Towards objective definition of psychopathology in post-traumatic stress disorder

You have full access to this article via your institution. Download PDF Owing to their reliance on imprecise clinical phenotypic definitions, current psychiatric diagnoses capture a broad

range of neurobiological alterations across patients. The difficulties that arise from these definitions are particularly striking for post-traumatic stress disorder (PTSD). For example, the

revision of its diagnostic criteria from DSM-IV to DSM5 resulted in only a ~ 50% overlap in case definition [1]. One way to overcome challenges inherent to these clinical definitions is to

anchor patient definitions in objectively quantifiable measures [2]. To identify biologically and clinically meaningful PTSD subtypes, we began with the perspective that cognitive task

behavior may be a particularly useful way to anchor patient phenotypes so that they are both objective and face-valid [3]. Within cognition, verbal memory is the domain most impaired in PTSD

patients on average [4]. We therefore treated verbal memory in a normative perspective, dividing patients based on whether they performed within or outside the healthy norm, and examined

resting-state functional magnetic resonance imaging (fMRI) network connectivity to understand mechanisms involved with differences in memory [3]. This is akin to a typical medical test,

which are often framed within a normative perspective. We found, and then replicated (total _N_ = 357), that after correction for multiple comparisons, connectivity in one brain system (the

ventral attention network; VAN) was reduced only in PTSD patients with impaired verbal memory, relative to either controls or patients with intact memory. Critically, moreover, memory and

VAN connectivity predicted treatment outcome, thus demonstrating clinical relevance, despite the discovery of the memory–VAN connection coming out of a mechanistic characterization rather

than one primarily targeting treatment prediction [3]. Patients in one of the samples went on to receive either prolonged exposure psychotherapy, a gold-standard treatment for PTSD, or a

wait list intervention control. Those patients with impaired memory and VAN connectivity failed to respond to prolonged exposure (and did not differ in the wait list arm), whereas those

without both abnormalities responded well. Finally, to understand how these insights may be useful in driving new therapeutics, we used simultaneous non-invasive transcranial magnetic

stimulation and electroencephalography (TMS/EEG) to map the brain’s response to single TMS pulses at various locations and implicated a region in the right prefrontal cortex [3]. These

results suggest that by anchoring on an objective measure (i.e., verbal memory), clinically and mechanistically meaningful biological differences can be observed and replicated. The TMS

findings further suggest an avenue for developing novel interventions for memory–VAN impaired patients, by targeting the right prefrontal cortex. More broadly, these findings open up a path

for transcending traditional clinical phenomenology and grounding clinically meaningful case definition in observable biomarkers. To ultimately impact clinical care, we anticipate that tools

such as EEG (a cheaper and more clinic-ready tool than fMRI) and machine learning (to make relevant brain signatures more robust) will be required. Nonetheless, our results suggest that it

is more a question of how, rather than whether, these types of biomarkers could transform diagnosis and treatment in psychiatry. FUNDING AND DISCLOSURE Dr. Etkin was funded by NIH grant DP1

MH116506. Dr. Etkin holds equity in Mindstrong Health, Akili Interactive, and Sizung for unrelated work. REFERENCES * Stein DJ, McLaughlin KA, Koenen KC, Atwoli L, Friedman MJ, Hill ED, et

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in posttraumatic stress disorder. Psychol Bull. 2015;141:105–40. Article  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Psychiatry and

Behavioral Sciences, Stanford University, Stanford, CA, USA Amit Etkin * Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA Amit Etkin * Veterans Affairs Palo Alto

Healthcare System, Sierra Pacific Mental Illness, Research, Educatioand Clinical Center (MIRECC), Palo Alto, CA, USA Amit Etkin Authors * Amit Etkin View author publications You can also

search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Amit Etkin. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to

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definition of psychopathology in post-traumatic stress disorder. _Neuropsychopharmacol._ 45, 226–227 (2020). https://doi.org/10.1038/s41386-019-0504-7 Download citation * Published: 05

September 2019 * Issue Date: January 2020 * DOI: https://doi.org/10.1038/s41386-019-0504-7 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get

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