Posted on Autism

High levels of oestrogen in the womb linked to autism

Scientists have identified a link between exposure to high levels of oestrogen sex hormones in the womb and the likelihood of developing autism. The findings are published today in the journal Molecular Psychiatry.

The discovery adds further evidence to support the prenatal sex steroid theory of autism first proposed 20 years ago.

In 2015, a team of scientists at the University of Cambridge and the State Serum Institute in Denmark measured the levels of four prenatal steroid hormones, including two known as androgens, in the amniotic fluid in the womb and discovered that they were higher in male foetuses who later developed autism. These androgens are produced in higher quantities in male than in female foetuses on average, so might also explain why autism occurs more often in boys. They are also known to masculinise parts of the brain, and to have effects on the number of connections between brain cells.

Today, the same scientists have built on their previous findings by testing the amniotic fluid samples from the same 98 individuals sampled from the Danish Biobank, which has collected amniotic samples from over 100,000 pregnancies, but this time looking at another set of prenatal sex steroid hormones called oestrogens. This is an important next step because some of the hormones previously studied are directly converted into oestrogens.

All four oestrogens were significantly elevated, on average, in the 98 foetuses who later developed autism, compared to the 177 foetuses who did not. High levels of prenatal oestrogens were even more predictive of likelihood of autism than were high levels of prenatal androgens (such as testosterone). Contrary to popular belief that associates oestrogens with feminisation, prenatal oestrogens have effects on brain growth and also masculinise the brain in many mammals.

Professor Simon Baron-Cohen, Director of the Autism Research Centre at the University of Cambridge, who led this study and who first proposed the prenatal sex steroid theory of autism, said: “This new finding supports the idea that increased prenatal sex steroid hormones are one of the potential causes for the condition. Genetics is well established as another, and these hormones likely interact with genetic factors to affect the developing foetal brain.”

Alex Tsompanidis, a PhD student in Cambridge who worked on the study, said: “These elevated hormones could be coming from the mother, the baby or the placenta. Our next step should be to study all these possible sources and how they interact during pregnancy.”

Dr Alexa Pohl, part of the Cambridge team, said: “This finding is exciting because the role of oestrogens in autism has hardly been studied, and we hope that we can learn more about how they contribute to foetal brain development in further experiments. We still need to see whether the same result holds true in autistic females.”

However, the team cautioned that these findings cannot and should not be used to screen for autism. “We are interested in understanding autism, not preventing it,” added Professor Baron- Cohen.

Dr Arieh Cohen, the biochemist on the team, based at the State Serum Institute in Copenhagen, said: “This is a terrific example of how a unique biobank set up 40 years ago is still reaping scientific fruit today in unimagined ways, through international collaboration.”

The research was supported by the Autism Research Trust, the Medical Research Council, and Wellcome.

Posted on Fibromyalgia

Are most patients with fibromyalgia misdiagnosed?

Fibromyalgia: a breakthrough diagnosis
Fibromyalgia: a breakthrough diagnosis


Recent studies have suggested that most people who have been diagnosed with fibromyalgia by physicians may not actually have the condition. A new Arthritis Care & Research study found that overall agreement between clinicians’ diagnosis of fibromyalgia and diagnosis by published criteria is only fair.

For the study, 497 patients visiting a rheumatology clinic completed a health assessment questionnaire as well as a questionnaire that assessed fibromyalgia diagnostic variables used by the American College of Rheumatology. Patients were also evaluated and diagnosed by rheumatology clinicians.

Of the 497 patients, 121 (24.3 percent) satisfied fibromyalgia criteria while 104 (20.9 percent) received a clinician’s diagnosis of fibromyalgia. The agreement between clinicians and criteria was 79.2 percent; however, agreement beyond chance was only fair. Physicians failed to identify 60 (49.6 percent) of criteria-positive patients and incorrectly identified 43 (11.4 percent) of criteria-negative patients.

“We have recently studied the same issue in 3,000 primary care patients and found about the same results. Therefore, our conclusions are secure,” said lead author Dr. Frederick Wolfe, of the National Data Bank for Rheumatic Diseases.

In an accompanying editorial Dr. Don Goldenberg, of Oregon Health & Science University, noted that to conclude that expert physicians often misdiagnose fibromyalgia implies that published criteria are superior to expert clinical judgement for the diagnosis of individual patients. He stressed that this fails to account for many of the variables present in clinical encounters, including time spent in evaluating and categorizing each patient’s multiple symptoms. “The diagnostic gold standard for fibromyalgia will continue to be the rheumatologist’s expert opinion, not classification criteria, no matter how well-refined and intentioned,” he wrote. “This is the only way to capture the variability and severity of inter-related symptoms as they play out over time.”

Posted on Autism

Transgender and gender-diverse individuals are more likely to be autistic and report higher autistic traits

Transgender flag

Transgender and gender-diverse adults are three to six times more likely as cisgender adults (individuals whose gender identity corresponds to their sex assigned at birth) to be diagnosed as autistic, according to a new study by scientists at the University of Cambridge’s Autism Research Centre.

Both autistic individuals and transgender and gender-diverse individuals are marginalized and experience multiple vulnerabilities. It is important that we safe-guard the rights of these individuals to be themselves, receive the requisite support, and enjoy equality and celebration of their differences, free of societal stigma or discriminationSimon Baron Cohen

This research, conducted using data from over 600,000 adult individuals, confirms previous smaller scale studies from clinics. The results are published today in Nature Communications.

A better understanding of gender diversity in autistic individuals will help provide better access to health care and post-diagnostic support for autistic transgender and gender-diverse individuals.

The team used five different datasets, including a dataset of over 500,000 individuals collected as a part of the Channel 4 documentary “Are you autistic?”. In these datasets, participants had provided information about their gender identity, and if they received a diagnosis of autism or other psychiatric conditions such as depression or schizophrenia. Participants also completed a measure of autistic traits.

Strikingly, across all five datasets, the team found that transgender and gender-diverse adult individuals were between three and six times more likely to indicate that they were diagnosed as autistic compared to cisgender individuals. While the study used data from adults who indicated that they had received an autism diagnosis, it is likely that many individuals on the autistic spectrum may be undiagnosed. As around 1.1% of the UK population is estimated to be on the autistic spectrum, this result would suggest that somewhere between 3.5.-6.5% of transgender and gender-diverse adults is on the autistic spectrum.

Dr Meng-Chuan Lai, a collaborator on the study at the University of Toronto, said: “We are beginning to learn more about how the presentation of autism differs in cisgender men and women. Understanding how autism manifests in transgender and gender-diverse people will enrich our knowledge about autism in relation to gender and sex. This enables clinicians to better recognize autism and provide personalised support and health care.”

Transgender and gender-diverse individuals were also more likely to indicate that they had received diagnoses of mental health conditions, particularly depression, which they were more than twice as likely as their cisgender counterparts to have experienced. Transgender and gender-diverse individuals also, on average, scored higher on measures of autistic traits compared to cisgender individuals, regardless of whether they had an autism diagnosis.

Dr Varun Warrier, who led the study, said: “This finding, using large datasets, confirms that the co-occurrence between being autistic and being transgender and gender-diverse is robust. We now need to understand the significance of this co-occurrence, and identify and address the factors that contribute to well-being of this group of people.”

The study investigates the co-occurrence between gender identity and autism. The team did not investigate if one causes the other.

Professor Simon Baron-Cohen, Director of the Autism Research Centre at Cambridge, and a member of the team, said: “Both autistic individuals and transgender and gender-diverse individuals are marginalized and experience multiple vulnerabilities. It is important that we safe-guard the rights of these individuals to be themselves, receive the requisite support, and enjoy equality and celebration of their differences, free of societal stigma or discrimination.”

Dr Warrier is a Research Fellow at St Catharine’s College and Professor Baron Cohen is a Fellow at Trinity College.

This study was supported by the Autism Research Trust, the Medical Research Council, the Wellcome Trust, and the Templeton World Charity Foundation., Inc. It was conducted in association with the NIHR CLAHRC for Cambridgeshire and Peterborough NHS Foundation Trust, and the NIHR Cambridge Biomedical Research Centre.

Posted on Autism

Autistic adults have a higher rate of physical health conditions

Doctor testing blood pressure

Autistic individuals are more likely to have chronic physical health conditions, particularly heart, lung, and diabetic conditions, according to a new study by researchers at the University of Cambridge. The results are published in the journal Autism.

This is a first step in better understanding why autistic individuals are so much more likely to have chronic physical health problemsElizabeth Weir

Earlier research has shown that autistic people on average die younger than others and that this may be, in part, due to chronic physical health conditions. Previous studies have also shown that autistic people are at higher risk of a variety of health conditions, but we don’t know what is driving these increased risks. Thus, better understanding of the physical health of autistic adults may help us improve both their quality and length of life.

1,156 autistic individuals and 1,212 non-autistic individuals took part in an anonymous, online survey developed by the team about their lifestyle choices and daily habits, personal and family medical history. The results indicate that autistic individuals are, on average, 1.5 to 4.3 times as likely to have a wide variety of health conditions, including low blood pressure, arrhythmias, asthma, and prediabetes. 

This new study is also the first to examine the influence of smoking, alcohol use, and BMI. Surprisingly, the results show that these lifestyle factors (which increase the risk of chronic physical health problems in the general population) do not account for the heightened risk of heart, lung, and diabetic conditions seen among autistic adults.

The study also explored the experiences of female respondents and of older adults, both of whom remain understudied groups. The results revealed that autistic females, even more so than autistic males, are more likely to report increased risks of physical health conditions. In addition, the types of conditions of risk depend on the person’s biological sex. For example, autistic females are 4.3 times more likely to have prediabetes than non-autistic females; however, autistic and non-autistic males are equally likely to have prediabetes. These results suggest that a “one size fits all” approach to the healthcare of autistic people may not be effective.

Elizabeth Weir, the PhD student who led the study, said: “This is a first step in better understanding why autistic individuals are so much more likely to have chronic physical health problems. While smoking, alcohol, and BMI may play a role, we now need to focus on what other biological (e.g. genetic, hormonal, etc), environmental, lifestyle (e.g. diet, exercise, sleep, etc) or healthcare-related factors are contributing to these health disparities.”

Professor Simon Baron-Cohen, Director of the Autism Research Centre at Cambridge, who was part of the team, said: “This new study highlights the physical health risks to autistic individuals, and has important implications for their healthcare. Understanding the reasons why these disparities exist will allow us to better support autistic individuals and improve the quality and length of their lives.”

Funding for this project was provided by the Autism Research Trust, the Rosetrees Trust, and the Cambridge and Peterborough NHS Foundation Trust. 

Posted on Fibromyalgia

Pleasure and Pain Brain Signals Disrupted in Fibromyalgia Patients

Deep Brain Stimulation
Deep Brain Stimulation


New research indicates that a disruption of brain signals for reward and punishment contributes to increased pain sensitivity, known as hyperalgesia, in fibromyalgia patients. Results published in Arthritis & Rheumatism, a journal of the American College of Rheumatology, suggest that this altered brain processing might contribute to widespread pain and lack of response to opioid therapy in patients with fibromyalgia.

Fibromyalgia is a chronic, musculoskeletal syndrome characterized by widespread joint and muscle pain along with other symptoms such as fatigue, sleep disturbances, and cognitive difficulty. Previous research estimates that fibromyalgia affects 3.4% of women and 0.5% of men in the U.S. Prevalence of this pain disorder increases with age, affecting more than 7% of women between 60 and 79 years of age. 

“In patients with fibromyalgia there is an alteration in the central nervous system pain processing and a poor response to topical pain treatments, trigger point injections and opioids,” said lead author Dr. Marco Loggia from Massachusetts General Hospital and Harvard Medical School in Boston. “Our study examines the disruption of brain function involved in the individual experience of pain anticipation and pain relief.” 

For the present study, the research team enrolled 31 patients with fibromyalgia and 14 healthy controls. Functional magnetic resonance imaging (MRI) and cuff pressure pain stimuli on the leg were performed on all subjects. During the MRI, participants received visual cues alerting them of impending pain onset (pain anticipation) and pain offset (relief anticipation). 

Results show that during pain anticipation and relief, fibromyalgia patients displayed less robust response within brain regions involved in sensory, affective, cognitive and pain regulating processes. The ventral tegmental area (VTA)—a group of neurons in the center of the brain involved in the processing of reward and punishment—displayed activation during pain anticipation and stimulation, but deactivation during anticipation of relief in healthy controls. In contrast, VTA responses during periods of pain, and anticipation of pain and relief, in fibromyalgia patients were significantly reduced or inhibited. 

Dr. Loggia concludes, “Our findings suggest that fibromyalgia patients exhibit altered brain responses to punishing and rewarding events, such as expectancy of pain and relief of pain. These observations may contribute to explain the heightened sensitivity to pain, as well as the lack of effectiveness of pain medications such as opioids, observed in these patients. Future studies should further investigate the neurochemical basis underlying these dysfunctions.”