Showing posts with label etiology. Show all posts
Showing posts with label etiology. Show all posts

Wednesday, 27 August 2025

Gold standard science isn't gold standard if it's applied selectively. Part 2: Research on causes of autism

In my previous blogpost, I discussed why many scientists can't take seriously the lofty ideals expressed in Trump's plans for Gold Standard Science, even though the basic principles seem excellent. Given the current Republican administration's catastrophic track record in undermining US science, their demands for high standards ring hollow. It appears that demands for Gold Standard Science will be weaponised against types of science they don't like. 

Today I provide evidence from the opposite side of the fence. If the Trump administration was really serious about Gold Standard Science, then they should lead by example and showcase projects that are impeccably rigorous, open and transparent. 

And what better place to start than with research on autism, which has been an obsession of Robert F Kennedy Jr (RFK), the 26th United States Secretary of Health and Human Services? The first inkling of what was to come was in April this year when the media reported that he had planned to find the cause of autism by September.  Then, on May 27th, NIH announced a new Autism Data Science Initiative, which appears to relate to JFK's plans. 

I watched with interest a video that was released on 10th June explaining the background of the project. The NIH staff presenting the video gave an evidence-based and balanced account of what is known about the etiology of autism, which was described as complex and multifactorial, involving different types of genetic causes which may interact with environmental factors. In considering the increase in autism diagnosis over time, it was noted that changes in diagnostic criteria, and the need for a diagnosis for access to services were implicated. They implicitly accepted, however, the notion that these factors were insufficient to explain the increase, and so we needed research on other factors. 

They then explained how to apply for a share of the $50 million allocated to the initiative, which seemed designed to encourage machine learning approaches to data mining of autism-relevant datasets "to explore the contribution of genetic and non-genetic factors to the causes of autism and or to identify patterns associated with intervention outcomes and the use of services for autism." 

A startling feature was that submissions had to be in by 27th June, one month after the scheme was announced, and 17 days after the instructional video was posted. The earliest start date was 1st September, perhaps prompted by RFK's idea of having autism etiology done and dusted by then. 

You might wonder how this works with NIH's review process: the answer is that it doesn't. The funding mechanism is an Other Transaction: "an assistance mechanism that is not a grant, contract, or cooperative agreement" and the proposal does not undergo traditional NIH review, but instead is subject to "an objective scientific review. This ensures the assessment of scientific or technical merit of applications by individuals with knowledge and expertise equivalent to that of the individuals whose applications of support they are reviewing". Though, so far, it seems that the top US autism researchers have not been consulted on this scheme. Furthermore, the phrase "Autism Data Science Initiative" isn't mentioned in the massive report from the Committee on Appropriations that was published on July 31st. So this has a decidedly ad hoc feel to it. 

This hurried process does not seem an optimal way to foster Gold Standard Science, which requires thought and care to go into research plans. There seem two possible explanations for this rushed approach. Either those who devised the scheme are so ignorant that they don't understand how long it takes to develop a strong research proposal, or they really don't want anyone to apply to the scheme other than specific cronies who will do their bidding. 

I had thought we might have to wait until the end of September when the successful grants are announced to see who the lucky grant recipients would be. From this video clip of a recent Cabinet meeting, however, it seems that the research has already been done, results are in and will be announced next month! 

Donald Trump and Jay Bhattacharya can talk about Gold Standard Science as much as they like: scientists can see for themselves this travesty of research process, which indicates that, when it comes to their own studies, those in power will know the answer before the data is in. No transparency, no pre-registration, no open data and code, no communication of error and uncertainty, no skepticism of findings or attempt to falsify hypotheses, and no impartial peer review. Truly this is Tinsel Standard Science.

Sunday, 26 May 2013

Schizophrenia and child abuse in the media

A couple of weeks ago, the Observer printed a debate headlined “Do we need to change the way we are thinking about mental illness?” I read it with interest, as I happen to think that we do need to change, and that the new Diagnostic and Statistical Manual of the American Psychiatric Association (DSM5) has numerous problems.

The discussion was opened by Simon Wessely, a member of the Royal College of Psychiatrists, who responded No. He didn’t exactly defend the DSM5, but he disagreed with the criticism that it reduces psychiatry to biology. The Yes response was by Oliver James, an author and clinical psychologist, who attacked the medical model of mental illness, noting the importance of experience, especially childhood experience, in causing psychiatric symptoms. I happen to take a middle way here; there’s ample evidence of biological risk factors for many forms of mental illness, but in our contemporary quest for biomarkers, the role of experience is often sidelined. The idea that you might be depressed because bad things have happened to you goes unmentioned in much contemporary research on affective disorders, for instance.

But, rather than getting into that debate, I want to make a more general point about evidence. In his statement, Oliver James came out with some statistics that surprised me. In particular, he said:
13 studies find that more than half of schizophrenics suffered childhood abuse. Another review of 23 studies shows that schizophrenics are at least three times more likely to have been abused than non-schizophrenics. It is becoming apparent that abuse is the major cause of psychoses.
The frustrating thing about this claim is that no sources were given. I don't work in this area, so I thought I’d see if I could track down the articles cited by James. My initial attempt was based on a hasty search of Web of Knowledge on the morning that the article appeared. I described the results of my searches on a blogpost that day, but a commentator pointed out that I'd limited myself to looking at the link between schizophrenia and sexual abuse, whereas James had been referring to childhood abuse in general. I realised that a fair and proper appraisal of his claims should look at this broader category, and accordingly I removed the original post until I could find time to do a more thorough job.

Accurate assessment of child abuse is difficult because it is often hidden away and many cases may be missed. Retrospective accounts of abuse are notoriously hard to validate: false memories can be induced, but true memories may be suppressed. All those writing in this field note the problems of getting accurate data, and the wide variations in rates of abuse reported in the general population, depending on how it is defined. For instance, Fryers and Brugha (2013) noted that for the general population, estimated rates of child physical abuse have ranged between 10% to 31% in males and 6% to 40% of females, and child sexual abuse from 3% to 29% in males and 7% to 36% in females.

Fryers and Brugha focused on prospective, longitudinal studies, taking evidence from over 200 studies. They concluded that “most abuses were associated statistically with almost all classes of disorder (psychosis being largely an exception)”, p 26, and “schizophrenia and closely related syndromes have not generally been much associated with previous child abuse but the picture is not simple.” P.27. They noted that one Australian cohort study found an increase in schizophrenic disorders in children who had been sexually abused, though this was an unusual finding in the context of the research literature as a whole.

Other recent meta-analyses have included case-control studies, where participants are recruited in adulthood, and histories of participants with schizophrenia are compared with those of a control group. Matheson et al (2012) summarised seven studies involving a comparison between patients with schizophrenia and non-psychiatric controls, but definitions of adversity varied widely. In some studies, 'adversity' extended beyond abuse, though physical, sexual and emotional abuse predominated in the definitions. Overall, this review gave results similar to those reported by James, with an adversity rate of 58% in the schizophrenia group and 27% in the controls. This high rate in those with schizophrenia depends, however, on one large study that included adversity factors going beyond abuse, such as having a parent with nervous or emotional problems, or a lot of conflict and tension in the household. In this same study, 91% of controls compared with 71% of those with schizophrenia described their childhood as "happy". If this study is excluded, rates of adversity in those with schizophrenia fall to 28% compared to 8% in controls – still a notable and statistically reliable effect, but with less dramatic absolute rates of adversity than those cited by James.

A larger meta-analysis including a total of 36 studies was conducted by Varese et al (2012), who obtained similar results:  a higher rate of childhood adversities in those who develop psychosis, with an odds ratio estimated at 2.78 (95% CI = 2.34-3.31). Significant associations of similar magnitude were found for all types of adversity other than parental death. The odds ratio is not, however, the same as a risk ratio, so should not be interpreted as indicating that those with schizophrenia are three times more likely to have suffered abuse. I don’t want to downplay the importance of the association, which is nevertheless striking, and supports the authors' conclusion that clinicians should routinely inquire about adverse events in childhood when seeing patients with psychiatric conditions.

Overall, the research literature confirms a reliable association between childhood adversity, including abuse, and schizophrenia in adulthood. The conclusion drawn by James, however, that “abuse is the major cause of psychoses” is not endorsed by any of the academic authors of the reviews I looked at. The complexity of causation in the field of neuroscience and mental health is a topic I hope to return to in a later blogpost, but for the time being, I would recommend another review of this literature by Sideli et al (2012), which discusses possible explanations for links between adversity and psychosis. Most researchers familiar with this area would endorse this quote by Fryers and Brugha (2013), reflecting on our state of knowledge in this area:
From all this work an understanding has emerged of the 'cause' of serious mental illness as complex, varied and multi-factorial, encompassing elements of genetic constitution, childhood experience, characteristics of personality, significant life events, the quality of relationships, economic and social situation, life-style choices such as alcohol and other drugs, and aging. Some of these factors have been elucidated to the point of representing acknowledged risk factors for specific forms of mental illness or mental illness in general, such as familial genes, relative poverty, major trauma, excessive alcohol consumption, extreme negative life-events, poor education, and long-term unemployment.

These may all be experienced in childhood and we do not need research to tell us that poverty, inadequate education and life events such as loss of a parent or displacement as a refugee by war, or trauma such as child sex abuse are bad. Nor should it need evidence of later consequences such as mental illness to argue for the prevention of such situations and experiences. The strongest argument is in terms of human rights. However, the issues are not generally given a high priority and people may think them exaggerated or assume that these things are just part of human life and children get over them anyway. But we should not be willing to accept these as inevitably part of human life, but fight for a better life for our children – and hope thereby for a better life for adults and the whole community.
But to come back to the impetus for the current blogpost, the point I’d really like to make is that if the Observer wants to run articles like this, where scientific evidence is cited, the editor should ask for sources for the evidence, and should provide these with the article. As noted by Prof Michael O'Donovan in a letter to the Observer, Oliver James is "unknown in the scientific community as a researcher into the origins of psychosis". This does not make his opinions worthless, but if he wants to argue his case from the scientific evidence, then we need to know what evidence he is using, just as we would expect for any reputable scientist making such claims. Most readers don't have the resources or skills to trawl through research databases trying to establish whether the evidence is accurately reported or cherry-picked. As O'Donovan points out, confident assertions about childhood causes of schizophrenia can only cause distress to families affected by this condition, and a responsible newspaper should take care to ensure that such claims have a verifiable basis.

References

Fryers, T., & Brugha, T. (2013). Childhood determinants of adult psychiatric disorder. Clinical Practice & Epidemiology in Mental Health, 9 (1), 1-50 DOI: 10.2174/1745017901309010001

Matheson, S. L., Shepherd, A. M., Pinchbeck, R. M., Laurens, K. R., & Carr, V. J. (2013). Childhood adversity in schizophrenia: a systematic meta-analysis. Psychological Medicine, 43(2), 225-238. doi: 10.1017/s0033291712000785

Sideli, L., Mule, A., La Barbera, D., & Murray, R. M. (2012). Do child abuse and maltreatment increase risk of schizophrenia? Psychiatry Investigation, 9, 87-99. doi.org/10.4306/pi.2012.9.2.87

Varese, F., Smeets, F., Drukker, M., Lieverse, R., Lataster, T., Viechtbauer, W., Read, J., van Os, J., & Bentall, R. (2012). Childhood adversities increase the risk of psychosis: A meta-analysis of patient-control, prospective- and cross-sectional cohort studies Schizophrenia Bulletin, 38 (4), 661-671 DOI: 10.1093/schbul/sbs050

Note: Thanks to the anonymous reviewer who noted the problem with my initial analysis