According to the authors of  “Protective effect of CRHR1 gene variants on the development of adult depression following childhood maltreatment: replication and extension“  [PMID: 19736354], theirs is “the first instance of Genes x Environment research that stress has been ascertained by more than 1 study using the same instrument“.  The gene they speak of is the Corticotropin-releasing hormone receptor 1 (CRHR1) gene (SNPs rs7209436, rs110402, rs242924 which can form a so-called T-A-T haplotype which has been associated with protection from early life stress (as ascertained using the Childhood Trauma Questionnaire CTQ)).

The research team examined several populations of adults and, like many other studies, found that early life stress was associated with symptoms of depressive illness but, like only 1 previous study, found that the more T-A-T haplotypes a person has (0,1,or 2) the less likely they were to suffer these symptoms.

Indeed, the CRHR1 gene is an important player in a complex network of hormonal signals that regulate the way the body (specifically the hypothalamic pituitary adrenal axis) transduces the effects of stress.  So it seems quite reasonable to see that individual differences in ones ability to cope with stress might correlate with genotype here.   The replication seems like a major step forward in the ongoing paradigm shift from “genes as independent risk factors” to “genetic risk factors being dependent on certain environmental forces”.  The authors suggest that a the protective T-A-T haplotype might play a role in the consolidation of emotional memories and that CRHR1 T-A-T carriers might have a somewhat less-efficient emotional memory consolidation (sort of preventing disturbing memories from making it into long-term storage in the first place?) – which is a very intriguing and testable hypothesis.

On a more speculative note … consider the way in which the stress responsivity of a developing child is tied to its mother’s own stress responsivity.  Mom’s own secretion of CRH from the placenta is known to regulate gestational duration and thus the size, heartiness and stress responsiveness of her newborn.  The genetic variations are just passed along from generation to generation and provide some protection here and there in an intertwined cycle of life.

The flowers think they gave birth to seeds,
The shoots, they gave birth to the flowers,
And the plants, they gave birth to the shoots,
So do the seeds they gave birth to plants.
You think you gave birth to the child.
None thinks they are only entrances
For the life force that passes through.
A life is not born, it passes through.

anees akbar

This past friday, I attended my first meditation session at my new yoga school.  I love this school and hope – someday – to make it through the full Ashtanga series and other sequences the instructors do.  In the meantime, I found myself sitting on my folded up blanket, letting my mind wander, listening to my breath and just trying to enjoy the moment.

What a wonderful experience it was … it felt great!  … I think I my have even given my brain a rest. A simple kindness to repay it for all it has done for me!

Although I did not know what I was supposed to be “doing” during meditation, the experience itself has me hooked and fascinated with a new research article, “Genetic control over the resting brain” [doi: 10.1073/pnas.0909969107]  by David Glahn and colleages.

Reading this paper, I learned that my brain “at rest” is really very active with neural activity in a series of interconnected circuits known as the default network.  Moreover, the research team finds that many of these interconnected circuits fire together in a way that is significantly influenced by genetic factors (overall heritability of about 0.42).  By analyzing the resting state (lay in the MRI and let your mind wander) patterns of activity in 333 folks from extended pedigrees, the team shows that certain interconnections (neural activity between 2 or more regions) within the default network are more highly correlated in people who are more related to each other.  For example, the left parahippocampal region was genetically correlated with many of the other brain areas in the default network.

Of course, these genetic effects on resting state connectivity are far from determinative, and the authors noted that some interconnections within the default network were more sensitive to environmental factors – such as functional connectivity between right temporal-parietal & posterior cingulate/precuneus & medial prefronal cortex.

Wow, so my resting state activity must – at some level – as a partial product of my genome – be rather unique and special.  It certainly felt that way as my mind wandered freely during meditation class. The authors point out that their heritability study lays more groundwork for follow-up gene hunting expeditions to isolate specific genetic variants.  This will be very exciting!

Some other items from their paper that I’ll be pondering in my next meditation class are the facts that these default neural networks are already present in the infant brain!  and in our non-human primate cousins (even when they are not conscious)!  Whoa!  These genetics & resting-state brain studies will really push our sense of what it means to be human, to be unique, to be interconnected by a common (genetic) thread from generation to generation over vast spatial and temporal distances (is this karma of sorts?).

I suppose yogis & other practitioners of meditation might be bemused at this recent avenue of “cutting edge” scientific inquiry – I mean – duh?!  of course, it makes sense that by remaining calm and sitting quietly that we would discover ourselves.

Related posts here, here, here

Reading the book makes me feel liberated from the medical labels that are all too readily slapped on healthy people.  There is much that is healthy about sadness and many reasons and contexts in which its quite natural.  From now on, instead of trying to escape from, or rid myself of sadness, I will embrace it and let myself feel it and work through it.  Who knows, maybe this is a good first step in a healthy coping process.

If depressed emotional states are more a part of the normal range of emotions (rather than separate disordered states) then does this allow us to make predictions about the underlying genetic bases for these states?    Perhaps not.   However, on page 172, the authors apply their critical view to the highly cited Caspi et al., article (showing that 5HTT genotype interacts with life stress in the presentation of depressive illness – critiqued here).  They note that the incidence of depression at 17% in the sample is much too high – most certainly capturing a lot of normal sadness.  Hence, the prevalent short allele in the 5HTT promoter might be better thought of as a factor that underlies how healthy people respond to social stress – rather than as a drug target or risk factor for psychiatric illness.

Coping with fear and anxiety is difficult.  At times when one’s life, livelihood or loved one’s are threatened, we naturally hightenen our senses and allocate our emotional and physical resources for conflict.  At times, when all is well, and resources, relationships and relaxation time are plentiful, we should unwind and and enjoy the moment.  But most of us don’t.  Our prized cognitive abilities to remember, relive and ruminate on the bad stuff out there are just too well developed – and we suffer – some more than others  (see Robert Saplosky’s book “Why Zebras Don’t Get Ulcers” and related video lecture (hint – they don’t get ulcers because they don’t have the cognitive ability to ruminate on past events).  Such may be the flip side to our (homo sapiens) super-duper cognitive abilities.

Nevertheless, we try to understand our fears and axieties and understand their bio-social-psychological bases. A recent paper entitled, “A Genetically Informed Study of the Association Between Childhood Separation Anxiety, Sensitivity to CO2, Panic Disorder, and the Effect of Childhood Parental Loss” by Battaglia et al. [Arch Gen Psychiatry. 2009;66(1):64-71] brought to mind many of the complexities in beginning to understand the way in which some individuals come to suffer more emotional anguish than others.  The research team addressed a set of emotional difficulties that have been categorized by psychiatrists as “panic disorder” and involving sudden attacks of fear, sweating, racing heart, shortness of breath, etc. which can begin to occur in early adulthood.

Right off the bat, it seems that one of the difficulties in understanding such an emotional state(s) are the conventions (important for $$ billing purposes) used to describe the relationship between “healthy” and “illness” or “disorder”.  I mean, honestly, who hasn’t experienced what could be described as a mild panic disorder once or twice?  I have, but perhaps that doesn’t amount to a disorder.  A good read on the conflation of normal stress responses and disordered mental states is “Transforming Normality into Pathology: The DSM and the Outcomes of Stressful Social Arrangements” by Allan V. Horwitz.

Another difficulty in understanding how and why someone might experience such a condition has to do with the complexities of their childhood experience (not to mention genes). Child development and mental health are inextrictably related, yet, the relationship is hard to understand.  Certainly, the function of the adult brain is the product of countless developmental unfoldings that build upon one another, and certainly there is ample evidence that when healthy development is disrupted in a social or physical way, the consequences can be very unfortunate and long-lasting. Yet, our ability to make sense of how and why an individual is having mental and/or emotional difficulty is limited.  Its a complex, interactive and emergent set of processes.

What I liked about the Battaglia et al., article was the way in which they acknowledged all of these complexities and – using a multivariate twin study design – tried to objectively measure the effects of genes and environment (early and late) as well as candidate biological pathways (sensitivity to carbon dioxide).  The team gathered 346 twin pairs (equal mix of MZ and DZ) and assessed aspects of early and late emotional life as well as the sensitivity to the inhalation of 35% CO2 (kind of feels like suffocating and is known to activate fear circuitry perhaps via the ASC1a gene).   The basic notion was to parcel out the correlations between early emotional distress and adult emotional distress as well as with a very specific physiological response (fear illicited by breathing CO2).  If there were no correlation or covariation between early and late distress (or the physiological response) then perhaps these processes are not underlain by any common mechanism.

However, the team found that there was covariation between early life emotion (criteria for separation anxiety disorder) and adult emotion (panic disorder) as well as the physiological/fear response illicited by CO2.  Indeed there seems to be a common, or continuous, set of processes whose disruption early in development can manifest as emotional difficulty later in development.  Furthermore, the team suggests that the underlying unifying or core process is heavily regulated by a set of additive genetic factors.  Lastly, the team finds that the experience of parental loss in childhood increased (but not via an interaction with genetic variation) the strength of the covariation between early emotion, late emotion and CO2 reactivity.  The authors note several limitations and cautions to over-interpreting these data – which are from the largest such study of its kind to date.

For individuals who are tangled in persistent ruminations and emotional difficulties, I don’t know if these findings help.  They seem to bear out some of the cold, cruel logic of life and evolution – that our fear systems are great at keeping us alive when we’ve had adverse experience in childhood, but not necessarily happy.  On the other hand, the covariation is weak, so there is no such destiny in life, even when dealt unfortunate early experience AND genetic risk.  I hope that learning about the science might help folks cope with such cases of emotional distress.

If you slam your hand in the car door and experience physical pain, medical science can offer you a “pain killer!“.  Certainly morphine (via its activation of the mu opioid receptor (OPRM1)) will make you feel a whole lot better.  However, if your boyfriend or girlfriend breaks up with you and you experience emotional pain, its not so clear whether medical science has, or should offer, such a treatment.  Most parents and doctors would not offer a pain killer.  Rather, it’s off to sulk in private, perhaps finding relief in the writings of countless poets who’ve attested to the acute pain that ensues when emotional bonds are broken.

Love hurts! But why should this be? Why does the loss of love hurt so much?

From a purely biological point of view, it seems obvious that during certain periods of life – childhood for instance – social bonds are important for survival.  Perhaps anything that helped make the breaking of such bonds feel bad, might be selected for?  Its a very complex evolutionary genetic problem to be sure.  One way to begin to solve this question might be to study genes like OPRM1 and ask how and why they might be important for survival.

Such is the case for Christina Barr and colleagues, who, in their paper, “Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates” [doi:10.1073/pnas.0710225105] examine relationships between emotional bonds and genetics in rhesus macaques.  The team examines an amino acid substitution polymorphism in the N-terminus of the OPRM1 protein (C77G which leads to an Arginine to Proline change at position 26).  This polymorphism is similar to the human polymorphism (covered here) A118G (which leads to an Asparagine to Aspartate change at position 40).  Binding studies showed that both the 77G and 118G alleles have a higher affinity for beta-endorphin peptides.

Interestingly, Barr and colleagues find that the classical “pain gene” OPRM1 G-allele carrier macaques display higher levels of attachment to their mothers during a critical developmental phase (18-24 months of age).  These G-allele carriers were also more prone to distress vocalizations when temporarily separated from their mothers and they also spent more time (than did CC controls) with their mothers when reunited.  Hence, there ?may be? some preliminary credence to the notion that a gene involved in feeling pleasant/unpleasant might have been used during evolution to reinforce social interactions between mother and child.  The authors place their results into a larger context of the work of John Bowlby who is known for developing a theory of attachment and the consequences of attachment style on later phases of emotional life.

Click here for a previous interview with Dr. Barr and a post on another related project of hers.

Here’s a gene whose relationship to mental function is very straightforward.  If you hold your breath, your blood pH falls (more CO2 leads to more free H+ protons dissolved in your blood stream).  You also may become anxious, or worse if you are forced to hold your breath.  How does this process work?

Ziemann et al., in their new paper, “The Amygdala Is a Chemosensor that Detects Carbon Dioxide and Acidosis to Elicit Fear Behavior” [doi 10.1016/j.cell.2009.10.029] show that the acid sensing ion channel-1a (ASIC1a) gene is a proton-sensing Na+ and Ca++ channel – designed to activate dendritic spines when sensing H+ and drive neuronal activity.  Mice that lack this gene are not sensitive to higher CO2 levels, but when the protein is replaced in the amygdala, the mice show fearful behavior in response to higher CO2 levels.  Mother nature has provided a very straightforward way – ASIC1a activation of our fear center – of letting us know that no oxygen is a BAD thing!

Nowadays, it seems that genomics is spreading beyond the rarefied realm of science and academia into the general, consumer-based popular culture.  Quelle surprise!?  Yes, the era of the personal genome is close at hand, even as present technology  provides – directly to the general consumer public – a  genome-wide sampling of many hundreds of thousands of single nucleotide variants.   As curious early adopters begin to surf their personal genomic information, one might wonder how they, and  homo sapiens in general, will ultimately utilize their genome information.  Interestingly, some have already adapted the personal genome to facilitate what homo sapiens loves to do most – that is, to interact with one another.  They are at the vanguard of a new and hip form of social interaction known as “personal genome sharing”.  People connecting in cyberspace – via  haplotype or sequence alignment – initiating new social contacts with distant cousins (of which there may be many tens of thousands at 5th cousins and beyond).  Sharing genes that regulate the social interaction of sharing genes, as it were.

A broader view of social genes, within the context of our neo-Darwinian synthesis, however, shows that the relationship between the genome and social behavior can be rather complex.  When genes contribute directly to the fitness of an organism (eg. sharper tooth and claw), it is relatively straightforward to explain how novel fitness-conferring genetic variants increase in frequency from generation to generation.  Even when genetic variants are selfish, that is, when they subvert the recombination or gamete production machinery, in some cases to the detriment of their individual host, they can still readily spread through populations.  However, when a new genetic variant confers a fitness benefit to unrelated individuals by enhancing a cooperative or reciprocally-altruistic form of social interaction, it becomes more difficult to explain how such a novel genetic variant can take hold and spread in a large, randomly mating population.  Debates on the feasibility natural selection acting “above the level of the individual” seem settled against this proposition.  However, even in the face of such difficult population genetic conundrums, research on the psychology, biology and evolutionary genetics of social interactions continues unabated.  Like our primate and other mammalian cousins, with whom homo sapiens shares some 90-99% genetic identity, we are an intensely social species as our literature, poetry, music, cinema, not to mention the more recent twittering, myspacing, facebooking and genome-sharing demonstrate.

Indeed, many of the most compelling examples of genetic research on social interactions are those that reveal the devastating impacts on psychological development and function when social interaction is restricted.  In cases of maternal and/or peer-group social separation stress, the effects on gene expression in the brain are dramatic and lead to long-lasting consequences on human emotional function.  Studies on loneliness by John Cacioppo and colleagues reveal that even the perception of loneliness is aversive enough to raise arousal levels which, may, have adaptive value.  A number of specific genes have been shown to interact with a history of neglect or maltreatment in childhood and, subsequently, increase the risk of depression or emotional lability in adulthood.  Clearly then, despite the difficulties in explaining how new “social genes” arise and take hold in populations, the human genome been shaped over evolutionary time to function optimally within the context of a social group.

From this perspective, a new paper, “Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans” by Sarina Rodrigues and colleagues [doi.org/10.1073/pnas.0909579106] may be of broad interest as a recent addition to a long-standing, but now very rapidly growing, flow of genetic research on genes and social interactions.  The research team explored just a single genetic variant in the gene encoding the receptor for a small neuropeptide known as oxytocin, a protein with well-studied effects on human social interactions.  Intra-nasal administration of oxytocin, for example, has been reported to enhance eye-gaze, trust, generosity and the ability to infer the emotional state of others.  In the Rodrigues et al., study, a silent G to A change (rs53576) within exon 3 of the oxytocin receptor (OXTR) gene is used to subgroup an ethnically diverse population of 192 healthy college students who participated in assessments for pro-social traits such as the “Reading the Mind in the Eyes” (RMET) test of empathetic accuracy as well as measures of dispositional empathy.  Although an appraisal of emotionality in others is not a cooperative behavior per se, it has been demonstrated to be essential for healthy social function.  The Rodrigues et al., team find that the subgroup of students who carried the GG genotype were more accurate and able to discern the emotional state of others than students who carried the A-allele.  Such molecular genetic results are an important branching point to further examine neural and cognitive mechanisms of empathy as well as long-standing population genetic concerns of how new genetic variants like the A-allele of rs53576 arose and managed to take-hold in human populations.

Regarding the latter, there are many avenues for inquiry, but oxytocin’s role in the regulation of the reproductive cycle and social behavior stands out as an ideal target for natural selection.  Reproductive and behavioral-genetic factors that influence the ritualized interactions between males and females have been demonstrated to be targets of natural selection during the process of speciation.  New variants can reduce the cross-mating of closely related species who might otherwise mate and produce sterile or inviable hybrid offspring.  So-called pre-mating speciation mechanisms are an efficient means, therefore, to ensure that reproduction leads to fit and fertile offspring.  In connection with this idea, reports of an eye-gaze assessment similar to the RMET test used by Rodrigues et al., revealed that women’s pupils dilate more widely to photos of men they were sexually attracted to during their period of the menstrual cycle of greatest fertility, thus demonstrating a viable link between social preference and reproductive biology.  However, in the Rodrigues et al., study, it was the G-allele that was associated with superior social appraisal and this allele is not the novel allele, but rather the ancestral allele that is carried by chimpanzees, macaques and orangutans.  Therefore, it does not seem that the novel A-allele would have been targeted by natural selection in this type of pre-mating social-interaction scenrio.  Might other aspects of OXTR function provide more insight then?  Rodrigues et al.,  explore the role of the gene beyond the social interaction dimension and note that OXTR is widely expressed in limbic circuitry and also plays a broader modulatory role in many emotional reactivity.  For this reason, they sought to assess the stress responsivity of the participants via changes in heart-rate that are elicited by the unpredictable onset of an acoustic startle.  The results show that the A-allele carriers showed greater stress reactivity and also greater scores on a 12-point scale of affective reactivity.  Might greater emotional vigilance in the face of adversity confer a fitness advantage for A-allele carriers? Perhaps this could be further explored.

Regarding the neural and cognitive mechanisms of empathy and other pro-social traits, the Rodrigues et al., strategy demonstrates that when human psychological research includes genetic information it can more readily be informed by a wealth of non-human animal models.  Comparisons of genotype-phenotype correlations at the behavioral, physiological, anatomical and cellular levels across different model systems is one general strategy for generating hypotheses about how a gene like OXTR mediates and moderates cognitive function and also why it (and human behavior) evolved.  For example, mice that lack the OXTR gene show higher levels of aggression and deficits in social recognition memory.  In humans, genetic associations of the A-allele with autism, and social loneliness form possible translational bridges.  In other areas of human psychology such as in the areas of attention and inhibition, several genetic variants correlate with specific  mental operations and areas of brain activation.  The psychological construct of inhibition, once debated purely from a behavioral psychological perspective, is now better understood to be carried out by a collection of neural networks that function in the lateral frontal cortex as well as basal ganglia and frontal midline.  Individual differences in the activation of these brain regions have been shown to relate to genetic differences in a number of dopaminergic genes, whose function in animal models is readily linked to the physiologic function of specific neural circuits and types of synapses.  In the area of social psychology, where such types of neuroimaging-genetic studies are just getting underway, the use of “hyper-scanning”, a method that involves the simultaneous neuroimaging of two or more individuals playing a social game (prisoners dilemma) reveals a co-activation of dopamine-rich brain areas when players are able to make sound predictions of other participant’s choices.  These types of social games can model specific aspects of reciprocal social interactions such as trust, punishment, policing, sanctions etc. that have been postulated to support the evolution of social behavior via reciprocal altruism.  Similar imaging work showed that intra-nasal administration of oxytocin potently reduced amygdala activation and decreased amygdala coupling to brainstem regions implicated in autonomic and behavioural manifestations of fear.  Such recent examples affirm the presence of a core neural circuitry involved in social interaction whose anatomical and physiological properties can be probed using genetic methods in human and non-human populations.

Although there will remain complexities in explaining how new “social genes” can arise and move through evolutionary space and time (let alone cyberspace!) the inter-flows of genetic data and social psychological function in homo sapiens will likely increase.  The rising tide should inevitably force both psychologists and evolutionary biologists to break out of long-standing academic silos and work together to construct coherent models that are consistent with cognitive-genetic findings as well as population- genetic and phylogenetic data.  Such efforts will heavily depend on a foundation of psychological research into “social genes” in a manner illustrated by Rodrigues et al.

*** PODCAST accompanies this post *** Thanks agian Dr. Rodrigues!!!

It was a great pleasure to speak with Professor Garet Lahvis from the Department of Behavioral Neuroscience at the Oregon Health and Science University, and learn more about how the biology of empathy and social behaviors in general can be approached with animal models that are suitable for genetic studies.  The podcast is HERE and the post on his lab’s recent paper, “Empathy Is Moderated by Genetic Background in Mice” is HERE.  Thank you again Dr. Lahvis!

** podcast interview accompanies this post ** Lab mice have it pretty good I suppose.  Chow, water and mating ad libitum, fresh bedding, no predators.  Back in grad school, I usually handled my little mouse subjects gently so as not to frighten them and always followed the guidelines for humane treatment.  At the end of the day, however, I must confess that I didn’t actually care or empathize much with them.  For the most part, my attitude was, “Hey, they’re just mice – its not like I have Stuart Little here!“   I wonder.

As genetics and psychology are increasingly used to jointly explore the mechanisms of human cognition, more and more papers – particularly in the area of social and emotional systems – will make me question the, “hey, they’re just mice” assumption.

The free and open PLoS ONE paper, “Empathy Is Moderated by Genetic Background in Mice” is one of interest in this regard.  The authors have devised an experimental paradigm to ask whether emotional distress (to a brief foot-shock) in one mouse can influence the emotional state of an observer.  According to the authors, one of the inbred mouse strains, “acquired a classical conditioning (Pavlovian) association, which engendered a freezing response that was dependent upon the previous experience of distress in nearby conspecifics.”

Such a model – which to me, looks pretty humane, that is, in light of what they have learned about mice and empathy, and especially since human volunteers routinely participate in such mild wrist-shock paradigms – will likely be very useful for studies of specific genes where one can compare the “empathy” scores of inbred strains with and without the genetic modification.

Many thanks to Dr. Christina S. Barr from the National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism-Laboratory of Clinical and Translational Studies, National Institutes of Health Animal Center for taking the time to comment on her team’s recent publication, “Functional CRH variation increases stress-induced alcohol consumption in primates” [doi:10.1073/pnas.0902863106] which was covered here.  On behalf of students and interested readers, I am so grateful to her for doing this!  Thank you Dr. Barr!

For readers who are unfamiliar with the extensive literature on this topic, can you give them some basic background context for the study?

“In rodents, increased CRH system functioning in parts of the brain that drive anxious responding (ie, amygdala) occurs following extended access to alcohol and causes animals to transition to the addicted state.  In rodent lines in which genetic factors drive increased CRH system functioning, those animals are essentially phenocopies of those in the post-dependent state.  We had a variant in the macaque that we expected would drive increased CRH expression in response to stress, and similar variants may exist in humans.  We, therefore, hypothesized that this type of genetic variation may interact with prior stress exposure to increase alcohol drinking.”

Can you tells us more about the experimental design strategy and methods?

“This was a study that relied on use of archived NIAAA datasets. The behavioral and endocrine data had been collected years ago, but we took a gene of interest, and determined whether there was variation. We then put a considerable amount of effort into assessing the functional effects of this variant, in order to have a better understanding of how it might relate to individual variation. We then genotyped archived DNA samples in the colony for this polymorphism.”

“I am actually a veterinarian in addition to being a neuroscientist- we have the “3 R’s”. Reduce, refine, and replace…..meaning that animal studies should involve reduced numbers, should be refined to minimize pain/distress and should be replaced with molecular studies if possible.  This is an example of how you can marry use of archived data and sophisticated molecular biology techniques/data analysis to come up with a testable hypothesis without the use of animal subjects. (of course, it means you need to have access to the datasets….;)”

How do the results relate to broader questions and your field at large?

“I became interested in this system because it is one that appears to be under intense selection.  In a wide variety of animal species, individuals or strains that are particularly stress-reactive may be more likely to survive and reproduce successfully in highly variable or stressful environments. Over the course of human evolution, however, selective pressures have shifted, as have the nature and chronicity of stress exposures.  In fact, in modern society, highly stress-reactive individuals, who are no less likely to be eaten by a predator (predation not being a major cause of mortality in modern humans), may instead be more likely to fall susceptible to various-stress related disorders, including chronic infections, diabetes, heart disease, accelerated brain aging, stress-related psychiatric disorders, and even drug and alcohol problems. Therefore, these genetic variants that are persistent in modern humans may make individuals more vulnerable to “modern problems.”

I do hope this helps. Let me know if it doesn’t, and I will try to better answer your questions.”

THANK YOU AGAIN VERY MUCH DR. BARR!!