清水 栄司

BACKGROUND: One of the most common interpersonal reactions to threat and anxiety is to seek reassurance from a trusted person. The Reassurance Seeking Questionnaire (ReSQ) measures several key aspects of reassurance seeking behaviour, including frequency, trust of sources, intensity, carefulness, and the emotional consequences of reassurance seeking. AIMS: The current study compares patterns and consequences of reassurance seeking in obsessive-compulsive disorder (OCD) and depression. METHOD: ReSQ scores were compared for three groups: 32 individuals with OCD, 17 individuals with depression, and 24 healthy comparison participants. RESULTS: We found that individuals with OCD tended to seek reassurance more intensely and employ self-reassurance more frequently than individuals with depression or healthy participants, and that if reassurance was not provided, they tended to feel a greater urge to seek additional reassurance. CONCLUSIONS: This study is the first to quantitatively elucidate differences in reassurance seeking between OCD and depression.

Stress-related disorders, such as post-traumatic stress disorder (PTSD) and panic disorders, are disproportionately prevalent in females. However, the biological mechanism underlying these sex differences in the prevalence rate remains unclear. In the present study, we examined sex differences in fear memory, fear extinction, and spontaneous recovery of fear. We investigated the presence of sex differences in recent and remote fear memory in mice using contextual fear conditioning, as well as sex differences in spontaneous recovery of fear memory using a consecutive fear extinction paradigm. We examined the number of fear extinction days required to prevent spontaneous recovery of fear in either sex. We investigated whether ovariectomy affected fear extinction and spontaneous recovery. We also measured the activation of extracellular signal-regulated kinase (ERK) 1 and 2 in the dorsal hippocampus and the medial prefrontal cortex following fear extinction sessions. In our results, we found no sex difference in recent or remote fear memory. However, females required more fear extinction sessions compared to males to prevent spontaneous recovery. Within-extinction freezing also differed between males and females. Moreover, females required more extinction sessions than males to increase ERK2 phosphorylation in the dorsal hippocampus. Our data suggest that contextual fear extinction was unstable in females compared to males and that such sex differences may be related to the ERK2 phosphorylation in the hippocampus. (C) 2015 Elsevier Inc. All rights reserved.

This study investigated the differences in early maladaptive schemas between adult outpatients with high-functioning autism spectrum disorder (n = 48) and a non-clinical controls (n = 86). Both groups completed the Young Schema Questionnaire. There were significant differences between the groups in all the early maladaptive schemas, except self-sacrifice and approval/recognition seeking. Logistic regression analysis revealed that early maladaptive schemas such as insufficient self-control, emotional deprivation, and vulnerability to harm and illness significantly discriminated between the groups, suggesting that some early maladaptive schemas are more important than others for depicting the characteristics of adults with autism spectrum disorder.

Transcranial direct current stimulation (tDCS) has been reported to modify cortical function by inducing alterations in the underlying brain function. P50auditory evoked potentials, as assessed using a paired auditory stimulus (S1 and S2) paradigm, are thought to reflect a sensory gating process in which the functional involvement of the dorsolateral prefrontal cortex (DLPFC) is suggested. P50 sensory gating has also been reported to be associated with the pathogenesis of psychiatric diseases such as schizophrenia and anxiety-related disorders. Here we investigated whether the tDCS over the DLPFC could modulate the cortical function leading to alteration of the P50 sensory gating. P50 gating indices (the S2/S1 ratio and Sl-S2 difference) were measured during the tDCS (current 1.0 mA, duration 15 min) over the DLPFC with different conditions (anodal, cathodal and sham). Ten male healthy volunteers were studied on separate days in a single blinded paradigm. We observed that the cathodaltDCS significantly altered the mean P50 gating indices compared to the other two conditions. Our results suggest that sensory gating could be modulated by cathodaltDCS on the left DLPFC but not by anodal/sham tDCS. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Several studies have shown that an isolated retrieval trial before the extinction session (retrieval-extinction) prevents the return of fear memory by inhibition of reconsolidation. Other studies have reported that retrieval-extinction did not prevent the return of the fear. To date, it is still unclear whether retrieval-extinction prevents the return of the original fear memory. A previous study revealed that reconsolidation of conditioned fear memory was not induced by the brevity of the retrieval session. Thus, we examined whether the number of retrievals in the retrieval-extinction paradigm was involved in the prevention of return of fear (Experiment 1). Furthermore, studies with different-age experimental subjects have shown conflicting results. We investigated the potential impact of age on the inhibitory effect of retrieval-extinction on the return of fear (Experiment 2). Our major findings were as follows: (1) Retrieval-extinction procedure did not prevent the return of fear, regardless of the intensity (number of presentations) of the stimulus inducing retrieval of fear memory. (2) The mice in both juvenile and adult age groups (4 and 8 weeks old) retrieved fear memory after retrieval-extinction. These results suggest the possibility that extinction after retrieval does not inhibit reconsolidation of previously consolidated fear memory. (C) 2015 Elsevier B.V. All rights reserved.

Objectives: We aimed to identify the factors that patients with major depressive disorder consider important for successful return to work (RTW) after absence due to their illness. Methods: A questionnaire was distributed to 72 patients who had returned to work after taking sick leave due to depression. Participants were asked to rate the importance of 29 statements related to RTW, indicate whether 11 factors had been implemented in their workplaces to facilitate RTW, and select the factors that they considered to be the primary causes of sickness absence. Results: Data from 40 respondents were analyzed. "Gradual increase in work hours and amount of work" was identified as the most important factor for successful RTW, whereas "significant improvement in depressive symptoms" was only the ninth most important factor. The workplace factor that was implemented most frequently was "gradual increase in work hours and amount of work." Finally, most respondents considered "weak character" to be the primary cause of sickness absence.

国内の看護領域における認知行動療法(CBT)の実践・研究の動向を概括するために、文献レビューを行った。和文献の検索に、医中誌WebおよびCiNiiを用い、検索条件は表題か抄録に「看護」かつ「行動療法」「認知療法」「認知行動療法」のいずれかを含む雑誌論文とした。英文献の検索にはMEDLINE、CINAHL、PsychoINFOを用い、検索条件は表題か本文に「nurs*」を含み、かつ「behavio* therapy」or「cognitive therapy」or「cognitive behavio* therapy」と「Japan」を含むものとした。整理した結果、合計72文献が分析対象となり、そのうち事例研究が54件、効果研究が18件であった。レビューの結果、認知行動療法は、精神疾患を中心にさまざまな看護領域で活用され、その多くが入院環境下で実施されていることが明らかになった。効果研究では、看護職による認知行動療法が効果的との報告が多く見られた。実施中のスーパービジョンなど質の担保方法についての報告が少なかった。

Cognitive restructuring is a fundamental method within cognitive behavioural therapy of changing dysfunctional beliefs into flexible beliefs and learning to react appropriately to the reality of an anxiety-causing situation. To clarify the neural mechanisms of cognitive restructuring, we designed a unique task that replicated psychotherapy during a brain scan. The brain activities of healthy male participants were analysed using functional magnetic resonance imaging. During the brain scan, participants underwent Socratic questioning aimed at cognitive restructuring regarding the necessity of handwashing after using the restroom. The behavioural result indicated that the Socratic questioning effectively decreased the participants' degree of belief (DOB) that they must wash their hands. Alterations in the DOB showed a positive correlation with activity in the left posterior parietal cortex (PPC) while the subject thought about and rated own belief. The involvement of the left PPC not only in planning and decision-making but also in conceptualization may play a pivotal role in cognitive restructuring.

DNA methylation is one of the essential factors in the control of gene expression. Alteration of the DNA methylation pattern has been linked to various neurological, behavioral and neurocognitive dysfunctions. Recent studies have pointed out the importance of epigenetics in brain development and functions including learning and memory. Nutrients related to one-carbon metabolism are known to play important roles in the maintenance of genomic DNA methylation. Previous studies have shown that the long-term administration of a diet lacking essential one-carbon nutrients such as methionine, choline and folic acid (methyl donors) caused global DNA hypermethylation in the brain. Therefore, the long-term feeding of a methyl-donor-deficient diet may cause abnormal brain development including learning and memory. To confirm this hypothesis, 3-week-old mice were maintained on a folate-, methionine- and choline-deficient (FMCD) or control (CON) diet for 3 weeks. We found that the methyl-donor deficiency impaired both novel object recognition and fear extinction after 3 weeks of treatment. The FMCD group showed spontaneous recovery of fear that differed from that in CON. In addition, we found decreased Gria1 gene expression and specific CpG hypermethylation of the Gria1 promoter region in the FMCD hippocampus. Our data suggest that a chronic dietary lack of methyl donors in the developmental period affects learning, memory and gene expressions in the hippocampus.

BACKGROUND: Mental contamination is a psychological sense of contamination that involves an internal, emotional feeling of dirtiness that may be evoked by unwanted thoughts and images, such as sexual assaults. AIMS: This study aimed to investigate which types of unwanted sexual experiences evoke the strongest mental contamination, and to test the hypothesis that cognitive appraisals of an unwanted sexual experience predict indices of mental contamination (i.e. feeling of dirtiness, urge to wash, internal negative emotions, and external negative emotions). METHOD: 148 female participants were asked to recall their most distressing unwanted sexual experiences. Indices of mental contamination and cognitive appraisals of the experience were then assessed. RESULTS: Our findings indicated that individuals recalling experiences related to rape felt more intense feelings of dirtiness than individuals recalling other types of unwanted sexual experience, such as verbal sexual assault, visual sexual assault, and forcible touching/frottage. In addition, hierarchical regression analyses demonstrated that a cognitive appraisal of perceived violation predicted all of the indices of mental contamination after controlling anxiety, depression, and fear of contact contamination. CONCLUSIONS: The present study demonstrated that an individual is at greatest risk of mental contamination if she has experienced rape/attempted rape, and if she makes a cognitive appraisal of violation regarding the incident.

BACKGROUND: Decision-making is reported to be impaired in anorexia nervosa (AN) and bulimia nervosa (BN), but the influence of mood status, pathophysiological eating, and weight concerns on the performance of decision-making ability between AN and BN is still unclear. The aims of this study were to investigate differential impairments in the decision-making process between AN, BN, and healthy controls (HC), and secondly, to explore the role of mood status, such as anxiety, depression, pathological eating, and weight concerns, in decision-making ability. METHODS: Patients suffering from AN (n = 22), BN (n = 36) and age-matched HC (n = 51) were assessed for their decision-making abilities using the Iowa Gambling Task (IGT). Self-reported questionnaires including the Eating Disorder Examination Questionnaire (EDE-Q), the Bulimia Investigatory Test, Edinburgh (BITE), the Eating Disorders Inventory, the Maudsley Obsessive-Compulsive Inventory measuring obsessive-compulsive traits, the Hospital Anxiety and Depression Scale, and the Toronto Alexithymia Scale were used to assess pathological eating concerns and attitude to feelings. RESULTS: Significant differences in IGT performance were observed between BN and HC. Significant negative correlation was found between IGT performance and the BITE symptom subscale in AN. In BN, there was a negative correlation between the EDE-Q weight concerns subscale and IGT performance. It was also found that increased anxiety, depression, and eating/weight concerns predicted poorer decision-making. CONCLUSION: Different patterns of association between pathological eating concerns/behaviors and performances in decision-making ability were found between AN, BN, and HC. Anxiety, depressive mood status, and eating/weight concerns were related to decision-making ability.

Objectives: Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric disorders, with some speculating that a reason for difficulty in its treatment might be its coexistence with autism spectrum. We investigated the tendency for autistic spectrum disorders (ASD) in patients with OCD from a neuroimaging point of view using voxel-based morphometry. Methods: We acquired T-1-weighted images from 20 patients with OCD and 30 healthy controls and investigated the difference in regional volume between the groups as well as the correlation between Autism-Spectrum Quotient (AQ) scores and regional cerebral volumes of patients with OCD. Results: Volumes in the bilateral middle frontal gyri were significantly decreased in patients with OCD compared to controls. Correlational analysis showed significant positive correlations between AQ scores and regional gray matter (GM) volumes in the left dorsolateral prefrontal cortex (DLPFC) and left amygdala. Furthermore, GM volumes of these regions were positively correlated with each other. Conclusions: The positive correlation of ASD traits in patients with OCD with regional GM volumes in the left DLPFC and amygdala could reflect the heterogeneity of patient symptoms. Our results suggest that differences in GM volume might allow classification of patients with OCD for appropriate therapy based on their particular traits.

Mirror movement (MM), or visible involuntary movements of a relaxed hand during voluntary fine finger movements of an activated opposite hand, can be observed in the hand that is on the unaffected side of patients with stroke. In the present study, we longitudinally examined the relationship between voluntary movement of the affected hand and MM in the unaffected hand in a single case. We report a 73-year-old woman with a right pontine infarct and left moderate hemiparesis. MM was observed as an extension movement of the unaffected right index finger during extension movement of the affected left index finger. The affected right index movement was found to increase, while MM of the unaffected left index finger was observed to decrease with time. These results indicate that the assessment of MM might be useful for studying the process of motor recovery in patients with stroke.

Fear extinction is a major task in our understanding of the biological mechanisms of exposure therapy, one of the most used treatments for stress-related disorders. It was recently reported that an extinction of 5 consecutive days prevents spontaneous recovery of fear memory. Memory age and the timing of fear extinction influence the effect of fear extinction. In this study, we used contextual fear extinction in adult male mice to examine whether memory age influences an extinction of 5 consecutive days and whether consecutiveness is necessary to prevent spontaneous recovery. Our results showed that, although fear memory was not affected by the passage of time, the old fear memory (28 days after fear conditioning) was more sensitive to fear extinction than the young fear memory (7 days after fear conditioning). Additionally, we demonstrated that consecutiveness of extinction sessions is not necessary to prevent spontaneous recovery. Instead, fear extinction sessions at spaced intervals were found to be more effective than consecutive extinction sessions for young fear memory. Our results suggest that taking memory age and the interval of fear extinction sessions into consideration would help to optimize exposure therapy. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

DNA methylation is one of the essential factors in the control of gene expression. Folic acid, methionine and choline (methyl donors)-all nutrients related to one-carbon metabolism-are known as important mediators of DNA methylation. A previous study has shown that long-term administration of a diet lacking in methyl donors caused global DNA hypermethylation in the brain (Pogribny et al., 2008). However, no study has investigated the effects of a diet lacking in methyl donors during the developmental period on emotional behaviors such as fear and anxiety-like behavior in association with gene expressions in the brain. In addition, it has not been elucidated whether a diet supplemented with methyl donors later in life can reverse these changes. Therefore, we examined the effects of methyl donor deficiency during the developmental period on fear memory acquisition/extinction and anxiety-like behavior, and the relevant gene expressions in the hippocampus in juvenile (6-wk) and adult (12-wk) mice. We found that juvenile mice fed a methyl-donor-deficient diet had impaired fear memory acquisition along with decreases in the gene expressions of Dnmt3a and Dnmt3b. In addition, reduced anxiety-like behavior with decreased gene expressions of Grin2b and Gabar2 was observed in both the methyl-donor-deficient group and the body-weight-matched food-restriction group. After being fed a diet supplemented with methyl donors ad libitum, adult mice reversed the alteration of gene expression of Dnmt3a, Dnmt3b, Grin2b and Gabar2, but anxiety-like behavior became elevated. In addition, impaired fear-memory formation was observed in the adult mice fed the methyl-donor-deficient diet during the developmental period. Our study suggested that developmental alterations in the one-carbon metabolic pathway in the brain could have effects on emotional behavior and memory formation that last into adulthood.

Several lines of evidence suggest that glial cell-line derived neurotrophic factor (GDNF) plays an important role in the pathophysiology of neuropsychiatric and neurodegenerative disorders. In this study, we investigated the association between GDNF serum levels and the clinical status of medicated patients with schizophrenia. Sixty-three medicated patients with schizophrenia and 52 age- and sex-matched healthy controls were recruited. Patients were evaluated using the brief psychiatry rating scale, the scale for the assessment of negative symptoms (SANS) and neuropsychological tests. Serum levels of GDNF were determined using an ELISA method. Serum levels of GDNF did not differ between schizophrenia patients and controls. Higher GDNF serum levels were associated with better performances on the Digit Span in healthy controls but not in schizophrenics. At the same time, higher GDNF serum levels were associated with severe attention deficits on the SANS subscale, in schizophrenics. Our preliminary study suggests that serum levels of GDNF may be an unsuitable biomarker for schizophrenia, although it may be associated with working memory in healthy controls and the pathophysiology of attention deficits in schizophrenia. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

右視床出血後に左片麻痺を呈した症例において、非麻痺側上肢運動の鏡像観察により、麻痺側上肢の鏡像運動が誘発された症例を経験した。症例は、80歳代男性で左上肢に軽度運動麻痺と重度感覚障害を認めた。運動課題は、鏡を症例の垂直に置いた状態で、症例に鏡を観察しながら右手指でペグを把持し前方の検者へ手渡す複合運動であった。課題中、症例に対し左上肢を安静に保つよう指示していたが、右上肢運動と同期するように不随意な運動が認められた。このことから、本課題で認められた不随意運動は、鏡像観察に伴う中枢神経系の賦活によって誘発された鏡像運動と考えられた。(著者抄録)