Anxiety

You are what you eat

Anyone who’s ever tried to cure the blues with Ben and Jerry’s knows that there is a link between our stomachs and our moods. Foods high in fat and sugar release pleasure chemicals like dopamine and opioids into our brains in much the same way that drugs do, and I’d certainly argue that french fries and a chocolate milkshake can perk up even the lousiest of days.

This brain-belly connection works in the opposite direction, too. Ever felt nauseous before giving a big presentation? Or had butterflies in your stomach on a first date? It’s this system relating feedback from your brain to your gut causing those sensations and giving you physical signals that something big is about to happen.

The healing power of the brain-gut connection

Anyone who's ever tried to cure the blues with Ben and Jerry's knows that there is a link between our stomachs and our moods. Foods high in fat or sugar release pleasure chemicals into the brain in much the same way that drugs do, and chocolate in particular is frequently touted as a mood-elevating treat. Now research from a team of pharmacologists in Ireland provides new support for this brain-gut connection, showing that probiotic bacteria, like those found in many strains of yogurt, can help to elevate mood and reduce anxiety. Formally referred to as the microbiome-gut-brain axis, this system has been implicated in stress responding, with gut microflora affecting the HPA (hypothalamic-pituitary-adrenal) axis and altering stress and anxiety responses. In the current study researchers gave mice Lactobacillus rhamnosus and then subjected them to various stress-inducing tests. Mice who had been fed the probiotic solution demonstrated less freezing or fear-response behaviors compared to those who were given plain broth. They were also more likely to explore exposed novel environments in an elevated maze, an indication of security and lack of anxiety. Finally, on a depression assessment mice were placed in a forced swim test (also called the behavioral despair test), where they were submerged in water and had to struggle to stay afloat. Lack of effort and time not spent attempting to swim are seen as indicators of depression and hopelessness, and probiotic-fed mice had less immobility time than broth-fed mice. Corroborating these behavioral results, test mice also had lower levels of corticosterone after being stressed than control mice.

This interaction between the brain and the gut is facilitated by the vagus nerve, the cranial nerve implicated in transmitting sensory information from internal organs to the brain. When this nerve was cut the effects of the probiotics disappeared and test mice had decreased exploratory behavior and greater periods of immobility, similar to the broth-fed mice.

The anxiolytic effects of L. rhamnosus seem to be tied to GABA, an inhibitory neurotransmitter involved in anxiety. Probiotic administration altered levels of GABA mRNA expression in regions of the brain including the amygdala, hippocampus and prefrontal cortex. In depressed individuals, GABA levels in the frontal cortex are shown to be reduced, however in the probiotic-fed animals cortical GABA levels were elevated. This led researchers to theorize that L. rhamnosus might help to protect against stressful or anxiety-producing events. GABA levels in the amygdala are also commonly elevated in depressed individuals, and GABA antagonists (which reduce the levels of the neurotransmitter in the brain) are sometimes used as antidepressants. In the current study, lower levels of GABA were found in the hippocampus and amygdala after probiotic consumption, suggesting an interaction between L. rhamnosus and the memory and emotional centers of the brain, potentially increasing associative learning and memory consolidation, and decreasing fear responding to stressful events.

The connection between diet and behavior doesn't just apply to stress. Certain highly specified restrictive diets have also been used to help treat and control a variety of neurological disorders, most notably epilepsy. First pioneered in the 1920s at John's Hopkins Children's Hospital, extreme high-fat/low-carbohydrate diets are gaining support as a possible alternative for drug-resistant epilepsy, though some physicians are still skeptical. The diet works by invoking ketosis, the process in which the body burns fat stores rather than carbohydrates for fuel. This typically occurs when the body is in a starvation state, and is also the premise on which low-carb diets are based. However, ketogenic diets also appear to have an antiepileptic effect, particularly effective in cases of severe pediatric epilepsy. Doctors are not sure why the treatment works, but one theory is that the ketone bodies produced by the liver when the body burns fat protect neurons from damage, though how or why this happens is still unknown.

A keystone paper from University College London published in 2008 was the first to empirically report the efficacy of the ketogenic diet, and a provocative profile in the New York Times of a family dealing with epilepsy, "keto" and the trials it brings has brought this treatment to national attention. The diet itself is strictly regimented and incredibly difficult to follow. It requires exact caloric measurements and proportions of protein, carbohydrates and fats, with roughly a 3-to-1 fat to carb/protein ratio. This relates to a diet of roughly 90% fat which can be dangerous, potentially triggering kidney problems and malnutrition. However the effectiveness of the treatment is gaining recognition, and patients who are on the ketogenic diet (mostly children) are carefully monitored for cholesterol levels and cardiovascular health.

Keto is now being looked at to potentially treat other serious medical disorders as well, such as Parkinson's disease and cancerous tumors. It is important to note though, that individuals being treated with a prescribed diet are also frequently on concomitant medication. Diet alone will not be able to cure all ailments, but the connection between diet and mental and physical health can not be denied, and in the very least it is a good place to start keeping yourself well and taking preventative action.

Psychiatry and psychedelia

Timothy Leary, the influential psychologist who popularized the use of LSD in the 1960s, is a polarizing figure in the debate on psychiatry and psychedelic drugs. While revered by some as the father of psychedelic research, he is reviled by others for his unconventional research methods, which culminated in Leary's lab, the Harvard Psiloybin Project, being shut down by the University in 1963. Following this set back, Leary established a private laboratory in a mansion in upstate New York where he continued conducting studies on his friends and followers. Leary's previously unseen recordings and notes from this period have recently been purchased and published by the New York Public Library, for the first time allowing us insight into the ground-breaking work done with these then novel substances. The backlash to Leary and his colleagues' extremist views regarding drug use, religion and politics (Richard Nixon at one point called Leary "the most dangerous man in America") potentially discredited any real benefits psychedelics may have in therapy for over 40 years. Experimentation and research with LSD, psilocybin (commonly known as hallucinogenic or "magic" mushrooms) and other psychedelic substances has been highly stigmatized and virtually impossible to conduct in a responsible laboratory setting. However, the restrictions against such research have gradually been lifted, and new studies are cautiously popping up heralding the clinical benefits of drugs like psilocybin and MDMA, or ecstasy.  These drugs are thought to help individuals who suffer from severe anxiety, post-traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD) and depression when paired with talk therapy methods. The effectiveness of these drugs is thought to lie in their ability to engender feelings of empathy, love and connectedness, fostering a sense of unity and compassion for oneself and fellow man. These feelings may potentially create an easier, more open environment for patients to discuss their concerns in, while safely being guided by clinicians on a therapeutic trip.

Some of the most notable research coming out of this renaissance is being conducted at John's Hopkins University, led by Dr. Roland Griffiths. Griffiths has shown that psilocybin can be used to effectively reduce levels of depression and anxiety in terminally ill cancer patients, anecdotally helping some patients to accept and come to terms with their approaching mortality.

Another influential use for this type of research is in patients with PTSD. With the recent announcement that antipsychotic drugs, frequently prescribed to help treat PTSD in combat veterans, are no more successful than placebos at improving symptoms, it seems that a new method is needed to help those suffering from severe trauma. Antidepressants are already known to be ineffective at treating PTSD, and doctors were hoping that antipsychotic medication, a stronger mood affecter, would be more successful at treating the associated symptoms, such as flashbacks, memory suppression, outbursts of anger, anxiety, anhedonia and depression. However, after six months of treatment only 5% of patients who received the drug had recovered, a number that was statistically negligible and not significantly different from those who had received a placebo.

Some researchers are now looking at more unconventional methods, such as psychedelics, as potential treatments for PTSD. Clinical researchers both in the US and in the Netherlands have shown that MDMA can be effective at reducing PTSD symptoms in survivors of rape or other traumatic events. Neurologically, MDMA stimulates serotonin in the brain, a neurochemical linked to feelings of  happiness and whose depletion is commonly attributed to depression. This activation takes place throughout the brain, but much of it is focused in the dorsal lateral prefrontal cortex (dlPFC), a region involved in higher order cognition, memory and associative learning. Simultaneously, there seems to be a decrease in amygdala activity, an area involved in fear and emotion. Taken together, these two changes in neural activity are thought to increase memory and rational, cognitive coping of the traumatic event, while down-playing the aversive negative emotions connected to it. Therefore, an individual would be able to replay the more painful details of a memory and rationally analyze and come to terms with them, facilitated by a boost in mood from serotonin and disconnected from the typical painful affective responses. This could potentially help a patient "relearn" their associations with this memory, thus allowing them to lose the negative and recreate positive affective associations for these recalled experiences.

However, just as there are side effects with any drug, so there are too with MDMA. The most notable and potentially harmful one is a resulting decrease in serotonin after the high has worn off. When the brain is flooded with a neurochemical it regulates itself to become less receptive to this neurotransmitter, adapting to re-obtain homeostasis in the chemical levels in the brain. The brain therefore becomes relatively depleted of serotonin over the next few days after taking MDMA, and after multiple uses (or abuses) of the drug this effect can become pervasive and long-lasting. While the amounts of depletion are not particularly severe after minimal use, in a patient who is already struggling with depression or anxiety this temporary loss could be potentially devastating.

Banning potentially valuable clinical research because of social concerns and constraints only hurts scientific progression and the community at large. However it is important to keep in mind that these psychedelic substances are powerful drugs with potentially very severe consequences. They should be investigated as their benefits to clinical populations could be immense, but they should still be used carefully as much is still unknown (just as much as unknown about most drugs, prescription or otherwise) about their mechanisms and effects. Responsible research is the best way to investigate the therapeutic possibilities of these drugs, and the existence of methodical record taking like Leary's can only help us in our quest to understand these substances and their effects on the mind.