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  1. Article ; Online: Circulating Neuroactive Steroid Levels in a Patient With Schizophrenia Who Showed Periodic Catatonia.

    Muneoka, Katsumasa / Shirayama, Yukihiko / Watanabe, Hiroyuki / Kimura, Hiroshi

    JCEM case reports

    2023  Volume 1, Issue 1, Page(s) luad009

    Abstract: Catatonia is an abnormal psychological and behavioral state related to stress. The treatment strategy suggests the involvement of neuroactive steroids in its pathophysiology. We report a hospitalized patient with schizophrenia in whom a catatonic state ... ...

    Abstract Catatonia is an abnormal psychological and behavioral state related to stress. The treatment strategy suggests the involvement of neuroactive steroids in its pathophysiology. We report a hospitalized patient with schizophrenia in whom a catatonic state occurred 7 times in 5.5 years. Blood levels of steroid hormones and adrenocorticotropic hormone (ACTH) were measured during the catatonic state and in the intervals between catatonic states (non-catatonic states). Cortisol and dehydroepiandrosterone sulfate (DHEAS) were significantly higher during catatonia than in the non-catatonic state. Cortisol significantly correlated with the ACTH level, whereas blood DHEAS and progesterone correlated only during the non-catatonic state. In addition, the cortisol to DHEAS ratios did not differ between catatonic and non-catatonic states. Although the correlating elevations of ACTH and cortisol implied activation of the hypothalamic-pituitary-adrenal axis (HPA-axis) in the catatonic state, DHEAS levels did not seem to increase in a manner dependent on the HPA-axis or the production of progesterone. The results suggest that the catatonic state was a neuroendocrinological state of HPA-axis activation with comparable increases in DHEAS levels.
    Language English
    Publishing date 2023-02-13
    Publishing country England
    Document type Case Reports
    ISSN 2755-1520
    ISSN (online) 2755-1520
    DOI 10.1210/jcemcr/luad009
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  2. Article ; Online: Infusions of beta-hydroxybutyrate, an endogenous NLRP3 inflammasome inhibitor, produce antidepressant-like effects on learned helplessness rats through BDNF-TrkB signaling and AMPA receptor activation, and strengthen learning ability.

    Shirayama, Yukihiko / Iwata, Masaaki / Miyano, Kanako / Hirose, Yuki / Oda, Yasunori / Fujita, Yuko / Hashimoto, Kenji

    Brain research

    2023  Volume 1821, Page(s) 148567

    Abstract: Beta-hydroxybutyrate (BHB), an endogenous NLRP3 inflammasome inhibitor, has been shown to be associated with the pathophysiology of depression in rodents. However its active mechanism has not been revealed. Herein, we probed both the pathways and brain ... ...

    Abstract Beta-hydroxybutyrate (BHB), an endogenous NLRP3 inflammasome inhibitor, has been shown to be associated with the pathophysiology of depression in rodents. However its active mechanism has not been revealed. Herein, we probed both the pathways and brain regions involved in BHB's antidepressant-like effects in a learned helplessness (LH) rat model of depression. A single bilateral infusion of BHB into the cerebral ventricles induced the antidepressant-like effects on the LH rats. The antidepressant-like effects of BHB were blocked by the TrkB inhibitor ANA-12 and the AMPA receptor antagonist NBQX, indicating that the antidepressant-like effects of BHB involve BDNF-TrkB signaling and AMPA receptor activation. Further, infusions of BHB into the prelimbic and infralimbic portions of medial prefrontal cortex, the dentate gyrus of hippocampus, and the basolateral region of amygdala produced the antidepressant-like effects on LH rats. However, infusions of BHB into the central region of amygdala, the CA3 region of hippocampus, and the shell and core regions of nucleus accumbens had no effect. Finally, a single bilateral infusion of BHB into the cerebral ventricles of naive rats strengthened learning ability on repeated active avoidance test where saline-infused animals failed to increase avoidance responses.
    MeSH term(s) Rats ; Animals ; Helplessness, Learned ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; 3-Hydroxybutyric Acid ; Brain-Derived Neurotrophic Factor/metabolism ; Receptors, AMPA ; Antidepressive Agents/pharmacology ; Depression/drug therapy ; Receptor, trkB/metabolism
    Chemical Substances Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; 3-Hydroxybutyric Acid (TZP1275679) ; Brain-Derived Neurotrophic Factor ; Receptors, AMPA ; Antidepressive Agents ; Receptor, trkB (EC 2.7.10.1)
    Language English
    Publishing date 2023-09-07
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1200-2
    ISSN 1872-6240 ; 0006-8993
    ISSN (online) 1872-6240
    ISSN 0006-8993
    DOI 10.1016/j.brainres.2023.148567
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  3. Article ; Online: The Toll-like receptor 4 antagonist TAK-242 induces antidepressant-like effects in a rat learned helplessness model of depression through BDNF-TrkB signaling and AMPA receptor activation.

    Shirayama, Yukihiko / Iwata, Masaaki / Fujita, Yuko / Oda, Yasunori / Hashimoto, Kenji

    Behavioural brain research

    2022  Volume 423, Page(s) 113769

    Abstract: Finding from animal models of depression indicated that Toll-like receptor 4 (TLR4) is associated with the pathophysiology of depression. Herein, the TLR4 antagonists TAK-242 and baicalin induced antidepressant-like effects in a rat learned helplessness ... ...

    Abstract Finding from animal models of depression indicated that Toll-like receptor 4 (TLR4) is associated with the pathophysiology of depression. Herein, the TLR4 antagonists TAK-242 and baicalin induced antidepressant-like effects in a rat learned helplessness model of depression. The antidepressant-like effects of both TLR4 antagonists were blocked by the TrkB inhibitor ANA-12. Also, the antidepressant-like effects of TAK-242 were blocked by the treatment with AMPA receptor antagonist NBQX. The antidepressant-like effects of the TLR4 antagonist TAK-242 involves BDNF-TrkB signaling and AMPA receptor activation.
    MeSH term(s) Animals ; Antidepressive Agents/pharmacology ; Behavior, Animal/drug effects ; Brain-Derived Neurotrophic Factor/drug effects ; Depression/drug therapy ; Disease Models, Animal ; Flavonoids/pharmacology ; Helplessness, Learned ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB/antagonists & inhibitors ; Receptor, trkB/drug effects ; Receptors, AMPA/antagonists & inhibitors ; Receptors, AMPA/drug effects ; Signal Transduction/drug effects ; Sulfonamides/pharmacology ; Toll-Like Receptor 4/antagonists & inhibitors
    Chemical Substances Antidepressive Agents ; Bdnf protein, rat ; Brain-Derived Neurotrophic Factor ; Flavonoids ; Receptors, AMPA ; Sulfonamides ; Toll-Like Receptor 4 ; ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate ; baicalin (347Q89U4M5) ; Ntrk2 protein, rat (EC 2.7.10.1) ; Receptor, trkB (EC 2.7.10.1)
    Language English
    Publishing date 2022-01-24
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2022.113769
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  4. Article ; Online: Associations among autistic traits, cognitive and affective empathy, and personality traits in adults with autism spectrum disorder and no intellectual disability.

    Shirayama, Yukihiko / Matsumoto, Kazuki / Hamatani, Sayo / Muneoka, Katsumasa / Okada, Akihiro / Sato, Koichi

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 3125

    Abstract: Reported empathy deficits in autism spectrum disorder (ASD) could be attributable to other ASD-related features. We evaluated 28 ASD adults with no intellectual disability and 24 age-matched non-ASD control subjects using the Autism-Spectrum Quotient (AQ) ...

    Abstract Reported empathy deficits in autism spectrum disorder (ASD) could be attributable to other ASD-related features. We evaluated 28 ASD adults with no intellectual disability and 24 age-matched non-ASD control subjects using the Autism-Spectrum Quotient (AQ), Questionnaire of Cognitive and Affective Empathy (QCAE), Interpersonal Reactivity Index (IRI), and NEO Personality Inventory-Revised (NEO). Compared to the controls, ASD participants showed lower scores for perspective taking, online simulation, cognitive empathy, and peripheral responsivity on the QCAE, and lower scores for perspective taking and empathic concern on the IRI. Within the ASD group, the AQ scores showed significant relationships with perspective taking, online simulation and cognitive empathy on the QCAE, and perspective taking on the IRI. The ASD group also showed higher scores for neuroticism and lower scores for extraversion on the NEO compared to the controls. However, there were no relationships between AQ scores and NEO factors within the ASD group. Multiple regression analysis with stepwise linear regression demonstrated that perspective taking score on the QCAE and extraversion score on the NEO were good predictor variables to autistic traits on the AQ. These findings help us to understand empathy and personality traits in ASD adults with no intellectual disability.
    MeSH term(s) Adult ; Affective Symptoms/physiopathology ; Autism Spectrum Disorder/physiopathology ; Autism Spectrum Disorder/psychology ; Autistic Disorder/physiopathology ; Autistic Disorder/psychology ; Cognition/physiology ; Empathy/physiology ; Female ; Humans ; Male ; Personality/physiology ; Personality Inventory ; Surveys and Questionnaires
    Language English
    Publishing date 2022-02-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-07101-x
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  5. Article ; Online: What Are the Causes for Discrepancies of Antidepressant Actions of (2R,6R)-Hydroxynorketamine?

    Hashimoto, Kenji / Shirayama, Yukihiko

    Biological psychiatry

    2017  Volume 84, Issue 1, Page(s) e7–e8

    MeSH term(s) Animals ; Antidepressive Agents/therapeutic use ; Depression/drug therapy ; Depression/etiology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Helplessness, Learned ; Ketamine/therapeutic use ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Species Specificity ; Time Factors
    Chemical Substances Antidepressive Agents ; Ketamine (690G0D6V8H)
    Language English
    Publishing date 2017-12-27
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2017.12.007
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    Zs.A 720: Show issues Location:
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  6. Article ; Online: Reduction of claudin-5 and aquaporin-4 in the rat hippocampal CA-1 and CA-3 regions of a learned helplessness model of depression.

    Hirose, Yuki / Oda, Yasunori / Yoshino, Kouhei / Yano, Fumiaki / Kimura, Makoto / Kimura, Hiroshi / Iyo, Masaomi / Shirayama, Yukihiko

    Pharmacology, biochemistry, and behavior

    2023  Volume 234, Page(s) 173676

    Abstract: Background: Although findings from both animal and clinical research indicate that the blood-brain barrier (BBB) contributes to the pathogenesis of various psychiatric disorders (including depression), the underlying mechanisms are unknown. We ... ...

    Abstract Background: Although findings from both animal and clinical research indicate that the blood-brain barrier (BBB) contributes to the pathogenesis of various psychiatric disorders (including depression), the underlying mechanisms are unknown. We investigated the levels of the tight-junction proteins claudin-5 and aquaporin-4 (AQP-4) in astrocytes of learned helplessness (LH) rats (an animal model of depression) and non-LH rats (a model of resilience).
    Methods: We administered inescapable mild electric shock to rats and then identified the LH and non-LH rats by a post-shock test. The expressions of claudin-5 and AQP-4 in several brain regions of the LH and non-LH rats were then evaluated by a western blot analysis.
    Results: The levels of both claudin-5 and AQP-4 in the CA-1 and CA-3 hippocampal areas of the LH group were significantly lower than those of the control group, whereas those of the non-LH rats were not significantly different from those of the control and LH rats.
    Conclusions: These results suggest that LH rats but not non-LH rats experienced down-regulations of claudin-5 and AQP-4 in the CA-1 and CA-3. It is possible that a region-specific modulation of claudin-5 and AQP-4 is involved in the mechanisms of vulnerability but not resilience in depression.
    MeSH term(s) Animals ; Humans ; Rats ; Aquaporins/metabolism ; Claudin-5/metabolism ; Depression/genetics ; Depression/metabolism ; Helplessness, Learned ; Hippocampus/metabolism ; Aquaporin 4/metabolism
    Chemical Substances Aquaporins ; Claudin-5 ; Aquaporin 4
    Language English
    Publishing date 2023-11-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 191042-5
    ISSN 1873-5177 ; 0091-3057
    ISSN (online) 1873-5177
    ISSN 0091-3057
    DOI 10.1016/j.pbb.2023.173676
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  7. Article ; Online: Author Correction: Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype.

    Zhang, Ji-Chun / Yao, Wei / Qu, Youge / Nakamura, Mayumi / Dong, Chao / Yang, Chun / Ren, Qian / Ma, Min / Han, Mei / Shirayama, Yukihiko / Hayashi-Takagi, Akiko / Hashimoto, Kenji

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 8059

    Language English
    Publishing date 2023-05-17
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-34971-6
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  8. Article ; Online: Effects of a single bilateral infusion of R-ketamine in the rat brain regions of a learned helplessness model of depression.

    Shirayama, Yukihiko / Hashimoto, Kenji

    European archives of psychiatry and clinical neuroscience

    2017  Volume 267, Issue 2, Page(s) 177–182

    Abstract: Effects of a single bilateral infusion of R-enantiomer of ketamine in rat brain regions of learned helplessness model of depression were examined. A single bilateral infusion of R-ketamine into infralimbic (IL) portion of medial prefrontal cortex (mPFC), ...

    Abstract Effects of a single bilateral infusion of R-enantiomer of ketamine in rat brain regions of learned helplessness model of depression were examined. A single bilateral infusion of R-ketamine into infralimbic (IL) portion of medial prefrontal cortex (mPFC), CA3 and dentate gyrus (DG) of the hippocampus showed antidepressant effects. By contrast, a single bilateral infusion of R-ketamine into prelimbic (PL) portion of mPFC, shell and core of nucleus accumbens, basolateral amygdala and central nucleus of the amygdala had no effect. This study suggests that IL of mPFC, CA3 and DG of hippocampus might be involved in the antidepressant actions of R-ketamine.
    MeSH term(s) Amygdala/drug effects ; Animals ; Antidepressive Agents/administration & dosage ; Antidepressive Agents/pharmacology ; Depression/drug therapy ; Disease Models, Animal ; Helplessness, Learned ; Hippocampus/drug effects ; Ketamine/administration & dosage ; Ketamine/pharmacology ; Male ; Nucleus Accumbens/drug effects ; Prefrontal Cortex/drug effects ; Rats ; Rats, Sprague-Dawley
    Chemical Substances Antidepressive Agents ; Ketamine (690G0D6V8H)
    Language English
    Publishing date 2017-03
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1045583-8
    ISSN 1433-8491 ; 0175-758X ; 0940-1334
    ISSN (online) 1433-8491
    ISSN 0175-758X ; 0940-1334
    DOI 10.1007/s00406-016-0718-1
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  9. Article ; Online: The Lack of Alterations in Metabolites in the Medial Prefrontal Cortex and Amygdala, but Their Associations with Autistic Traits, Empathy, and Personality Traits in Adults with Autism Spectrum Disorder: A Preliminary Study.

    Shirayama, Yukihiko / Matsumoto, Kazuki / Osone, Fumio / Hara, Akira / Guan, Siqing / Hamatani, Sayo / Muneoka, Katsumasa / Sato, Koichi / Okada, Akihiro / Yokokawa, Tokuzou

    Journal of autism and developmental disorders

    2022  Volume 54, Issue 1, Page(s) 193–210

    Abstract: Proton magnetic resonance spectroscopy ( ...

    Abstract Proton magnetic resonance spectroscopy (
    MeSH term(s) Adult ; Humans ; Autism Spectrum Disorder/metabolism ; Autistic Disorder ; Empathy ; Amygdala/diagnostic imaging ; Glutamic Acid/metabolism ; Personality ; Prefrontal Cortex/diagnostic imaging ; Prefrontal Cortex/metabolism
    Chemical Substances Glutamic Acid (3KX376GY7L)
    Language English
    Publishing date 2022-10-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 391999-7
    ISSN 1573-3432 ; 0162-3257
    ISSN (online) 1573-3432
    ISSN 0162-3257
    DOI 10.1007/s10803-022-05778-7
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  10. Article ; Online: Associations among autistic traits, cognitive and affective empathy, and personality traits in adults with autism spectrum disorder and no intellectual disability

    Yukihiko Shirayama / Kazuki Matsumoto / Sayo Hamatani / Katsumasa Muneoka / Akihiro Okada / Koichi Sato

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 12

    Abstract: Abstract Reported empathy deficits in autism spectrum disorder (ASD) could be attributable to other ASD-related features. We evaluated 28 ASD adults with no intellectual disability and 24 age-matched non-ASD control subjects using the Autism-Spectrum ... ...

    Abstract Abstract Reported empathy deficits in autism spectrum disorder (ASD) could be attributable to other ASD-related features. We evaluated 28 ASD adults with no intellectual disability and 24 age-matched non-ASD control subjects using the Autism-Spectrum Quotient (AQ), Questionnaire of Cognitive and Affective Empathy (QCAE), Interpersonal Reactivity Index (IRI), and NEO Personality Inventory-Revised (NEO). Compared to the controls, ASD participants showed lower scores for perspective taking, online simulation, cognitive empathy, and peripheral responsivity on the QCAE, and lower scores for perspective taking and empathic concern on the IRI. Within the ASD group, the AQ scores showed significant relationships with perspective taking, online simulation and cognitive empathy on the QCAE, and perspective taking on the IRI. The ASD group also showed higher scores for neuroticism and lower scores for extraversion on the NEO compared to the controls. However, there were no relationships between AQ scores and NEO factors within the ASD group. Multiple regression analysis with stepwise linear regression demonstrated that perspective taking score on the QCAE and extraversion score on the NEO were good predictor variables to autistic traits on the AQ. These findings help us to understand empathy and personality traits in ASD adults with no intellectual disability.
    Keywords Medicine ; R ; Science ; Q
    Subject code 150
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
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