RE: Post-traumatic Stress as the Primary Cause for Cognitive Decline—Not the Whole Story, and Perhaps No Story at All

JNCI: Journal of the National Cancer Institute, Oct 2017

Hermelink, Kerstin, Bühner, Markus, Münzel, Karin, Mahner, Sven, Harbeck, Nadia

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RE: Post-traumatic Stress as the Primary Cause for Cognitive Decline—Not the Whole Story, and Perhaps No Story at All

JNCI J Natl Cancer Inst ( RE: Post-traumatic Stress as the Primary Cause for Cognitive Decline-Not the Whole Story, and Perhaps No Story at All Kerstin Hermelink 0 1 Markus Bu¨ hner 0 1 Karin Mu¨ nzel 0 1 Sven Mahner 0 1 Nadia Harbeck 0 1 0 The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions , please 1 Affiliations of authors: Breast Center, Department of Gynecology and Obstetrics, CCCLMU University Hospital of Munich , Munich, Germany (KH, SM , NH); Department of Psychology, Division of Psychological Methods and Assessment, Ludwig Maximilian University of Munich , Munich , Germany ( MB); Department of Psychology, Division of Neuropsychology, Ludwig Maximilian University of Munich , Munich, Germany, KM - We would like to comment on the editorial ( 1 ) accompanying our recent article in the Journal, written by our esteemed colleagues Sanne B. Schagen and Jeffrey S. Wefel. We welcome the opportunity to discuss some issues raised in the editorial regarding both the current and previous studies from our group ( 2,3 ) that we feel need clarification and further consideration. We are strongly criticized for combining commission errors and omission errors on the Go/Nogo test—according to the editorialists, “both secondary outcomes measuring errors on a reaction time test”—in a Go/Nogo error score. We wish to point out that commission errors and omission errors are not secondary but primary outcomes of the Go/Nogo, a test of selfregulation ( 4 ), and that the exact score used in our analyses— combined commission and omission errors on the Go/Nogo test of the Testbatterie zur Aufmerksamkeitspr u¨fung (TAP) ( 5 )—was validated in German breast cancer patients ( 6 ). As an aside, the literature on cancer-related cognitive dysfunction is full of combined scores like domain-specific and overall cognitive function scores, for understandable reasons, and we used an overall score ourselves. Between studies, there is considerable variation in the composition of measures that go into these scores, and the vast majority of them have never been validated. The editorialists allege that we created a variable “termed ‘degree of PTSD.’” This obscure term is quoted six times in the editorial although it does not appear in either of our articles. The variable that was used to measure the burden of post-traumatic stress was (number of) PTSD symptoms. As correctly stated in the editorial, PTSD symptoms were assessed with clinical diagnostics based on a validated interview ( 7 ). Contrary to the editorialists’ claims, the interview is suited to diagnose symptoms, as stated in its manual: “The Structured Clinical Interview for DSM-IV (SCID) is a semi-structured clinical interview to assess symptoms, syndromes, and diagnoses” (page 4, translation by K. Hermelink). We would further like to note that the stopping rules, which we disregarded to allow a full assessment of PTSD symptoms, do not contribute to the interview’s validity but are intended to save time if the interviewer is interested in diagnoses. We are accused of ignoring that in our study “overall cognitive decline is not mediated by PTSD.” In fact, we saw mediation of overall cognitive change by PTSD symptoms (effect of cancer without mediation, P ¼ .04; with mediation, P ¼ .07), but the mediation effect was not statistically significant (bootstrapped 95% confidence interval ¼ –0.06 to 0.03), probably because of a lack of power. We did observe and report statistically significant bivariate associations of age- and education-corrected overall cognitive change at T3 with PTSD symptoms at T3 as well as T2 (P ¼ .001 and P ¼ .002, respectively). Finally, the editorialists’ statement that “Hermelink et al. start out. . .asserting that it is very ‘unlikely that (PTSD) does not impact the brain’” is a misquotation. The sentence reads, “It seems very unlikely that distress, sleep problems, and prolonged sick leave, among other factors associated with having cancer, do not impact the brain” ( 2 ). 1. Schagen SB , Wefel JS . Post-traumatic stress as the primary cause for cognitive decline-not the whole story, and perhaps no story at all . J Natl Cancer Inst . 2017 ; 109 ( 10 ): djx091 . 2. Hermelink K , Bu¨ hner M, Sckopke P , et al. Chemotherapy and post-traumatic stress in the causation of cognitive dysfunction in breast cancer patients . J Natl Cancer Inst . 2017 ; 109 ( 10 ): djx057 . 3. Hermelink K , Voigt V , Kaste J , et al. Elucidating pretreatment cognitive impairment in breast cancer patients: The impact of cancer-related post-traumatic stress . J Natl Cancer Inst . 2015 ; 107 ( 7 ): djv099 . 4. Lezak MD , Howieson DB , Loring DW. Neuropsychological Assessment . 4th ed. New York: Oxford University Press; 2004 . 5. Zimmermann P , Fimm B . Testbatterie zur Aufmerksamkeitspr u¨fung (TAP) . Version 2 .2 [Tests of Attentional Performance]. Herzogenrath, Germany: Psytest; 2009 . 6. Scherwath A , Poppelreuter M , Weis J , Schulz-Kindermann F , Koch U , Mehnert A. [ Psychometric evaluation of a neuropsychological test battery measuring cognitive dysfunction in cancer patients-recommendations for a screening tool] . Fortschr Neurol Psychiatr . 2008 ; 76 ( 10 ): 583 - 593 . 7. Wittchen H , Zaudig M , Fydrich T. SKID . Strukturiertes Klinisches Interview f u¨r DSM-IV. Achse I und II . Handanweisung. Go¨ ttingen, Germany: Hogrefe; 1997 .


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Hermelink, Kerstin, Bühner, Markus, Münzel, Karin, Mahner, Sven, Harbeck, Nadia. RE: Post-traumatic Stress as the Primary Cause for Cognitive Decline—Not the Whole Story, and Perhaps No Story at All, JNCI: Journal of the National Cancer Institute, 2017, DOI: 10.1093/jnci/djx147