New study examines thousands of brains from two decades of research to reveal differences between male and female brain structure.
Courtesy of University of Cambridge
Reviewing over 20 years of neuroscience research into sex differences in brain structure, a Cambridge University team has conducted the first meta-analysis of the evidence, published this week in the journal Neuroscience and Biobehavioral Reviews.
The team, led by doctoral candidate Amber Ruigrok and Professors John Suckling and Simon Baron-Cohen in the Department of Psychiatry, performed a quantitative review of the brain imaging literature testing overall sex differences in total and regional brain volumes. They searched all articles published between 1990 and 2013. A total of 126 articles were included in the study, covering brains from individuals as young as birth to 80 years old.
They found that males on average have larger total brain volumes than women (by 8-13%). On average, males had larger absolute volumes than females in the intracranial space (12%; >14,000 brains), total brain (11%; 2,523 brains), cerebrum (10%; 1,851 brains), grey matter (9%; 7,934 brains), white matter (13%; 7,515 brains), regions filled with cerebrospinal fluid (11.5%; 4,484 brains), and cerebellum (9%; 1,842 brains). Looking more closely, differences in volume between the sexes were located in several regions. These included parts of the limbic system, and the language system.
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Specifically, males on average had larger volumes and higher tissue densities in the left amygdala, hippocampus, insular cortex, putamen; higher densities in the right VI lobe of the cerebellum and in the left claustrum; and larger volumes in the bilateral anterior parahippocampal gyri, posterior cingulate gyri, precuneus, temporal poles, and cerebellum, areas in the left posterior and anterior cingulate gyri, and in the right amygdala, hippocampus, and putamen.
By contrast, females on average had higher density in the left frontal pole, and larger volumes in the right frontal pole, inferior and middle frontal gyri, pars triangularis, planum temporale/parietal operculum, anterior cingulate gyrus, insular cortex, and Heschl’s gyrus; bilateral thalami and precuneus; the left parahippocampal gyrus, and lateral occipital cortex.
The results highlight an asymmetric effect of sex on the developing brain. Amber Ruigrok, who carried out the study as part of her PhD, said: “For the first time we can look across the vast literature and confirm that brain size and structure are different in males and females. We should no longer ignore sex in neuroscience research, especially when investigating psychiatric conditions that are more prevalent in either males or females.”
Professor Suckling added: “The sex differences in the limbic system include areas often implicated in psychiatric conditions with biased sex ratios such as autism, schizophrenia, and depression. This new study may therefore help us understand not just typical sex differences but also sex-linked psychiatric conditions. It is important to note that we only investigated sex differences in brain structure, so we cannot infer anything about how this relates to behaviour or brain function. Integrating across different levels will be an important goal for future research.”
Professor Baron-Cohen commented: “Although these very clear sex differences in brain structure may reflect an environmental or social factor, from other studies we know that biological influences are also important, including prenatal sex steroid hormones (such as fetal testosterone) as well as sex chromosome effects. Such influences need to be teased out, one by one.”
Dr Meng-Chuan Lai, another member of the team, noted: “The advantage of conducting a meta-analysis is that we can summarise the best knowledge from a vast, heterogeneous literature, with a very large sample size. However, we found a bias in the existing literature towards the use of volunteers over 18 years old, probably because this is the easiest age group to recruit and to brain scan. We need more research exploring brain development over the entire lifespan, especially in the early, formative years.”
Editors note: Original publication can be found here.
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Celebrated geneticist James Watson, one of several researchers who won the Nobel Prize for discovering the structure of DNA, has just published what can only be called a cancer manifesto in Open Biology. It’s full of fairly harsh criticisms for current cancer researchers, but also suggests several ways forward in the “war on cancer.” Among other claims, Watson asserts that antioxidants like vitamin C — often recommended as cancer-prevention supplements — could be causing some forms of cancer. He also has harsh words for personalized medicine, and the laziness of cancer researchers.
Watson, now in his 80s, has spent a great deal of his life raising money to fund cancer research at Cold Spring Harbor Laboratory, where he’s served as director since the late 1960s. Clearly anticipating his own mortality, he mourns the lack of good leadership in cancer research:
That we now have no General of influence, much less power, say an Eisenhower or even better a Patton, leading our country’s War on Cancer says everything. Needed soon is a leader that has our cancer drug development world working every day and all through the night.
He suggests that the problem is researchers are slacking, only putting in “never frantic, largely five-day working week[s].”
He goes on to say that the current craze for “personalized medicine” that will treat cancer is just not going to work. But the main problem comes from government money being misspent:
The now much-touted genome-based personal cancer therapies may turn out to be much less important tools for future medicine than the newspapers of today lead us to hope. Sending more government cancer monies towards innovative, anti-metastatic drug development to appropriate high-quality academic institutions would better use National Cancer Institute’s (NCI) monies than the large sums spent now testing drugs for which we have little hope of true breakthroughs. The biggest obstacle today to moving forward effectively towards a true war against cancer may, in fact, come from the inherently conservative nature of today’s cancer research establishments.
He goes on to say that conventional thinking about cancer is all wrong. Antioxidants may be undermining cancer therapies and even causing cancer:
In light of the recent data strongly hinting that much of late-stage cancer’s untreatability may arise from its possession of too many antioxidants, the time has come to seriously ask whether antioxidant use much more likely causes than prevents cancer.
All in all, the by now vast number of nutritional intervention trials using the antioxidants β-carotene, vitamin A, vitamin C, vitamin E and selenium have shown no obvious effectiveness in preventing gastrointestinal cancer nor in lengthening mortality. In fact, they seem to slightly shorten the lives of those who take them. Future data may, in fact, show that antioxidant use, particularly that of vitamin E, leads to a small number of cancers that would not have come into existence but for antioxidant supplementation. Blueberries best be eaten because they taste good, not because their consumption will lead to less cancer.
It is thought that antioxidants can prevent damage to DNA from oxygen radicals. But, argues Watson, we want oxygen radicals in cancer cells because this can cause the cells to die. Taking antioxidants might be preventing cancer drugs from destroying cancer cells. Instead, he recommends patients combine anti-antioxidants with cancer drugs.
Watson also recommends an area of research, into a class of proteins called RNAi, which can be used to shut down the activity of genes. He claims that we need less than a billion dollars to win the war on cancer if we focus on RNAi research:
The total sum of money required for RNAi methodologies to reveal the remaining major molecular targets for future anti-cancer drug development need not be more than 500–1000 million dollars. Unfortunately, the NCI now is unlikely to take on still one more big science project when it is so hard-pressed to fund currently funded cancer programmes … Further financial backing, allowing many more cancer-focused academic institutions to also go big using RNAi-based target discovery as well as to let them go on to the early stages of subsequent drug discovery, is not beyond the might of the world’s major government research funding bodies nor that of our world’s many, many super billionaires. The main factor holding us back from overcoming most of metastatic cancer over the next decade may soon no longer be lack of knowledge but our world’s increasing failure to intelligently direct its ‘monetary might’ towards more human-society-benefiting directions.
Watson also wants researchers to focus on a protein called Myc, which is believed to regulate the activity of 15% of our genes. Its activity is also linked to many kinds of cancer. Using RNAi methods, it’s possible we could figure out a way to control Myc, and thus shut down pathways to cancer.
Watson’s manifesto, “Oxidants, antioxidants, and the current incurability of metastatic cancers,” in Open Biology