適応障害患者における Wechsler 式知能検査所見と臨床的特徴の検討

近年，職場ストレスにより抑うつ状態をはじめ心身の不調を来し休職したり，学校や社会に不適応を起こし不登校，ひきこもりになったりする適応障害患者が増えている．診断基準上，適応障害を引き起こす要因であるストレスの大きさは問われないが，一方でどのような人が適応障害になりやすいかという研究はこれまでない．本研究では，適応障害患者に対する成人用Wechsler 式知能検査第３版（Wechsler Adult Intelligence Scale Third Edition; WAIS-Ⅲ）の所見と臨床的特徴からそれらを検討した．　適応障害と診断されWAIS-Ⅲを施行された患者50名（14歳～48歳，男性29名，女性21名）を対象とした．IQ が70未満の精神遅滞と診断された者は除外した．臨床評価として，初診時年齢，発症年齢，精神主訴の有無，身体主訴の有無，初診時における社会参加の有無，初診時GAF（Global Assessment Scale）を用いた．WAIS-Ⅲは言語理解（Verbal Comprehension; VC），作動記憶（Working Memory; WM）， 知覚統合（Perceptual Organization; PO）， 処理速度（Processing Speed； PS）の４つの群指数に分類される．対象者を群指数パターンによってクラスタ分析を行った．　その結果，３つのクラスタパターンに分類された．群指数に関しては，クラスタ１はWM がVCとPS よりも有意に低く，クラスタ２はPS がVC とWM よりも有意に低く，クラスタ３はPS がVC，WM，PO よりも有意に低かった．また，IQ に関しては，クラスタ３> クラスタ１＞クラスタ２の順に高くそれぞれ有意差が認められた．クラスタ間の臨床的特徴を検討したところ，クラスタ３は身体主訴が有意に少なかったが，他の項目で有意差は認められなかった．さらに，対象者全体で見ると，GAF とWM において正の相関が認められた．　以上から，適応障害患者においてはWM とPS という認知機能低下が認められる可能性があり，特に社会適応の観点からWM に注目して診療を行うことが大切であると考えられた．Recently, there has been an increase in the number of patients with adjustment disorder (AD) who are absent from work or school. Such patients often withdraw from active social life because of a depressed mood and psychosomatic symptoms caused by workplace stress or maladjustment to their social environment. The diagnostic criteria for AD do not account for the level of stressful life events, and evidence regarding the association of cognitive features with the extent of maladjustment and clinical characteristics of AD is scarce. In this study, we examined the association between cognitive characteristics assessed with the Wechsler Adult Intelligence Scale-Third Edition (WAIS-Ⅲ) and clinical features in patients with AD.In this study, we included 50 patients with AD who completed the WAIS-Ⅲ (29 men and 21 women, age range: 14-48 years old). Patients with a diagnosis of mental retardation and an IQ less than 70 were excluded. At the initial visit, the following clinical features were measured: age at initial visit, age of onset, the presence of mental and/or somatic symptoms, social participation, and Global Assessment of Functioning (GAF) scale score. The WAIS-Ⅲ consists of four index scores: verbal comprehension (VC), working memory (WM), perceptual organization (PO), and processing speed (PS). Participants were classified into three groups by cluster analysis according to their WAIS-Ⅲ index score profiles.In Group 1, the WM index was significantly lower than both the VC index and PS index, whereas, in Group 2, the PS index was significantly lower than the VC and WM indices. Meanwhile, in Group 3, the PS index was significantly lower than the VC, WM, and PO indices. Group 3 had significantly higher full-scale intelligence quotient (FIQ) scores than did both Groups 1 and 2, while Group 1 had significantly higher FIQ scores than did Group 2. In addition, the proportion of patients who had somatic symptoms in Group 3 was significantly lower than that in Groups 1 and 2. In the analysis of all participants, we observed a positive correlation between GAF scores and the WM index.In conclusion, patients with AD are thought to have impairments in both WM and PS. We suggest that evaluation of AD from the perspective of WM might be useful to better understand a patient’s social maladjustment

Helping-Like Behaviour in Mice Towards Conspecifics Constrained Inside Tubes

Prosocial behaviour, including helping behaviour, benefits others. Recently, helping-like behaviour has been observed in rats, but whether it is oriented towards rescue, social contact with others, or other goals remains unclear. Therefore, we investigated whether helping-like behaviour could be observed in mice similar to that in rats. Because mice are social animals widely used in neuroscience, the discovery of helping-like behaviour in mice would be valuable in clarifying the psychological and biological mechanisms underlying pro-sociability. We constrained mice inside tubes. Subject mice were allowed to move freely in cages with tubes containing constrained conspecifics. The subject mice released both cagemates and stranger mice but did not engage in opening empty tubes. Furthermore, the same behaviour was observed under aversive conditions and with anesthetised conspecifics. Interestingly, hungry mice opened the tubes containing food before engaging in tube-opening behaviour to free constrained conspecifics. Mice showed equal preferences for constrained and freely moving conspecifics. We demonstrated for the first time that mice show tube-opening behaviour. Furthermore, we partly clarified the purpose and motivation of this behaviour. An effective mouse model for helping-like behaviour would facilitate research on the mechanisms underlying prosocial behaviour

Layer-specific expression of extracellular matrix molecules in the mouse somatosensory and piriform cortices

In the developing central nervous system (CNS), extracellular matrix (ECM) molecules have regulating roles such as in brain development, neural-circuit maturation, and synaptic-function control. However, excluding the perineuronal net (PNN) area, the distribution, constituent elements, and expression level of granular ECM molecules (diffuse ECM) present in the mature CNS remain unclear. Diffuse ECM molecules in the CNS share the components of PNNs and are likely functional. As cortical functions are greatly region-dependent, we hypothesized that ECM molecules would differ in distribution, expression level, and components in a region- and layer-dependent manner. We examined the layer-specific expression of several chondroitin sulfate proteoglycans (aggrecan, neurocan, and brevican), tenascin-R, Wisteria floribunda agglutinin (WFA)-positive molecules, hyaluronic acid, and link protein in the somatosensory and piriform cortices of mature mice. Furthermore, we investigated expression changes in WFA-positive molecules due to aging. In the somatosensory cortex, PNN density was particularly high at layer 4 (L4), but not all diffuse ECM molecules were highly expressed at L4 compared to the other layers. There was almost no change in tenascin-R and hyaluronic acid in any somatosensory-cortex layer. Neurocan showed high expression in L1 of the somatosensory cortex. In the piriform cortex, many ECM molecules showed higher expression in L1 than in the other layers. However, hyaluronic acid showed high expression in deep layers. Here, we clarified that ECM molecules differ in constituent elements and expression in a region- and layer-dependent manner. Region-specific expression of ECM molecules is possibly related to functions such as region-specific plasticity and vulnerability

Effects of Partial Isolation on Mice Behavior

　Background: The effects of an isolated human environment with little societal contact are a topic of interest in clinical psychiatry. Studies using animal models are important for investigating the effects of such an environment. Considering that the modern human environment that allows partial and limited communication even for those who are isolated from the society, raising mice in social isolation, a method that has been conventionally adopted with mice, is not an accurate simulation.　Method: Therefore, in our experiment, to better simulate the partial isolation that is often observed in humans, we devised a method of dividing the breeding cage into two compartments using a transparent sheet, raising four mice in one section and a single mouse in the other (we defined it as physical isolation). We then compared the behavioral patterns of group-reared, conventionally socially isolated, and physically isolated mice to determine the effects of limited communication restrictions on individual mice.　Result: When the new rearing method of physical isolation was adopted, there was no significant difference in the time spent around cages with and without familiar mice, or around cages with strange mice and cages with familiar mice, as observed in group rearing, confirming that social behavior is suppressed in the same way as in social isolation. However, there was no significant increase in immobility time on the forced swim test or tail suspension test, as observed in social isolation, suggesting no increase in anxiety or depression. In the cotton bud biting test, the number of attacks was significantly lower than the other two rearing methods, confirming a decrease in aggression.　Conclusion: Our findings, which show that mice placed in such an environment may experience less stress than when being raised in groups, despite suffering problems with their development of sociability, are of considerable interest

Alpha-pinene and dizocilpine (MK-801) attenuate kindling development and astrocytosis in an experimental mouse model of epilepsy

Understanding the molecular and cellular mechanisms involved during the onset of epilepsy is crucial for elucidating the overall mechanism of epileptogenesis and therapeutic strategies. Previous studies, using a pentylenetetrazole (PTZ)-induced kindling mouse model, showed that astrocyte activation and an increase in perineuronal nets (PNNs) and extracellular matrix (ECM) molecules occurred within the hippocampus. However, the mechanisms of initiation and suppression of these changes, remain unclear. Herein, we analyzed the attenuation of astrocyte activation caused by dizocilpine (MK-801) administration, as well as the anticonvulsant effect of α-pinene on seizures and production of ECM molecules. Our results showed that MK-801 significantly reduced kindling acquisition, while α-pinene treatment prevented an increase in seizures incidences. Both MK-801 and α-pinene administration attenuated astrocyte activation by PTZ and significantly attenuated the increase in ECM molecules. Our results indicate that astrocyte activation and an increase in ECM may contribute to epileptogenesis and suggest that MK-801 and α-pinene may prevent epileptic seizures by suppressing astrocyte activation and ECM molecule production

Anti-stress effects of the hydroalcoholic extract of Rosa gallica officinalis in mice

Rosa gallica, a plant of the Rosa genus, has been used widely since the 13th century and is cultivated in many areas as a medicinal plant for the preparation of herbal medicines. However, details of the neuropsychological effects of R. gallica remain unclear; therefore we aimed to investigate the neuropsychological effects of a water-soluble extract of R. gallica in male C57BL/6N mice under normal conditions and under chronic stress. We administered a water-soluble extract of R. gallica to mice and performed a series of behavioral experiments to compare the treated animals with the untreated controls. No significant differences in activity level, anxiety-like behavior, depression-like behavior, body weight, and body temperature were observed between R. gallica-treated mice and control mice. However, in mice subjected to chronic stress, the observed decrease in activity was smaller in the R. gallica-treated mice than in the control mice. The oral administration of R. gallica did not affect the normal behavior of mice. However, when the mice were subjected to stress, R. gallica exerted an anti-stress effect. Therefore, R. gallica has potential as a medicinal plant for the purpose of stress prevention

Home visits provide a better understanding of the psychopathology of a case of eating disorder

Eating disorders (ED) are characterized by abnormal eating behaviors that negatively affect the patient’s medical or psychiatric health, with symptoms usually developing during adolescence. Treatment for ED varies across patients and the disease time-course, reflecting differences in psychopathology and medical comorbidities. Here, we provide a brief review of the standard management strategy for ED and emphasize the importance of individualized treatment. To illustrate this, we present a case of ED in which a halt in development was observed during a home visit, which is an unusual component in the treatment of ED. Furthermore, as a result of our collective experience in treating ED, we recognize that discussion among multidisciplinary healthcare professionals is important to improve outcomes

Comprehensive behavioral study of the effects of vanillin inhalation in mice

Vanillin is widely used in food and cosmetics, among other substances, for its sweet smell. However, the neuropsychological effects of vanillin inhalation have not been elucidated. In this study, we investigated the effect of vanillin inhalation on mouse behavior. First, we investigated whether the aroma of vanillin was attractive or repulsive for mice. Thereafter, the mice inhaled vanillin for 20 min before each test in a series of behavioral tests (elevated plus maze, open field, Y-maze, tail suspension, cotton bud biting, and Porsolt forced swim tests). In these tests, the mice showed a neutral response to vanillin. Mice that inhaled vanillin had a suppressed pain response in the hot plate test. In addition, the grip strength of the forelimbs of mice that inhaled vanillin was decreased. No significant differences were found between the mice inhaling vanillin and control mice in the open field, Y-maze, tail suspension, forced swimming, and aggression tests. These results show that vanillin inhalation has anti-nociceptive effects, similar to other routes of administration. The results also show that vanillin inhalation does not cause significant behavioral effects

Behavioural effects of inhalation exposure to dizocilpine (MK-801) in mice

The complex pathophysiology of brain disorders and the difficulty of delivering therapeutic agents to the brain remain major obstacles in the research and development of new therapeutic methods for brain disorders. Therefore, delivering existing therapeutic agents to the central nervous system is expected to provide benefits in various diseases. In this study, we investigated whether inhaled central nervous system drugs reached the brain and affected mouse behaviour. Dizocilpine (MK-801), which increases locomotor activity in mice, was mainly used to study this hypothesis. First, we administered MK-801, an N-methyl-d-aspartate receptor antagonist, to mice via inhalation and examined whether it induced excessive activity similar to that observed after intraperitoneal administration. We also examined the time- and dose-dependency of drug induced changes in mouse behaviour after MK-801 inhalation. Next, we investigated whether inhalation of scopolamine, pentobarbital, and imipramine also affected mouse behaviour. Mice that inhaled MK-801 showed MK-801–induced hyperactivity similar to that observed following intraperitoneal administration. Furthermore, the extent of activity changed in a time- and dose-dependent manner after MK-801 inhalation. Inhalation of pentobarbital, scopolamine, and imipramine also changed mouse behaviour. These results demonstrate that inhalation of MK-801 exerts effects similar to those achieved with intraperitoneal and oral administration in mice. Thus, central nervous system agonists can reach the brain efficiently via inhalation. This finding may facilitate the development of improved therapies for brain disorders