Faculty Bibliography

Formation of aversive memories sometimes involves a pathogenic cognitive process that could lead to the development of posttraumatic stress disorder (PTSD). Here, we explore chronobiological aspects of shifts in aversive memory encoding abilities around habitual sleep onset periods (SOPs). Thirty university students, who were randomly assigned to one of two groups, watched a suspenseful movie for 2 h, beginning either 3h prior to their habitual sleep onset periods (pre-SOP group) or 1h after their habitual sleep onset periods (post-SOP group). Recognition accuracy was tested 15 min after the movie finished and again 10h after the movie finished, after a sleep period. Overall recognition accuracy was higher in the post-SOP women than in the pre-SOP women, while that in the pre-SOP men was higher than that in the post-SOP men. The recognition accuracy gap (aversive-neutral) was significantly greater in the post-SOP women than in the pre-SOP women throughout both recognition sessions, while there was a non-significant group difference for men. These findings suggest that habitual SOP is a watershed in women's ability to learn to identify aversive events. Women more correctly encode aversive episodes post-SOP than pre-SOP, which could contribute to high PTSD prevalence in women.

Although D-cycloserine (DCS), a partial agonist of the N-methyl-d-aspartate (NMDA) receptor, and valproic acid (VPA), a histone deacetylase inhibitor, have been investigated for their roles in the facilitation of emotional learning, the effects on non-emotional declarative and procedural learning have not been clarified. We performed a randomized, blind, placebo-controlled, 4-arm clinical trial to determine the effects of DCS and VPA on the overnight properties of declarative and procedural learning in 60 healthy adults. Subjects were orally administrated a placebo, 100 mg DCS, 400 mg VPA, or a combination of 100 mg DCS and 400 mg VPA before they performed declarative and procedural learning tasks. Subjects then had their performance retested the following day. We observed that DCS facilitated procedural but not declarative learning and that VPA did not contribute to learning. Surprisingly, however, VPA attenuated the enhancement effect of DCS when coadministered with it. These results suggest that DCS acts as an enhancer of hippocampus-independent learning and that VPA may have an extinguishing pharmacological effect on excitatory post-synaptic action potentials that NMDA receptors regulate within procedural learning.

Working memory (WM) capacity improvement is impacted by sleep, and possibly by N-methyl-D-aspartate (NMDA) agonists such as D-cycloserine (DCS), which also affects procedural skill performance. However, the mechanisms behind these relationships are not well understood. In order to investigate the neural basis underlying relationships between WM skill learning and sleep, DCS, and both sleep and DCS together, we evaluated training-retest performances in the n-back task among healthy subjects who were given either a placebo or DCS before the task training, and then followed task training sessions either with wakefulness or sleep. DCS facilitated WM capacity enhancement only occurring after a period of wakefulness, rather than sleep, indicating that WM capacity enhancement is affected by a cellular heterogeneity in synaptic plasticity between time spent awake and time spent asleep. These findings may contribute to development, anti-aging processes, and rehabilitation of higher cognition.

BACKGROUND: Japan is located in an area prone to natural disasters, and major earthquakes have occurred recently in rural areas where the proportion of elderly adults is high. Although elderly persons are vulnerable members of communities at a time of disaster, the prevalence of mental disorders among this population has yet to be reported in Japan. This study aimed to determine the prevalence of mental disorders and suicidal thoughts among community-dwelling elderly persons 3 years after an earthquake and to identify risk factors associated with their quality of life (QOL). METHODS: Face-to-face interviews were conducted with 496 community-dwelling persons aged 65 years or older in areas of Japan where 2 major earthquakes had occurred during a 3-year period. The main outcome was diagnosis of a mental disorder or suicidality. RESULTS: During the 3-year period after the earthquake, 1.6% of men and 5.5% of women had received a diagnosis of major depression. There were no cases of posttraumatic stress disorder. Women were more likely than men to report suicidality (7.8% vs 3.8%, P = 0.075). CONCLUSIONS: The prevalence of mental disorders was lower than that reported in previous studies. Despite the low prevalence of mental disorders, the percentage of community-dwelling elderly persons with subclinical mental health symptoms was high. The results indicate that appropriate public health and medical interventions are warranted after a natural disaster.

BACKGROUND: Neuroendocrine hormones, which regulate both homeostasis and stress responses, provide homeostatic recovery and sleep suppression to brains under stress. We examined the effects of total sleep deprivation on subsequent enhancement of aversive event memory, implicit fear recognition, and fear conditioning in healthy humans. METHODS: Three different recognitions (explicit event, implicit emotion, and physiological response) were assessed in two groups of 14 healthy young volunteers (sleep control and sleep deprived) with aversive (motor vehicle accident films) and nonaversive episodic memory stimuli. Both groups were tested on Day 1 of the experiment and again on Days 3 and 10; the sleep-deprived group was totally deprived of initial nocturnal sleep after the first trial on Day 1. RESULTS: Event recognition performances were similar in both groups throughout the study. Implicit fear recognition remained high for aversive stimuli, with generalization of implicit fear recognition occurring for nonaversive stimuli on Day 3 in the sleep control group. Physiological fear and generalized fear responses were observed for every episode, and delayed enhancement of physiological response was only observed for misidentified aversive episodes in the sleep control group on Day 3. However, in the sleep-deprived group, generalization of implicit fear recognition for nonaversive stimuli on Day 3 and all physiological and generalized fear responses on Days 3 and 10 were comprehensively extinguished. CONCLUSIONS: Clinically, trauma-exposed victims often experience acute insomnia, indicating that such insomnia might provide prophylactic benefits in reducing the development of posttraumatic stress disorder via extinction of the fear-magnifying effects of memory.

BACKGROUND: Few epidemiological studies have examined complicated grief in the general population, especially in Asian countries. Therefore, this study aimed to explore the prevalence and predictors of complicated grief among community dwelling individuals in Japan. METHODS: A questionnaire survey regarding grief and related issues was conducted on community dwelling individuals aged 40-79 who were randomly sampled from census tracts. Complicated grief was assessed using the Brief Grief Questionnaire. Stepwise logistic regression analysis was conducted in order to identify predictors of complicated grief. RESULTS: Data from 969 responses (response rate, 39.9%) were subjected to analysis. The analysis revealed 22 (2.4%) respondents with complicated grief and 272 (22.7%) with subthreshold complicated grief. Respondents who were found to be at a higher risk for developing complicated grief had lost their spouse, lost a loved one unexpectedly, lost a loved one due to stroke or cardiac disease, lost a loved one at a hospice, care facility or at home, or spent time with the deceased everyday in the last week of life. LIMITATIONS: Limitations of this study include the small sample size, the use of self-administered questionnaire, and the fact that the diagnoses of complicated grief were not based on robust diagnostic criteria. CONCLUSIONS: The point prevalence of complicated grief within 10years of bereavement was 2.4%. Complicated grief was maintained without significant decrease up to 10years after bereavement. When subthreshold complicated grief is included, the prevalence of complicated grief boosts up to a quarter of the sample, therefore, routine screening for complicated grief among the bereaved is desired. Clinicians should pay particular attention to the bereaved families with abovementioned risk factors in order to identify people at risk for future development of complicated grief.

It has been speculated that humans have an inherent ability to overcome sleepiness that counteracts homeostatic sleep pressure. However, it remains unclear which cortical substrate activities are involved in the ability to overcome sleepiness during the execution of cognitive tasks. Here we sought to confirm that this ability to overcome sleepiness in task execution improves performance on cognitive tasks, showing activation of neural substrates in the frontal cortex, by using a modified n-back (2- and 0-back) working memory task and functional near-infrared spectroscopy. The change in alertness was just correlated with performances on the 2-back task. Activity in the right prefrontal cortex changed depending on alertness changes on the 2- and 0-back tasks independently, which indicates that activity in this region clearly reflects the ability to overcome sleepiness; it may contribute to the function of providing sufficient activity to meet the task load demands. This study reveals characteristics of the ability to overcome sleepiness during the n-back working memory task which goes beyond the attention-control function traditionally proposed.

BACKGROUND: Although some previous studies have suggested that posttraumatic growth (PTG) is comprised of several factors with different properties, few have examined both the association between PTG and posttraumatic stress disorder (PTSD) and between PTG and resilience, focusing on each of the factors of PTG. This study aimed to examine the hypothesis that some factors of PTG, such as personal strength, relate to resilience, whereas other factors, such as appreciation of life, relate to PTSD symptoms among Japanese motor vehicle accident (MVA) survivors. METHODS: This cross-sectional study was performed with 118 MVA survivors at 18 months post MVA. Data analyzed included self-reporting questionnaire scores on the Posttraumatic Growth Inventory (PTGI), the Impact of Event Scale- Revised (IES-R), and the Sense of Coherence (SOC) scale, which is one of the most widely used scales for measuring resilience. Correlations between scores on the PTGI and IES-R, the PTGI and SOC scale, and the IES-R and SOC scale were established by calculating Spearman's correlation coefficients. RESULTS: PTGI was positively correlated with both SOC and PTSD symptoms, in spite of an inverse relationship between SOC and PTSD symptoms. Relating to others, new possibilities, and personal strength on the PTGI were correlated positively with SOC, and spiritual change and appreciation of life on the PTGI were positively correlated with PTSD symptoms. CONCLUSIONS: Some factors of PTG were positively correlated with resilience, which can be regarded as an outcome of coping success, whereas other factors of PTG were positively correlated with PTSD symptoms, which can be regarded as signifying coping effort in the face of enduring distress. These findings contribute to our understanding of the psychological change experienced by MVA survivors, and to raising clinicians' awareness of the possibility that PTG represents both coping effort coexisting with distress and outcome of coping success.

AIM: The aim of this study was to examine the utility of the Peritraumatic Distress Inventory (PDI) as a predictor of subsequent post-traumatic stress disorder (PTSD) in severe motor vehicle accident survivors. METHODS: Patients consecutively admitted to the intensive care unit were assessed immediately and 1 month after accidents in this prospective study. The predictive value for post-traumatic stress symptoms at 1 month of the PDI at initial assessment was examined by using multivariate regression analysis. Moreover, the accuracy of the PDI as a predictor of PTSD was determined using receiver operator characteristic curve analysis. Post-traumatic stress symptoms were assessed using the Impact of Event Scale - Revised questionnaire, and PTSD was assessed using the Clinician-Administered PTSD Scale. RESULTS: Seventy-nine patients completed the Impact of Event Scale - Revised questionnaire, and 64 patients participated in a structured interview. Of 64 patients, 13 met the diagnostic criteria of full or partial PTSD. The PDI was an independent predictor of post-traumatic stress symptoms (P = 0.003). The data indicated that a cut-off score of 23 maximized the balance between sensitivity (77%) and specificity (82%) in this study. Compared with negative predictive value (93%), positive predictive value was not high (53%). CONCLUSION: The study suggests the predictive usefulness of the PDI for subsequent PTSD in accident survivors. Its adequate usage should be further elaborated.

The interaction between amygdala-driven and hippocampus-driven activities is expected to explain why emotion enhances episodic memory recognition. However, overwhelming behavioral evidence regarding the emotion-induced enhancement of immediate and delayed episodic memory recognition has not been obtained in humans. We found that the recognition performance for event memory differs from that for emotional memory. Although event recognition deteriorated equally for episodes that were or were not emotionally salient, emotional recognition remained high for only stimuli related to emotional episodes. Recognition performance pertaining to delayed emotional memory is an accurate predictor of the context of past episodes.