Article
Multidisciplinary Sciences
Fen Yang, Yuanyue Zhang, Ruiying Qiu, Ning Tao
Summary: Insufficient sleep duration and poor sleep quality are positively associated with hypertension among oil workers in Xinjiang, China. Factors such as gender, age, length of service, and shift work status also play a role in the relationship between sleep and hypertension.
Article
Multidisciplinary Sciences
Robin K. Yuan, Kirsi-Marja Zitting, Liyaan Maskati, Jeff Huang
Summary: This study examines how the COVID-19 pandemic has affected sleep health globally. The findings suggest that lockdown policies have led to changes in sleep timing and duration, with a modest increase in time in bed (TIB) and a delay in sleep timing. These changes were more pronounced in the earlier months of the pandemic and may diminish as restrictions are lifted.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Anna Andreasson, John Axelsson, Jos A. Bosch, Leonie J. T. Balter
Summary: This study showed that long sleep duration is associated with poorer self-rated health only if combined with poor sleep quality, while good sleep quality can protect individuals with long sleep duration from poor health. Fatigue and sleep quality are potential pathways linking both short and long sleep durations with self-rated health. Different dimensions of sleep interact in their association with health, highlighting the importance of an integrative approach in future research.
Article
Psychiatry
Pei Xue, Ilona Merikanto, Frances Chung, Charles M. Morin, Colin Espie, Bjorn Bjorvatn, Jonathan Cedernaes, Anne-Marie Landtblom, Thomas Penzel, Luigi De Gennaro, Brigitte Holzinger, Kentaro Matsui, Harald Hrubos-Strom, Maria Korman, Damien Leger, Sergio Mota-Rolim, Courtney J. Bolstad, Michael Nadorff, Giuseppe Plazzi, Catia Reis, Rachel Ngan Yin Chan, Yun Kwok Wing, Juliana Yordanova, Adrijana Koscec Bjelajac, Yuichi Inoue, Markku Partinen, Yves Dauvilliers, Christian Benedict
Summary: Short and long sleep duration after receiving mRNA vaccines is associated with a higher risk of post-COVID symptoms. The study suggests that short and long sleepers are more likely to experience prolonged COVID-19 symptoms compared to normal sleepers. Further research is needed to validate these findings in cohorts with confirmed SARS-CoV-2 infection.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Wei Cheng, Edmund Rolls, Weikang Gong, Jingnan Du, Jie Zhang, Xiao-Yong Zhang, Fei Li, Jianfeng Feng
Summary: This study conducted a large-scale analysis on children's sleep duration and psychiatric problems for the first time, revealing a negative correlation between children's sleep duration, dimensional psychopathology, cognition, and brain structure. The study also found correlations between parental psychopathology and children's sleep problems. Higher brain volume in certain areas was associated with longer sleep duration.
MOLECULAR PSYCHIATRY
(2021)
Article
Endocrinology & Metabolism
Yejin Kim, Hye-Ji An, Young-Gyun Seo
Summary: This study aimed to establish the optimal cutoffs of sleep timing and duration to assess various cardiovascular disease risk factors. The findings showed that bedtime between 9:00 PM to 0:30 AM for men and 10:00 PM to 11:00 PM for women is appropriate. The cutoff range was slightly earlier for participants aged 65 years and older. Early MSFsc between 12:00 AM to 3:00 AM and sleep durations around 6 hours were associated with the optimal cutoffs for assessing CVD risk factors.
DIABETES RESEARCH AND CLINICAL PRACTICE
(2023)
Article
Peripheral Vascular Disease
Shahab Haghayegh, Susanne Strohmaier, Rikuta Hamaya, A. Heather Eliassen, Walter C. Willett, Eric B. Rimm, Eva S. Schernhammer
Summary: This study found that difficulty falling or staying asleep and short sleep duration were associated with a higher risk of hypertension among women. Therefore, screening for poor sleep may help identify individuals at higher risk for hypertension.
Article
Clinical Neurology
Oliver Vogel, Daniel Niederer, Jan Wilke, Inaam El-Rajab, Lutz Vogt
Summary: There is no direct association between physical activity levels and sleep quality in older adults. However, a shorter sleep duration of 5 to 6 hours was associated with higher levels of physical activity.
FRONTIERS IN NEUROLOGY
(2021)
Article
Clinical Neurology
Yiyi Zhou, Zhengzhong Wang, Jieming Lu, Zongming Yang, Die Li, Zhebin Yu, Peng Shen, Mengling Tang, Mingjuan Jin, Hongbo Lin, Kun Chen, Jianbing Wang
Summary: In this study, it was found that long siesta was associated with increased risk of hypertension in women but not in men. Short siesta may be related to decreased risk of hypertension in short sleepers but not in people with adequate or even long sleep. However, these findings were not significant in long sleepers.
Review
Clinical Neurology
Aayushi Sen, Xin You Tai
Summary: This review examines the relationship between sleep and cognition, particularly focusing on the sub-domain of executive function. It explores the impact of sleep deprivation and optimal sleep duration on cognitive performance, and highlights the importance of sleep quality. It also discusses the potential biological mechanisms underlying the relationship between sleep and cognition, such as changes in brain structure and function.
CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS
(2023)
Article
Multidisciplinary Sciences
Yingjie Su, Changluo Li, Yong Long, Liudang He, Ning Ding
Summary: This study aimed to explore the association between sleep duration on workdays and blood pressure in non-overweight/obese population. The results showed that both short sleep duration (< 6 h) and long sleep duration (>= 8 h) on workdays were significantly associated with increased systolic blood pressure (SBP). The significant association was found in females and the White population.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Syed Afroz Keramat, Khorshed Alam, Rabeya Basri, Farzana Siddika, Zubayer Hassan Siddiqui, Joshua Okyere, Abdul-Aziz Seidu, Bright Opoku Ahinkorah
Summary: Sleep difficulty is a global public health concern affecting a large proportion of the population. Poor sleep duration (short or long sleep length) and quality are associated with an increased risk of obesity in adults. Therefore, raising public awareness of the significance of good sleep hygiene and promoting healthy sleeping habits should be considered to address the rising obesity rate.
Article
Clinical Neurology
Yoo Jin Um, Yejin Kim, Yoosoo Chang, Hyun-Suk Jung, In Young Cho, Sang Won Jeon, Seungho Ryu
Summary: This study examined the longitudinal relationship between sleep duration, sleep quality, and their changes with the risk of depressive symptoms. The results showed that shorter sleep duration and poorer sleep quality were associated with incident depressive symptoms, suggesting that insufficient sleep quantity and quality contribute to depression risk.
JOURNAL OF AFFECTIVE DISORDERS
(2023)
Article
Biology
Xin You Tai, Cheng Chen, Sanjay Manohar, Masud Husain
Summary: Sleep duration between six and eight hours is associated with optimal cognitive performance and larger grey matter volume in specific areas of the brain.
COMMUNICATIONS BIOLOGY
(2022)
Article
Clinical Neurology
Yanyuan Dai, Baixin Chen, Le Chen, Alexandros N. Vgontzas, Julio Fernandez-Mendoza, Maria Karataraki, Xiangdong Tang, Yun Li
Summary: This study found an association between insomnia with objective short sleep duration and hypertension. Short sleep duration in patients with chronic insomnia disorder was associated with a higher risk of hypertension. Additionally, for every hour decrease in total sleep time, there was a slight increase in systolic and diastolic blood pressure in patients with chronic insomnia disorder.
JOURNAL OF SLEEP RESEARCH
(2023)
Article
Environmental Sciences
Ge Mu, Xiuquan Nie, Shijie Yang, Zi Ye, Man Cheng, Lieyang Fan, Weihong Qiu, Qiyou Tan, Min Zhou, Yanjun Guo, Weihong Chen
Summary: This study evaluated the associations between personal PM2.5 concentrations and DNA methylation, and investigated how PM2.5-related DNA methylation affects lung function. The results showed significant associations between PM2.5-related DNA methylation and lung function, indicating the potential role of DNA methylation in the link between PM2.5 exposure and lung function alteration.
ENVIRONMENTAL POLLUTION
(2023)
Article
Environmental Sciences
Xiuyu Cao, Xiaojie You, Dongming Wang, Weihong Qiu, You Guo, Min Zhou, Weihong Chen, Xiaokang Zhang
Summary: A study in Ganzhou, China found that there are significantly positive associations between ambient ozone levels and hospitalizations for circulatory diseases, including hypertension, coronary heart disease, cerebrovascular disease, and heart failure. The risk of hospitalization increased with each 10 mu g/m3 increase in ozone concentration. These associations remained significant after adjusting for other air pollutants and varied in different seasons, genders, and age groups.
Article
Environmental Sciences
Zi Ye, Man Cheng, Lieyang Fan, Jixuan Ma, Yingdie Zhang, Pei Gu, Yujia Xie, Xiaojie You, Min Zhou, Bin Wang, Weihong Chen
Summary: In this study, the potential role of miRNAs in zinc-related hyperglycemia and type 2 diabetes mellitus (T2DM) was explored through population-based studies and in vitro experiments. MiR-144-3p was found to be positively associated with urinary zinc, hyperglycemia, and the risk of T2DM. In vitro experiments confirmed that zinc-induced increase in miR-144-3p expression suppressed the target gene Nrf2 and downstream antioxidant enzymes, and aggravated insulin resistance.
ENVIRONMENT INTERNATIONAL
(2023)
Article
Environmental Sciences
Jiahao Song, Man Cheng, Bin Wang, Min Zhou, Zi Ye, Lieyang Fan, Linling Yu, Xing Wang, Jixuan Ma, Weihong Chen
Summary: This study aimed to explore the potential role of miR-4301 in PM2.5 exposure-associated lung function reduction. The results showed that personal PM2.5 exposure was negatively associated with lung function and plasma miR-4301 expression. Additionally, miR-4301 partially mediated the lung function reduction associated with PM2.5 exposure, possibly through regulating the Wnt signaling pathway.
ENVIRONMENTAL POLLUTION
(2023)
Article
Environmental Sciences
Ruyi Liang, Xiaobing Feng, Da Shi, Linling Yu, Meng Yang, Min Zhou, Yongfang Zhang, Bin Wang, Weihong Chen
Summary: This study investigated the associations between the chemical compound 1,3-butadiene (BD) exposure and glucose dyshomeostasis and diabetes in the general population. The results showed that BD exposure was positively associated with an increased risk of glucose dyshomeostasis, prediabetes, and diabetes, and serum alkaline phosphatase (ALP) mediated these associations.
ENVIRONMENTAL RESEARCH
(2023)
Article
Environmental Sciences
Xiuquan Nie, Ge Mu, Yanjun Guo, Shijie Yang, Xing Wang, Zi Ye, Qiyou Tan, Mengyi Wang, Min Zhou, Jixuan Ma, Weihong Chen
Summary: This study found that urinary selenium concentration was positively associated with total cholesterol and low-density lipoprotein, but not with triglycerides and high-density lipoprotein. Methylation sites cg06964030 and cg15824094 partly mediated the association between selenium and total cholesterol. These findings provide insights into the effects and mechanisms of selenium exposure on lipid metabolism and highlight the importance of controlling selenium exposure and intake to prevent high blood lipids.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Environmental Sciences
Xuedan Xu, Jixuan Ma, Wending Li, Yutong You, Qin Jiang, Pinpin Long, Kang Liu, Tingting Mo, Jing Jiang, Wei Wang, Yanshou Lei, Tingyue Diao, Shuping Ruan, Xiaozheng Wang, Huan Guo, Weihong Chen, Tangchun Wu
Summary: In this study, associations between polycyclic aromatic hydrocarbons (PAHs) exposure and long non-coding RNA (lncRNA) were explored. The levels of urinary PAHs metabolites and plasma lncRNAs were measured, and several PAHs-related lncRNAs were identified. Tissue specificity analysis revealed that these lncRNAs might specifically express in organs targeted by PAHs exposure. Moreover, the associations between plasma levels of certain lncRNAs and their levels in leukocytes were also investigated.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Public, Environmental & Occupational Health
Xiaojie You, Xiuyu Cao, You Guo, Dongming Wang, Weihong Qiu, Chuanfei Zhou, Min Zhou, Weihong Chen, Xiaokang Zhang
Summary: A time series study in Ganzhou found positive associations between both short-term and long-term exposure to PM2.5 and hospital admissions for circulatory system diseases (CSD). The study provides valuable insights into the adverse effects of PM2.5 on CSD.
FRONTIERS IN PUBLIC HEALTH
(2023)
Article
Environmental Sciences
Ruyi Liang, Xiaobing Feng, Da Shi, Bin Wang, Yongfang Zhang, Wei Liu, Linling Yu, Zi Ye, Min Zhou, Weihong Chen
Summary: This study aimed to assess the association between pyrethroid exposure and glucose homeostasis, as well as the interaction between obesity and pyrethroid exposure. The findings indicated that pyrethroid exposure was associated with glucose dyshomeostasis, and the association between pyrethroid exposure and increased fasting plasma glucose (FPG) level was enhanced by general obesity.
ENVIRONMENTAL POLLUTION
(2023)
Article
Environmental Sciences
Mengyi Wang, Min Zhou, Qiyou Tan, Linling Yu, Chaoqian Dong, Ruyi Liang, Wei Liu, Yongfang Zhang, Minjing Li, XiuQuan Nie, Tao Jing, Weihong Chen
Summary: This study aimed to assess the associations between triazine herbicides and glycemia-related risk indicators in general adults. The results showed that triazine herbicides exposure was positively associated with abnormal glucose metabolism, and decreasing serum IgM partly mediated these associations among uninfected participants.
ENVIRONMENTAL POLLUTION
(2023)
Article
Environmental Sciences
Qiyou Tan, Bin Wang, Zi Ye, Ge Mu, Wei Liu, Xiuquan Nie, Linling Yu, Min Zhou, Weihong Chen
Summary: Ozone pollution has adverse health effects and this study aimed to investigate the association between ozone exposure and glucose homeostasis. The results showed a positive association between ozone exposure and fasting plasma glucose, insulin, and insulin resistance, and a negative association with beta cell function. Ozone exposure was also related to increased C-reactive protein, oxidative DNA damage, and lipid peroxidation in a dose-response manner. The findings suggest that ozone exposure can damage glucose homeostasis and obese individuals may be more susceptible. Systemic inflammation and oxidative stress may be potential pathways in the glucose homeostasis damage induced by ozone exposure.
ENVIRONMENTAL POLLUTION
(2023)
Article
Environmental Sciences
Yongfang Zhang, Min Zhou, Ruyi Liang, Linling Yu, Man Cheng, Xing Wang, Bin Wang, Weihong Chen
Summary: The associations and potential mechanisms of low to moderate arsenic exposure with fasting plasma glucose (FPG) and type 2 diabetes mellitus (T2DM) were investigated in a cohort study. The results showed a significant association between arsenic exposure and increased FPG levels and risks of IFG, T2DM, and AGR among general Chinese adults.
ENVIRONMENTAL RESEARCH
(2023)
Article
Public, Environmental & Occupational Health
Weihong Qiu, Heng He, Lieyang Fan, Xiaobing Feng, Minjing Li, Chaoqian Dong, Zhenzhen Li, Wei Liu, Ruyi Liang, Yingdie Zhang, Yongfang Zhang, Pei Gu, Bin Wang, Weihong Chen
Summary: Non-optimal ambient temperatures can affect lung function, leading to inflammation and oxidative damage, especially under low temperatures.
INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH
(2023)
Article
Engineering, Environmental
Qiyou Tan, Shijie Yang, Bin Wang, Mengyi Wang, Linling Yu, Ruyi Liang, Wei Liu, Jiahao Song, Yanjun Guo, Min Zhou, Weihong Chen
Summary: This study investigates the longitudinal relationships between PCB exposure and glucose homeostasis and T2D risk in the Chinese population. The study also examines the interactions between PCB exposure, genetic susceptibility, and lifestyle. The findings suggest that PCB-118 exposure is positively associated with FPG, FPI, insulin resistance, and incident T2D risk. Additionally, the T2D polygenic risk score is positively associated with FPG and incident T2D risk. Individuals with a high T2D-PRS and high PCB-118 have significantly increased FPG and T2D risk.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Environmental Sciences
Yang Liu, Dongming Wang, Xuezan Huang, Ruyi Liang, Zhouzheng Tu, Xiaojie You, Min Zhou, Weihong Chen
Summary: Based on the Global Burden of Disease Study 2019, exposure to non-optimal temperature is associated with increased mortality and morbidity of type 2 diabetes. From 1990 to 2019, globally, the burden of type 2 diabetes attributable to non-optimal temperature has significantly increased, especially in high temperature regions and areas with lower socio-economic development. Appropriate temperature interventions are necessary to mitigate climate change and the rising burden of diabetes.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2023)
Article
Clinical Neurology
Melanie Strauss, Lucie Griffon, Maxime Elbaz, Isabelle Arnulf, Mounir Chennaoui, Damien Leger
Summary: This study examines decision-making impairments in individuals with central disorders of hypersomnolence (CDH), specifically narcolepsy type 1 (NT1). The results suggest that both NT1 and other CDH patients have decreased learning abilities to avoid losses, which is associated with alterations in vigilance. The study provides new insights into the nature of decision-making impairments in CDH and suggests the potential for minimizing these alterations by restoring adequate vigilance.
Article
Clinical Neurology
Kyriakos Dimitriadis, Christina Stathakopoulou, Nikolaos Pyrpyris, Eirini Beneki, Elena Adamopoulou, Stergios Soulaidopoulos, Ioannis Leontsinis, Alexandros Kasiakogias, Aggelos Papanikolaou, Panagiotis Tsioufis, Konstantinos Aznaouridis, Dimitris Tsiachris, Konstantina Aggeli, Konstantinos Tsioufis
Summary: This review provides a comprehensive analysis of the common pathophysiology between sleep disordered breathing (SDB) and mitral regurgitation (MR), and discusses the effects of SDB treatment on MR and the effects of mitral valve surgery or transcatheter repair on obstructive and central sleep apnea (OSA and CSA).
Article
Clinical Neurology
Szu-Yu Hou, Ching-Ju Chiu, Jeanne Laraine Shea, Chih-Liang Wang, Hsiao-Han Tang, Po-Ching Kuo, Yi-Chieh Yang, Chih-Hsing Wu
Summary: The study aimed to examine the effects of age, menopausal status, and symptoms on sleep patterns and circadian rhythms in midlife women. Premenopausal women had the most unstable day-to-day rhythms, and women with more severe symptoms experienced greater sleep problems. Psychological symptoms were the strongest predictors for all sleep parameters.
Article
Clinical Neurology
Ya-Wen Hsiao, Wei-Lun Lin, Yu-Hui Chou, Shin-Huei Liu, Ting-Wei Ernie Liao, Shih-Ann Chen, Li-Wei Lo
Summary: This study aimed to investigate the effects of RDN on heart inflammation associated with COSA. The results suggest that RDN treatment may prevent COSA-associated heart inflammation through the JAK2-STAT3 signaling pathway.
Article
Clinical Neurology
Amy C. Reynolds, Kelly A. Loffler, Nicole Grivell, Brandon W. J. Brown, Robert J. Adams
Summary: This study aimed to understand the experience of sleep disorder diagnosis and treatment in shift workers and propose patient-informed solutions to improve access to health services. The findings showed that there were varied experiences with diagnosis and management, often taking a long time to seek help from healthcare providers after noticing symptoms. The study also identified the need for education and awareness initiatives, convenient screening and referral pathways, and tailored models of care.
Article
Clinical Neurology
Hsi -Chung Chen, Nai-Wei Hsu, Ching-Heng Lin
Summary: This study found a relationship between daytime sleepiness and mortality risk among older adults. The moderating effects of sex and physical function were examined. Specifically, the passive factor predicted mortality risk in women with good muscle power, while the active factor predicted mortality risk in men with good muscle power.
Article
Clinical Neurology
Sean P. A. Drummond, Bei Bei
Summary: This study proposes a parsimonious two-stage model for defining stages of Cognitive Behavioural Therapy for Insomnia (CBT-I) based on Sleep Restriction Therapy (SRT). Using data from a randomized clinical trial, the model helps identify patterns of treatment progression and their association with baseline insomnia severity. The model holds potential for further research on various CBT-I processes that are currently not fully understood.
Article
Clinical Neurology
Janet Jezkova, Karel Sonka, Jakub Kreisinger, Petra Prochazkova, Helena Tlaskalova-Hogenova, Sona Nevsimalova, Jitka Buskova, Radana Merkova, Tereza Dvorakova, Iva Prihodova, Simona Dostalova, Radka Roubalova
Summary: In recent years, there has been a growing interest in the influence of gut microbiota on sleep physiology. The gut microbiota affects the central nervous system and circadian rhythms, and can be associated with sleep disorders. This study observed the gut microbiota composition of patients with different types of narcolepsy and idiopathic hypersomnia, and found changes in beta diversity in these patient groups compared to healthy controls. However, after adjusting for confounding factors, the differences were no longer statistically significant. The study suggests that using metabolomics and proteomics approaches to study the role of microbiota in sleep disorders may be beneficial.
Article
Clinical Neurology
Mauro Manconi, Linda C. van der Gaag, Francesca Mangili, Corrado Garbazza, Silvia Riccardi, Christian Cajochen, Susanna Mondini, Francesca Furia, Elena Zambrelli, Simone Baiardi, Alessandra Giordano, Nicola Rizzo, Cristina Fonti, Elsa Viora, Armando D'Agostino, Alessandro Cicolin, Fabio Cirignotta, Daniele Aquilino, Alessandra Barassi, Renata del Giudice, Giulia Fior, Orsola Gambini, Barbara Giordano, Alma Martini, Chiara Serrati, Rossana Stefanelli, Silvio Scarone, Mariapaola Canevini, Valentina Fanti, Hans-Christian Stein, Anna Maria Marconi, Erica Raimondo, Emanuela Viglietta, Rossella Santoro, Giuliana Simonazzi, Alessandra Bianconcini, Francesco Meani, Nicoletta Piazza, Filippos Filippakos, Thomas Gyr
Summary: The Life-ON study provides the largest polysomnographic dataset coupled with longitudinal subjective assessments of sleep quality in pregnant women to date. Sleep disorders are highly frequent and distributed differently during pregnancy and postpartum. Routine assessment of sleep disturbances in the perinatal period is necessary to improve early detection and clinical management.
Article
Clinical Neurology
Zhihua Huang, Anqi Duan, Zhihui Zhao, Qing Zhao, Yi Zhang, Xin Li, Sicheng Zhang, Luyang Gao, Chenhong An, Qin Luo, Zhihong Liu
Summary: This study aims to investigate pulmonary arterial hypertension (PAH) phenotypes and their prognostic implications by clustering overnight cardiorespiratory signals in PAH patients. Three distinct clusters were identified, with patients in Cluster 3 exhibiting worse clinical outcomes. The presence of nocturnal hypoxemia and obstructive sleep apnea (OSA) in PAH patients was associated with increased risk of clinical worsening. Tailored management strategies addressing both PAH and nocturnal hypoxemia may improve clinical outcomes.
Article
Clinical Neurology
Yudan Lv, Yujun Wen, Ramalingam Vetrivelan, Jun Lu
Summary: This study demonstrated that the projections from the pontine parabrachial nucleus (PB) to the basal forebrain (BF) and medial septum (MS) can activate the cerebral cortex and hippocampus, providing important insights into the activities of these brain regions during the sleep-wake cycle.
Article
Clinical Neurology
Annika M. Myers, Megan E. Rech, Bengi Baran, Cara Palmer, Dimitrios Mylonas, Candice A. Alfano
Summary: This study found that N2 sleep spindles are associated with emotional functioning in school-aged children. Higher spindle density is related to decreased state-based emotional arousal towards negative affective images, and higher spindle peak frequency is associated with greater use of the positive emotion regulatory strategy of savoring.
Article
Clinical Neurology
Hung Youl Seok, Yong Won Cho
Summary: This study investigated the long-term impact of dopamine agonist treatment on altered central sensory processing in restless legs syndrome (RLS) patients. The results showed that dopamine agonist treatment effectively reduced RLS symptoms but did not reverse the altered central sensory processing observed on testing. These findings suggest that RLS pathophysiology is multifactorial and not solely driven by dopaminergic dysfunction.
