brain density in the amygdala and limbic circuitry, areas implicated in emotion regulation and fear responses, impairing their perception and reaction to emotional stimuli. Those with short alleles have a higher risk of depression, although this association is somewhat tenuous as the 5-HTT gene directly only accounts for 10% of an individual’s susceptibility to anxiety or depression. Most likely, it is a gene-environment interaction that determines an individual’s likelihood of developing depression, as individuals with short alleles are more prone to react poorly or with greater anxiety to bad news.

Thus, returning to The Atlantic article, to what extent can our environment really foster a positive affect, and do things like city planning–improving traffic flow or building green spaces–really influence our overall levels of happiness? How much do the little things in our environment matter? Sure it’s unpleasant to sit in traffic and much more agreeable to eat lunch under a tree, but in the greater manifestation of mood do these things affect us on such a fundamental level? After the immediate physical or aesthetic enjoyment, are there pervasive lingering effects? Surely it is more the people we surround ourselves with and our own internal perception of events that determines our mood. How much of an effect do we have on our own happiness and how much is determined by our surroundings? What truly makes us happy?