1.Effects of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Criteria Changes for Schizophrenia on Diagnoses of First-Episode Schizophrenia Spectrum Disorders
WooRi CHO ; Sung-Wan KIM ; Seung-Hee WON ; Bong-Ju LEE ; Naohisa TSUJINO ; Youji TAKUBO ; Taiju YAMAGUCHI ; Takahiro NEMOTO ; Ling LI ; Thi-Hung LE ; Fatima Zahra RAMI ; Young-Chul CHUNG
Psychiatry Investigation 2025;22(2):212-217
Objective:
Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified.
Methods:
This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held.
Results:
Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively).
Conclusion
These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.
2.Effects of Epothilone D on Social Defeat Stress-induced Changes in Microtubule-related and Endoplasmic Reticulum Stress Protein Expression
Thi-Hung LE ; Ling LI ; Fatima Zahra RAMI ; Jung-Mi OH ; Sungkun CHUN ; Young-Chul CHUNG
Clinical Psychopharmacology and Neuroscience 2025;23(1):110-119
Objective:
Epothilone D (EpoD), microtubule (MT) stabilizing agent, demonstrated promising results in the animal models of Alzheimer’s disease, Parkinson’s disease and schizophrenia. The present study sought to investigate preventive effects of EpoD on altered changes of MT related proteins and endoplasmic reticulum (ER) stress proteins induced by social defeat stress (SDS).
Methods:
We measured protein expression levels of -tubulin and its post-translational modifications, MT-associated protein 2, stathmin1 and 2 with their phosphorylated forms, and ER stress markers, 78-kDa glucose-regulated protein (GRP-78) and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) in the prefrontal cortex (PFC) and hippocampus (HIP) of C57BL/6J strain mice treated with EpoD (2 mg/kg) or its vehicle, dimethylsulfoxide (DMSO), and exposed to SDS.
Results:
We observed lower levels of acetylated -tubulin, MAP2, p-STMN (Ser16), and GRP-78 in the PFC of the EpoD-Con group when compared to the DMSO-Con group. On the other hand, in the HIP, there were significantly higher levels of tyrosinated -tubulin and GRP-78 in the EpoD-Defeat group compared to the DMSO-Defeat group.Furthermore, the level of MAP2 in the HIP was found to be lower in the EpoD-Con group compared to the DMSO-Con group.
Conclusion
Our results suggest that EpoD exhibits a dual impact, manifesting both beneficial and detrimental effects on the aberrant changes of MT-related proteins and ER stress proteins induced by SDS, depending on the brain regions.These findings underscore the complexity of EpoD’s effects, necessitating further exploration to understand its intricate mechanisms in cellular pathways linked to SDS.
3.Effects of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Criteria Changes for Schizophrenia on Diagnoses of First-Episode Schizophrenia Spectrum Disorders
WooRi CHO ; Sung-Wan KIM ; Seung-Hee WON ; Bong-Ju LEE ; Naohisa TSUJINO ; Youji TAKUBO ; Taiju YAMAGUCHI ; Takahiro NEMOTO ; Ling LI ; Thi-Hung LE ; Fatima Zahra RAMI ; Young-Chul CHUNG
Psychiatry Investigation 2025;22(2):212-217
Objective:
Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified.
Methods:
This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held.
Results:
Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively).
Conclusion
These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.
4.Effects of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Criteria Changes for Schizophrenia on Diagnoses of First-Episode Schizophrenia Spectrum Disorders
WooRi CHO ; Sung-Wan KIM ; Seung-Hee WON ; Bong-Ju LEE ; Naohisa TSUJINO ; Youji TAKUBO ; Taiju YAMAGUCHI ; Takahiro NEMOTO ; Ling LI ; Thi-Hung LE ; Fatima Zahra RAMI ; Young-Chul CHUNG
Psychiatry Investigation 2025;22(2):212-217
Objective:
Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified.
Methods:
This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held.
Results:
Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively).
Conclusion
These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.
5.Effects of Epothilone D on Social Defeat Stress-induced Changes in Microtubule-related and Endoplasmic Reticulum Stress Protein Expression
Thi-Hung LE ; Ling LI ; Fatima Zahra RAMI ; Jung-Mi OH ; Sungkun CHUN ; Young-Chul CHUNG
Clinical Psychopharmacology and Neuroscience 2025;23(1):110-119
Objective:
Epothilone D (EpoD), microtubule (MT) stabilizing agent, demonstrated promising results in the animal models of Alzheimer’s disease, Parkinson’s disease and schizophrenia. The present study sought to investigate preventive effects of EpoD on altered changes of MT related proteins and endoplasmic reticulum (ER) stress proteins induced by social defeat stress (SDS).
Methods:
We measured protein expression levels of -tubulin and its post-translational modifications, MT-associated protein 2, stathmin1 and 2 with their phosphorylated forms, and ER stress markers, 78-kDa glucose-regulated protein (GRP-78) and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) in the prefrontal cortex (PFC) and hippocampus (HIP) of C57BL/6J strain mice treated with EpoD (2 mg/kg) or its vehicle, dimethylsulfoxide (DMSO), and exposed to SDS.
Results:
We observed lower levels of acetylated -tubulin, MAP2, p-STMN (Ser16), and GRP-78 in the PFC of the EpoD-Con group when compared to the DMSO-Con group. On the other hand, in the HIP, there were significantly higher levels of tyrosinated -tubulin and GRP-78 in the EpoD-Defeat group compared to the DMSO-Defeat group.Furthermore, the level of MAP2 in the HIP was found to be lower in the EpoD-Con group compared to the DMSO-Con group.
Conclusion
Our results suggest that EpoD exhibits a dual impact, manifesting both beneficial and detrimental effects on the aberrant changes of MT-related proteins and ER stress proteins induced by SDS, depending on the brain regions.These findings underscore the complexity of EpoD’s effects, necessitating further exploration to understand its intricate mechanisms in cellular pathways linked to SDS.
6.Effects of Epothilone D on Social Defeat Stress-induced Changes in Microtubule-related and Endoplasmic Reticulum Stress Protein Expression
Thi-Hung LE ; Ling LI ; Fatima Zahra RAMI ; Jung-Mi OH ; Sungkun CHUN ; Young-Chul CHUNG
Clinical Psychopharmacology and Neuroscience 2025;23(1):110-119
Objective:
Epothilone D (EpoD), microtubule (MT) stabilizing agent, demonstrated promising results in the animal models of Alzheimer’s disease, Parkinson’s disease and schizophrenia. The present study sought to investigate preventive effects of EpoD on altered changes of MT related proteins and endoplasmic reticulum (ER) stress proteins induced by social defeat stress (SDS).
Methods:
We measured protein expression levels of -tubulin and its post-translational modifications, MT-associated protein 2, stathmin1 and 2 with their phosphorylated forms, and ER stress markers, 78-kDa glucose-regulated protein (GRP-78) and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) in the prefrontal cortex (PFC) and hippocampus (HIP) of C57BL/6J strain mice treated with EpoD (2 mg/kg) or its vehicle, dimethylsulfoxide (DMSO), and exposed to SDS.
Results:
We observed lower levels of acetylated -tubulin, MAP2, p-STMN (Ser16), and GRP-78 in the PFC of the EpoD-Con group when compared to the DMSO-Con group. On the other hand, in the HIP, there were significantly higher levels of tyrosinated -tubulin and GRP-78 in the EpoD-Defeat group compared to the DMSO-Defeat group.Furthermore, the level of MAP2 in the HIP was found to be lower in the EpoD-Con group compared to the DMSO-Con group.
Conclusion
Our results suggest that EpoD exhibits a dual impact, manifesting both beneficial and detrimental effects on the aberrant changes of MT-related proteins and ER stress proteins induced by SDS, depending on the brain regions.These findings underscore the complexity of EpoD’s effects, necessitating further exploration to understand its intricate mechanisms in cellular pathways linked to SDS.
7.Effects of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Criteria Changes for Schizophrenia on Diagnoses of First-Episode Schizophrenia Spectrum Disorders
WooRi CHO ; Sung-Wan KIM ; Seung-Hee WON ; Bong-Ju LEE ; Naohisa TSUJINO ; Youji TAKUBO ; Taiju YAMAGUCHI ; Takahiro NEMOTO ; Ling LI ; Thi-Hung LE ; Fatima Zahra RAMI ; Young-Chul CHUNG
Psychiatry Investigation 2025;22(2):212-217
Objective:
Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified.
Methods:
This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held.
Results:
Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively).
Conclusion
These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.
8.Effects of Epothilone D on Social Defeat Stress-induced Changes in Microtubule-related and Endoplasmic Reticulum Stress Protein Expression
Thi-Hung LE ; Ling LI ; Fatima Zahra RAMI ; Jung-Mi OH ; Sungkun CHUN ; Young-Chul CHUNG
Clinical Psychopharmacology and Neuroscience 2025;23(1):110-119
Objective:
Epothilone D (EpoD), microtubule (MT) stabilizing agent, demonstrated promising results in the animal models of Alzheimer’s disease, Parkinson’s disease and schizophrenia. The present study sought to investigate preventive effects of EpoD on altered changes of MT related proteins and endoplasmic reticulum (ER) stress proteins induced by social defeat stress (SDS).
Methods:
We measured protein expression levels of -tubulin and its post-translational modifications, MT-associated protein 2, stathmin1 and 2 with their phosphorylated forms, and ER stress markers, 78-kDa glucose-regulated protein (GRP-78) and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) in the prefrontal cortex (PFC) and hippocampus (HIP) of C57BL/6J strain mice treated with EpoD (2 mg/kg) or its vehicle, dimethylsulfoxide (DMSO), and exposed to SDS.
Results:
We observed lower levels of acetylated -tubulin, MAP2, p-STMN (Ser16), and GRP-78 in the PFC of the EpoD-Con group when compared to the DMSO-Con group. On the other hand, in the HIP, there were significantly higher levels of tyrosinated -tubulin and GRP-78 in the EpoD-Defeat group compared to the DMSO-Defeat group.Furthermore, the level of MAP2 in the HIP was found to be lower in the EpoD-Con group compared to the DMSO-Con group.
Conclusion
Our results suggest that EpoD exhibits a dual impact, manifesting both beneficial and detrimental effects on the aberrant changes of MT-related proteins and ER stress proteins induced by SDS, depending on the brain regions.These findings underscore the complexity of EpoD’s effects, necessitating further exploration to understand its intricate mechanisms in cellular pathways linked to SDS.
9.Effects of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Criteria Changes for Schizophrenia on Diagnoses of First-Episode Schizophrenia Spectrum Disorders
WooRi CHO ; Sung-Wan KIM ; Seung-Hee WON ; Bong-Ju LEE ; Naohisa TSUJINO ; Youji TAKUBO ; Taiju YAMAGUCHI ; Takahiro NEMOTO ; Ling LI ; Thi-Hung LE ; Fatima Zahra RAMI ; Young-Chul CHUNG
Psychiatry Investigation 2025;22(2):212-217
Objective:
Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified.
Methods:
This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held.
Results:
Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively).
Conclusion
These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.
10.Effects of Social Defeat Stress on Microtubule Regulating Proteins and Tubulin Polymerization
Thi-Hung LE ; Jung-Mi OH ; Fatima Zahra RAMI ; Ling LI ; Sung-Kun CHUN ; Young-Chul CHUNG
Clinical Psychopharmacology and Neuroscience 2024;22(1):129-138
Objective:
Microtubule (MT) stability in neurons is vital for brain development; instability is associated with neuropsychiatric disorders. The present study examined the effects of social defeat stress (SDS) on MT-regulating proteins and tubulin polymerization.
Methods:
After 10 days of SDS, defeated mice were separated into susceptible (Sus) and unsusceptible (Uns) groups based on their performance in a social avoidance test. Using extracted brain tissues, we measured the expression levels of α-tubulin, acetylated α-tubulin, tyrosinated α-tubulin, MT-associated protein-2 (MAP2), stathmin (STMN1), phospho stathmin serine 16 (p-STMN1 [Ser16]), phospho stathmin serine 25 (p-STMN1 [Ser25]), phospho stathmin serine 38 (p-STMN1 [Ser38]), stathmin2 (STMN2), phospho stathmin 2 serine 73 (p-STMN2 [Ser73]), 78-kDa glucose-regulated protein (GRP-78), and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) using Western blot assay. The tubulin polymerization rate was also measured.
Results:
We observed increased and decreased expression of acetylated and tyrosinated α-tubulin, respectively, decreased expression of p-STMN1 (Ser16) and increased expression of p-STMN1 (Ser25), p-STMN2 (Ser73) and GRP-78 and CHOP in the prefrontal cortex and/or hippocampus of defeated mice. A reduced tubulin polymerization rate was observed in the Sus group compared to the Uns and Con groups.
Conclusion
Our findings suggest that SDS has detrimental effects on MT stability, and a lower tubulin polymerization rate could be a molecular marker for susceptibility to SDS.

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