Neuropsychiatry characterization of patients with mitochondrial gene abnormalities

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 11670959
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Yokohama City University
• Principal Investigator: YAMADA Yoshiteru Yokohama City University Hospital, Assistant Professor, 医学部附属病院, 助教授 (70220415)
• Co-Investigator(Kenkyū-buntansha): ONISHI Hideki Yokohama City University Hospital, Assistant Professor, 精神科, 医師 (30275028)
• Project Period (FY): 1999 – 2002
• Keywords: Mitochondrial gene / Diabetes mellitus / Dementia / Mental symptoms

Research Abstract

Detailed clinical survey of four patients and their relatives with mitochondrial DNA mutation performed. Every patient and available two mothers had A3243G mutation, After eight years' follow up (in the longest case) of patients, no new case who presented neuropsychiatric symptoms had appeared. Their mental symptoms were adult-onset, and some are almost constant and others had remitted but repeated.
We compared a case manifested progressive central nervous system disorders (especially mental symptoms) with cases without progressive central nervous system disorder. Mentally remitted states are continued and neither brain atrophy nor low density areas were observed radiologically in the patients who presented mental symptoms without stroke like episodes. But in the case with stroke like episodes, brain atrophy was progressive and dementia was worsened. Blood levels of lactate and pyruvate were elevated in the case with stroke like episodes than cases without episode. Single photon emission tomography (SPECT) images from one patient showed improvement of regional cerebral blood flow after the treatment. Mental symptoms did not improved with psychotropic drugs only, but with complementary addition of coenzymes some psychotropics mode some benefits.
Hirsute properties of our patients made us to check their skin. Skin biopsy samples of an available patient showed accumulation of abnormal mitochondria in erector muscle of hairs. Similar finding were *bserved in sweat glands and pericytes. His sweating was delayed in sweating test. This may indicate possible abnormality in temperature control of multisysytemic involvements in MELAS.
Diversity of the clinical phenotype is common in mitochondrial disease. Some of mental ill states are caused by mitochondrial abnormalities also, yet relation between genetic abnormalities and mental symptoms is not unclear. Further analysis and evaluation is needed.