Aberrant resting-state functional connectivity of major depressive disorder with higher risk of suicide.

Aim: Suicide prevention for depressive patients is an important clinical issue in psychiatry. However, not all depressive patients plan or attempt suicide. In this study, we investigated the differences of functional brain networks between a high-risk group and a low-risk group for suicide by comparing resting-state functional connectivity (rsFC). Methods: The subjects were 29 patients with major depressive disorder, nine of whom had attempted suicide. The suicidal ideation of all subjects was assessed with the Columbia-Suicide Severity Rating Scale, then the subjects were divided into two groups based on the most severe suicidal ideation (MSI) in their lifetime. We compared rsFC between the two groups. Results: Of the 29 subjects, 16 were in the severe MSI group. We found that the severe MSI group members had significantly smaller rsFC in two networks: one comprised the right dorsolateral prefrontal cortex and the default-mode network, and the other comprised the left rostrolateral prefrontal cortex and the striatum, amygdala, and hippocampus. These regions are reported to be associated with rumination, retrieval suppression, and delay discounting (DD). Conclusion: Our results suggest that functional networks related to rumination, retrieval suppression, and DD might be impaired in depressive patients with severe suicidal ideation. It might be beneficial for psychiatrists to assess these characteristics in terms of suicide prevention for depressive patients.

Visualizing the Process of Disaster Mental Health Services in the Joso Flood by Network Analyses of Emails.

Joso City, Ibaraki Prefecture, Japan was severely affected by flooding of the River Kinugawa in September 2015. Local psychiatric organizations immediately began providing disaster mental health services (DMHS). In post-disaster settings, DMHS involving organizational interventions by multiple regional institutions are required to support disaster victims. However, little is known about the process of coordinating multiple institutions or determining whether appropriate support has been provided. To elucidate the characteristics of communications that enable effective disaster medical team formation, we conducted network analyses of sender-recipient pairs of emails during the period of DMHS activity. The network analysis is a research method that represents various objects as a network of nodes and edges and explores their structural characteristics. We obtained 2,450 time-series emails from five core members of DMHS, including 32,865 pairs of senders and recipients. The network generated by the emails was scale-free, and its structure changed according to the phases of disaster recovery. In the ultra-acute phase, which lasted about 1 week, spreading information and recruiting people to provide disaster support was given the highest priority. In the acute phase, which lasted about 1 month, support and swift decision-making were essential for directing large numbers of staff. In the mid- to long-term phase, support for staff to share information and experience in small groups was observed. Network analyses have revealed that disaster medical teams must change their communication styles during the mission to adapt to different health needs corresponding to each post-disaster phase.

What kinds of factors affect the academic outcomes of university students with mental disorders? A retrospective study based on medical records.

AIMS: University students that suffer from mental disorders seem to have difficulty graduating. Therefore, we investigated risk and protective factors of dropping out with the aim of improving such students' academic outcomes. METHODS: First, we statistically compared the academic outcomes of 203 undergraduate students who received treatment in the Department of Psychiatry of the Tsukuba University Health Center to those of matched controls. Second, clinical factors of 370 mentally ill students were statistically compared between the dropout and graduate groups. RESULTS: Mentally ill students experienced significantly greater difficulties graduating. Furthermore, the ratio of females and the year of study at initial consultation were significantly lower in the dropout group. However, duration of illness, social withdrawal, temporary leaves of absence, percentage of diagnosis of F2, history of truancy, CGI-S/GI score, number of suicide attempts, visits to us, family consultations with us and grade repeating were longer or greater in the dropout group. Ultimately, the number of suicide attempts, CGI-S score, social withdrawal and leaves of absence were significantly associated with dropping out. Moreover, duration of social withdrawal and leaves of absence were significantly correlated with CGI-GI score. CONCLUSION: We found that the number of suicide attempts, CGI-S score, social withdrawal and extended enrollment were risk factors for dropping out, while the therapeutic effect seemed to be a protective factor. As risk factors involved states of social maladjustment, it is necessary not only to treat mental disorders, but also to provide assistance such as educational and individual support for daily living.

Repetitive patterns in rapid optical variations in the nearby black-hole binary V404 Cygni.

How black holes accrete surrounding matter is a fundamental yet unsolved question in astrophysics. It is generally believed that matter is absorbed into black holes via accretion disks, the state of which depends primarily on the mass-accretion rate. When this rate approaches the critical rate (the Eddington limit), thermal instability is supposed to occur in the inner disk, causing repetitive patterns of large-amplitude X-ray variability (oscillations) on timescales of minutes to hours. In fact, such oscillations have been observed only in sources with a high mass-accretion rate, such as GRS 1915+105 (refs 2, 3). These large-amplitude, relatively slow timescale, phenomena are thought to have physical origins distinct from those of X-ray or optical variations with small amplitudes and fast timescales (less than about 10 seconds) often observed in other black-hole binaries-for example, XTE J1118+480 (ref. 4) and GX 339-4 (ref. 5). Here we report an extensive multi-colour optical photometric data set of V404 Cygni, an X-ray transient source containing a black hole of nine solar masses (and a companion star) at a distance of 2.4 kiloparsecs (ref. 8). Our data show that optical oscillations on timescales of 100 seconds to 2.5 hours can occur at mass-accretion rates more than ten times lower than previously thought. This suggests that the accretion rate is not the critical parameter for inducing inner-disk instabilities. Instead, we propose that a long orbital period is a key condition for these large-amplitude oscillations, because the outer part of the large disk in binaries with long orbital periods will have surface densities too low to maintain sustained mass accretion to the inner part of the disk. The lack of sustained accretion--not the actual rate--would then be the critical factor causing large-amplitude oscillations in long-period systems.

[Effects of Mental Disorders on the Academic Outcomes of University Students--A Retrospective Study Using Medical Records from a Health Services Center].

OBJECTIVE: Falling behind in class is a serious problem for university students as it can lead to social problems and increase the risk of suicide. Although it is common for students suffering from mental disorders to fall behind academically, there have been few studies investigating the difficulties these students face in order to graduate from university. Therefore, we investigated factors associated with dropping out of school with the purpose of creating a strategy to improve the academic outcomes of students who regularly seek psychiatric consultation. SUBJECTS: We investigated undergraduate students who received consultation at Tsukuba University's Health Services Center Psychiatry Department and whose academic outcomes between the 2004 and 2013 academic years were known. METHODS: Academic outcomes were obtained from Tsukuba University's grade management system by permission of the authority. The students were divided into either a graduate or dropout group depending on their academic outcomes. The medical records for both groups were retrospectively investigated, and factors that were predicted to affect academic outcomes were assessed using statistical methods. RESULTS: The dropout group was younger in grade and had a greater severity of illness at initial consultation. Moreover, this group had a greater number of consultation visits, showed less cooperation with the instructor in charge, had a significantly longer duration of social with drawal and temporary leave of absence from school, and had a significantly greater number of students with grade retention. When a time factor was incorporated in the analysis, the presence of grade retention/temporary leave of absence from school and social withdrawal was significantly correlated with dropping out of school. CONCLUSION: It was revealed that not only the mental disorder itself, but also psychosocial severity and the maladjusted state that occur secondary to such mental disorder influence academic outcomes. These results indicated that in order to improve academic outcomes, it is necessary not only to appropriately treat the disorder, but to also provide university community support for social maladjusted states of the students in psychiatric treatments, such as social withdrawal, educational support for daily living, individual support for daily living, and academic support, through cooperation with the educational organization.

[A case of "oneiroid Erlebnisform" influenced by the Great East Japan Earthquake].

Following the Great East Japan Earthquake, although there are a growing number of reports on the care of the mental health of victims and supporters, the influence of this disaster on individuals with mental disorders has not yet been sufficiently clarified. Here, we present a case of "oneiroid Erlebnisform" (Mayer-Gross, W.), which was influenced by the disaster and relapsed one year after the earthquake. We discussed the meaning of this experience and the factors leading to recurrence in this case. A male international student in his thirties had repeatedly suffered from acute episodic alteration of consciousness. Although he had experienced anxiety just after the disaster, he showed improvement during his temporary evacuation to Western Japan. Nearly one year after the disaster, however, he relapsed, with symptoms characteristic of an oneiroid state. The patient stated that he was a fuel rod in the Fukushima nuclear power plant, and he then immersed himself in a bathtub full of water in order to avoid meltdown. According to ICD-10, the patient was diagnosed with acute polymorphic psychotic disorder without symptoms of schizophrenia (F23.0). In addition to the alteration of consciousness as the main symptom, since there was no decrease in the level of personolity function, it was also considered that the diagnosis of this case was atypical psychosis, as proposed by Mitsuda and Hatotani. In the oneiroid experience, a variety of visual hallucinations, illusions, and images had appeared one after another. We can find catastrophe and salvation as the main themes in this state, related to the disaster and nuclear accident. Unloading situation after thesis defense, insufficient sleep, poor medication adherence, and the increased frequency of earthquakes were important factors in the recurrence of the present case. To continue research in Japan after the earthquake, the decision was accompanied by anxiety for the patient. One year after the earthquake, the patient was trying to enter a doctoral program with continued anxiety over the nuclear accident. When the frequency of earthquakes increased again, the patient was taking an entrance examination. There is a possibility that the anxiety in this situation led to the recurrence. People are vulnerable to being exposed to the fear of a disaster even after experiencing relief. This situation may increase the risk of recurrence.

[An analysis of mental disorders of international students visiting the Mental Health Service at Tsukuba University Health Center].

With the expected increase in the number of international students coming to Japan as part of the Ministry of Education, Culture, Sports, Science & Technology's "300,000 Foreign Student (Global 30) Plan", the demands on university mental health facilities will also increase. However, the rate of mental disorders of recent international students has not been fully evaluated. As part of an initiative to establish effective treatment measures for the mental health of international students, we investigated the present status and recent trends of these students who visited the Mental Health Service (MHS) in the Tsukuba University Health Center. The demographic characteristics, pathway, stress, and diagnosis of international students who visited the MHS from 2005 to 2010 were investigated retrospectively based on medical records. The subjects were 59 international students (15 male, 44 female; mean age: 28.4). The consultation rate of international students was significantly lower than that of Japanese students each year. Although the rate is almost stable in Japanese students (2.1-2.5%), it has increased significantly in international students, from 0.5% in 2005 to 1.4% in 2010. A larger percentage of the subjects were from Asia (66%), compared to the former Soviet Union (10%) and Europe (7%). A greater proportion of the subjects were graduate students (67%). The diagnoses were as follows: depression (34%), adjustment disorder (32%), insomnia (15%), and schizophrenia (9%). The percentage requiring emergency consultation was 24%, including the most severe cases that had to return to their home country. Sixty-nine percent of the subjects stayed in Japan for more than 1 year. Half of the subjects decided to visit the MHS themselves. The results of the present study show that the consultation rate of international students was lower than that of Japanese students in spite of the "culture shock" experienced by international students. This result is in agreement with previous reports. Among international students, however, there is a trend indicating an increase of visits to the MHS in recent years, approaching the rate for Japanese students. Preparations for emergency consultation are still important.

Hyperperfusion in primary somatosensory region related to somatic hallucination in the elderly.

AIM: The purpose of the present study was to investigate the regional cerebral blood flow (rCBF) of patients with delusional disorder, somatic type (DDST) exhibiting somatic hallucination. METHODS: Five patients diagnosed with DDST, as well as 20 control subjects, were examined. All subjects underwent technetium-99m ethyl cysteinate dimer brain perfusion single-photon emission computed tomography. Statistical analysis was performed with SPM5, using a two-sample t-test model to test the regional population effect on rCBF. RESULTS: Patients with DDST had a significant increase in perfusion in the left post-central gyrus and the right paracentral lobule, both of which are involved in somatic sensory processing. CONCLUSION: Somatic hallucination might be associated with increased perfusion in the primary somatosensory regions.

Diagnostic classification of schizophrenia by neural network analysis of blood-based gene expression signatures.

Gene expression profiling with microarray technology suggests that peripheral blood cells might be a surrogate for postmortem brain tissue in studies of schizophrenia. The development of an accessible peripheral biomarker would substantially help in the diagnosis of this disease. We used a bioinformatics approach to examine whether the gene expression signature in whole blood contains enough information to make a specific diagnosis of schizophrenia. Unpaired t-tests of gene expression datasets from 52 antipsychotics-free schizophrenia patients and 49 normal controls identified 792 differentially expressed probes. Functional profiling with DAVID revealed that eleven of these genes were previously reported to be associated with schizophrenia, and 73 of them were expressed in the brain tissue. We analyzed the datasets with one of the supervised classifiers, artificial neural networks (ANNs). The samples were subdivided into training and testing sets. Quality filtering and stepwise forward selection identified 14 probes as predictors of the diagnosis. ANNs were then trained with the selected probes as the input and the training set for known diagnosis as the output. The constructed model achieved 91.2% diagnostic accuracy in the training set and 87.9% accuracy in the hold-out testing set. On the other hand, hierarchical clustering, a standard but unsupervised classifier, failed to separate patients and controls. These results suggest analysis of a blood-based gene expression signature with the supervised classifier, ANNs, might be a diagnostic tool for schizophrenia.

Alterations in GABA(A) receptor expression in neonatal ventral hippocampal lesioned rats: comparison of prepubertal and postpubertal periods.

Rats with neonatal ventral hippocampal lesions (NVHL) have been studied as a neurodevelopmental animal model of schizophrenia. NVHL rats exhibit postpubertal emergence of hyperresponsiveness to stress, suggesting increased mesolimbic dopamine (DA) activity. However, previous studies have not yielded clear evidence of this. Disturbances in the gamma-amino-butyric acid (GABA)-ergic system as well as the dopaminergic system are thought to be present in schizophrenia. To determine whether GABA(A) receptors play a role in the abnormal postpubertal behavior in NVHL rats, we compared changes in expression of mRNA of GABA(A) receptor subunits and in [(35)S] t-butylbicyclophosphorothionate ([(35)S] TBPS) binding in the prepubertal and postpubertal periods. Male pups were lesioned with ibotenic acid at postnatal day 7 (PD 7), and in situ hybridization and quantitative autoradiography were then performed. In NVHL rats, alpha1 subunit mRNA expression in prefrontal cortex was decreased at PD 35 (prepubertal period; by 21.7%), but increased at PD 56 (postpubertal period; by 21.4%) when compared with sham controls. beta2 subunit mRNA expression was increased in PFC in the postpubertal period (by 24.3%). beta3 subunit mRNA expression was increased in the caudate-putamen in the postpubertal period (by 37.2%). [(35)S] TBPS binding was increased in PFC only in the postpubertal period (by 17.7%). These findings suggest that dysfunction of the GABAergic system exists in NVHL rats. Furthermore, developmental and regional changes in GABA(A) receptor expression appear to occur in compensation for the attenuation of GABAergic system activity in NVHL rats.

[A case of Brugada syndrome with convulsive seizure during antidepressant administration: relation of antidepressant agents and arrhythmia leading to sudden death].

Brugada syndrome is an arrhythmogenetic disease characterized by electrocardiographic ST segment elevation in right precordial leads, which is called "coved type", and an increased risk of sudden death as the result of ventricular fibrillation. We presented a case of Brugada syndrome with a convulsive seizure, during administration of a tricyclic antidepressant for the treatment of a depressive state. A 43-year-old man with bipolar II disorder and obsessive-compulsive disorder was admitted to our hospital for the treatment of a depressive state. There was no medical history of heart failure. Nortriptyline was effective for his depressive as well as for obsessive symptoms. During the treatment, however, he presented a convulsive syncope. Electrocardiography (ECG) showed "coved type" ST segment elevation, and the patient consulted a cardiologist. Electrophysiological study revealed Brugada syndrome, and an implantable cardioverter defibrillator was placed. An overdose of antidepressants has been reported to produce a Brugada-type ECG because of its Na channel antagonism. However, in the present case, the abnormal ECG findings occurred following a usual dosage of nortriptyline. Thus, it is suggested that Brugada syndrome is related to a susceptibility to antidepressants in the present case. Every psychiatrist managing antidepressant therapy should be aware of Brugada syndrome and this ECG pattern, which may be a marker of sudden death.

Hypersalivation induced by olanzapine with fluvoxamine.

Hypersalivation has been reported as a side effect of atypical antipsychotics such as clozapine and olanzapine. As it is very common for antipsychotics to cause dry mouth due to anticholinergic effects, hypersalivation seems to be paradoxical. We present the case of a 34-year-old Japanese man with delusional disorder, somatic type (DSM-IV). He had chronic neck pain as well as somatic hallucination with hypochondriacal delusion for 4 years. Since combination therapy with atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs) has been introduced in the treatment of refractory psychiatric disorders such as schizophrenia, olanzapine (10 mg/day) was added to fluvoxamine treatment (200 mg/day) in this case. Subsequently, hypersalivation was induced without any extrapyramidal symptoms. It is suggested that hypersalivation was an adverse effect of olanzapine. Possible interaction olanzapine with fluvoxamine might increase the risk of the adverse effect. When combination therapy of atypical antipsychotics and SSRI is introduced, it should be used cautiously with careful observation. Underlying pharmacological and clinical problems will be discussed.

High-dose of multiple antipsychotics and cognitive function in schizophrenia: the effect of dose-reduction.

We evaluated the effect of antipsychotic dose-reduction on the neurocognitive function of 17 schizophrenic patients (11 male and 6 female, mean age=42.4+/-11.3) who have been taking high-doses of multiple conventional antipsychotics. The mean (+/-SD) of total daily antipsychotic doses (in mg/day, chlorpromazine-equivalent) was 2,253 (+/-668) at baseline, which was reduced to 1,315 (+/-276). Possible changes in neurocognitive function were assessed using Wisconsin card sorting test (WCST) and continuous performance test (CPT). As controls, we examined WCST and CPT in 6 schizophrenic patients (4 male and 2 female, mean age=47.7+/-14.2) who had been taking high-doses of multiple antipsychotics (mean daily antipsychotic dose=1,753+/-165 mg) and declined to change their antipsychotic regimen. In WCST, the mean number of total correct answers significantly increased (53.2+/-16.3 vs. 63.8+/-19.6, P=0.035, Wilcoxon signed rank test); perseverative errors significantly decreased (54.4+/-27.3 vs. 35.4+/-20.1, P=0.013, Wilcoxon signed rank test) after the antipsychotic dose-reduction. In contrast, the control group showed no significant difference between the two WCST performances conducted with a three-month interval. The improvements in WCST performance significantly correlated with the decreases in PANSS negative syndrome score in the subject patients. No significant change was observed in CPT performances in either group. Our preliminary data shows that, in schizophrenic patients taking high-doses of multiple conventional antipsychotics, dose-reduction might lead to improvements in cognitive functions.

Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.

The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.

Decreased cell proliferation in the dentate gyrus of rats after repeated administration of cocaine.

Cell proliferation in the dentate gyrus of hippocampus was assessed using in vivo labeling with 5-bromo-2'-deoxyuridine (BrdU) in adult rats that were administered cocaine (20 mg/kg) for 14 consecutive days. Rats showed increased stereotypy at a challenge dose of cocaine after 1 week of withdrawal, suggesting the acquisition of behavioral sensitization. Twenty-four hours after final injection of repetitive cocaine administration, a 26% decrease in BrdU-positive cells was observed, compared with control rats. However, this returned to control level within 1 week. No differences were observed in rats that received a single injection of cocaine. Differentiation of newly formed cells was not influenced. These data imply that the regulation of hippocampal cell proliferation by cocaine may be involved in the development of certain symptoms of addiction, such as cognitive impairment and acquisition of behavioral sensitization.