Risk factors of depression after prolonged low-dose rate environmental radiation exposure

Yen, Pimei Nancy; Lin, I‐Feng; Chang, Wushou P.; Wang, Jung‐Der; Chang, Tien–Chun; Kuo, Kuan-Liang; Hwang, Jing-Shiang; Liu, I-Chao; Chen, Yi-Ting; Yang, Chen-Chang

doi:10.3109/09553002.2014.916830

Cited by 19 publications

(9 citation statements)

References 49 publications

(52 reference statements)

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“…Longer term (6 mo) assessments of behavior necessitated the use of tumorfree mice and were designed to assess potential radiation-induced changes in anxiety, depression, and extinction (5,6,8,(50)(51)(52)(53). The EPM, LDB, and FST tests provide indirect measures of anxiety-and depression-like behavior, respectively (10,47).…”

Section: Methodsmentioning

confidence: 99%

Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

Montay‐Gruel

Acharya

Petersson

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

409

447

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Here, we highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy·s −1 ). Compared with conventional dose-rate (CONV; 0.07-0.1 Gy·s −1 ) modalities, we showed that FLASH did not cause radiation-induced deficits in learning and memory in mice. Moreover, 6 months after exposure, CONV caused permanent alterations in neurocognitive end points, whereas FLASH did not induce behaviors characteristic of anxiety and depression and did not impair extinction memory. Mechanistic investigations showed that increasing the oxygen tension in the brain through carbogen breathing reversed the neuroprotective effects of FLASH, while radiochemical studies confirmed that FLASH produced lower levels of the toxic reactive oxygen species hydrogen peroxide. In addition, FLASH did not induce neuroinflammation, a process described as oxidative stress-dependent, and was also associated with a marked preservation of neuronal morphology and dendritic spine density. The remarkable normal tissue sparing afforded by FLASH may someday provide heretofore unrealized opportunities for dose escalation to the tumor bed, capabilities that promise to hasten the translation of this groundbreaking irradiation modality into clinical practice.ultra-high dose-rate irradiation | cognitive dysfunction | neuronal morphology | neuroinflammation | reactive oxygen species R adiation therapy (RT) remains an essential part of cancer treatment, and, today, the benefit of RT would increase dramatically if normal tissues surrounding the tumor could tolerate higher doses of radiation (1-3). In the last decade, major advances in high-precision treatment delivery and multimodal imaging have improved tolerance to RT (4), but the selective protection of normal tissue remains a significant clinical challenge and the radiation-induced toxicities still adversely impact the patient's quality of life. This latter fact largely remains an unmet medical need, and points to the urgency of developing improved RT modalities for combating those cancers refractory to treatment.This issue is especially critical for those afflicted with brain tumors, including glioblastoma multiforme (GBM), for which standard treatment consists of surgical resection followed by RT and concomitant chemotherapy (temozolomide). Typical radiotherapeutic protocols for GBM induce neurocognitive complications, including impairments in learning and memory, attention, and executive function and a variety of mood disorders (5-8). A breadth of past work from our laboratories has linked adverse neurocognitive outcomes following cranial irradiation to a range of neuropathologies, including reductions in dendritic complexity and spine density (9-12), reductions in microvascular density (13-15), reduced myelination and synapse density, and increased neuroinflammation (16,17). These changes are persistent and problematic in the conventionally irradiated brain and have prompted efforts to more fully develop a truly innovative approach to RT, where we have concept...

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Section: Methodsmentioning

confidence: 99%

Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

Montay‐Gruel

Acharya

Petersson

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

409

447

View full text Add to dashboard Cite

show abstract

“…Radiation exposure has been found to alter mood [28][29][30][31]. To determine the effects of FLASH and CONV irradiation on anxiety-like and social behaviors, mice were administered the LDB test and the SIT.…”

Section: Flash-rt Minimizes Radiation-induced Novel Object Memory Impmentioning

confidence: 99%

Neuroprotection of Radiosensitive Juvenile Mice by Ultra-High Dose Rate FLASH Irradiation

Alaghband

Cheeks

Allen

et al. 2020

Cancers

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Major advances in high precision treatment delivery and imaging have greatly improved the tolerance of radiotherapy (RT); however, the selective sparing of normal tissue and the reduction of neurocognitive side effects from radiation-induced toxicities remain significant problems for pediatric patients with brain tumors. While the overall survival of pediatric patients afflicted with medulloblastoma (MB), the most common type primary brain cancer in children, remains high (≥80%), lifelong neurotoxic side-effects are commonplace and adversely impact patients’ quality of life. To circumvent these clinical complications, we have investigated the capability of ultra-high dose rate FLASH-radiotherapy (FLASH-RT) to protect the radiosensitive juvenile mouse brain from normal tissue toxicities. Compared to conventional dose rate (CONV) irradiation, FLASH-RT was found to ameliorate radiation-induced cognitive dysfunction in multiple independent behavioral paradigms, preserve developing and mature neurons, minimize microgliosis and limit the reduction of the plasmatic level of growth hormone. The protective “FLASH effect” was pronounced, especially since a similar whole brain dose of 8 Gy delivered with CONV-RT caused marked reductions in multiple indices of behavioral performance (objects in updated location, novel object recognition, fear extinction, light-dark box, social interaction), reductions in the number of immature (doublecortin+) and mature (NeuN+) neurons and increased neuroinflammation, adverse effects that were not found with FLASH-RT. Our data point to a potentially innovative treatment modality that is able to spare, if not prevent, many of the side effects associated with long-term treatment that disrupt the long-term cognitive and emotional well-being of medulloblastoma survivors.

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“…[ 18 ] Scholars have indicated long-term, low-dose rate radiation exposure would cause psychological stress and an increased risk of depression decades later. [ 19 ] Review to Chernobyl accident and Japan's nuclear disaster also presented significant association of radiation exposure and subsequent psychological distress. [ 20 – 24 ] The current study further confirmed the association of concern over radiation exposure with psychological distress.…”

Section: Discussionmentioning

confidence: 99%

Knowledge deficiency of work-related radiation hazards associated with psychological distress among orthopedic surgeons

Fan¹,

Wang²,

Guo

et al. 2017

Medicine

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Knowledge and concern degree about work-related radiation hazards remained unknown among orthopedic surgeons. The aim of the cross-sectional study is to investigate whether the knowledge degree of work-related radiation is associated with psychological distress among orthopedic surgeons. This cross-sectional study sent electronic questionnaire via WeChat to orthopedic surgeons nationwide. Concern and knowing degree over radiation exposure was evaluated by a single self-reported question. Professional evaluation of concern degree was reflected by general psychological distress, which was assessed with the Kessler 10 scale (K10) and depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D). Only 43.23% (115/266) respondents knew well about radiation and a total of 78.20% (208/266) respondents considered radiation exposure as a great concern. Among those who reported concerns about radiation exposure, a total of 57.69% (120/208) respondents reported knowing little about radiation. Respondents who reported concerns over radiation exposure were significantly associated with higher scores on CES-D and K10 (P < .05). Among respondents who reported concerns over radiation exposure, those who have fewer knowledge about radiation, had higher CES-D and K10 scores than those who knew well about radiation (P < .05). Among respondents who reported no concerns over radiation exposure, those who knew little about radiation still had higher CES-D and K10 scores (P < .05). Fewer radiation knowledge tends to induce more radiation concerns associated with higher psychological distress in orthopedic surgeons. Radiation knowledge should be enhanced for surgeons who daily work with radiation-related fluoroscopy.

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Risk factors of depression after prolonged low-dose rate environmental radiation exposure

Abstract: Long-term, low-dose rate radiation exposure early in life might cause subsequent psychological stress and an increased risk of depression decades later.

Cited by 19 publications

References 49 publications

Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

Neuroprotection of Radiosensitive Juvenile Mice by Ultra-High Dose Rate FLASH Irradiation

Knowledge deficiency of work-related radiation hazards associated with psychological distress among orthopedic surgeons

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