Authorship：Lead author   Language：English  

DOI： 10.1016/j.ajp.2024.104314

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

We report a case of a 61-year-old female with 22q11.2 deletion syndrome (22q11.2DS) and a novel heterozygous nonsense variant in MAP1A, identified through whole-genome sequencing (WGS). The patient presented with intellectual developmental disorder, treatment-resistant schizophrenia (SCZ), and multiple congenital anomalies. Despite aggressive pharmacotherapy, she experienced persistent auditory hallucinations and negative symptoms. WGS revealed a 3 Mb deletion at 22q11.2 and a nonsense variant in MAP1A (c.4652T>G, p.Leu1551*). MAP1A, encoding microtubule-associated protein 1A, is crucial for axon and dendrite development and has been implicated in autism spectrum disorder and SCZ. The MAP1A variant may contribute to the severe psychiatric phenotype, as it is thought to influence synaptic plasticity, a process also affected by 22q11.2 deletion. This case highlights the importance of WGS in identifying additional pathogenic variants that may explain phenotypic variability in 22q11.2DS. Thus, WGS can lead to a better understanding of the genetic architecture of 22q11.2DS. However, further studies are needed to elucidate the role of secondary genetic contributors in the diverse clinical presentations of 22q11.2DS.

DOI： 10.1002/npr2.12477

Web of Science

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PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

AIM: Clinical studies reported that patients with schizophrenia are at a higher risk of developing dementia than people without schizophrenia. However, early neuropathological studies have shown that the incidence of Alzheimer's disease (AD) in schizophrenia patients does not differ from that in controls. These inconsistent results may be attributable to the inclusion of non-AD dementia, but there have been few clinicopathological studies in older patients with schizophrenia based on the current neuropathological classification. This study aimed to investigate the neuropathological basis of incident dementia in older patients with schizophrenia. METHODS: We systematically examined 32 brains of old patients with schizophrenia using standardized pathological methods. The severity of dementia-related neuropathologies was analyzed using standardized semiquantitative assessments. After excluding patients who fulfilled the neuropathological criteria, clinicopathological variables were compared between patients with and without incident dementia to identify potential differences. RESULTS: Seven patients fulfilled the pathological criteria for AD (n = 3), argyrophilic grain disease (AGD) (n = 2), dementia with Lewy bodies (n = 1), and AGD/progressive supranuclear palsy (n = 1). Among 25 patients for whom a neuropathological diagnosis was not obtained, 10 had dementia, but the clinicopathological findings did not differ from the remaining 15 patients without dementia. CONCLUSION: Two types of older schizophrenia patient present dementia: patients with co-existing neurodegenerative disease and patients who do not meet pathological criteria based on the current classification. To understand the neurobiological aspects of incident dementia in older patients with schizophrenia, further clinicopathological studies are needed that do not simply analyze incident dementia as a comorbidity of conventional dementia-related neuropathologies.

DOI： 10.1111/pcn.13597

Web of Science

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The mitochondrial (m.) 3243A>G mutation is known to be associated with various mitochondrial diseases including mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Their clinical symptoms have been estimated to occur with an increased mitochondrial DNA (mtDNA) heteroplasmy and reduced activity of oxidative phosphorylation (OXPHOS) complexes, but their trends in the central nervous system remain unknown. Six autopsied mutant cases and three disease control cases without the mutation were enrolled in this study. The mutant cases had a disease duration of 1-27 years. Five of six mutant cases were compatible with MELAS. In the mutant cases, cortical lesions including a laminar necrosis were frequently observed in the parietal, lateral temporal, and occipital lobes; less frequently in the frontal lobe including precentral gyrus; and not at all in the medial temporal lobe. The mtDNA heteroplasmy in brain tissue samples of the mutant cases was strikingly high, ranging from 53.8% to 85.2%. The medial temporal lobe was preserved despite an inhospitable environment having high levels of mtDNA heteroplasmy and lactic acid. OXPHOS complex I was widely decreased in the mutant cases. The swelling of smooth muscle cells in the vessels on the leptomeninges, with immunoreactivity (IR) against mitochondria antibody, and a decreased nuclear/cytoplasmic ratio of choroidal epithelial cells were observed in all mutant cases but in none without the mutation. Common neuropathological findings such as cortical laminar necrosis and basal ganglia calcification were not always observed in the mutant cases. A high level of mtDNA heteroplasmy was observed throughout the brain in spite of heterogeneous cortical lesions. A lack of medial temporal lesion, mitochondrial vasculopathy in vessels on the leptomeninges, and an increased cytoplasmic size of epithelial cells in the choroid plexus could be neuropathological hallmarks helpful in the diagnosis of mitochondrial diseases.

DOI： 10.1111/bpa.13199

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PubMed

Authorship：Lead author   Language：English  

DOI： 10.1111/pcn.13532

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：東京 : ワールドプランニング  

CiNii Books

Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I033703546

Language：Japanese   Publisher：東京 : ワールドプランニング  

CiNii Books

Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I033628636

Language：Japanese   Publisher：東京 : ワールドプランニング  

CiNii Books

Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I033628625

Language：Japanese   Publisher：東京 : ワールドプランニング  

CiNii Books

Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I033374977

Language：Japanese   Publisher：東京 : ワールドプランニング  

CiNii Books

Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I033333937

Event date： 2024.10

Language：English   Presentation type：Oral presentation (general)  

Event date： 2024.7

Event date： 2024.5

Presentation type：Symposium, workshop panel (nominated)  

Event date： 2023.11

Presentation type：Symposium, workshop panel (nominated)  

Event date： 2023.7

Presentation type：Oral presentation (general)