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Article ; Online: Depression and lifestyle: Focusing on nutrition, exercise, and their possible relevance to molecular mechanisms.

Kunugi, Hiroshi

2023 Volume 77, Issue 8, Page(s) 420–433

Abstract: Accumulating evidence has suggested the important role of lifestyle factors in depressive disorder. This paper aimed to introduce and outline recent research on epidemiological and intervention studies on lifestyle-related factors in depressive disorder ... ...

Abstract	Accumulating evidence has suggested the important role of lifestyle factors in depressive disorder. This paper aimed to introduce and outline recent research on epidemiological and intervention studies on lifestyle-related factors in depressive disorder with a special focus on diet. Evidence on exercise, sleep. and related behaviors is also described. Here, findings from meta-analytic studies are emphasized and related studies by the author's research group are introduced. Dietary factors that increase the risk of the illness include energy overload, skipping breakfast, unhealthy diet styles such as Western diet, inflammation-prone diet, and high consumption of ultraprocessed food (UPF). Nutritional imbalances such as inadequate intake of protein, fish (Ω3 polyunsaturated fatty acids), vitamins (folate and vitamin D), and minerals (iron and zinc) increases the risk of depression. Poor oral hygiene, food allergy, addiction to alcohol, and smoking constitute risk factors. Sedentary lifestyle and increased screen time (e.g. video games and the internet) confer the risk of depression. Insomnia and disturbed sleep-wake rhythm are also involved in the pathogenesis of depression. There is accumulating evidence at the meta-analysis level for interventions to modify these lifestyle habits in the protection and treatment of depressive disorder. Main biological mechanisms of the link between lifestyle factors and depression include monoamine imbalance, inflammation, altered stress response, oxidative stress, and dysfunction of brain-derived neurotrophic factor, although other players such as insulin, leptin, and orexin also play a role. To increase resilience to modern stress and ameliorate depression through modification of lifestyle habits, a list of 30 recommendable interventions is presented.
MeSH term(s)	Animals ; Depression ; Exercise ; Diet ; Risk Factors ; Inflammation
Language	English
Publishing date	2023-04-25
Publishing country	Australia
Document type	Meta-Analysis ; Journal Article
ZDB-ID	1292906-2
ISSN	1440-1819 ; 1323-1316
ISSN (online)	1440-1819
ISSN	1323-1316
DOI	10.1111/pcn.13551
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Article ; Online: Gut Microbiota and Pathophysiology of Depressive Disorder.

Kunugi, Hiroshi

Annals of nutrition & metabolism

2021 Volume 77 Suppl 2, Page(s) 11–20

Abstract: Background: Accumulating evidence has suggested that the bi-directional communication pathway, the microbiota-gut-brain axis, plays an important role in the pathophysiology of many neuropsychiatric diseases including major depressive disorder (MDD). ... ...

Abstract	Background: Accumulating evidence has suggested that the bi-directional communication pathway, the microbiota-gut-brain axis, plays an important role in the pathophysiology of many neuropsychiatric diseases including major depressive disorder (MDD). This review outlines current evidence and promising findings related to the pathophysiology and treatment of MDD. Summary: There are at least 4 key biological molecules/systems underlying the pathophysiology of MDD: central dopamine, stress responses by the hypothalamic-pituitary-adrenal axis and autonomic nervous system, inflammation, and brain-derived neurotrophic factor. Animal experiments in several depression models have clearly indicated that gut microbiota is closely related to these molecules/systems and administration of probiotics and prebitotics may have beneficial effects on them. Although the results of microbiota profile of MDD patients varied from a study to another, multiple studies reported that bacteria which produce short-chain fatty acids such as butyrate and those protective against metabolic diseases (e.g., Bacteroidetes) were reduced. Clinical trials of probiotics have emerged, and the majority of the studies have reported beneficial effects on depression symptoms and related biological markers. Key Messages: The accumulating evidence suggests that research on the microbiota-gut-brain axis in major depressive disorder (MDD) is promising to elucidate the pathophysiology and to develop novel treatment of MDD, although there is still a long distance yet to reach the goals.
MeSH term(s)	Animals ; Depressive Disorder, Major/drug therapy ; Depressive Disorder, Major/metabolism ; Gastrointestinal Microbiome ; Humans ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Probiotics/therapeutic use
Language	English
Publishing date	2021-07-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	392341-1
ISSN	1421-9697 ; 0250-6807 ; 1018-9688
ISSN (online)	1421-9697
ISSN	0250-6807 ; 1018-9688
DOI	10.1159/000518274
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Article: [Intestinal Flora and Mental Disorders: A Focus on Mood Disorders and Autism Spectrum Disorder].

Kunugi, Hiroshi

Brain and nerve = Shinkei kenkyu no shinpo

2021 Volume 73, Issue 8, Page(s) 871–877

Abstract: The intestinal flora plays a key role in the stress response and barrier function of the gut, both of which are closely associated with the pathophysiology of mental health conditions, such as mood disorders and autistic spectrum disorder through the ... ...

Abstract	The intestinal flora plays a key role in the stress response and barrier function of the gut, both of which are closely associated with the pathophysiology of mental health conditions, such as mood disorders and autistic spectrum disorder through the phenomenon of brain-gut interaction. Despite increasing accumulation of empirical data regarding the contribution of the gut microbiota to these disorders, studies have reported inconsistent results. Notably, short chain fatty acid-producing bacteria and those implicated in the pathophysiology of metabolic diseases appear to be associated with the psychiatric conditions. Clinical trials have shown some evidence to suggest the beneficial effects of probiotics in depressive and neurodevelopmental disorders. Limited studies have discussed this subject; however, the role of the intestinal flora in the pathophysiology and treatment of mental disorders appears to be a promising field of research.
MeSH term(s)	Autism Spectrum Disorder/therapy ; Gastrointestinal Microbiome ; Humans ; Mental Disorders ; Mood Disorders/therapy ; Probiotics/therapeutic use
Language	Japanese
Publishing date	2021-08-10
Publishing country	Japan
Document type	Journal Article
ZDB-ID	390389-8
ISSN	1344-8129 ; 1881-6096 ; 0006-8969
ISSN (online)	1344-8129
ISSN	1881-6096 ; 0006-8969
DOI	10.11477/mf.1416201854
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Article ; Online: Possible involvement of Interleukin-17A in the deterioration of prepulse inhibition on acoustic startle response in mice.

Wakabayashi, Chisato / Kunugi, Hiroshi

Neuropsychopharmacology reports

2023 Volume 43, Issue 3, Page(s) 365–372

Abstract: Aim: Proinflammatory cytokines such as interleukin-6 (IL-6) and IL-17A have been implicated in the pathophysiology of schizophrenia which often shows sensorimotor gating abnormalities. This study aimed to examine whether a proinflammatory cytokine, IL- ... ...

Abstract	Aim: Proinflammatory cytokines such as interleukin-6 (IL-6) and IL-17A have been implicated in the pathophysiology of schizophrenia which often shows sensorimotor gating abnormalities. This study aimed to examine whether a proinflammatory cytokine, IL-17A, induces impairment in sensorimotor gating in mice. We also examined whether IL-17A administration affects GSK3α/β protein level or phosphorylation in the striatum. Methods: Recombinant mouse IL-17A (low-dose: 0.5 ng/mL and high-dose: 50 ng/mL with 10 μL/g mouse body weight, respectively) or vehicle was intraperitoneally administered into C57BL/6 male mice 10 times in 3 weeks (sub-chronic administration). Prepulse inhibition test using acoustic startle stimulus was conducted 4 weeks after the final IL-17A administration. We evaluated the effect of IL-17A administration on protein level or phosphorylation of GSK3α/β in the striatum by using Western blot analysis. Results: Administration of IL-17A induced significant PPI deterioration. Low-dose of IL-17A administration significantly decreased both GSK3α (Ser21) and GSK3β (Ser9) phosphorylation in mouse striatum. There was no significant alteration of GSK3α/β protein levels except for GSK3α in low-dose IL-17A administration group. Conclusion: We demonstrated for the first time that sub-chronic IL-17A administration induced PPI disruption and that IL-17A administration resulted in decreased phosphorylation of GSKα/β at the striatum. These results suggest that IL-17A could be a target molecule in the prevention and treatment of sensorimotor gating abnormalities observed in schizophrenia.
MeSH term(s)	Mice ; Male ; Animals ; Prepulse Inhibition ; Reflex, Startle/physiology ; Interleukin-17 ; Mice, Inbred C57BL ; Acoustics
Chemical Substances	Interleukin-17
Language	English
Publishing date	2023-06-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2574-173X
ISSN (online)	2574-173X
DOI	10.1002/npr2.12351
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Article ; Online: Recent advances in understanding depressive disorder: Possible relevance to brain stimulation therapies.

Kunugi, Hiroshi / Tikhonova, Maria

Progress in brain research

2022 Volume 270, Issue 1, Page(s) 123–147

Abstract: Recent research has provided novel insights into the major depressive disorder (MDD) and identified certain biomarkers of this disease. There are four main mechanisms playing a key role in the related pathophysiology, namely (1) monoamine systems ... ...

Abstract	Recent research has provided novel insights into the major depressive disorder (MDD) and identified certain biomarkers of this disease. There are four main mechanisms playing a key role in the related pathophysiology, namely (1) monoamine systems dysfunction, (2) stress response, (3) neuroinflammation, and (4) neurotrophic factors alteration. Robust evidence on the decreased homovanillic acid in the cerebrospinal fluid (CSF) of patients with MDD supports a rationale for therapeutic stimulation of the medial forebrain bundle activating the dopamine reward system. Both activation and suppression of the hypothalamic-pituitary-adrenal (HPA) axis in MDD and related conditions indicate usefulness of its evaluation for the disease subtyping. Elevated proinflammatory cytokines (specifically, interleukin-6) in CSF imply the role of neuroinflammation resulting in activation of the tryptophan-kynurenine pathway. Finally, neuroplasticity and trophic effects of the brain-derived neurotrophic factor (BDNF) may be related to both structural abnormalities of the brain in MDD and the underlying mechanisms of various therapies. In addition, the gut-brain interaction is pivotal, since lack of beneficial microbes confer the risk of MDD through negative effects on the dopamine system, HPA axis, and vagal nerve. All these factors may be highly relevant to treatment of MDD with contemporary brain stimulation therapies.
MeSH term(s)	Brain ; Depressive Disorder, Major/drug therapy ; Dopamine/metabolism ; Humans ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System
Chemical Substances	Dopamine (VTD58H1Z2X)
Language	English
Publishing date	2022-03-07
Publishing country	Netherlands
Document type	Journal Article
ISSN	1875-7855 ; 0079-6123
ISSN (online)	1875-7855
ISSN	0079-6123
DOI	10.1016/bs.pbr.2022.01.023
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Article ; Online: Hypoproteinemia predicts disease severity and mortality in COVID-19: a call for action.

Ali, Amira Mohammed / Kunugi, Hiroshi

Diagnostic pathology

2021 Volume 16, Issue 1, Page(s) 31

Abstract: Proteins represent the major building blocks of body tissues, and they regulate signaling involved in most cellular activities. Coronavirus disease 2019 (COVID-19) infection has been associated with high fatality, especially among older adults. The main ... ...

Abstract	Proteins represent the major building blocks of body tissues, and they regulate signaling involved in most cellular activities. Coronavirus disease 2019 (COVID-19) infection has been associated with high fatality, especially among older adults. The main cause of death is pulmonary tissue damage and multiple organ failure. The disease is associated with a hypercatabolic state that entails excessive protein loss. This review commentary sheds the light on hypoproteinemia in symptomatic/hospitalized COVID-19 with a special emphasis on its pathophysiology, screening, as well as its contribution to disease severity and adverse effects.
MeSH term(s)	Aged ; COVID-19/complications ; COVID-19/mortality ; Female ; Humans ; Hypoproteinemia/diagnosis ; Hypoproteinemia/etiology ; Hypoproteinemia/mortality ; Lung/virology ; Male ; SARS-CoV-2/pathogenicity ; Severity of Illness Index
Language	English
Publishing date	2021-04-13
Publishing country	England
Document type	Letter
ISSN	1746-1596
ISSN (online)	1746-1596
DOI	10.1186/s13000-021-01092-5
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Article ; Online: Approaches to Nutritional Screening in Patients with Coronavirus Disease 2019 (COVID-19).

Ali, Amira Mohammed / Kunugi, Hiroshi

International journal of environmental research and public health

2021 Volume 18, Issue 5

Abstract: Malnutrition is common among severe patients with coronavirus disease 2019 (COVID-19), mainly elderly adults and patients with comorbidities. It is also associated with atypical presentation of the disease. Despite the possible contribution of ... ...

Abstract	Malnutrition is common among severe patients with coronavirus disease 2019 (COVID-19), mainly elderly adults and patients with comorbidities. It is also associated with atypical presentation of the disease. Despite the possible contribution of malnutrition to the acquisition and severity of COVID-19, it is not clear which nutritional screening measures may best diagnose malnutrition in these patients at early stages. This is of crucial importance given the urgency and rapid progression of the disease in vulnerable groups. Accordingly, this review examines the available literature for different nutritional screening approaches implemented among COVID-19 patients, with a special focus on elderly adults. After a literature search, we selected and scrutinized 14 studies assessing malnutrition among COVID-19 patients. The Nutrition Risk Screening 2002 (NRS-2002) has demonstrated superior sensitivity to other traditional screening measures. The controlling nutritional status (CONUT) score, which comprises serum albumin level, cholesterol level, and lymphocytes count, as well as a combined CONUT-lactate dehydrogenase-C-reactive protein score expressed a predictive capacity even superior to that of NRS-2002 (0.81% and 0.92% vs. 0.79%) in midlife and elder COVID-19 patients. Therefore, simple measures based on routinely conducted laboratory investigations such as the CONUT score may be timely, cheap, and valuable alternatives for identifying COVID-19 patients with high nutritional risk. Mini Nutritional Assessment (MNA) was the only measure used to detect residual malnutrition and high malnutrition risk in remitting patients-MNA scores correlated with hypoalbuminemia, hypercytokinemia, and weight loss. Older males with severe inflammation, gastrointestinal symptoms, and pre-existing comorbidities (diabetes, obesity, or hypertension) are more prone to malnutrition and subsequently poor COVID-19 prognosis both during the acute phase and during convalescence. Thus, they are in need of frequent nutritional monitoring and support while detecting and treating malnutrition in the general public might be necessary to increase resilience against COVID-19.
MeSH term(s)	Adult ; Aged ; COVID-19 ; Geriatric Assessment ; Humans ; Male ; Malnutrition/diagnosis ; Malnutrition/epidemiology ; Nutrition Assessment ; Nutritional Status ; Risk Assessment ; SARS-CoV-2
Language	English
Publishing date	2021-03-09
Publishing country	Switzerland
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph18052772
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Article: Screening for Sarcopenia (Physical Frailty) in the COVID-19 Era.

Ali, Amira Mohammed / Kunugi, Hiroshi

International journal of endocrinology

2021 Volume 2021, Page(s) 5563960

Abstract: Although the numbers of aged populations have risen considerably in the last few decades, the current coronavirus disease 2019 (COVID-19) has revealed an extensive vulnerability among these populations. Sarcopenia is an age-related disorder that ... ...

Abstract	Although the numbers of aged populations have risen considerably in the last few decades, the current coronavirus disease 2019 (COVID-19) has revealed an extensive vulnerability among these populations. Sarcopenia is an age-related disorder that increases hospitalization, dependencies, and mortality in older adults. It starts to develop in midlife or even earlier as a result of unbalanced diet/poor nutrition and low levels of physical activity, in addition to chronic disorders such as obesity and diabetes mellitus. Given that social isolation is adopted as the most protective measure against COVID-19, the level of physical activity and the intake of adequate diet have considerably declined, especially among older adults-denoting an increased possibility for developing sarcopenia. Research also shows a higher vulnerability of sarcopenic people to COVID-19 as well as the development of wasting disorders such as sarcopenia and cachexia in a considerable proportion of symptomatic and recovering COVID-19 patients. Muscular wasting in COVID-19 is associated with poor prognosis. Accordingly, early detection and proper management of sarcopenia and wasting conditions in older adults and COVID-19 patients may minimize morbidity and mortality during the current COVID-19 crisis. This review explored different aspects of screening for sarcopenia, stressing their relevance to the detection of altered muscular structure and performance in patients with COVID-19. Current guidelines recommend prior evaluation of muscle strength by simple measures such as grip strength to identify individuals with proven weakness who then would be screened for muscle mass loss. The latter is best measured by MRI and CT. However, due to the high cost and radiation risk entailed by these techniques, other simpler and cheaper techniques such as DXA and ultrasound are given preference. Muscle loss in COVID-19 patients was measured during the acute phase by CT scanning of the pectoralis muscle simultaneously during a routine check for lung fibrosis, which seems to be an efficient evaluation of sarcopenia among those patients with no additional cost. In recovering patients, muscle strength and physical performance have been evaluated by electromyography and traditional tests such as the six-minute walk test. Effective preventive and therapeutic interventions are necessary in order to prevent muscle loss and associated physical decline in COVID-19 patients.
Language	English
Publishing date	2021-05-21
Publishing country	Egypt
Document type	Journal Article ; Review
ZDB-ID	2502951-4
ISSN	1687-8345 ; 1687-8337
ISSN (online)	1687-8345
ISSN	1687-8337
DOI	10.1155/2021/5563960
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Article ; Online: Skeletal Muscle Damage in COVID-19: A Call for Action.

Ali, Amira Mohammed / Kunugi, Hiroshi

Medicina (Kaunas, Lithuania)

2021 Volume 57, Issue 4

Abstract: Both laboratory investigations and body composition quantification measures (e.g., computed tomography, CT) portray muscle loss in symptomatic Coronavirus disease 2019 (COVID-19) patients. Muscle loss is associated with a poor prognosis of the disease. ... ...

Abstract	Both laboratory investigations and body composition quantification measures (e.g., computed tomography, CT) portray muscle loss in symptomatic Coronavirus disease 2019 (COVID-19) patients. Muscle loss is associated with a poor prognosis of the disease. The exact mechanism of muscle damage in COVID-19 patients, as well as the long-term consequences of muscle injury in disease survivors, are unclear. The current review briefly summarizes the literature for mechanisms, assessment measures, and interventions relevant to skeletal muscle insult in COVID-19 patients. Muscle injury is likely to be attributed to the cytokine storm, disease severity, malnutrition, prolonged physical inactivity during intensive care unit (ICU) stays, mechanical ventilation, and myotoxic drugs (e.g., dexamethasone). It has been assessed by imaging and non-imaging techniques (e.g., CT and electromyography), physical performance tests (e.g., six-minute walk test), anthropometric measures (e.g., calf circumference), and biomarkers of muscle dystrophy (e.g., creatine kinase). Interventions directed toward minimizing muscle loss among COVID-19 patients are lacking. However, limited evidence shows that respiratory rehabilitation improves respiratory function, muscle strength, quality of life, and anxiety symptoms in recovering older COVID-19 patients. Neuromuscular electrical stimulation may restore muscle condition in ICU-admitted patients, albeit empirical evidence is needed. Given the contribution of malnutrition to disease severity and muscle damage, providing proper nutritional management for emaciated patients may be one of the key issues to achieve a better prognosis and prevent the after-effects of the disease. Considerable attention to longer-term consequences of muscle injury in recovering COVID-19 patients is necessary.
MeSH term(s)	COVID-19 ; Humans ; Intensive Care Units ; Muscle, Skeletal ; Quality of Life ; SARS-CoV-2
Language	English
Publishing date	2021-04-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina57040372
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Article ; Online: Propolis, Bee Honey, and Their Components Protect against Coronavirus Disease 2019 (COVID-19): A Review of In Silico, In Vitro, and Clinical Studies.

Ali, Amira Mohammed / Kunugi, Hiroshi

Molecules (Basel, Switzerland)

2021 Volume 26, Issue 5

Abstract: Despite the virulence and high fatality of coronavirus disease 2019 (COVID-19), no specific antiviral treatment exists until the current moment. Natural agents with immune-promoting potentials such as bee products are being explored as possible ... ...

Abstract	Despite the virulence and high fatality of coronavirus disease 2019 (COVID-19), no specific antiviral treatment exists until the current moment. Natural agents with immune-promoting potentials such as bee products are being explored as possible treatments. Bee honey and propolis are rich in bioactive compounds that express strong antimicrobial, bactericidal, antiviral, anti-inflammatory, immunomodulatory, and antioxidant activities. This review examined the literature for the anti-COVID-19 effects of bee honey and propolis, with the aim of optimizing the use of these handy products as prophylactic or adjuvant treatments for people infected with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Molecular simulations show that flavonoids in propolis and honey (e.g., rutin, naringin, caffeic acid phenyl ester, luteolin, and artepillin C) may inhibit viral spike fusion in host cells, viral-host interactions that trigger the cytokine storm, and viral replication. Similar to the potent antiviral drug remdesivir, rutin, propolis ethanolic extract, and propolis liposomes inhibited non-structural proteins of SARS-CoV-2 in vitro
MeSH term(s)	Animals ; Antiviral Agents/chemistry ; Antiviral Agents/therapeutic use ; COVID-19/epidemiology ; COVID-19/metabolism ; Chlorocebus aethiops ; Clinical Trials as Topic ; Flavanones/chemistry ; Flavanones/therapeutic use ; Honey ; Molecular Dynamics Simulation ; Nigella sativa/chemistry ; Propolis/chemistry ; Propolis/therapeutic use ; SARS-CoV-2/metabolism ; Vero Cells ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; Flavanones ; Propolis (9009-62-5) ; naringin (N7TD9J649B)
Language	English
Publishing date	2021-02-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26051232
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