“Precision psychiatry”: A promising direction so far

Sir,

After launching of “The Precision Medicine Initiative” in 2015, precision medicine has got new momentum, in recent years, at least in Western countries.[1] Precision medicine has been defined as “an emerging approach for treatment and prevention that takes each person's variability in genes, environment, and lifestyle” into account.[2] Interestingly, the foundation of precision medicine is not recent one; it dates back from Hippocrates in 400 BC to Claude Bernard, a physiologist in 19^th century.[3,4] Archibald Gabbord, who talked about the importance of individual “chemical differences” in an article in 1902, is considered to be the father of precision medicine.[5,6] What might have been the goal of precision medicine might have been borrowed from Gabbord as “The task of the practitioner is far more than to apply the knowledge supplied to him from the laboratories; he … calls upon his experience to guide him as to how he may best help the particular patient [manage his disease] with the least possible damage.”[6] The dictionary definition of “precision is 'the quality, condition, or fact of being exact and accurate' and 'refinement in a measurement, calculation, or specification'.”[7] Adoption of the term “precision psychiatry” may rightly be the first step toward that.[8,9] The basic presumption of precision psychiatry remains in applying existing concepts and constructs of precision medicine along with developing newer ones in diagnosis and treatment in the field of clinical psychiatry. While, with the advent of newer technologies for assessment and management, precision medicine has potential to be more “quantitatively” precise, this is not the same in case of precision psychiatry. Research claims that precision psychiatry would not only be “quantitatively” different but would be different “qualitatively” also, thereby leading to a paradigm shift. Given the scenario where there is lack of clarity in pathophysiological mechanism of psychiatric disorders and symptoms, overlapping among them which is more complicated by symptom heterogeneity for a psychiatric diagnosis, it would not be far fletched to expect that “precision psychiatry”, if it attains what it has envisioned to, shall bring a paradigm shift in clinical psychiatry. While a “causal” connection has been apparent for psychosocial factors, same for biological factors for psychiatric illness remained mostly inconclusive, thereby limiting the effectiveness of currently available management for psychiatric illnesses. One critical issue to understand regarding causation and course of mental illness is how multiples systems across mental apparatus overlap and failure of one element in the system does not lead to system-wide failure or how one or more elements are there for back up if other elements fail to function or intrinsic mechanisms exist for systemic stability.[9] Few other limiting factors in clinical psychiatry are in having symptom-based diagnosis instead of mechanism based,[10] in ascertaining prognosis, in predicting response to treatment and guiding treatment. To add to these challenges, there is epigenetics which disrupts the process of genetic maturation of an individual thereby altering disease process of a psychiatric disorder. Recently, Williams proposed a neural circuit-based taxonomy for anxiety and depression.[11] He elaborated about the putative types of dysfunction, which is not parallel to traditional diagnostic boundaries but covers the heterogeneity of depression and anxiety. For example, it has been a quite common experience to clinicians that two patients suffering from depression do not respond identically to an antidepressant despite identical sociodemographic and clinical profiles. With the help of “big data” (mentioned below), one would be able to predict and be precise to choose an antidepressants molecule individualized and précised for an index patient. Similarly, a patient suffering from schizophrenia choosing an antipsychotic still requires more than two trials for a significant proportion of patients. With the help of precision psychiatry and “big data” from converging scientific disciplines as discussed below, one would be able to choose an antipsychotic after considering many other factors including genetic ones related to the patient. This would, in turn, increase the precision of treatment for an index patient. Recently, the advent of brain imaging techniques with enough spatial and temporal resolution to quantify neural connections gives a thrust toward heterogeneity of depression and anxiety.[12] With convergence of several disciplines of science, massive information of patient characteristics – “big data”– should lead us to the goal. Newer technologies are expected to help us to attain contextual precision diagnosis by understanding mental causation in symptom circuits, by diagnosing environmental reactivity and with a collaborative diagnostic process where active participation of and feedback from patients would be important. Contextual precision diagnosis, when in practice, has a promise to be more idiographic and sensitive to changes in psychopathology and would add to current symptom-based diagnostic system, if not replacing it. It would not only talk about symptoms and environment but also would take positive affective states of the patient into account, thereby increasing therapeutic relevance.[10] As no single biomarker shall probably not define any single psychiatric illness and would not be able to explain heterogeneity of psychiatric diagnosis, working on parallel theories and thereby on combinatorial profile of biomarkers appear to be the next logical direction. To achieve that “precision psychiatry” deals with several domains which are designed to cover physiology, environmental characteristics, cognitive neuroscience and neuropsychology, neural circuits, “big data”, molecular biosignature. “Big data” shall be grabbed from electronic health records, large databanks, and mobile devices data. Molecular biosignature shall be obtained from basic sciences and “panomics” which include proteomics, metabolomics, genomics, transcriptomics, and epigenomics. Data for neural circuits and cognitive neuroscience shall be gathered from fMRI or diffusion MRI, memory, attention, negative affect, cognitive control, and salience. Environmental data shall be obtained from trauma history and lifestyle. Data gathered from all these sources would be analyzed using “systems biology” and computational psychiatry tools which would give us “biosignatures”– a set of system biomarkers, thereby giving different diagnosis and endophenotypes for population of interest with similar cluster of symptoms.[9,11] Clearly, partnership between scientists and industry and support from respective government with similar strategic direction would be crucial at this point. If “precision psychiatry” can achieve what it is envisaged to, it will surely redefine the field of clinical psychiatry in future. It is true that we can be hopeful only on the premise that several converging approaches make progress as it has been postulated to. Till then, it remains as a promising direction only.

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Conflicts of interest

There are no conflicts of interest.