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      Relaxation Response in Stressed Volunteers: Psychometric Tests and Neurotrophin Changes in Biological Fluids

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          Background: To evaluate the beneficial effects of relaxation response (RR) training in adult stressed subjects by evaluating the psychometric response recorded at relaxation session. Cortisol as well as nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) mediators were quantified in both saliva and tears, and their levels were related to each other and to the psychometric response.

          Methods: Stressed subjects ( n = 23; 10M/13F; age range 21–53 years old) were voluntarily enrolled in the study. RR training sessions were carried out for 2 months, 1 day per week, at the same time (3–5 p.m.). Two different psychological questionnaires, the Perceived Stress Scale-10 (PSS-10) and the Beck Depression Inventory - Short Form (BDI-SF) and Ocular Surface Disease Index (OSDI) tests, were administered before each session. Saliva and tears were sampled for cortisol (EIA), NGF (ELISA), and BDNF (ELISA) quantifications. Questionnaires' data were analyzed and compared to biochemical ones.

          Results: All subjects reported beneficial effects from training. RR significantly reduced the psychological stress indexes ( p = 0.039 for PSS-10 and p = 0.001 for BDI-SF). Specifically, RR training lowered the perception of Perceived Helplessness (items 1, 3, 10; p < 0.05) in PSS-10 and increased the Perceived Self-Efficacy ( p < 0.05). OSDI score was in the normal range (0–25). Biochemically, a decrease in cortisol, a trend to a decrease in NGF, and an increase in BDNF levels were observed in saliva samples after RR treatment. Furthermore, a trend to a decrease in NGF and an increase in BDNF were quantified in tear samples. A correlation between PSS-10 total score and saliva NGF variation (%) as well as between BDI-SF total score and BDNF tear levels were also observed.

          Conclusion: RR training appeared useful to lowering psychological, mental, and physical stress, as supported by both psychological total and single scores. The finding on biochemical levels of BDNF in saliva and tears are sustained by previous studies while those of NGF require further investigation. Overall, these data on a small population highlight the potential use of RR training and potential neurotrophic changes in biological fluids, in stressed volunteers.

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          Most cited references 49

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          Salivary cortisol as a biomarker in stress research.

          Salivary cortisol is frequently used as a biomarker of psychological stress. However, psychobiological mechanisms, which trigger the hypothalamus-pituitary-adrenal axis (HPAA) can only indirectly be assessed by salivary cortisol measures. The different instances that control HPAA reactivity (hippocampus, hypothalamus, pituitary, adrenals) and their respective modulators, receptors, or binding proteins, may all affect salivary cortisol measures. Thus, a linear relationship with measures of plasma ACTH and cortisol in blood or urine does not necessarily exist. This is particularly true under response conditions. The present paper addresses several psychological and biological variables, which may account for such dissociations, and aims to help researchers to rate the validity and psychobiological significance of salivary cortisol as an HPAA biomarker of stress in their experiments.
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            Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation

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              Reliability and validity of the Ocular Surface Disease Index.

              To evaluate the validity and reliability of the Ocular Surface Disease Index (OSDI) questionnaire. Participants (109 patients with dry eye and 30 normal controls) completed the OSDI, the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), the McMonnies Dry Eye Questionnaire, the Short Form-12 (SF-12) Health Status Questionnaire, and an ophthalmic examination including Schirmer tests, tear breakup time, and fluorescein and lissamine green staining. Factor analysis identified 3 subscales of the OSDI: vision-related function, ocular symptoms, and environmental triggers. Reliability (measured by Cronbach alpha) ranged from good to excellent for the overall instrument and each subscale, and test-retest reliability was good to excellent. The OSDI was valid, effectively discriminating between normal, mild to moderate, and severe dry eye disease as defined by both physician's assessment and a composite disease severity score. The OSDI also correlated significantly with the McMonnies questionnaire, the National Eye Institute Visual Functioning Questionnaire, the physical component summary score of the Short Form-12, patient perception of symptoms, and artificial tear usage. The OSDI is a valid and reliable instrument for measuring the severity of dry eye disease, and it possesses the necessary psychometric properties to be used as an end point in clinical trials.

                Author and article information

                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                17 June 2021
                : 12
                1Department of Psychology, Salesian University of Rome , Rome, Italy
                2Department of Neuroscience, IRCCS Children's Hospital Bambino Gesù , Rome, Italy
                3Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of the Sacred Heart , Rome, Italy
                4Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Sciences; IRCCS – Fondazione Bietti , Rome, Italy
                5Department of Laboratory and Infectivological Sciences, UOC Chemistry, Biochemistry and Molecular Biology Clinic, Fondazione Policlinico Universitario A. Gemelli IRCCS , Rome, Italy
                6Hebrew Hospital Rome Ophthalmology Department , Rome, Italy
                7Prevention and Health Care Department, Campus Bio Medico University , Rome, Italy
                8Cellular Biology and Neurosciences, Istituto Superiore di Sanita , Rome, Italy
                Author notes

                Edited by: Tianhua Niu, Tulane University, United States

                Reviewed by: Zhaohui Steve Qin, Emory University, United States; Chao Xu, University of Oklahoma Health Sciences Center, United States

                *Correspondence: Alessandra Micera alessandra.micera@ 123456fondazionebietti.it

                This article was submitted to Molecular Psychiatry, a section of the journal Frontiers in Psychiatry

                †These authors have contributed equally to this work

                Copyright © 2021 Zappella, Biamonte, Balzamino, Manieri, Cortes, Santucci, Di Stasio, Rizzuto and Micera.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 50, Pages: 9, Words: 6262
                Funded by: Ministero della Salute 10.13039/501100003196
                Original Research


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