The Quest for the Holy Grail of Psychiatry

Our brain: the final frontier. This is the unending quest of research into biomarkers. Its continuing mission: to explore strange new theories, to seek out new mental illnesses and new diagnoses, to boldly go where no psychiatric research has gone before.

The quest for biomarkers (measurable indicators of a biological state or condition) of mental disorders has gone on for decades without success. The recently proposed research strategy of the National Institute of Mental Health (NIMH) know as Research Domain Criteria (RDoC), has proposed to set aside the DSM diagnoses used to frame past mental health research and utilize data from neuroscience, genomics and behavioral science to spell out the etiology of mental illness.

Psychiatrist Giovanni Fava views the RDoC model as “the reflection of an intellectual crisis in psychiatry.” While its “blanket” approach aims to see that all possible biological and behavioral measurements are utilized, Fava thinks it will result in conflicting results that may be difficult to interpret. He said it was “misguided” to assume that nothing will be missed with such a strategy and that “innovative classification systems will ensue automatically.” The complexity of the new approach and the potential for interpretive problems it is illustrated by this recently published article in World Psychiatry, “Biomarkers and clinical staging in psychiatry.”

He pointed out that major clinical challenges were left without independent research. Among these challenges was the problem of the loss of clinical effects during long-term antidepressant treatment. And despite a lack of any evidence to support their superiority, antidepressant drugs are increasingly used as a first-line treatment for anxiety disorders. Studies on psychological treatment were also “scandalously under-supported.”

A major problem in the development of the Research Domain Criteria project has been the fact that its strong ideological endorsement by leading figures of the National Institute of Mental Health has resulted in suppression of an adequate debate. How many investigators who are likely to submit funding applications to that agency may afford disclosing that the emperor has no clothes and that the strategy may be a road to nowhere?

Fava et. al thought the exclusive reliance upon diagnostic criteria had impoverished the clinical process and did not reflect “the complex thinking that underlies decisions in psychiatric practice.” Current diagnostic definitions of psychiatric disorders are based on collections of symptoms from very heterogeneous populations and are likely to yield “spurious results when exploring biological correlates of mental disturbances.”

The large studies of biomarkers across diagnostic categories proposed by RDoC are anticipated to yield improved clinical information. But “such a view is based on the concept of assessment as a collection of symptoms devoid of any clinical judgment and interpretation.” There is no evidence to support the research direction taken by RDoC. Fava et al. noted that although Kapur, Phillips and Insel proposed that new biomarker-defined subtypes be identified, they were not able to “provide exemplifications suggesting that this approach was likely to yield meaningful clinical results in psychiatry.” Incidentally, Thomas Insel is the current director of the NIMH.

Using meta-analyses of biomarkers commonly used in cardiovascular medicine as an example, Fava et al. noted the presence of publication bias and selective reporting. They said biomarkers could end up being the result of various mechanisms and not necessarily the result of a specific disease process.

The complexity of the brain and the spurious nature of measurements that can be recorded constitute a major difficulty for psychiatry. Specifically, the neuroplastic properties make the brain a unique organ that essentially has to be studied and understood in a longitudinal, lifetime and transgenerational perspective.

Biological reductionism was said to have resulted in an approach that is far from the “explanatory pluralism” required by clinical practice. The exclusion of the methodological triad of observation (outer viewing), introspection (inner viewing), and dialogue (inter-viewing) makes this approach unscientific. Either the human realm was excluded from scientific inquiry or the scientific approach was conformed to the reductionistic, mechanistic requirements of the biomedical paradigm.

This restrictive ideology characterizes the Research Domain Criteria. It is time to enrich such criteria with clinically relevant dimensions and add clinical validity to the reliability and reductionism-focused mainstream of psychiatry research.

Elsewhere (“We Are But Thinking Reeds”) I’ve spoken of the necessity to see human nature as a psychosomatic unity of body (soma) and soul (psyche). The human mind is more than just a manifestation of brain activity. Any approach to “mental” illness research that fails to acknowledge this will never entirely succeed in its quest to find the holy grail of psychiatry.