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DTNBP1, which encodes dysbindin-1, is one of the best-supported susceptibility genes for schizophrenia, and hippocampal volume reduction is one of the major neuropathological findings in schizophrenia. Consistent with these findings, dysbindin-1 has been shown to be diminished in glutamatergic hippocampal neurons in schizophrenic patients. The aim of this study was to directly investigate the effects of two single nucleotide polymorphisms of the DTNBP1 gene on regional brain volumes in human subjects.
128 subjects participated in the study. All subjects were genotyped with respect to two single nucleotide polymorphisms of the DTNBP1 gene (rs2619522 and rs1018381) and underwent structural magnetic resonance imaging (MRI). MRI data were preprocessed and statistically analyzed using standard procedures as implemented in SPM5, in particular the voxel-based morphometry (VBM) toolbox.
We found significant effects of the DTNBP1-SNP rs2619522 on regional brain volumes bilaterally in the hippocampus as well as in the anterior middle frontal gyrus and the intraparietal cortex. T/T homozygotes showed significantly lower grey matter volumes in these brain regions than carriers of the G allele.
Compatible with previous findings on a role of the dysbindin-1 gene in hippocampal functions as well as in major psychoses, the present study provides first direct in-vivo evidence that the DTNBP1-SNP rs2619522 is associated with variation of grey matter volumes bilaterally in the human hippocampus.
Along the coast of the Adriatic, several small projects have developed to improve treatment of patients with Schizophrenia. All these projects have benefited from links with the Department of Psychiatry in Cambridge.
In Ljubljana, The Ljubljana Prodrome Project has developed a system of early intervention and treatment which has a strong research arm. It has contributed knowledge about how psychosis develops, and shown that treatment in the prodromal phase of illness gives patients significant advantages.
The Assertive Outreach Team in Ljubljana Psychiatric Hospital has reduced readmissions for the chronic patients it deals with. Case Management in the Community has also been established at Vrapce Hospital Zagreb, where there has also been established a ward for first episodes of Psychosis. Non Governmental Organisations have been working with patients and their families in Central Croatia, using group interventions for carers.
In Sarajevo, one doctor is working with identifying psychosis early.
All of these projects are successful and amount to a major contribution in improving treatment for schizophrenia for patients in these countries.
Staff from Croatia and Slovenia have visited the UK to learn Early Detection and Intervention techniques and case management.
Further development nationally of these techniques for delivery of Mental Health Care in the Community is now awaited.
The authors are presenting the case report of a patient who was taken care for the Community Mental Health Team in Croatia, following the recommendations of WHO 2004 as well as IRIS guidelines, considering Basic standards for management of patients with serious mental illness in the community developed by GAMIAN-Europe.
Authors are presenting work of a case manager on the case of the patient who himself takes the responsibility to ensure that the needs of patient and his family are met, by acting in a more pro-active fashion (Assertive case management (ACT)). A care-plan for the patient is presented, which details all the care which the patient was receiving, and who is providing the care. This plan is agreed at the meeting of the patient, the family, the case -manager, the psychiatrist, and other team members who are providing some of the care (Social worker, Psychologist, Occupational worker). The plan is agreed collaboratively with the patient and the family and signed by all parties concerned, including the psychiatrist. The plan is reviewed at a formal meeting of those concerned at the end of the treatment.
We recommend developing Community Mental Health Teams in Croatia which are based on the ACT principle. They are more expensive and more demanding in terms of face to face patient contact, but it is evidence based that they give better long term results.
Experience-dependent cortical plasticity observed during post-training sleep has been hypothesized to be part of the global process of memory consolidation. Combining the temporal resolution of microstructure detectors and the spatial resolution of low-resolution brain electromagnetic tomography (LORETA) makes it possible to investigate when and where the experience-dependent reactivation occurs under normal (undisturbed) sleeping conditions.
After an adaptation night, in the 2nd and 3rd night 48 young healthy volunteers were randomly assigned either to a control condition or to an experimental condition (declarative memory task: paired-associate word list or procedural memory task: mirror tracing). Sleep stages and sleep microstructures (slow waves, spindles and theta bursts) were detected automatically by means of the Somnolyzer 24x7. Changes in LORETA sources (experimental minus control night) were correlated with changes in memory performance (morning minus evening recall).
Overnight improvements in the mirror tracing task were correlated with increased slow-wave sources in the right posterior parietal cortex (r = .70,p < 0.01) during NREM sleep and with desynchronized (r = −.76,p < 0.01) and synchronized (r = .62,p < 0.01) rolandic mu rhythm sources during periods with theta bursts in REM sleep. Overnight improvements in the declarative memory task were significantly correlated with increased spindle sources (r = .52, p < .01) in frontal, temporal and cingulate brain regions.
The present study supports the hypotheses of (1) a use-dependent reset of synaptic plasticity during slow-wave sleep (restorative function), (2) an experience-dependent reactivation during spindle episodes (stabilizing function) and (3) an off-line neuronal reprocessing during REM sleep (improvement without further training for novel tasks).
Authors are presenting a case of co morbid panic disorder and psychosis with a focus on the successful treatment of the panic disorder via a CBT approach. The patient has had only one episode of psychosis.
The cognitive model of panic disorder is used as a template to consider this young man's psychotic experiences, in the context of some types of delusional beliefs, especially those involving the catastrophic and atypical misinterpretation of the physiological sensations associated with anxiety.
This case is emphasising the therapeutic value in certain patients of focussing therapy on the non-psychotic symptoms once the acute psychotic state has been managed.
The authors presented their acitivities in prevention of mobbing, suiciality, pathological gambling, and antistigma programs aimed for the persons treated for combat PTSD.
Social dialogue is achieved through numerous outpatient activities that included systematic information and education, public discussions, conducted studies, public program promotions, performance presentations, koordination, and active engagement of various professionals (psychiatrists, psychologists, pedagogues, social workers, jurists, politicians, employees in civil service, associations and syndicate, employers, and volonteers).
Numerous public disscussions and professional gatherings have been held, professional and scientific studies have been conducted, programs have been presented in public through various media, web-pages have been created and brochures have been written. The created positve atmosphere leveled up the awarenes, what resulted in propositions for drawing up broader, national strategies, and some pending legal solutions.
Social dialoge is represented by all types of information exchange, conslutations, and discussions between social partners and government representatives about issues of common interest related to social or economic policy. In situations when some primalily social events partially participate in the genesis of psychological disorders, a psychiatrist may take part in the dialogue, pointing out the existance of the problem, defining the problem and offering professional solutions for prevention. In order to have a social dialogue it is necessary to have most extensive public support and understanding that only with joint endeavor of all citizens the problem may be, and must be, solved.
Earlier studies reported that subjective sleep quality correlates with objective polysomnographically measured sleep initiation and continuity, but less with sleep architecture.
This study aimed to investigate relations between subjective and objective sleep in normals (N), insomnia comorbid with generalized anxiety disorder (G) and apnea (A).
One hundred and seventy-seven normals (50.9±19.6a), 100 insomniac G patients (37.9±10.6a) and 51 A patients (51.3±9.7a) completed the self-rating scale for sleep and awakening quality (Saletu et al. 1997) regarding two polysomnographic nights analyzed by the Somnolyzer (Anderer et al. 2005). Correlations were calculated based on changes between the first (adaptation) and second polysomnographic night to diminish inter-individual variances of sleep perception.
In N, subjective sleep quality (S-QUA) demonstrated correlations (p < 0.01) with sleep efficiency (EFF), wake after sleep onset (WASO), S2, S1%, REM, S1, frequency of awakenings (FW), latency to continuous sleep (L-CONT), sleep latency (S-LAT) and slow-wave sleep, while awakening quality (A-QUA) showed weak (p < 0.05) correlations with EFF and WASO. Somatic complaints (S-COM) correlated (p < 0.05) with WASO and REM. In G, correlations (p < 0.01) were obtained between S-QUA and EFF, WASO, S2, L-CONT and S-LAT (p < 0.05), while A-QUA correlated with S2, WASO and EFF. In A, S-QUA correlated (p < 0.01) with EFF, S2, S1%, S2%, L-CONT, WASO and less (p < 0.05) with S-LAT and S1. A-QUA correlated with S2, S2% (p < 0.01), L-CONT and EFF (p < 0.05). S-COM correlated with S-CONT (p < 0.01) and S-LAT (p < 0.05).
EFF, WASO, S2 and less S-LAT determine good S-QUA in all groups.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
Toca 511 (vocimagene amiretrorepvec) is an investigational retroviral replicating vector that selectively infects dividing cancer cells, integrates into the genome and replicates due to immune defects in tumors. Toca 511 spreads through tumors and stably delivers the gene encoding an optimized yeast cytosine deaminase that converts the prodrug Toca FC (investigational, extended-release of 5-fluorocytosine) into 5-fluorouracil. In preclinical models, 5-fluorouracil kills infected dividing cancer cells, myeloid derived suppressor cells and tumor associated macrophages, enabling immune activation against the tumor. In this dose ascending Ph1 trial (NCT01470794), Toca 511 was injected into the resection cavity wall of patients with rHGG, followed by courses of oral Toca FC. Additional cohorts included combination with bevacizumab or lomustine. Across the Ph1 program, the safety profile remains favorable. Objective responses (ORs) were assessed by IRR using MRI scans prior to Toca FC treatment as baseline. ORs occurred 6-19 months after Toca 511 administration, suggesting an immunologic mechanism. The ORs were observed in 4 patients with IDH1-wildtype and 2 patients with IDH1-mutant tumors, including 5 complete responses (CRs) with the investigational therapy alone, and 1 CR in combination with bevacizumab. The median duration of response (mDoR) was 35.1+ months. As of AUG2017, all responders were CR and remain alive. In a 23-patient subgroup who received high doses of Toca 511 and met Ph3 trial criteria, mOS was 14.4 months, 3-year survival rate was 26.1%, and mDoR was 35.7+ months with a durable response rate of 21.7%. Data suggest a positive association of durable response with OS.
Delays in rotavirus vaccine schedule could improve performance in low- and middle-income countries (LMICs). However, delaying the first dose could be detrimental if infants experience severe rotavirus gastroenteritis (RVGE) early in life. Our objective was to describe the timing and predictors of severe RVGE in unvaccinated children in LMICs. We analysed the placebo arms from two clinical trials (cohort 1: NCT00241644; cohort 2: NCT00362648). We estimated the rate, cumulative incidence (per 1000 infants) and age distribution of severe RVGE episodes. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI) for the association between baseline factors and severe RVGE. Cumulative incidence at 6 months of age was 23/1000 (95% CI 15–30) in cohort 1 and 6/1000 (95% CI 3–8) in cohort 2. Early antibiotic use (compared with no use) was associated with 2.03 (95% CI 1.18–3.48) and 1.41 (95% CI 0.80–2.51) times the rate of severe RVGE in cohorts 1 and 2, respectively. The cumulative incidence of severe RVGE was low at 6 months of age, suggesting that a 4-week delay in the vaccination schedule may not result in a large number of severe RVGE episodes prior to vaccine receipt.
Sleep disturbances are prominent correlates of acute mood episodes and inadequate recovery in bipolar disorder (BD), yet the mechanistic relationship between sleep physiology and mood remains poorly understood. Using a series of pre-sleep mood inductions and overnight sleep recording, this study examined the relationship between overnight mood regulation and a marker of sleep intensity (non-rapid eye movement sleep slow wave activity; NREM SWA) during the interepisode phase of BD.
Adults with interepisode BD type 1 (BD; n = 20) and healthy adult controls (CTL; n = 23) slept in the laboratory for a screening night, a neutral mood induction night (baseline), a happy mood induction night, and a sad mood induction night. NREM SWA (0.75–4.75 Hz) was derived from overnight sleep EEG recordings. Overnight mood regulation was evaluated using an affect grid pleasantness rating post-mood induction (pre-sleep) and the next morning.
Overnight mood regulation did not differ between groups following the sad or happy inductions. SWA did not significantly change for either group on the sad induction night compared with baseline. In BD only, SWA on the sad night was related to impaired overnight negative mood regulation. On the happy induction night, SWA increased relative to baseline in both groups, though SWA was not related to overnight mood regulation for either group.
These findings indicate that SWA disruption may play a role in sustaining negative mood state from the previous night in interepisode BD. However, positive mood state could enhance SWA in bipolar patients and healthy adults.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
A systematic review was conducted to evaluate whether healthier dietary consumption among children and adolescents impacts executive functioning. PubMed, Education Resources Information Center, PsychINFO and Thomson Reuters’ Web of Science databases were searched, and studies of executive functioning among children or adolescents aged 6–18 years, which examined food quality, macronutrients and/or foods, were included. Study quality was also assessed. In all, twenty-one studies met inclusion criteria. Among the twelve studies examining food quality (n 9) or macronutrient intakes (n 4), studies examining longer-term diet (n 6) showed positive associations between healthier overall diet quality and executive functioning, whereas the studies examining the acute impact of diet (n 6) were inconsistent but suggestive of improvements in executive functioning with better food quality. Among the ten studies examining foods, overall, there was a positive association between healthier foods (e.g. whole grains, fish, fruits and/or vegetables) and executive function, whereas less-healthy snack foods, sugar-sweetened beverages and red/processed meats were inversely associated with executive functioning. Taken together, evidence suggests a positive association between healthy dietary consumption and executive functioning. Additional studies examining the effects of healthier food consumption, as well as macronutrients, on executive functioning are warranted. These studies should ideally be conducted in controlled environments and use validated cognitive tests.
Civilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate.
The joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009.
There were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2–39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2–22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1–4.1], less so when previously deployed (OR 1.6, 95% CI 1.1–2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8–1.8). Adjustment for a differential ‘healthy warrior effect’ cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status.
Efforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.
To examine cross-national patterns and correlates of lifetime and 12-month comorbid DSM-IV anxiety disorders among people with lifetime and 12-month DSM-IV major depressive disorder (MDD).
Nationally or regionally representative epidemiological interviews were administered to 74 045 adults in 27 surveys across 24 countries in the WHO World Mental Health (WMH) Surveys. DSM-IV MDD, a wide range of comorbid DSM-IV anxiety disorders, and a number of correlates were assessed with the WHO Composite International Diagnostic Interview (CIDI).
45.7% of respondents with lifetime MDD (32.0–46.5% inter-quartile range (IQR) across surveys) had one of more lifetime anxiety disorders. A slightly higher proportion of respondents with 12-month MDD had lifetime anxiety disorders (51.7%, 37.8–54.0% IQR) and only slightly lower proportions of respondents with 12-month MDD had 12-month anxiety disorders (41.6%, 29.9–47.2% IQR). Two-thirds (68%) of respondents with lifetime comorbid anxiety disorders and MDD reported an earlier age-of-onset (AOO) of their first anxiety disorder than their MDD, while 13.5% reported an earlier AOO of MDD and the remaining 18.5% reported the same AOO of both disorders. Women and previously married people had consistently elevated rates of lifetime and 12-month MDD as well as comorbid anxiety disorders. Consistently higher proportions of respondents with 12-month anxious than non-anxious MDD reported severe role impairment (64.4 v. 46.0%; χ21 = 187.0, p < 0.001) and suicide ideation (19.5 v. 8.9%; χ21 = 71.6, p < 0.001). Significantly more respondents with 12-month anxious than non-anxious MDD received treatment for their depression in the 12 months before interview, but this difference was more pronounced in high-income countries (68.8 v. 45.4%; χ21 = 108.8, p < 0.001) than low/middle-income countries (30.3 v. 20.6%; χ21 = 11.7, p < 0.001).
Patterns and correlates of comorbid DSM-IV anxiety disorders among people with DSM-IV MDD are similar across WMH countries. The narrow IQR of the proportion of respondents with temporally prior AOO of anxiety disorders than comorbid MDD (69.6–74.7%) is especially noteworthy. However, the fact that these proportions are not higher among respondents with 12-month than lifetime comorbidity means that temporal priority between lifetime anxiety disorders and MDD is not related to MDD persistence among people with anxious MDD. This, in turn, raises complex questions about the relative importance of temporally primary anxiety disorders as risk markers v. causal risk factors for subsequent MDD onset and persistence, including the possibility that anxiety disorders might primarily be risk markers for MDD onset and causal risk factors for MDD persistence.
Regular church attendance is strongly associated with a higher probability of voting. It is an open question as to whether this association, which has been confirmed in numerous surveys, is causal. The repeal of the laws restricting Sunday retail activity (‘blue laws’) is used to measure the effects of church-going on political participation. Blue laws’ repeal caused a 5 percent decrease in church attendance. Its effect on political participation was measured and it was found that, following the repeal, turnout fell by approximately 1 percentage point. This decline in turnout is consistent with the large effect of church attendance on turnout reported in the literature, and suggests that church attendance may have a significant causal effect on voter turnout.
Though poorly defined, hypersomnia is associated with negative health outcomes and new-onset and recurrence of psychiatric illness. Lack of definition impedes generalizability across studies. The present research clarifies hypersomnia diagnoses in bipolar disorder by exploring possible subgroups and their relationship to prospective sleep data and relapse into mood episodes.
A community sample of 159 adults (aged 18–70 years) with bipolar spectrum diagnoses, euthymic at study entry, was included. Self-report inventories and clinician-administered interviews determined features of hypersomnia. Participants completed sleep diaries and wore wrist actigraphs at home to obtain prospective sleep data. Approximately 7 months later, psychiatric status was reassessed. Factor analysis and latent profile analysis explored empirical groupings within hypersomnia diagnoses.
Factor analyses confirmed two separate subtypes of hypersomnia (‘long sleep’ and ‘excessive sleepiness’) that were uncorrelated. Latent profile analyses suggested a four-class solution, with ‘long sleep’ and ‘excessive sleepiness’ again representing two separate classes. Prospective sleep data suggested that the sleep of ‘long sleepers’ is characterized by a long time in bed, not long sleep duration. Longitudinal assessment suggested that ‘excessive sleepiness’ at baseline predicted mania/hypomania relapse.
This study is the largest of hypersomnia to include objective sleep measurement, and refines our understanding of classification, characterization and associated morbidity. Hypersomnia appears to be comprised of two separate subgroups: long sleep and excessive sleepiness. Long sleep is characterized primarily by long bedrest duration. Excessive sleepiness is not associated with longer sleep or bedrest, but predicts relapse to mania/hypomania. Understanding these entities has important research and treatment implications.
The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) has found that the proportional elevation in the US Army enlisted soldier suicide rate during deployment (compared with the never-deployed or previously deployed) is significantly higher among women than men, raising the possibility of gender differences in the adverse psychological effects of deployment.
Person-month survival models based on a consolidated administrative database for active duty enlisted Regular Army soldiers in 2004–2009 (n = 975 057) were used to characterize the gender × deployment interaction predicting suicide. Four explanatory hypotheses were explored involving the proportion of females in each soldier's occupation, the proportion of same-gender soldiers in each soldier's unit, whether the soldier reported sexual assault victimization in the previous 12 months, and the soldier's pre-deployment history of treated mental/behavioral disorders.
The suicide rate of currently deployed women (14.0/100 000 person-years) was 3.1–3.5 times the rates of other (i.e. never-deployed/previously deployed) women. The suicide rate of currently deployed men (22.6/100 000 person-years) was 0.9–1.2 times the rates of other men. The adjusted (for time trends, sociodemographics, and Army career variables) female:male odds ratio comparing the suicide rates of currently deployed v. other women v. men was 2.8 (95% confidence interval 1.1–6.8), became 2.4 after excluding soldiers with Direct Combat Arms occupations, and remained elevated (in the range 1.9–2.8) after adjusting for the hypothesized explanatory variables.
These results are valuable in excluding otherwise plausible hypotheses for the elevated suicide rate of deployed women and point to the importance of expanding future research on the psychological challenges of deployment for women.