Premorbid intellectual ability in schizophrenia influence family appraisal related to cognitive impairments: a cross-sectional study on cognitive impairment and family assessments.

BACKGROUND: Patients with schizophrenia are unaware of their cognitive impairments. Misperception of cognitive impairment is an important factor associated with real-world functional outcomes in patients with schizophrenia. The patient's family member plays a crucial role in detecting patients' cognitive impairments when the patients are unaware of their own cognitive impairments. Previous studies have reported that not only the patient's subjective rating, but also the patient's family members' rating of their cognitive impairment may not be precise. However, it is unclear why family ratings are inaccurate, and which factors impact family ratings. This study investigated whether family ratings differed significantly from the patients' subjective ratings of the patients' cognitive impairments and sought to determine the reason for the differences between the family ratings and the patients' neurocognitive performances. We investigated the relationship between patients' subjective ratings, family ratings for patients' cognitive impairments, neuropsychological performance, and other aspects, including premorbid IQ and clinical symptoms. METHOD: We evaluated 44 patients with schizophrenia for cognitive function using neuropsychological tests; in addition, both the patients and their families rated the patients' cognitive impairments through questionnaires. We used the Mann-Whitney U test to examine whether the family ratings differed significantly from the patients' self-reported ratings of their cognitive impairment. We conducted multiple regression analysis and structural equation modeling to determine why the patients' subjective ratings and the family ratings were not definitively associated with the patients' neurocognitive performances. We performed multiple regression analysis with a stepwise method with neurocognitive performance, premorbid IQ, positive symptoms, and negative symptoms as independent variables and family ratings of patients' cognitive impairments as dependent variables. RESULTS: We found that the family ratings differed significantly from the patients' subjective self-reported ratings of their cognitive impairments. Our results showed that the premorbid IQ of patients is the strongest predictor of family ratings. Furthermore, among the neurocognitive domains, only the processing speed of patients was associated with family ratings. CONCLUSIONS: We found that the family ratings were not consistent with the patients' subjective self-reported ratings and the family ratings were most affected by the patients' premorbid intellectual abilities. These results suggest that the families' current assessments of the patients' current cognitive impairments were affected by the patients' premorbid intellectual ability rather than the patients' current neurocognitive performance. Patients' processing speed predicted family ratings; however, family members' ratings were not related to verbal learning/memory, executive function, and language of patients. Therefore, our findings highlight that patients' family ratings may differ from patients' subjective ratings, results of performance-based neuropsychological tests, and clinician ratings.

The effects of cognitive remediation therapy using the frontal/executive program for autism spectrum disorder.

OBJECTIVE: The cognitive features and treatment of autism spectrum disorder have been the subject of much debate in recent years. Therapeutic approaches to date have focused on skills acquisition, support tailored to the characteristics of autism spectrum disorder, and interventions in social cognitive functioning; there have been few reports describing interventions aimed at neurocognitive dysfunction. In this study, we focus on impairment of executive functioning in autism spectrum disorder patients and investigate improvements in executive functioning and their generalization to social functioning. METHOD: The intervention adopted for this study was cognitive remediation therapy using the frontal/executive program. To investigate the effectiveness of frontal/executive program, 15 subjects who consented to participate in the study were randomly assigned to an intervention group or control group. Frontal/executive program was administered to the intervention group for about six months. Both groups were evaluated using the same scales: BACS-J, WCST, and CPT for cognitive assessment; SCoRS-J, GAF, and LASMI for social functioning; and GSE for self-efficacy. RESULTS: Both groups had lower scores for cognitive functioning than normal individuals at baseline. After completion of frontal/executive program, the intervention group showed improved performance on BACS-J for overall score, digit sequencing, verbal fluency, and Tower of London tasks. Improvements were also seen on SCoRS-J and LASMI scales of social functioning. CONCLUSIONS: This was the first study to use frontal/executive program to focus on neurocognitive dysfunction in autism spectrum disorder patients. Frontal/executive program is effective in improving impaired executive functioning in autism spectrum disorder patients and may also lead to improvements in some aspects of social functioning.

Normal development of human brain white matter from infancy to early adulthood: a diffusion tensor imaging study.

Diffusion tensor imaging (DTI), which measures the magnitude of anisotropy of water diffusion in white matter, has recently been used to visualize and quantify parameters of neural tracts connecting brain regions. In order to investigate the developmental changes and sex and hemispheric differences of neural fibers in normal white matter, we used DTI to examine 52 healthy humans ranging in age from 2 months to 25 years. We extracted the following tracts of interest (TOIs) using the region of interest method: the corpus callosum (CC), cingulum hippocampus (CGH), inferior longitudinal fasciculus (ILF), and superior longitudinal fasciculus (SLF). We measured fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD). Approximate values and changes in growth rates of all DTI parameters at each age were calculated and analyzed using LOESS (locally weighted scatterplot smoothing). We found that for all TOIs, FA increased with age, whereas ADC, AD and RD values decreased with age. The turning point of growth rates was at approximately 6 years. FA in the CC was greater than that in the SLF, ILF and CGH. Moreover, FA, ADC and AD of the splenium of the CC (sCC) were greater than in the genu of the CC (gCC), whereas the RD of the sCC was lower than the RD of the gCC. The FA of right-hemisphere TOIs was significantly greater than that of left-hemisphere TOIs. In infants, growth rates of both FA and RD were larger than those of AD. Our data show that developmental patterns differ by TOIs and myelination along with the development of white matter, which can be mainly expressed as an increase in FA together with a decrease in RD. These findings clarify the long-term normal developmental characteristics of white matter microstructure from infancy to early adulthood.

Application of the Japanese Verbal Learning Test to Patients With Alzheimer's Disease in the Early Stage.

INTRODUCTION: This study aimed to investigate the mechanism of memory function in the context of explicit memory in early-stage Alzheimer's disease (AD) using the short-form Japanese Verbal Learning Test (JVLT-9). METHODS: Participants were 20 patients with early-stage AD and a control group of 23 healthy older adults (normal controls: NC), each of whom was administered the JVLT-9, which is a verbal list learning task used to assess explicit memory comprehensively. Between-group differences for each score were investigated using the Mann-Whitney U test. A two-way analysis of variance (ANOVA) was performed for the number of correct recalls by group (AD/NC) × JVLT-9 task. In addition, the AD group was divided into a CDR 0.5 group and a CDR 1.0 group, and it was performed as a group (CDR 0.5/1.0) × JVLT-9 task two-way ANOVA. RESULTS: The results demonstrated that the AD group had lower immediate recall, learning rate, semantic clustering, and recognition discrimination and significantly higher intrusion errors compared to the NC group. Further, JVLT-9 recall and recognition rates were found to be lower with higher CDR (an index of dementia severity). CONCLUSION: These results are largely consistent with the features of explicit memory in AD reported in the English version, confirming the clinical utility of the JVLT-9 as a test of explicit memory function.

The relationship between script memory for everyday events and schizotypy: an investigation through a development of Japanese Situational Feature Recognition Test.

Background: Script memory is stored information about a sequential structure of an activity (e.g., going shopping), including what actors do, the purpose of the activity, and the likely consequences of the actor's actions. It has been reported that script memory is impaired among schizophrenia patients. The present research investigated the relationship between schizotypal personality tendencies (schizotypy) and script memory by testing Japanese individuals. Method: First, a new test to measure the intactness of the script memory was created by asking the public to report activities they often perform and what behaviors each activity contains. The test contains 15 everyday activities, each accompanied by 15 behavior choices, either strongly associated, completely unrelated, or weakly associated with the activity. Next, undergraduate participants were presented with the test and chose appropriate behaviors for each activity (Study 1 and 2). Their extent of schizotypy was measured using Schizotypal Personality Questionnaire Brief (SPQ-B). Study 3 targeted the public of various ages. In addition to Study 2 procedure, participants reported the extent of psychological burden for performing each activity, their life satisfaction, and subjective evaluation of their memory ability. Results: All studies consistently found that the script memory performance was worse for individuals with higher schizotypy. Signal detection indices for accurate discrimination between correct and incorrect choices, which were A' in Study 1 and C in Study 2 and 3, negatively correlated with the SPQ-B scores (r = -0.16, -0.11, -0.17, respectively). Study 3 found that the relationship between schizotypy and memory task performance was mediated by the extent of psychological burden. When a signal detection index (d') for the memory task was regressed on the SPQ-B, while the psychological burden scores being a mediator, the mediation effect was significant (B = 0.003, SE = 0.001, 95% CI [0.001, 0.005]). Conclusion: Individuals with higher schizotypy seem to associate unrelated behaviors to an event, forming script memory with irrelevant information, maybe due to the schizotypy symptom of having peculiar thoughts. The newly created test must be validated using a clinical population to expand its potential to be used in clinical research.

Is there a spinal tap responder in progressive supranuclear palsy? The first prospective study.

OBJECTIVE: Progressive supranuclear palsy (PSP) is a progressive neurodegenerative disease, and sometimes shows idiopathic normal pressure hydrocephalus (iNPH)-like presentations. We aimed to evaluate spinal tap responsiveness in patients with PSP, including the effect of sham spinal tap. METHODS: Eleven patients with PSP, ten with probable/definite iNPH, and eight control patients were prospectively enrolled. All participants underwent sham spinal tap and spinal tap procedures. Gait was evaluated using wearable inertial sensors. We defined "tap responders" as individuals with a 10% or more improvement from baseline in any of the gait parameters (timed up-and-go test total time, stride length, and velocity during straight walking under single-task and cognitive dual-task conditions). We compared the ratio of responders in patients with PSP to patients with iNPH and controls. RESULTS: The ratio of tap responders and the ratio of sham tap responders in patients with PSP were significantly higher than those in control patients, and not different from those in patients with iNPH. PSP patients with iNPH-like MRI features tended to respond to the spinal tap compared to those without such imaging features. Notably, one patient with PSP, who responded to the spinal tap beyond the effect of sham spinal tap, was treated by the shunt operation. CONCLUSION: This is the first prospective study to demonstrate tap and shunt responsiveness in patients with PSP while highlighting the placebo effects of the spinal tap in patients with PSP or iNPH. Our findings suggest that some PSP patients have impaired cerebrospinal fluid circulation, contributing to a distinct component of the clinical spectrum.

Decreased short-latency afferent inhibition in individuals with mild cognitive impairment: A TMS-EEG study.

TMS combined with EEG (TMS-EEG) is a tool to characterize the neurophysiological dynamics of the cortex. Among the TMS paradigms, short-latency afferent inhibition (SAI) allows the investigation of inhibitory effects mediated by the cholinergic system. The aim of this study was to compare cholinergic function in the DLPFC between individuals with mild cognitive impairment (MCI) and healthy controls (HC) using TMS-EEG with the SAI paradigm. In this study, 30 MCI and 30 HC subjects were included. The SAI paradigm consisted of 80 single pulse TMS and 80 SAI stimulations applied to the left DLPFC. N100 components, global mean field power (GMFP) and total power were calculated. As a result, individuals with MCI showed reduced inhibitory effects on N100 components and GMFP at approximately 100 ms post-stimulation and on ß-band activity at 200 ms post-stimulation compared to HC. Individuals with MCI showed reduced SAI, suggesting impaired cholinergic function in the DLPFC compared to the HC group. We conclude that these findings underscore the clinical applicability of the TMS-EEG method as a powerful tool for assessing cholinergic function in individuals with MCI.

Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain.

Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement.

The Relationship between Daily Behavior Changes and Vaccine Attitudes at the Early Stage of the COVID-19 Pandemic among Japanese People from Different Demographics: A Retrospective and Exploratory Examination Using a Free-Response Survey.

This study investigated how daily behaviors of Japanese people changed during the early stages of the COVID-19 pandemic and whether the change was mediated by demographics. It also examined whether the magnitude of behavior change in a demographic group is related to their attitudes towards the COVID-19 vaccine. 301 Japanese responded to an online survey in February 2021, in which they first wrote some activities they frequently performed before the virus outbreak and then wrote about activities in their current life. The number of gathered answers were 1858 for 'before' and 1668 for 'after', and they were grouped into 19 behavior categories. Overall, behaviors such as traveling, eating out, and shopping were much less frequently described in the 'after' condition; while housework, food delivery, and pandemic prevention were mentioned more. However, the change pattern was significantly influenced by demographics of age, gender, having children or not, and household income. Especially women, younger generations, and people without children showed the greatest extent of behavior change compared with the other demographic cohorts. These groups were reported to be vaccine-hesitant in the literature. This study suggests that individuals with hesitant attitudes towards vaccines are more willing to change their behaviors to control viral transmission.

The relationship between leisure activities and mental health: The impact of resilience and COVID-19.

Engaging in leisure activities promotes mental health. The effect is likely associated with resilience as the broaden-and-build theory suggests positive emotions elicited from leisure increase mental resources for stress coping. The present research examined whether participating in different leisure activities at a given time increases the level of resilience, which in turn reduces psychological problems. It also investigated the changes in people's leisure activities due to the COVID-19 outbreak and the impact of these changes on their mental health. Japanese participants (N = 300) responded to two online surveys conducted before (January 2020) and after the outbreak (February 2021). They selected the leisure activities they had engaged in from 100 choices and reported their levels of resilience and depressive symptoms. An analysis of covariates revealed that the total number of selected activities significantly reduced in the second survey, but the levels of resilience and depressive symptoms remained constant. Regression analysis showed that the reduction in leisure activities did not predict depressive symptoms. However, structural equation modeling established that the relationship between leisure and depression was mediated by resilience, supporting the initial hypothesis. Importantly, this relationship slightly differed by age group, likely because popular activities and their psychological impacts vary depending on age.

The effect of damage to the white matter network and premorbid intellectual ability on postoperative verbal short-term memory and functional outcome in patients with brain lesions.

Cognitive reserve is the capacity to cope with cognitive decline due to brain damage caused by neurological diseases. Premorbid IQ has been investigated as a proxy for cognitive reserve. To date, no study has focused on the effects of premorbid IQ in patients with brain tumors, considering the damage to white matter tracts. We investigated whether a higher premorbid IQ has a beneficial impact on postoperative verbal short-term memory and functional outcomes in patients with brain tumors. A total of 65 patients with brain tumors (35 right and 30 left hemisphere lesions) and 65 healthy subjects participated in the study. We used multiple regression analysis to examine whether white matter tract damage and premorbid IQ affect postoperative verbal short-term memory, and the interaction effects of premorbid IQ with damage to white matter tract on postoperative verbal short-term memory. Path analysis was used to investigate the relationship between damage to the white matter tract and premorbid IQ on postoperative functional ability. Our results showed that damage to the left arcuate fasciculus affected postoperative functional ability through verbal short-term memory, working memory, and global cognition in patients with left hemisphere lesions. In the right hemisphere lesion group, high premorbid IQ had a positive effect on functional ability by mediating verbal short-term memory, verbal working memory, and global cognition. We found that damage to the eloquent pathway affected postoperative verbal short-term memory regardless of the premorbid IQ level. However, a higher premorbid IQ was associated with better postoperative verbal short-term memory and functional outcomes when the brain lesions were not located in a crucial pathway. Our findings suggest that premorbid IQ and damage to the white matter tracts should be considered predictors of postoperative functional outcomes.

The relationship between cognitive reserve focused on leisure experiences and cognitive functions in bipolar patients.

Bipolar disorder (BP) is characterized by cognitive decline. Individual differences exist in maintaining cognitive function due to daily physical activity and sleep. We examined the relationship between leisure experiences as proxies for cognitive reserve (CR) and cognitive function in patients with bipolar disorder after adjusting for daily physical activity and sleep. The CR of patients with BP (n = 24) and healthy study controls (HC) (n = 24) was assessed using premorbid IQ, years of education, and leisure activity history. Performance-based neuropsychological tests were performed to evaluate cognitive function. A self-reported scale was used to assess resilience. Physical activity and sleep were measured using an activity meter. Verbal fluency, story memory, and verbal memory were significantly positively correlated with the kinds of leisure experiences in patients with BP. A hierarchical regression analysis accounting for confounding factors showed that verbal fluency and memory were associated with the kinds of leisure experiences. Neither years of education nor resilience were significantly associated with neuropsychological scores. Various leisure experiences in patients with BP are associated with higher language-related cognitive functioning. Engaging in various leisure experiences may affect higher cognitive functions related to language.

Decrease in gamma-band auditory steady-state response in patients with treatment-resistant schizophrenia.

BACKGROUND: Thirty percent of patients with schizophrenia do not respond to non-clozapine antipsychotics and are termed treatment-resistant schizophrenia (TRS). The 40-Hz auditory steady-state response (ASSR) is a well-known to be reduced in patients with schizophrenia compared to healthy controls (HCs), suggesting impaired gamma oscillation in schizophrenia. Given no ASSR study on TRS, we aimed to examine the neurophysiological basis of TRS employing 40-Hz ASSR paradigm. METHOD: We compared ASSR measures among HCs, patients with non-TRS, and patients with TRS. TRS criteria were defined by a score of 4 or higher on two items of the Positive and Negative Syndrome Scale (PANSS) positive symptoms despite standard antipsychotic treatment. Participants were examined for ASSR with 40-Hz click-train stimulus, and then time-frequency analysis was performed to calculate evoked power and phase-locking factor (PLF) of 40-Hz ASSR. RESULTS: A total of 79 participants were included: 27 patients with TRS (PANSS = 92.6 ± 15.8); 27 patients with non-TRS (PANSS = 63.3 ± 14.7); and 25 HCs. Evoked power in 40-Hz ASSR was lower in the TRS group than in the HC group (F2,79 = 8.37, p = 0.015; TRS vs. HCs: p = 0.012, d = 1.1) while no differences in PLF were found between the groups. CONCLUSION: These results suggest that glutamatergic and GABAergic neurophysiological dysfunctions are involved in the pathophysiology of TRS. Our findings warrant more comprehensive and longitudinal studies for deep phenotyping of TRS.

Developmental trajectories of the fronto-temporal lobes from infancy to early adulthood in healthy individuals.

Brain development during early life in healthy individuals is rapid and dynamic, indicating that this period plays a very important role in neural and functional development. The frontal and temporal lobes are known to play a particularly important role in cognition. The study of healthy frontal and temporal lobe development in children is therefore of considerable importance. A better understanding of how these brain regions develop could also aid in the diagnosis and treatment of neurodevelopmental disorders. Some developmental studies have used magnetic resonance imaging (MRI) to examine infant brains, but it remains the case that relatively little is known about cortical brain development in the first few years of life. In the present study we examined whole brain, temporal lobe and frontal lobe developmental trajectories from infancy to early adulthood in healthy individuals, considering gender and brain hemisphere differences. We performed a cross-sectional, longitudinal morphometric MRI study of 114 healthy individuals (54 females and 60 males) aged 1 month to 25 years old (mean age ± SD 8.8 ± 6.9). We measured whole brain, temporal and frontal lobe gray matter (GM)/white matter (WM) volumes, following previously used protocols. There were significant non-linear age-related volume changes in all regions. Peak ages of whole brain, temporal lobe and frontal lobe development occurred around pre-adolescence (9-12 years old). GM volumes for all regions increased significantly as a function of age. Peak age was nevertheless lobe specific, with a pattern of earlier peak ages for females in both temporal and frontal lobes. Growth change in whole brain GM volume was larger in males than in females. However, GM volume growth changes for the temporal and frontal lobes showed a somewhat different pattern. GM volume for both temporal and frontal lobes showed a greater increase in females until around 5-6 years old, at which point this tendency reversed (GM volume changes in males became greater), with male GM volume increasing for a longer time than that of females. WM volume growth changes were similar across regions, all increasing rapidly until early childhood but slowing down thereafter. All regions displayed significant rightward volumetric asymmetry regardless of sex. Furthermore, the right temporal and frontal lobes showed a greater volumetric increase than the left for the first several years, with this tendency reversing at around 6 years of age. In addition, the left frontal and temporal lobes increased in volume for a longer period of time. Taken together, these findings indicated that brain developmental trajectories differ depending on brain region, sex and brain hemisphere. Gender-related factors such as sex hormones and functional laterality may affect brain development.

Effect of explicit instruction on Japanese Verbal Learning Test in schizophrenia patients.

After random assignment of 20 schizophrenia patients to either an explicit or normal instruction group, the Japanese Verbal Learning Test was administered to them. Results reveal that explicit instruction group patients demonstrated more improved memory performance using semantic clustering, suggesting that explicit and direct teaching facilitates patients' learning of information.

Membrane fatty acid levels as a predictor of treatment response in chronic schizophrenia.

Abnormal fatty acid composition in neural membranes, that is, the balance between essential polyunsaturated fatty acids (EPUFAs) and saturated fatty acids, has been suggested to be related to the psychotic symptoms and cognitive impairment of schizophrenia. This study was conducted to test the hypothesis that the ability of atypical antipsychotic drugs to ameliorate positive symptoms and cognitive function relevant to daily living would be predicted by baseline EPUFAs concentrations in the erythrocyte membrane in subjects with schizophrenia. A total of 24 actively psychotic patients with schizophrenia participated in the study. After blood drawing, they were treated with olanzapine or perospirone. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative symptoms (SANS), as well as the script tasks, a measure of event schema recognition, were administered at baseline and 3months after the start of treatment. Erythrocyte membrane fatty acid levels were analysed using a gas chromatography system. Scores of SAPS and SANS, as well as script task performance, were improved during treatment with either antipsychotic drug. Regression analysis indicates baseline EPUFAs concentrations were positively and negatively related with percent improvement of positive symptoms and script task performance, respectively. The results of this study suggest composition of phospholipids in the erythrocyte membrane provide a feasible marker to predict treatment response in patients with schizophrenia.

Useful visual field in patients with schizophrenia: a choice reaction time study.

This study examined the size of the useful visual field in patients (9 men, 6 women) with schizophrenia. A choice reaction task was conducted, and performances at 2.5, 5, 7, 10, and 25 degrees in both visual fields were measured. Three key findings were shown. First, patients had slower choice reaction times (choice RTs) than normal controls. Second, patients had slower choice RTs in the right visual field than in the left visual field. Third, patients and normal controls showed the same U-shaped choice RT pattern. The first and second findings were consistent with those of other studies. The third finding was a clear indication of the patients' performance in peripheral vision, and a comparison with normal controls suggested that there was no difference in the size of the useful visual field, at least within

Childhood maltreatment history and attention bias variability in healthy adult women: role of inflammation and the BDNF Val66Met genotype.

Childhood maltreatment has been associated with greater attention bias to emotional information, but the findings are controversial. Recently, a novel index of attention bias, i.e., attention bias variability (ABV), has been developed to better capture trauma-related attentional dysfunction. However, ABV in relation to childhood trauma has not been studied. Here, we examined the association of childhood maltreatment history with attention bias/ABV in 128 healthy adult women. Different types of childhood maltreatment were assessed with the Childhood Trauma Questionnaire. Attention bias/ABV was measured by the dot-probe task. Possible mechanisms whereby childhood maltreatment affects attention bias/ABV were also explored, focusing on blood proinflammatory markers and the BDNF Val66Met polymorphism. We observed a significant positive correlation between childhood emotional abuse and ABV (P = 0.002). Serum high-sensitivity tumor necrosis factor-α levels were significantly positively correlated with ABV (P < 0.001), but not with childhood maltreatment. Jonckheere-Terpstra trend test showed a significant tendency toward greater ABV with increasing numbers of the BDNF Met alleles (P = 0.021). A two-way analysis of variance further revealed that the genotype-by-emotional abuse interaction for ABV was significant (P = 0.022); individuals with the Val/Met and Met/Met genotypes exhibited even greater ABV when childhood emotional abuse was present. These results indicate that childhood emotional abuse can have a long-term negative impact on emotional attention control. Increased inflammation may be involved in the mechanism of ABV, possibly independently of childhood maltreatment. The BDNF Met allele may dose-dependently increase ABV by interacting with childhood emotional abuse.

The efficacy of memantine in the treatment of civilian posttraumatic stress disorder: an open-label trial.

Background: Currently, there is a paucity of pharmacological treatment options for posttraumatic stress disorder (PTSD), and the development of a novel pharmacotherapeutic approach has become a matter of great interest. Objective: We conducted a 12-week open-label clinical trial to examine the efficacy and safety of memantine, an N-methyl-D-aspartate receptor antagonist, in the treatment of civilian PTSD. Method: Thirteen adult patients with DSM-IV PTSD, all civilian women, were enrolled. They were monitored at an ambulatory care facility every week until 4 weeks and then every 4 weeks until 12 weeks. Memantine was added to each patient's current medication, with the initial dosage of 5 mg/day and then titrated. Concomitant medications were essentially kept unchanged during the trial. The primary outcome was PTSD diagnosis and severity assessed with the Posttraumatic Diagnostic Scale (PDS). Results: Of the 13 cases, one dropped out and two were discarded due to the protocol deviation, and the analysis was done for the remaining 10. Mean PDS total scores decreased from 32.3 ± 9.7 at baseline to 12.2 ± 7.9 at endpoint, which was statistically significant with a large effect (paired t-test: p = .002, d = 1.35); intrusion, avoidance, hyperarousal symptoms were all significantly improved from baseline to endpoint. Six patients no longer fulfilled the diagnostic criteria of PTSD at endpoint. Some adverse, but not serious, effects possibly related to memantine were observed, including sleep problems, sleepiness, sedation, weight change and hypotension. Conclusions: Memantine significantly reduced PTSD symptoms in civilian female PTSD patients and the drug was well tolerated. Future randomized controlled trials are necessary to verify the efficacy and safety of memantine in the treatment of PTSD.

Antecedentes: Actualmente, hay escasez de opciones de tratamiento farmacológico para el trastorno de estrés postraumático (TEPT), y el desarrollo de un enfoque farmacoterapéutico nuevo se ha transformado en materia de gran interés.Objetivo: Llevamos a cabo un ensayo clínico abierto de 12 semanas para examinar la eficacia y seguridad de memantina, un antagonista del receptor de N-metil-d-aspartato, en el tratamiento del TEPT en civiles.Método: Se inscribieron trece pacientes adultas con TEPT según DSM-IV, todas mujeres civiles. Fueron monitoreadas en un centro de atención ambulatoria semanalmente por 4 semanas, y luego cada 4 semanas hasta las 12 semanas. Se agregó memantina al tratamiento farmacológico actual de cada paciente, con dosis inicial de 5 mg/día y titulación posterior. Los fármacos concomitantes fueron mantenidos esencialmente sin cambios durante el estudio. El objetivo primario fue el diagnóstico de TEPT y su severidad, evaluada con la Escala de Diagóstico Postraumático (PDS, por su sigla en inglés).Resultados: De los 13 casos, uno abandonó y 2 fueron descartados debido a desvío del protocolo, y el análisis fue realizado con los 10 restantes. El puntaje total promedio de PDS disminuyó de 32.3 ± 9.7 en el basal a 12.2 ± 7.9 al término, lo que fue estadísticamente significativo con un tamaño de efecto grande (prueba t pareada: p=.002, d=1.35); los síntomas de intrusión, evitación e hiperactivación mejoraron todos en forma al término respecto a la basal. Seis pacientes dejaron de cumplir los criterios de TEPT al término. Se observaron algunos efectos adversos, pero no serios, posiblemente relacionados a memantina, que incluyeron problemas del sueño, somnolencia, sedación, cambios en el peso e hipotensión.Conclusiones: La memantina redujo significativamente los síntomas de TEPT en pacientes mujeres civiles con TEPT y el fármaco fue bien tolerado. Se requieren ensayos controlados aleatorizados en el futuro para verificar la eficacia y seguridad de la memantina en el tratamiento del TEPT.

Association of CRP genetic variation with symptomatology, cognitive function, and circulating proinflammatory markers in civilian women with PTSD.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with increased inflammation. C-reactive protein (CRP) is a marker of systemic inflammation, and recently, single nucleotide polymorphisms (SNPs) in the CRP gene have been associated with increased blood CRP protein levels and illness severity in PTSD patients. However, the mechanism by which the CRP SNPs are involved in PTSD remains unclear. Here we investigated the association of CRP genetic variation with blood proinflammatory protein levels, symptomatology, and cognitive function, and further explored the moderating effect of childhood maltreatment history, in adult patients with PTSD. METHODS: Fifty-seven Japanese civilian women with PTSD and 73 healthy control women were enrolled. Three SNPs in the CRP gene, namely rs2794520, rs1130864, and rs3093059, were genotyped, and analyses focused on rs2794520 (T/C). Serum levels of high-sensitivity CRP (hsCRP), high-sensitivity tumor necrosis factor-α (hsTNF-α), and interleukin-6 were measured. PTSD symptoms were evaluated by the Posttraumatic Diagnostic Scale. Cognitive function was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status. Childhood maltreatment history was assessed by the Childhood Trauma Questionnaire. RESULTS: Patients with the rs2794520 CC/CT genotype, compared to those with the TT genotype, showed significantly higher levels of hsCRP (p=0.009) and hsTNF-α (p=0.001), more severe PTSD symptoms (p=0.036), and poorer cognitive function (p=0.018). A two-way analysis of variance revealed a significant genotype-by-maltreatment interaction for more severe PTSD avoidance symptom (p=0.012). LIMITATIONS: The relatively small sample size limited our findings. CONCLUSIONS: These findings may provide an insight into the etiology of PTSD from the inflammatory perspective.