ウツビョウ ノ ノウカガク

Depression is a very popular mental disorder that affects about １０％ of population throughout life and its prevalence is around ２ to ５％. More than ３０，０００ people died by suicide per year in Japan and about half of suicides were estimated to be suffered from depression. Although depression is treatable by pharmacotherapy, the diagnosis of depression is still difficult for primary care doctor because there is no reliable marker. We are now trying to find a new marker for depression with molecular biology and brain imaging study. We are also analyzing the mood changes during menstruation cycles and between pre and post operation of deep brain stimulation for Parkinson’s disease patients. In this article, I review the strategy for understanding of depression in our department with brain sciences

Genetic polymorphisms of serotonin and dopamine transporters in mental disorders

Transporter-assisted uptake of serotonin (5-HT) and dopamine (DA) has been accounted for activities in human behavior or mental status, because they are the sites of action of widely used antidepressant and psychoactive drugs. Both the human serotonin transporter (5-HTT) and human dopamine transporter (DAT1) genes are good candidates for etiological involvement in various psychiatric conditions. The serotonin transporter gene has two types of functional polymorphisms. One is serotonin transporter linked polymorphic region (5-HTTLPR) consisting of length variation of the repetitive sequence containing 20～23-bp-long repeat elements in the 5’-upstream region of the gene. Another polymorphism is that serotonin transporter variable number of tandem repeats(5-HTTVNTR) in its second intron. Both polymorphisms affect the transcription ratio of5-HTT gene and may modify neuronal transmission by changing its protein expression. On the other hand, DAT1 gene has a variable number of tandem repeats type polymorphism(DAT1VNTR) in the 3’-untranslated region of the mRNA, which was also reported to change its gene expression. So polymorphic variations of transporters would change the behavioral and neuropathological tendency. Here, the feature of those two transporters and their relations to psychiatric disorders are described

Mental changes in PD with STN-DBS

The physical benefits of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease(PD) patients are well documented, but the mental benefits are uncertain, particularly in Japanese patients. This study evaluated the clinical and neuropsychological characteristics before and after STN-DBS surgery in Japanese PD patients. PD patients (n=13, age 67.0 ± 7.8 years) were evaluated pre-surgery (baseline) and at one and six months post-surgery by two trained psychiatrists. The motor symptoms were assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score. The neuropsychological and psychiatric tests performed were the Mini-Mental State Examination, the Wisconsin Card Sorting Test (WCST), the verbal fluency test (VFT), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale (HAM-A). The UPDRS motor score (p<0.001) and HAM-A score (p=0.004) showed significant improvement at one month post-surgery, but a significant decline was observed in the WCST total error (p=0.005) and the semantic VFT score (p<0.001). The phonetic VFT also showed a substantial decline (p=0.015) at one month post-surgery. At six months post-surgery, the improvement in the UPDRS motor score was maintained, and the scores on the neuropsychological and psychiatric tests had returned to baseline. Although bilateral STN-DBS did not appear to have long-term effects on neuropsychological and psychiatric outcomes, the microlesion effects associated with STN-DBS appear to increase the risk of transient cognitive and psychiatric complications. These complications should be monitored by careful observation of neurological and psychiatric symptoms

Mental changes in PD with STN-DBS

The physical benefits of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease(PD) patients are well documented, but the mental benefits are uncertain, particularly in Japanese patients. This study evaluated the clinical and neuropsychological characteristics before and after STN-DBS surgery in Japanese PD patients. PD patients (n=13, age 67.0 ± 7.8 years) were evaluated pre-surgery (baseline) and at one and six months post-surgery by two trained psychiatrists. The motor symptoms were assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score. The neuropsychological and psychiatric tests performed were the Mini-Mental State Examination, the Wisconsin Card Sorting Test (WCST), the verbal fluency test (VFT), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale (HAM-A). The UPDRS motor score (p<0.001) and HAM-A score (p=0.004) showed significant improvement at one month post-surgery, but a significant decline was observed in the WCST total error (p=0.005) and the semantic VFT score (p<0.001). The phonetic VFT also showed a substantial decline (p=0.015) at one month post-surgery. At six months post-surgery, the improvement in the UPDRS motor score was maintained, and the scores on the neuropsychological and psychiatric tests had returned to baseline. Although bilateral STN-DBS did not appear to have long-term effects on neuropsychological and psychiatric outcomes, the microlesion effects associated with STN-DBS appear to increase the risk of transient cognitive and psychiatric complications. These complications should be monitored by careful observation of neurological and psychiatric symptoms

断酒に至る過程に関する実態調査

断酒に至るまでには，どのような問題があり，その問題に断酒会会員がどのように対処しながら，断酒に至ったかを明らかにすることが目的である．断酒会会員２９４人を調査対象として質問紙および留め置き調査を行った．回収率は５６．８％（１６７名：男性１５０名，女性１７名）であった．調査対象者の平均年齢は５８．６±１１．１（mean±SD）（男性５９．７±１０．５，女性４８±１１．７）歳であった．初回飲酒年齢は平均１８．４±６．３歳であり，１５歳未満の初回飲酒は男性２８名，女性５名であった．飲酒歴は平均２５．４±１１．３年（男性２６．４，女性１６．５年）で，平均断酒期間は１０年１ヵ月±９年６ヵ月（男性１０年７ヵ月，女性４年６ヵ月）であった．調査対象者は飲酒によって家庭や仕事における深刻な問題を引き起こしたため，酒量の調節を試みたが，逆に飲酒量が増し連続飲酒状態に陥り医療機関を受診していた．断酒例会への継続参加により，断酒が可能となり，信用と健康を取り戻し，自信となっていることがあきらかになった．アルコール依存症者が再び社会で正常な日常生活が送れるようになる為には断酒が唯一の方法であることがあらためて確認された．Aim : The purpose of this survey is to clarify alcohol-related problems, the coping methods and how to reach total abstinence in the self-help group members for total abstinence. Method : A mail survey and/or a placement method survey of alcohol dependency were conducted in two prefectures. Subjects were ２９４ recovering alcoholic and they were members of regular meeting for total abstinence. The response rate was５６．８％（１５０males,１７females）. Results : Subjects average age was ５８．６±１１．１ （mean±SD） years （male, ５９．７±１０．５； female, ４８±１１．７ years）. The average of first alcoholic experience of them was at the age of １８．４±６．３. Twenty eight men （１８．６％） and five women （２９．４％） started drinking at the age of less than １５years old. Average duration of drinking was ２５．４±１１．３ years （male, ２６．４； female, １６．５years）, and average abstinence periods were １０．１±９．５years （male, １０．６； female, ４．５years）. They tried to regulate the amount of alcohol because of serious social problems at a home and/or workplace by drinking. However, they could not visit hospitals or clinics until they lapsed into the continuous excessive drinking state. They could quit drinking with continuous participation to regular meeting for total abstinence （Dansyu Reikai） and regained trust, health, and self-confidence. Conclusion : These results suggest that the method to quit drinking is not a self-regulation of amount of alcohol but an attendance of Dansyu Reikai （self-help group participation）

ABCA7 Gene Expression and Genetic Association Study in Schizophrenia

Introduction: Although ATP-binding cassette sub-family A member 7 gene (ABCA7) is known to be associated with Alzheimer’s disease, the relationship between ABCA7 and schizophrenia has been unknown. Methods: Schizophrenia patients (n = 50; 24 males, 62.1 ± 0.50 years old) and age- and sex-matched healthy controls (n = 50) were recruited for the mRNA analysis. Additionally, a case-control study for the rs3764650 genotypes was performed with 1308 samples (control subjects; n = 527, schizophrenia patients; n = 781). All participants were Japanese, unrelated to each other, and living in the same area. Results: The distributions of the rs3764650 genotypes in schizophrenia patients were not different from that of controls. However, the ABCA7 mRNA expression levels in schizophrenia patients were significantly higher than those in controls by a logistic regression analysis. Additionally, the ABCA7 mRNA expression levels in schizophrenia patients were correlated with the rs3764650 genotypes in a dose-dependent manner. Discussion: The ABCA7 mRNA expression levels in peripheral blood with the rs3764650 genotypes may be related to pathological mechanisms in schizophrenia and may be a biological marker for schizophrenia

Assessment of human stress and depression by DNA microarray analysis

Precise assessment of stress is an imminent issue to deal with stress-related social, medical and psychological problems. Psychological stress is known to stimulate the neuroendocrine, sympathetic nervous, and immune systems. By analyzing mRNA expression levels in leukocytes, which express receptors for hormones, neurotransmitters, growth factors, cytokines, and other stress related signals, levels of stress may be adequately measured. In a series of studies, our group has developed a cDNA microarray specifically designed to measure the mRNA levels of stress-related genes in peripheral blood leukocytes. This microarray enabled us to sensitively detect the response to psychological stress. In addition, our preliminary study suggests that the array could differentiate patients with depression from sex- and age-matched control subjects

School teachers' awareness of internet addiction in elementary school students: a regional survey in Japan

In recent years, concerns about internet addiction (IA) among children have been increasing. This study focused on the awareness of IA in elementary school teachers. A web-based anonymous survey was conducted in November 2021. The participants completed an original questionnaire about their awareness of IA. The participants were divided into three groups based on their positions in the classroom: class teachers, support teachers, and administrative teachers. Out of 283 participants, over 70% had not approached students with IA and had little practical knowledge about the disorder. Support and administrative teachers had more opportunities to interact with students with IA than class teachers (p &lt; 0.001 in both cases). Support teachers had more opportunities to ask their colleagues about IA than class teachers (p &lt; 0.01); similarly, administrative teachers also had more opportunities to discuss IA with colleagues than class teachers (p = 0.04). Preventive interventions are recommended for people who communicate with children with IA. Students with IA might cause anxiety among teachers; therefore, preventive education strategies should be implemented with the cooperation of psychiatrists, psychologists, and public health nurses

Factors associated with development and distribution of granular/fuzzy astrocytes in neurodegenerative diseases

Granular/fuzzy astrocytes (GFAs), a subtype of “aging‐related tau astrogliopathy,” are noted in cases bearing various neurodegenerative diseases. However, the pathogenic significance of GFAs remains unclear. We immunohistochemically examined the frontal cortex, caudate nucleus, putamen and amygdala in 105 cases composed of argyrophilic grain disease cases (AGD, N = 26), and progressive supranuclear palsy (PSP, N = 10), Alzheimer’s disease (AD, N = 20) and primary age‐related tauopathy cases (PART, N = 18) lacking AGD, as well as 31 cases bearing other various neurodegenerative diseases to clarify (i) the distribution patterns of GFAs in AGD, and PSP, AD and PART lacking AGD, (ii) the impacts of major pathological factors and age on GFA formation and (iii) immunohistochemical features useful to understand the formation process of GFAs. In AGD cases, GFAs consistently occurred in the amygdala (100%), followed by the putamen (69.2%) and caudate nucleus and frontal cortex (57.7%, respectively). In PSP cases without AGD, GFAs were almost consistently noted in all regions examined (90–100%). In AD cases without AGD, GFAs were less frequent, developing preferably in the putamen (35.0%) and caudate nucleus (30.0%). PART cases without AGD had GFAs most frequently in the amygdala (35.3%), being more similar to AGD than to AD cases. Ordered logistic regression analyses using all cases demonstrated that the strongest independent factor of GFA formation in the frontal cortex and striatum was the diagnosis of PSP, while that in the amygdala was AGD. The age was not significantly associated with GFA formation in any region. In GFAs in AGD cases, phosphorylation and conformational change of tau, Gallyas‐positive glial threads indistinguishable from those in tufted astrocytes, and the activation of autophagy occurred sequentially. Given these findings, AGD, PSP, AD and PART cases may show distinct distributions of GFAs, which may provide clues to predict the underlying processes of primary tauopathies

Case Report Effects of Adenotonsillectomy on Neurocognitive Function in Pediatric Obstructive Sleep Apnea Syndrome

Obstructive sleep apnea syndrome (OSAS) in children does not only present with symptoms of sleep disturbances but also with associated symptoms such as growth failure, enuresis, academic learning difficulties, and behavioral problems, including attention deficit/hyperactivity disorder-(ADHD-) like symptoms. We evaluated neurocognitive functions before and after adenotonsillectomy in a patient with OSAS. An 11-year-old boy suspected of having ADHD with nocturnal enuresis was referred for evaluation. He was found to have adenotonsillar hypertrophy. Presence of snoring was evident only after detailed medical interview. Polysomnography confirmed the diagnosis of OSAS, which was subsequently treated by adenotonsillectomy. The apnea/hypopnea index decreased from 21.9 at baseline to 1.8 after surgery, and the frequency of enuresis fell from almost nightly to 2-3 times per month. Neurocognitive and behavioral assessment after the treatment of OSAS showed significant improvement in cognitive functions, especially attention capacity and considerable amelioration of behavioral problems including ADHD-like symptoms. As the most common cause of pediatric OSAS is adenotonsillar hypertrophy, medical interview and oropharyngeal examination should always be performed in children suspected of having ADHD. The necessity of sleep evaluation for children with ADHD-like symptoms was also emphasized