The gastrointestinal (GI) tract in humans provides a home for many (10¹⁴) bacterial organisms. The colonization of the GI by bacteria, or microbiota, starts at birth and continues throughout early development and life. These microbiota affect many bodily functions, aiding metabolism, modulating inflammation, and defending against harmful micro-organisms. Each person has a unique profile of microbiota, which is influenced by genetics and the environment. Healthy people, however, generally have similar numbers and distributions of microbiota. Interestingly, disorders of the GI tract have a high comorbidity with mental illness.

It is not surprising then that research in this field has grown, with labs hoping to gain a better understanding of the ‘gut-brain-axis.’ If these labs can elucidate the effect of microbes in the GI tract on the central nervous system, they could shed light on why more than half of patients with irritable bowel syndrome meet the criteria for mood disorders, or how GI tract disorders and mental illnesses can be more effectively treated.

Many researchers are currently focusing on how variations in the composition of microbiota impact physiology and contribute to disease, such as obesity and inflammation. Increasingly, studies have been revealing that these microbiota communicate with the brain and influence its function and behavior, potentially by neural, endocrine, and immune pathways.

In 2010, Jane Foster and colleagues at McMaster University in Ontario found that microbiota may affect gene activity during central nervous system development. They compared how germ-free and normal mice act on an

Elevated plus maze used for testing anxiety-like behaviors in mice (from the Mouse Phemone Database)

elevated plus maze (shown to the right) that is used for testing anxious behaviors. Normally, mice avoid areas they might be seen and spend more time in the less visible arms of the maze.

While the normal, control mice did spend more time in the ‘closed’ over ‘open’ arms, germ-free mice spent more time in the open arms, exploring them and showing less anxious behaviors. After the experiment, Foster and her team examined the brains of the mice and found alterations in the gene expression levels of several genes in the germ-free mice, particularly in those affecting brain-derived neurotrophic factor (BDNF) and serotonin (5HT). BDNF and 5HT had been previously suggested to affect emotion and anxiety.

Importantly, the study shows that the absence of microbiota can alter behavior and suggests that the microbiota in the GI may impact gene expression during the sensitive period of early brain development. Although studies in mice need to be proven translatable to humans, a pediatrician was interested in collaborating with Foster to determine if he could determine a way to fix the microbiota profile of some of his patients before puberty.

Using germ-free animals and animals exposed to infections, researchers have suggested a role for microbiata in regulating mood, anxiety, cognition, and pain. More research is needed to decide whether formulating or modifying gut microbiota could serve as a possible therapeutic for central nervous system disorders. Foster suggests combining preclinical work on microbiota with clinical work on the impact of antibiotics and probiotics on brain development and function. This could allow researchers to better understand bottom-up control and provide inspiration for novel interventions in mental illness. In the end, communication between scientists and clinicians in various fields and domains is crucial to determine the relationship between gut microbiota and the central nervous system.

Sources:

Microbes Manipulate Your Mind – The Guardian

Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour – Nature Reviews Neuroscience

Effects of gut microbiota on the brain: implications for psychiatry – Journal of Psychiatry and Neuroscience

Reduced anxiety-like behavior and central neurochemical change in germ-free mice – Neurogastroenterology and Moltility

We all know androgens and estrogens as sex hormones, right? You know, those chemicals that regulate reproductive behavior and ensure the continuation of species. There is definitely behavioral evidence of the biological importance of these steroid hormones, but could there be a way to quantitatively measure exposure to them? There is research that says yes, or at least, possibly.

Based on correlational data, the hypothesis that digit ratio can be used as a marker of prenatal hormone exposure has been floating around. Supposedly, having a ring finger (fourth digit, “4D”) that is larger than your second finger, “2D” is indicative of androgen exposure, and more masculinization. In contrast, having a second digit that is equal to in length or longer than your fourth digit is the more feminine phenotype, resulting from less androgen exposure.This, however, is a largely over-simplified perspective.

In a 2009 study, Sheri Berenbaum and colleagues compared the digit ratios of normal males (n=66) and females (n=90) with those of women who suffered from complete androgen insensitivity syndrome (CAIS, n=16). If the hypothesis was correct, these women would be expected to have high 2D:4D ratios, and they did – as compared to men – but not relative to the control women. Additionally, the study found no predictability of group membership (control male, control female, CAIS female) based on digit ratio, whether the subjects were given equal probability of being in either group or basing the probability on group size…group sizes which were oddly varied in this particular study.

Another thing I found peculiar was the method used to obtain the finger measurements – rather than directly measuring the participants’ fingers, the researchers used photocopies of their hands, which would seem to allow for more variation (pressure, straightening of fingers, etc.) Interestingly, the paper mentions that male and female skeletons do not show digit ratio differences, and that the androgen action might be having more of an effect on tissue distribution than bone growth.

More recently, Zhengui Zheng and Martin Cohn at the University of Florida reported a study in mice suggesting that digit ratio is a function of the balance between androgen and estrogen signaling within a particular period of prenatal development. Essentially, the researchers demonstrated differential expression between digits in androgen receptors (AR) and estrogen receptors (ER) that ends up having an effect of chondrocyte (cartilage cell) proliferation. They were able to manipulate digit ratio either by antagonizing the receptors or treating the mice with estrogen or DHT (the precursor to testosterone). ER antagonism masculinized ratios in both males and females (smaller 2D:4D) and AR antagonism feminized the ratios in males. Also, males exposed to estradiol showed feminized ratios and females exposed to DHT showed masculinized ratios. The data also showed that the ratio changes could be accounted for principally by changes in the fourth digit. Perhaps there is some weight to this theory, and perhaps skeletal development is involved…
But why is this interesting? While sex hormones are evolutionarily vital, how significant could the relative lengths of our fingers possibly be? Part of what makes these kinds of studies so cool is that the changes in AR and ER signaling taking place in digit development are occur concurrently with changes in AR and ER signaling that tend to masculinize and feminize the brain. There have been studies that have found evidence for correlation between various behaviors, fertility, sexual orientation etc. and digit ratio. Indeed, there is a lot more biologically based research to be done, but this finger phenomenon is certainly an interesting one. I’ll be looking into more behavioral studies for next time…

Fingers as a Marker of Prenatal Androgen Exposure – Endocrinology
Developmental basis of sexually dimorphic digit ratios – PNAS

Ever wonder why people still “talk with their hands” when they’re on the telephone? We often use hand gestures while speaking even at times when the listener cannot see them. Gestures are processed in the same areas of the brain as speech (think sign language): the left inferior frontal gyrus (Broca’s) and the posterior middle temporal gyrus (Wenicke’s area). Hand movements help us to communicate more efficiently and emphasize certain points of the message we are trying to convey to our conversational partners. They’re an indication of our thought process throughout the discussion. Evolutionary insight proposes that the language brain regions, which originally supported the pairing of body language and meaning, have been adapted in humans for spoken language; however, we still don’t know precisely the reason why people gesture, and more interestingly, why some people use gestures more often than others.

A team of German researchers recently conducted a study suggesting a strong relationship between gesturing, fluid intelligence, and brain development. The scientists at Humboldt-Universität zu Berlin selected fifty-one 11th graders gifted in math and science for their experiment and separated them into groups of high and average fluid intelligence, which is responsible for learning and recognizing patterns. They asked both groups to solve analogy tasks that involved pairing sets of geometric configurations correctly. The students with higher fluid intelligence obviously performed better on the task than the students with average fluid intelligence, but they also produced more representational hand and arm gestures while describing how they solved the problems.

All of the students verbally explained the same method to solve the problems, but the students’ intelligence could be distinguished by simply observing their hand movements. The researchers considered that specifically the motion of hands rotating around an imaginary axis (a strategy that was never mentioned in the students’ accounts of the problems) was a reflection of mentally rotating the shapes and using spatial reasoning. Participants with higher fluid intelligence therefore engaged in more active mental representation during problem solving.

Furthermore, fMRI scans of the students’ brains showed that individuals with higher fluid intelligence and who had demonstrated more hand gestures showed greater cortical thickness in Broca’s areas and other areas in the left hemisphere such as the superior frontal cortex.

Both gesture and speech appear to be founded on the same underlying system of simulated action in mental imagery. We haven’t concluded whether gestures facilitate the development of fluid intelligence or whether the gestures themselves are its product. However, since young children are shown to gesture when learning new concepts and expressing new ideas, the activity may facilitate in cognitive development by simulating thought.

Show Your Hands – Are You Really Clever? Reasoning, Gesture Production and Intelligence – Linguistics: An Interdisciplinary Journal of the Language Sciences

What would happen if humans were like turtles – alone at birth with no mom to guide them back home? We probably would not survive very long before getting attacked and/or eaten by something bigger than us. For many animal species, instinct guides survival. But for humans and other mammal species, nurture as an infant is crucial to our development.

Weaver et al investigated the phenomenon of nurture in rats. They noted that some rat moms extensively licked and groomed their pups, while others ignored their pups. Pups that received attention during the first week of life grew up to be happy and calm, while those that were ignored grew up to be anxious, and were more prone to disease. Epigenetics studies the genomic changes that occur in response to the external environment. The differences in behavior are due to a change in a glucocortocoid receptor (GR) gene during development. At birth, the gene is highly methylated and inactive. If a rat mother is attentive towards her pups, the pups’ GR gene gradually demethylates, making the gene more active. These pups will be more relaxed in response to stress. Those that were not given attention, and do not express the GR gene, respond poorly to stress. You can try being a rat mom in an interactive game here .

A related study by McGowan et al studied hippocampal tissue in humans that had committed suicide and been abused as a child, and humans that had committed suicide with no history of child abuse. When compared to controls and subjects that were not abused, the subjects that had been abused had decreased level of a GR protein. This shows that events later in life (such as those leading to a suicide) do not actually alter genetic makeup, rather, it is the early childhood interactions which cause epigenetic changes leading to adult behavior. These data are consistant with those of the rats and  show the importance and effect of having proper nurture as a child.

But in reality, how important is it to be calm and controlled in response to stress? Rats are found in urban areas as well as in the wild.

What were to happen if one of the calm happy rats were to stumble upon a mouse (or, in this case, rat) trap? It would be less concerned about danger and be more likely to die, whereas an anxious rat would be guarded and could better survive the harsh environment.

What is the significance of these epigenetic changes for humans? Maybe living in a developed society has prevented us from realizing just how much nurture plays a role in development. Do those born into a war-ridden society have an inactive GR gene and thus a guarded and anxious personality? This is probably advantageous for survival.

In our society, we will of course never be left alone immediately after birth to fend for ourselves. But, what degree of nurture must we receive in order to grow up to be productive members of society? Why are species like turtles able to survive without a mom? Epigenetic studies will be key in future questions concerning nature and nurture.