The Lack of Correlation Between Most Mental Illness and Brain States

In a 1920 book by Carl August Wickland there is a discussion of the lack of correlation between brain states and mental illness. We read this:

"Dr. W. M. L. Coplin, Director of the Bureau of Health and Charities, Philadelphia, Pennsylvania, said 'Insanity, in most cases, is unaccompanied by any perceptible change in the brain structure. The brain of the patient, when examined under a microscope, shows absolutely nothing which differs in any way from the appearance of the brain of the perfectly sane person. It is therefore evident that the insanity might be due to toxemia, the effect of some subtle organism in the nature of bacilla.... Something causes insanity but what it is, we do not yet know.'

Dr. Britton D. Evans, Superintendent of the Morris Plains, New Jersey, Insane Asylum, stated: 'Brain tumor or brain fever may not affect the mind.... A man may have trouble of the brain and still have a normal mind.'

Dr. Th. Ziehen, a noted German alienist, and an authority on hysteria, wrote: 'For many functional neuroses there is as yet no accurate limitation and definition. As pathological anatomy does not aid us, no uniform and exclusive cause for hysteria can be demonstrated.'

Dr. William Hanna Thomson, physician to the Roosevelt Hospital and Professor of the Practice of Medicine and Diseases of the Nervous System, New York University Medical College, in referring to Tuke's Dictionary of Psychological Medicine, asserted that:  'The contributors to this great encyclopedia are from the most eminent professors, experts, and superintendents of insane asylums in Great Britain, the United States, France, Germany, Hungary, Belgium, Denmark, Switzerland and Russia. In the articles by the writers on kleptomania, dipsomania, chronic mania, etc., there is not a word about the pathological anatomy, (because none can be found). Just so it is in the article on melancholia, puerperal insanity, katatonia, circular insanity, homicidal insanity or epileptic insanity; in none of these is there a word about pathological anatomy, for the sufficient reason that not one of these forms of insanity shows any pathological or diseased condition in the brain different from the sound brain of a healthy man killed in an accident.'

He also said: 'It is high time that we now look in the direction of toxemia (or blood poisoning) for the explanation of the insanities which produce no changes whatever in the brain.' ”

The quotes above date from about 100 years ago. For a modern take on these questions, we can look at some of the chapters of the free online psychiatry textbook "Critical Psychiatry Textbook" by Peter C. Gøtzsche, MD. In Chapter 3 Gøtzsche states this: "Despite 15 years of intense studying, I have been unable to find any important contribution of biological psychiatry to our understanding of the causes of psychiatric disorders and how they should best be treated."  

Gøtzsche cites psychiatry textbooks that attempt to link small brain differences with mental illness. He gives many examples indicating that such textbooks routinely make untrue claims based on weak evidence. He points out that many of these textbooks are citing unreliable studies with too-small sample sizes. He also raises an important point that casts doubt on the unreliability of all such claims: the fact that nowadays people suffering from mental illness are massively prescribed brain drugs, and many think that such drugs themselves may produce changes in brain states, including shrinkage of brain tissue. If drugs may change some part of the brain, and the mentally ill people being studied have been long taking such drugs, then any difference in their brains may be caused by the drugs themselves, rather than such changes being the cause of their mental illness. 

He states this about brain imaging studies (often used to try to back up claims of a physical basis for mental illness):

"This whole area is a mess of highly unreliable research. A 2009 meta-analysis found that the false positive rate in neuroimaging studies is between 10% and 40%.  And a 2012 report written for the American Psychiatric Association about neuroimaging biomarkers concluded that 'no studies have been published in journals indexed by the National Library of Medicine examining the predictive ability of neuroimaging for psychiatric disorders for either adults or children.' 

One good research paper can sometimes make hundreds of poor studies redundant. This is the case for a 2012 systematic review by Joshua Carp that surveyed the methodological state of the art in a random sample of 241 fMRI studies. Carp found that many of the studies didn’t report on critical methodological details about experimental design, data acquisition, or analysis, and many studies were underpowered. Data collection and analysis methods were highly flexible. The researchers had used 32 unique software packages, and there were nearly as many unique analysis pipelines as there were studies. Carp concluded that because the rate of false positive results increases with the flexibility of the design, the field of functional neuroimaging may be particularly vulnerable to false positives. Fewer than half of the studies reported the number of people rejected from analysis and the reasons for rejection, and the median sample size per group was only 15, which generates an enormous risk of selective publication of those results that happened to agree with the investigators’ prejudice."

The doctor includes many additional paragraphs challenging the reliability of brain imaging techniques. He points out people analyzing brain scans have an almost infinite variety of possible "analysis pipelines" they can choose from, each of which is a different way of analyzing the data. He suggests that you can show almost anything you want from brain scan data, simply by fiddling around with different analysis pipelines until one such analysis pipeline shows what you are trying to show.  He then states this:

"The experience of the Editor-in-Chief of Molecular Brain is also relevant to consider when assessing the merits of brain scanning studies in psychiatry. In 2020, he described what happened when he requested to see the raw data in 41 of the 180 manuscripts he had handled. Upon his requests, 21 of the 41 manuscripts were withdrawn by the authors, and he rejected a further 19 'because of insufficient raw data,' which suggested that the raw data might not exist, at least for some of the cases. Thus, only 1 of 41 papers (2%) passed his reasonable test."

A 2016 paper ("Finding the Elusive Psychiatric 'Lesion' With 21st-Century Neuroanatomy: A Note of Caution") has this abstract:

"The widespread use of MRI has led to a wealth of structural and functional anatomical findings in patients with diverse psychiatric disorders that may represent insights into pathobiology. However, recent technical reports indicate that data from popular MRI research-particularly structural MRI, resting--state functional MRI, and diffusion tensor imaging--are highly sensitive to common artifacts (e.g., head motion and breathing effects) that may dominate the results. Because these and other important confounders of MRI data (e.g., smoking, body weight, metabolic variations, medical comorbidities, psychoactive drugs, alcohol use, mental state) tend to vary systematically between patient and control groups, the evidence that findings are neurobiologically meaningful is inconclusive and may represent artifacts or epiphenomena of uncertain value. The authors caution that uncritically accepting from study to study findings that may represent fallacies of all sorts carries the risk of misinforming practitioners and patients about biological abnormalities underlying psychiatric illness."

Referring to major depressive disorder, a 2019 paper published in Nature states this: "MRI scans cannot be used to aid in the diagnosis or treatment planning of patients with MDD." A 2019 scientific paper states this: "Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent."  The frequent "nonreplications" are apparently studies that fail to show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). The paper very weakly concludes that "subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD."  Given such frequent nonreplications, we may be skeptical about the "subtle differences" claimed. Gøtzsche  states, "The fact is that ADHD is a social construct and that no reliable studies have shown any biological origin for this construct, or that the brains of people with this diagnosis are different to the brains of other people."

A 2021 study is entitled "Systematic Review of Functional MRI Applications for Psychiatric Disease Subtyping." Hinting at a lack of good quality evidence that brain scans can be useful for psychiatric diagnosis, the paper says that "this subfield is at an incipient exploratory stage, and all retrieved studies were mostly proofs of principle where further validation and increased sample sizes are craved for," noting that "results for all explored diseases are inconsistent." Another 2021 study states this about MRI brain scan studies: "In a reflection on the history and future use of MRI in psychiatry, Etkin commented on the lack of reproducible, diagnosis-specific neuroimaging findings." A 2019 paper says that MRI brain imaging "still has only a minor role in the clinical assessment of patients at early stages of psychosis and whether it should be implemented as routine screening instrument in psychotic patients has continued to generate debate." Another paper says brain lesions of causal relevance occur in only 6% to 10% of schizophrenia patients, and then says that only 3% of secondary schizophrenia arises in the presence of systemic physical illness. The actual numbers are probably less, as estimates of this type (made by neuroscientists who love to suggest neural causes) are typically overestimates. 

In an illuminating article by Bruce E. Levine, we read the following:

"Published in the journal Neuron in 2022, Raymond Dolan—considered one of the most influential neuroscientists in the world—co-authored 'Functional Neuroimaging in Psychiatry and the Case for Failing Better,' concluding, 'Despite three decades of intense neuroimaging research, we still lack a neurobiological account for any psychiatric condition.'  Reflecting on the more than 16,000 neuroimaging articles published during the last 30 years, Dolan and his co-authors concluded: 'It remains difficult to refute a critique that psychiatry’s most fundamental characteristic is its ignorance. . . . Casting a cold eye on the psychiatric neuroimaging literature invites a conclusion that despite 30 years of intense research and considerable technological advances, this enterprise has not delivered a neurobiological account (i.e., a mechanistic explanation) for any psychiatric disorder, nor has it provided a credible imaging-based biomarker of clinical utility.' ”

Below is a recent quote from Allan Levinthal, PhD:

"In stark contrast to the discoveries by medical researchers of biological causation for many physical illnesses, psychiatric researchers have failed to find physiological or genetic causation for the most diagnosed mental disorders—the anxiety disorders and depression—negating the rationale for the prescription of these drugs. This failure has occurred despite (a) the expenditure by the NIMH of tens of billions of research dollars over this same more than century-long time span in a fruitless search for physical causation of these mental disorders and (b) patients spending tens of billions of dollars annually on these prescriptions."