The varied causes of depression

There is a new review article in CMAJ about the neurobiology of depression. And then there is the multi-part series on depression over at Neurotopia by the excellent Sci.

So I thought I’ll link these for the benefit of my readers. While it may sound an oxymoron to do a review of a review, let me briefly summarize the review article.

The article lists three important contributing factors for depression. The first is genetics; the second childhood stress and the third ongoing or recent psychosocial stress. And of course different neurobiological mechanisms underlie all three factors.

To take by way of example, we have the famed monoamine theory of depression whereby low baseline serotonin (and norepenipherine) levels in the brain are held responsible for depressive symptoms. This hypothesis derives most evidence from the effects of anti-depressants on the brain. Now depression also has a genetic heritable component (this is apparent from twin studies); some of the heritability of depression can be explained by polymorphisms of various genes affecting the serotonin system, primary among them being the gene affecting Serotonin Transporter or SERT. thus, the underlying serotonin system can be treated as one biological system that has a strong genetic component.

To take by way of second example, consider the hypothalamic-pituitary-adrenal axis that is involved in response to stress. This system is abnormally developed if the child is exposed to stress in a critical developmental window. Experiments with rats and monkeys confirm that abnormal and stressful environment during early childhood, leads to abnormal functioning of this axis, that later pre-disposes to depression. thus, this HPA axis may be taken as a proxy for the component that is due to development and epigenetics.

To take by way of third example, consider the Brain Derived Neurotropic factor in the brain. This BDNF is responsible for survival of new neurons and for new synapse formation (synaptic plasticity) during adulthood; new neurons and new synapses help us to learn (by neurogenisis in the hippocampus), especially when the environment is stressful; now there are two polymorphisms of the gene coding for BDNF; the ‘MET’ allele cause reduced hippocampal volume at birth, hypoactivity in resting state in hippocampus, increased metabolism in hippocampus while learning and relatively poor hiipocampal dependent memory-function. From all this it is apparent that MET allele somehow leads to less synthesis of BDNF and thus low learning in hippocampus as a result of reduced neurogenesis / synaptogenesis. Now, the same MET allele also raises the risk of depressionand the mediating factor is the stress responsivity of the individual. Thus, the BDNF may mediate the sensitivity of a person to the same external psychosocial stress and might be very crucial via the gene-environment interaction effects. Also prolonged stress, which may result in prolonged BDNF secretions and thus lead to toxicity and opposite paradoxical effects may be another putative mechanism linkibng stress exposure in adulthood to underlying pathophysiology of reduced neurogenesis.

The above may seem too simplistic but it points us in the right direction- some neurobiological systems like the serotonin system may be largely genetic in nature and our treatment approaches based around this fact. Others like the HPA axis malfunctioning may be entirely environmental in their origin, and maybe preventive interventions like ensuring stress free childhood for all, should be the policy focus here. Depending on the plasticity of later HPA axis, therapy or medications may be the treatment options. Finally, other neurobiological systems involved, like the BDNF and stress sensitivity/over-exposure, may display complex gene-environment interactions and again knowing the nature of these systems will help us counter the symptoms using a combination of CBT/ medication.

Depression is definitely a much complex disorder to be completely understood on the basis of a single review article, or even a series of blog posts, , but the underlying neurobiological mechanisms and systems clearly indicate how genetics, environment (especially during critical developmental window) and and epigenetics (gene-environment interactions) are involved in its etiology and how different interventions and treatments taking these into account have to be developed.
aan het Rot, M., Mathew, S., & Charney, D. (2009). Neurobiological mechanisms in major depressive disorder Canadian Medical Association Journal, 180 (3), 305-313 DOI: 10.1503/cmaj.080697

Blog Action Day: Poverty and IQ: from the archives

Well, today is blog action day 2008, and the topic for today is Poverty.

I am afraid I will be posting one of my old posts today: a post relating Poverty and SES to IQ and I am also publishing some relevant comments as the comment length generally exceeded the article length:-):

The post, comments and my response to comments are as follows; I would love to rekindle debate on SES/Poverty and IQ again and am looking for more discussions. Also please check out this earlier post on the simillar poverty and IQ topic:

Original Post: Is low IQ the cause of income inequality and low life expectancy or is it the other way round?

As per this post from the BPS research digest, Kanazawa of LSE has made a controversial claim that economic inequality is not the cause of low life expectancy, but that both low life expectancy and economic inequality are a result of the low IQ of the poor people. The self-righteous reasoning is that people with low IQ are not able to adapt successfully to the stresses presented by modern civilization and hence perish. He thinks he has data on his side when he claims that IQ is eight times more strongly related to life expectancy, than is socioeconomic status. What he forgets to mention(or deliberately ignores) is growing evidence that IQ is very much determinant on the socioeconomic environment of its full flowering and a low IQ is because of two components- a low genetic IQ of parent plus a stunted growth of IQ/intelligence due to impoverished environment available because of the low socio-economic status of the parents.

A series of studies that I have discussed earlier, clearly indicate that in the absence of good socioeconomic conditions, IQ can be stunted by as large as 20 IQ points. Also discussed there, is the fact that the modern civilization as a whole has been successful in archiving the sate of socioeconomic prosperity that is sufficient for the full flowering of inherent genetic IQ of a child and as such the increments in IQ as we progress in years and achieve more and more prosperity (the Flynn effect) has started to become less prominent. This fact also explains the Kanazawa finding that in ‘uncivilized’ sub-Saharan countries the IQ is not related to life expectancy, but socio-economic status is. although, he puts his own spin on this data, a more parsimonious ( and accurate) reason for this is that in the sub-Saharan countries, even the well -of don’t have the proper socio-economic conditions necessary for the full flowering of IQ and thus the IQ of both the well-off and poor parents in these countries is stunted equally. Thus, the well-off (which are not really that well-off in comparison to their counterparts in the western countries) are not able to be in any more advantageous position (with respect to IQ) than the poor in these countries. The resultant life expectancy effect is thus limited to that directly due to economic inequality and the IQ mediated effect of economic inequality is not visible.

What Kanazawa deduces from the same data and how he chooses to present these findings just goes on to show the self-righteous WASP attitude that many of the economists assume. After reading Freakonomics, and discovering how the authors twist facts and present statistics in a biased manner to push their idiosyncratic theories and agendas, it hardly seems surprising that another economist has resorted to similar dishonest tactics – shocking people by supposedly providing hard data to prove how conventional wisdom is wrong. Surprisingly, his own highlighting of sub-Saharan counties data that shows that life-expectancy is highly dependent on socio-economic conditions in these countries is highly suggestive of the fact that in cultures where the effects og economic inequality are not mediated via the IQ effects, economic inequality is the strongest predictor of low life expectancy.

Instead of just blaming the people for their genes/ stupidity, it would be better to address the reasons that lead to low IQs and when they are tackled, directly address the social inequality problem , as in the author’s own findings, when IQ is not to blame for the low life expectancy, the blame falls squarely on economic inequality (as in the sub-Saharan countries data) .


Asterion said…

First of all, I beg you pardon for my limited english.
I find quite interesting your findings. But there could be an issue which limits the reasoning: how the IQ is meassured? or what does it really meassures? Does it really defines how smart or clever a person is?
I think there must be a lot of denounces about it. So, I think it’s important to recognize the limits of this aproach based on IQ meassurment limitants. Of course, there could be a reference in your and Kanazawa’s articles (I have not seen none of them).
All of this is beacuse I have met childs quite smarts living in the poorest zones of my city (Bogotá,
Colombia), I would say all of them seems to be quite smart, at least form my point if view. They are all really quick undertanding abstract problems and linking things. I think they have a strong capability to analize any situation. So, if you are able to meassure their IQ using problems wich need, for instance, to apply Phitagora’s theorem, surelly they will be in trouble. So I think education could explain better economic inequalities and, thus, low life expentacy.
I never have explored this issue, so I would thank you refering me to some relevant literature related. Even telling me if I am quite wrong or not.

Always learning…

Sandy G said…

Hi Julian,

I appreciate your thoughtful comments. It is true that intelligence consists of a number of factors (as large as 8-10 broad factors), and is also differentiated as crystallized(Gc) and fluid (Gf); but for most analysis a concept of a general underlying common factor , spearman’s g, is taken as reflective of intelligence and measured by the IQ scores.

In this sense, IQ/g does reflect how clever or smart a person is, but success/outcome in life is affected by other factors like motivation, effort, creativity etc.

I agree that many children in impoverished environments are quite smart, but you would be surprised to discover how providing an enriched environment to them, at their critical developmental periods,would have resulted in lasting intelligence gains. They are smart, but could have been smarter, if they had the right socioeconomic environment. On the other hand, an average child from well-to-do family would be able to maximally develop its inherent capabilities and thus stand a stronger chance than the poor smart child, whose capabilities haven’t flowered fully.

Cultural bias in IQ measures have been found in the past, but the field has vastly improved now and these biases are fast disappearing leading to more accurate and valid cross-cultural comparisons.

The key to remember here is that poor socio-economic condition affects longevity via multiple pathways- one of them is direct by limiting access to good health care and nutrition, but there are also indirect effects mediated by , as you rightly pointed, education (poor people get less education and not vice versa) and also intelligence.

Garett Jones said…

Two words: East Asia.

If bad social and economic outcomes were the key driver of low IQ, then we’d expect East Asians to have had low IQ’s back when they were poor–say, back in the 50’s and 60’s. Check out Table 4 of my paper (page 28) to see if that’s the case…

Guess not. So, East Asians have been beating Causasians on IQ tests (on average) for as far back as we have data. You can get more historical data along these lines from Lynn’s (2006) book, Race Difference in Intelligence.

And one can go even further back if you look at brain size, which correlates about 0.4 with IQ. Asian brains have been well-known to be larger than Caucasian brains for as long as folks have been measuring both of them. Hard to fit that in with WASP-driven science…

So simple reverse causality surely plays some role, but it can’t explain East Asia…..

Sandy G said…

Hi Garret,

Thanks for dropping by and commenting.

I guess we agree on more things, than we disagree on. For example, in section IID of your paper, you concur with my explanation of Flynn effect that it is most probably due to the increase in living conditions and due to environmental factors enabling the full flowering of potential. Environment can and does have a strong disruptive negative effect, though it only has a limited positive enabling effect (no amount of good environment can give you an intelligence that is disproportionate to what your genes endow on you; but even minor lack of right environmental inputs or toxins, can lead to dramatic stunted achievement of that potential intelligence).

Also, it is heartening to note, that early on in your paper you take the position that your paper will not settle genetic vs environmental debate on IQ, but would only provide evidence that national IQ is a good indicator of ntaional productivity.

I have no issue with the same and agree that if one disregards the process by which adult stable IQs are archived, then the stable adult IQ that has been archived would be a very good predictor of productivity and economic status (in a free market environment where other conditions re not adversely affecting success). There is no qualms with the causal relation between a better IQ leading to better SES, in a fair world.

What I do strongly disagree with is the assumption that low IQ is solely dependent on genetic factors. Bad socio-economic factors are the key drivers of low IQ- especially in situations where the socio-economic status is so low that it does’nt guarantee access to basic amenities of life like proper nutrition/ health care.

It is interesting to note that poor SES would cause stunted growth of IQ, and due to the causal relation between IQ and SES would lead to less productivity and lower income, thus maintaining or even aggravating the low SES. This is the downward vicious cycle from which it is very hard to emerge. This type of economy and culture would definitly have lower IQ than what could have been achieved in the right conditions. The sub-saharan countries that Kanazawa used in his study, match this pattern and some of the African countries National IQ (as per data appendix in your paper) viz. Kenya: 72, south afric: 72, ghana : 71 confirms to this pattern).

The opposite observation, that a spiraling economy should radically lead to high IQs is not reasonable, as the circle is vicious only in the downward direction. Monumental leaps in SES would not lead to dramatic effects in IQ, if the earlier SES levels were just sufficient to ensure that no negative effects of environment come into play. The Flynn effect is a tribute to the fact that high jumps in SES (above the base level) only lead to small incremental changes in IQ.

Another thing to keep in mind is that when the SES to low IQ causal link is suggested it is only for the achievement of the stable adult IQ and instrumental during the critical childhood developmental periods. Although, environmental toxins do have the capability to adversely affect IQ during adulthood, and there is emerging evidence for plasticity and neurogenesis in adulthood, a simpler and reasonably model is whereby adult IQ is stable and not much affected by SES changes (either up or down) once it has been stabilized. Thus, even if some positive effects of rising SES have to be observed, they would be observable only in children exposed to that SES and not in the IQ of the rest of the adult population, that has already acheived a stable IQ.

Thus, I do not agree with your explanation of the east Asian example. To me the data set appears to be very limited ( no IQ results before the 1950’s; no data sets for the same country or population over time) and even if we assume that only after the 1980s the SES of these countries rose above the minimal needed SES, we still do not have the data for the IQ of children born under theses SES condition, to proclaim that ther eis no rise in IQ.

Further, it is quite plausible that productivity is dependent on many other factors than IQ, some of which are directly related to SES independent of IQ. Given a base level of SES, in which the East Asians had managed to develop their inherent genetic IQ to the fullest, the SES may still not be good enough to convert that IQ advantage to productivity. For example, a given household that has sufficient SES to provide good nutrition and health care, and thus ensure that its children archive their full IQ potentiality, may still not have enough resources to send them to a good school (or any school for that matter), may lack access to basic infrastructure support which handicaps the utilization of its intelligence and so on. Thus despite having the human capital, lack of the more prosaic monetary capital, may prevent them from archiving their full productivity. Thus, IQ may increase first to the maximal achievable level and only then SES increase dramatically.

It would be interesting to turn the East Asian example on its head and beg the question that if IQ is the definitive causal relation leading to SES , how do you explain the anomaly that despite high IQ’s in 1950s (or for that matter Asian big brain since time immemorial) he East Asian countries did not have the corresponding productivity levels or SES. You might counter by saying that IQ -> SES causal link is mediated by factors like free markets, reforms etc to ensure that proper economic conditions are in place etc etc and only if these ideal market conditions are in place then only IQ predicts SES.

To that my simple counter-argument would be that SES -> IQ causal link also works but only in conditions when the SES is below the base level and that SES would not predict IQ absolutely. Given the same optimal SES in differnet countries, different cultures (which have different genetic pools) will have different IQ levels based on their inherent genetic capabilities.
As per this the IQ of east asians can be explained as either arising from the fact that they have already archived the SES required for full flowering; or that they still have to archive their highest IQ levels and their IQ levels are genetically vastly superior and may show more rise in future.

From Anecdotal evidence I can tell you that an average Indian has far more intelligence and creativity potential that the average IQ of 82 would suggest; most of the high SES families that have archived that high IQ migrate to US/ west and archive high SES there.
What brings down the national average is the sad fact that still a lot of Indians live below the poverty line – living in sub-optimal SES conditions that leads them to have low IQ’ than what their genes or genetic makeup would suggest.

Looking forward to a fruitful discussion.
PS: Despite the tone of my original mail, I have high regards for economists in general and people like Amartya sen, Kahnman and Traversky in particular.

12:31 PM
Anonymous said…

Interesting blog entry. Has the author of it actually read the paper he is criticizing? I noticed that it costs $15 online. If not, is the author of the blog certain that the statistical methods employed by Kanazawa do not take his complaints into account implicitly? One hopes that the author is not criticizing a peer-reviewed scientific paper without having read it.

Sandy G said…

Dear Anonymous,

It would be better if, after having read the paper (otherwise by your own high standards you wouldn’t have defended an article without having read it first), you would be kind enough to tell the readers of this blog how Kanazawa has taken the effects of low SES-low IQ developmentally mediated effect in consideration in his study.

You are correct in guessing that I haven’t read the article (I believe in free access; so neither publish nor read material that is not freely available). I’ll welcome if you or someone else could mail me the relevant portions or post them on this blog (under fair use).

As for invoking authority covertly by referring to peer-review in a prestigious journal, I would like to disclose that I haven’t taken a single course or class in psychology- either in school or college- so if authority is the determinant: you can stick to reading articles in scholarly journals by those who have doctoral degrees. Blogs are not for you. Otherwise, if you believe more in open discussions and logical arguments, lets argue on facts and study method weaknesses etc and rely more on public-review to catch any discrepancies.

What I could gather from the abstract was that “The macro-level analyses show that income inequality and economic development have no effect on life expectancy at birth, infant mortality and age-specific mortality net of average intelligence quotient (IQ) in 126 countries”. I take this to mean, that SES has no effect on longevity , if the effects of IQ are factored out. the ‘if’ is very important. This a very perverse position. This assumes that longevity is due to IQ and if IQ mediated difference in longevity data is factored out, the effcets on longevity of SES are negligible. This depends on an a priori assumption that longevity is primarily explained by IQ; and only after taking its effects into consideration, we need to look for an effect of SES on longevity.

What prevents the other, more valid and real interpretation : that SES predicts longevity and that there is little effect of IQ on longevity net of SES. Here the variation in longevity is explained by SES and after taking that into account, it would be found that, independent of IQ as a consequent of SES, IQ by itself would have little effect on longevity. the same set of data leads to this interpretation, because IQ and SES are related to a great degree and both are also related to longevity. It is just a matter of interpretation, that which is the primary cause and which an effect.

To take an absurd position, I can argue that longevity predicts/ causes both SES and IQ and reverse the causal link altogether. One can take a theoretical stand, that if people live longer , we have more labor force, blah, blah,blah… so more prodcutivity so better SES; further longevity menas that there are more wise old folks in the society and as IQ is mostly deterinmed by social influences (I do not subscribe to this, I am just taking an absurd position to show the absurdity of Kanazawa position), hence longevity of the population(more wise men) causes high IQs.

Also, please note that the above conclusion is only for the macro data he has. That interpretation is independent of his micro level data that found that self-reported health was more predicted by IQ than by SES. That micro data has nothing to do with the interpretation of the macro data. Again I don’t know where he got the micro data, but I’m sure that would be a developed world population sample.
I am somewhat familiar with the macro data on which he is basing such claims, and there I do not see any reason to prefer his interpretation over other more realistic interpretations.

In the future, lets discuss merits of arguments, and not resort to ad hominem attacks over whether someone is qualified to make an argument or not. (in my opinion, by reading an abstract too, one can form a reasonable idea of what the arguments and methodologies employed are, and is thus eligible to comment)

Nature via Nurture : aggressiveness in Dorsophilia

As per a recent PNAS article , Dorsophilia have a gene called Cyp6a20 which is expressed more in the head when the flies are not socially isolated but have social experience. This increase in gene expression is correlated with a decrease in aggression. Thus, this gene codes for not only the genetic component of the inheritableness of aggressiveness in the Dorsophilia, but also the environmental effect of social stimulus on aggressiveness and how that environmental influence is itself dependent on genes. To make it clear, Dorsophilia that had this gene mutated showed a change in aggressiveness only for flies that were reared in social groups and had no effect when they were reared as socially isolated.

To me, this seems another case where nature and nurture do not necessarily have to work exclusively, but work in concord to give observable phenotypes. It is interesting to note that this same gene is also expressed in olfactory sensilla and this suggest that aggressiveness – socialization effect may be mediated by pheromone effects.

Stress contagion: from parents to the child?

Greg Downey at the excellent Neuroanthroplogy blog comments on a recent article by Mary Caserta, on the relationship between parental stress and illness in the children and the child’s immune response. What the research team found was that :

Family processes have a substantial impact on children’s social and emotional well-being, but little is known about the effects of family stress on children’s physical health. To begin to identify potential links between family stress and health in children, we examined associations between specific aspects of family psychosocial stress and the frequency of illnesses in children, measures of innate and adaptive immune function, and human herpesvirus 6 (HHV-6) reactivation

Greg, thinks of several possible reasons for this association:

  1. Stressed out parents interact differently with their children and stress them.
  2. Mirror neurons or similar systems may underlie the fact that the child may be mirroring the internal stressed environment of the parent and consequently feeling stressed.
  3. Chemical mechanisms including pheromones released on being stressed (!!) may be at work and responsible for the contagion.
  4. Reverse causation: the stick children may be causing the parents to feel more stressed.

I find all the above explanations (except 3) interesting and plausible, but Greg has also ignored another potential reason. Being an anthropologist he has overlooked the genetic aspect. What if some underlying gene which endows the parent to feel more stressed is also responsible for the children being more susceptible to illness/ having more auto-immune response. After all the stress system and immune system are very much cloistered together. It is not hard to imagine that a gene that causes vulnerability to stress( or felling stressed) also increases sensitivity to environmental pathogens and sensitivity of immune response. As the child is sharing 50 % of the gene of the parent, there is a great likelihood that the sensitivity to stress and sensitivity to pathogens may be inherited in the same manner. Food for thought.

War and Peace

There is a new article by John Horgan, in the Discover Magazine regarding the eternal question of whether aggressiveness is in our genes and inevitable or can be done away with and lead to peaceful human existence.

I was introduced to psychology by reading Eric Fromm’s excellent treatise on the same titled The Anatomy of human destructivity, in which he passionately argues that the animals are not cruel or destructive; but that it is a uniquely human trait. that book is a classic and I recommend it whole heartedly to anyone who has interest in the matter.

The Discover magazine article in particular quotes too of my favorite scientists: Robert Sapolsky and Frans De walls and they are on the side of ‘peaceful humans’ . It also has discusses those hwo belive in a darker view of human nature.

Some excerpts follow:

Frans de Waal stands in a watchtower at the Yerkes National Primate Research Center north of Atlanta, talking about war. As three hulking male chimpanzees and a dozen females loll below him, the renowned primatologist rejects the idea that war stems from “some sort of blind aggressive drive.” Observations of lethal fighting among chimpanzees, our close genetic relatives, have persuaded many people that war has deep biological roots. But de Waal says that primates, and especially humans, are “very calculating” and will abandon aggressive strategies that no longer serve their interests. “War is evitable,” de Waal says, “if conditions are such that the costs of making war are higher than the benefits.”
De Waal acknowledges that “we have a tendency, and all the primates have a tendency, to be hostile to non–group members.” But he and other experts insist that humans and their primate cousins are much less bellicose than the public has come to believe. Studies of monkeys, apes, and Homo sapiens offer ample hope that we can overcome our aggressive tendencies and greatly reduce or maybe even eliminate warfare.

Biologist Robert Sapolsky is a leading challenger of what he calls the “urban myth of inevitable aggression.” At his Stanford University office, peering out from a tangle of gray-flecked hair and beard, he tells me that primate studies contradict simple biological theories of male belligerence—for example, those that blame the hormone testosterone. Aggression in primates may actually be the cause of elevated testosterone, rather than vice versa. Moreover, artificially increasing or decreasing testosterone levels within the normal range usually just reinforces previous patterns of aggression rather than dramatically transforming behavior; beta males may still be milquetoasts, and alphas still bullies. “Social conditioning can more than make up for the hormone,” Sapolsky says.

De Waal suspects that environmental factors contribute to the bonobos’ benign character; food is more abundant in their dense forest habitat than in the semi-open woodlands where chimpanzees live. Indeed, his experiments on captive primates have established the power of environmental factors. In one experiment, rhesus monkeys, which are ordinarily incorrigibly aggressive, grew up to be kinder and gentler when raised with mild-mannered stump-tailed monkeys.

De Waal has also reduced conflict among monkeys by increasing their interdependence and ensuring equal access to food. Applying these lessons to humans, de Waal sees promise in alliances, such as the European Union, that promote trade and travel and hence interdependence. “Foster economic ties,” he says, “and the reason for warfare, which is usually resources, will probably dissipate.”

Fry has also identified 74 “nonwarring cultures” that—while only a fraction of all known societies—nonetheless contradict the depiction of war as universal. His list includes nomadic hunter-gatherers such as the !Kung in Africa and Aborigines in Australia. These examples are crucial, Fry says, because our ancestors are thought to have lived as nomadic hunter-gatherers from the emergence of the Homo lineage just over 2 million years ago in Africa until the appearance of agriculture and permanent settlements about 12,000 years ago. That time span constitutes 99 percent of our history.

Lethal violence certainly occurred among those nomadic hunter-gatherers, Fry acknowledges, but for the most part it consisted not of genuine warfare but of fights between two men, often over a woman. These fights would sometimes precipitate feuds between friends and relatives of the initial antagonists, but members of the band had ways to avoid these feuds or cut them short. For example, Fry says, third parties might step between the rivals and say, “‘Let’s talk this out’ or ‘You guys wrestle, and the winner gets the woman.’”

Go to Top