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.

The brain’s social network

Neuroscientists often attempt to attribute various behaviors and traits to certain regions of the brain. These findings make for neat science and great headlines, and while some of these results are little better than phrenology claims, many are highly reliable. The good ones are confirmed and replicated by multiple labs and substantiated using a variety of different methods, such as lesioning or animal and human imaging models. For example, we know with relative certainty that much of the occipital lobe is in charge of processing visual information and that the hippocampus is heavily involved in transitioning from short-term to long-term memory. However, there is much in our behavior and our brains that we still do not understand, and it is highly tempting to simply assign certain sections of the brain to different traits when in fact the underlying mechanisms are much more complicated. This tendency has become increasingly easy in the past decade with the rise of functional neuroimaging studies, where a region of the brain is seen to “light up” with activity when performing certain types of tasks. Voxel-based morphometry (VBM) studies take these investigations a step further, looking at how gray matter volume in our brains correlates to different traits and behaviors. Two recent examples of VBM studies have investigated the neural correlates of social networking and extroversion, finding connections between amygdala size (among other regions) and social tendencies.

The first study, out of University College London and published in the Proceedings of the Royal Society Biological Sciencesfound that people with more Facebook friends had increased gray matter volume in certain regions of the brain associated with social interactions. The authors of the study hypothesized that the number of one’s online friends could predict the relative brain size of regions important for social networking, particularly those involved in social cognition and mentalizing (the ability to recognize social cues and take another’s perspective). These areas include the fronto-parietal cortical circuit, medial prefrontal cortex, and amygdala. However, these frontal cortical regions were not identified in the study, and instead the researchers discovered greater volume in the left middle temporal gyrus, right entorhinal cortex, and right posterior superior temporal sulcus, as well as the amygdala to a lesser extent. These areas are implicated in social cognition, perception of movement and intention (both physical and social), and autobiographical and associative memory. Based on these findings, the authors speculate that individuals with greater brain volume in these regions are more adept at the skills needed to maintain online socio-personal connections, such as enhanced memory of face-name combinations and awareness of movement of individuals in social circles. However, of these regions only the amygdala was correlated with real life social interactions, and none of the other originally proposed areas were found to correlate with social network size.

The second study, published this week in PLoS ONE, also reports that individuals who are more extroverted show increased volume in the amygdala, as well as in the orbitofrontal cortex (OFC). Researchers from the Netherlands administered the NEO Five Factor personality assessment to 65 individuals to subjectively measure extroversion and neuroticism levels. They also had participants undergo an MRI scan and used VBM analysis to measure the size of certain pre-determined regions of the brain against extroversion scores, including the amygdala, anterior cingulate cortex, and OFC. Controlling for age, sex, and total gray matter volume, researchers discovered that individuals who scored higher on the extroversion scale had significantly larger amygdala and orbitofrontal cortices, as well as finding a significant correlation between total gray matter volume and extroversion scores.

As stated above, the amygdala is one of the brain’s emotional centers and is important in social interactions, both online and offline. It is crucially implicated in recognizing and processing positive and negative emotions, both in oneself and from the facial expressions of others. The OFC is also commonly associated with emotion regulation, as well as reward valuation and decision-making, mainly through its connections to limbic structures such as the amygdala, striatum, and hypothalamus. However, it is not typically linked to social interactions, and the authors speculate that their findings are evidence of the amygdala and OFC’s involvement in a greater sensitivity to positive experiences and social interactions, rather than interpersonal skills themselves.

While the findings from these two studies are intriguing and compliment one another nicely, caution must be taken in the interpretation placed on these results. Correlation analyses state only an association, not a causation, and, as recently brilliantly exhibited by Business Week, these connections can be highly questionable at times. This is particularly true of imaging studies, where investigators can go fishing for regions to attribute their target behaviors to. Interpretations of correlations are quick to come by, and rationales for connections in unexpected areas of the brain can be justified all too easily when a publication is on the line. A priori regions of interest are thus crucially important, providing groundings for current explorations based on previous studies and alternative research methods. I am in no way denouncing VBM studies and their value and viability generally, or these studies in particular, however, I do caution against the interpretations that can be carelessly made with them. Additionally, in studies like these, it is unknown whether the size of the regions predicts the behavior or if the brain adapts and grows to incorporate new connections based on the repetition and reinforcement of certain actions. In regards to the studies at hand, their confirmation of the amygdala’s role in social interactions is highly supported, however, it is unknown whether the increase in brain size is a predictor of social ability and network size, or whether practice of interpersonal skills helps to foster neurogenesis in these regions.

The neuronal defense

There’s been a lot of discussion recently about structural and hormonal changes in the brain being to blame for misbehavior, whether it’s a philandering husband (or senator) or a psychopath. To some extent these are valid arguments; higher testosterone levels have been linked to sensation seeking and greater sexual desire, and abnormalities in the limbic system–particularly the amygdala, which processes fear and emotion, and the frontal cortex, which is in charge of inhibition and rational thought–are often seen in persons who commit crimes. However, to use these structural phenomena as excuses or arguments, as in, “My brain made me do it,” is akin to proclaiming, “Yes, I did this.” Obviously, there are rare and extenuating circumstances when an individual’s actions are truly no longer under their own control, such as in the case of a tumor in the frontal lobe changing the temperament and personality of an individual. However, for the vast majority of individuals, we are our brains, and saying you are “pre-wired” to cheat or fight or steal is not an excuse. If anything, it is a greater indication of the potential for recidivism and an added incentive for either punishment or preventative measures.

Excess testosterone is not a pathology like schizophrenia or mental retardation, which can be used as a defense in court for criminal actions. Additionally, if you blame chemicals like testosterone or a lack of oxytocin for misbehavior, then what is to stop us from exonerating people who commit crimes because they are on a synthetic drug like crack cocaine or PCP? And, seeing as how presumably not all men with increased testosterone cheat and not all individuals with abnormal amygdalas commit crimes or become sociopaths, it is difficult to argue that your brain and neurotransmitters make you do something when these same conditions do not compel others down a similar path.

David Eagleman’s article in The Atlantic is a particularly insightful and eloquent investigation into both sides of this issue that I highly recommend. Instead of focusing on the question of guilt and the implications that recent advances in neuroscience and neuroimaging have on culpability, Eagleman wisely shifts his focus to sentencing and the constructive ways we can incorporate our new crude knowledge of the brain into the justice system. For example, he suggests concentrating on the potential for recidivism and reform instead of retribution when determining sentencing. Drug courts have already started shifting towards this perspective, supported by the recent initiative by the Global Commission on Drug Policy, marking the 40 year anniversary of the War on Drugs. Not only is it important to provide drug users with treatment instead of punishment, our economy simply can not accommodate the deluge of drug-related crimes into the penal system, most strikingly demonstrated by the decision in California this month to release 3,000 prisoners before their sentences were up due to a lack of resources.

Child criminal courts have also dealt with the issue of neuroanatomical defenses for quite some time, as it is widely established that the frontal cortex is the last area of the brain to finish developing, not reaching full maturation until the mid-20s. Countless juvenile defenders have used this argument to insist that their client was not a rational individual at the time of their crime, and, therefore, should not be held accountable for their impulsive and illegal actions. While this is certainly a valid point–and one that is typically taken into consideration when distributing sentencing–it is important to bear in mind that not all 15 year-olds commit crimes. Therefore, this universal neural stage of adolescence that we all pass through is not necessarily a credible criminal defense; otherwise, all teenagers would be running rampant and wreaking even more havoc than they already do. Also, there are innumerable studies citing the increased risk of offense in impoverished or violent areas, yet this is not used as an excuse for a crime in these communities. This evidence is absolutely a reason to reform the social system that creates these pockets of poverty and risk, but it does not compel juries to acquit defenders of their crimes simply because of the neighborhood they were raised in.

At some point, people must take responsibility for their actions and face up to the consequences and not blame an integral part of themselves of going rogue and acting out of character. When you make a decision, it is your brain acting and your neurons firing; you can not excuse an action because of the claim that you could not control these impulses. There is no outside force urging you to act or not; it is your own will being administered and carried out. Eagleman’s idea of a spectrum of culpability is a sensible one that I support, and I fully agree that in the vast majority of offenses, reform and rehabilitation should be the goal, rather than retribution. However, this still leaves the topic rife with ambiguity, for where do you draw the line? At what point will we stand up and take responsibility for our own actions?

(Thanks to Tristan Smith for The Atlantic article.)