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MRI-derived cortical folding measures are an indicator of largely genetically driven early developmental processes. However, the effects of genetic risk for major mental disorders on early brain development are not well understood.
We extracted cortical complexity values from structural MRI data of 580 healthy participants using the CAT12 toolbox. Polygenic risk scores (PRS) for schizophrenia, bipolar disorder, major depression, and cross-disorder (incorporating cumulative genetic risk for depression, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit hyperactivity disorder) were computed and used in separate general linear models with cortical complexity as the regressand. In brain regions that showed a significant association between polygenic risk for mental disorders and cortical complexity, volume of interest (VOI)/region of interest (ROI) analyses were conducted to investigate additional changes in their volume and cortical thickness.
The PRS for depression was associated with cortical complexity in the right orbitofrontal cortex (right hemisphere: p = 0.006). A subsequent VOI/ROI analysis showed no association between polygenic risk for depression and either grey matter volume or cortical thickness. We found no associations between cortical complexity and polygenic risk for either schizophrenia, bipolar disorder or psychiatric cross-disorder when correcting for multiple testing.
Changes in cortical complexity associated with polygenic risk for depression might facilitate well-established volume changes in orbitofrontal cortices in depression. Despite the absence of psychopathology, changed cortical complexity that parallels polygenic risk for depression might also change reward systems, which are also structurally affected in patients with depressive syndrome.
A new optimized quasi-helically symmetric configuration is described that has the desirable properties of improved energetic particle confinement, reduced turbulent transport by three-dimensional shaping and non-resonant divertor capabilities. The configuration presented in this paper is explicitly optimized for quasi-helical symmetry, energetic particle confinement, neoclassical confinement and stability near the axis. Post optimization, the configuration was evaluated for its performance with regard to energetic particle transport, ideal magnetohydrodynamic stability at various values of plasma pressure and ion temperature gradient instability induced turbulent transport. The effects of discrete coils on various confinement figures of merit, including energetic particle confinement, are determined by generating single-filament coils for the configuration. Preliminary divertor analysis shows that coils can be created that do not interfere with expansion of the vessel volume near the regions of outgoing heat flux, thus demonstrating the possibility of operating a non-resonant divertor.
School-based transition planning is legally mandated for all students with disabilities. Much of the existing school psychology literature discusses procedures to construct a transition plan, with little attention given to evaluating the effectiveness of the plan. In this chapter, we argue that school-to-work transition planning should occur within a problem-solving framework as it is rare that a transition plan will be entirely successful as originally written. As such, transition-planning steps should include (a) identification of transition-plan goals, (b) analysis of transition needs and strengths, (c) transition-plan implementation and monitoring, and (d) transition-plan evaluation and adjustment. We also extend the school psychology literature by applying the person–environment–occupation (PEO) model (Law et al., 1996) to transition problem solving. Implications for the roles of school psychologists engaged in transition planning are discussed throughout.
Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness.
A total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects.
Disease state (pFWE < 0.042) and number of hospitalizations (pFWE< 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF.
Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.
Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.
We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.
We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.
This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).
To examine the theory of the mind (TOM) in BPD patients.
Fifteen BPD patients (age>18) meeting criteria for BPD were compared to 16 healthy matched controls on two measures of TOM: mental state decoding (MSD) and mental state reasoning (MSR). MSD is the ability to perceive social cues (faces expression, voices) while MSR is the ability to infer on mental states with experiment, learning, context. MSR was measured by the faux pas recognition task assessing the ability to identify a faux pas in a social situation (range 0-60) and a comic strips task measuring the ability to infer intention (range 0-28). MSD was assessed by a video task reporting the ability to infer false belief and intention of deceit on visual motor action. Depressive symptoms (Beck Depression Inventory) and axis II comorbidity traits (Personality Disorder Questionnaire-4+) were also assessed.
Mean (SD) age was 26.0 (4.1) and two participants were of male gender (6.5%). BPD patients scored significantly lower than controls on the both MSR measures: faux pas task mean (SD) scores of 46.6(14.1) vs 58.0(2.8) (p=0.002) and comic strips mean (SD) scores of 26.1(1.5) vs 27.4(1.3) (p=0.001). No significant differences were found on the video task. Multivariate analyses showed that faux pas score was predicted by BPD diagnosis independently from level of depressive symptoms, history of hypomanic episode, schizotypic and antisocial personality disorder traits (F=4.32, df=6, p< 0.01).
BPD is associated with a TOM deficit on mental state reasoning tasks even after controlling for confounding variables.
Few studies have suggested the efficacy of cognitive-behavioural therapy (CBT) in inpatients suffering from major depressive disorder (MDD). The present study aims at examining the efficacy of Ultra-brief CBT (UCBT) in depressed inpatients.
Twenty-two patients (age>18) admitted to the psychiatric ward of Toulouse University Hospital for MDD were randomised to receive for two weeks either UCBT (n=11) or treatment as usual (TAU) (n=11). UCBT consisted in 6 sessions of CBT while TAU consisted in supportive sessions. Both types of sessions were performed by psychiatric residents. Both groups also received pharmacological and institutional cares. Primary outcome was depressive symptoms assessed by the Beck Depression Inventory (BDI-II) and the Hamilton Depressive Rating Scale (HDRS) before and after treatment (2 weeks).
There were no differences between the groups on any baseline variables. Mean age was 48.4 (SD=12.7) and 36.4% (n=8) were of male gender. Mean baseline HDRS scores were 23.3(SD=6.3) and 19.3(SD=3.9) and BDI scores were 36.7(SD=12) and 36.1(SD=7.5) for the UCBT and TAU groups respectively. At the end of treatment, mean HDRS scores were 12.3(SD=10.1) and 14.4(SD=7.8) and BDI scores were 18.8(SD=16.8) and 20.6(SD=11.4) for the CBT and TAU groups respectively. Both groups displayed a significant decrease on HDRS and BDI scores (all p< 0.05). An analyse of variance showed an interaction time by group in favour of the UCBT group on HDRS score (F=6.66; p=0.018).
Our results suggest that UCBT might be more efficacious than supportive therapy in depressed inpatients.
Although the Peritraumatic Distress Inventory (PDI) and Peritraumatic Dissociative Experiences Questionnaire (PDEQ) are both useful for identifying adults at risk of developing acute and chronic post-traumatic stress disorder (PTSD), they have not been validated in school-aged children. The present study aims at assessing the psychometric properties of the PDI and PDEQ in a sample of French-speaking school children.
One-hundred and thirty-three school-aged victims of road traffic accidents were consecutively enrolled into this study via the emergency room. Mean(SD) age was 11.7(2.2) and 56.4% (n=75) of them were of male gender. The 13-item self-report PDI (range 0-52) and the 10-item self report PDEQ (range 10-50) were assessed within one week of the accident. Symptoms of PTSD were assessed 1 and 6 months later using the 20-item self-report Child Post-Traumatic Stress Reaction Index (CPTS-RI) (range 0-80).
Mean(SD) PDI and PDEQ scores were 19.1(10.1) and 21.1(7.6), respectively, while mean(SD) CPTS-RI scores at 1- and 6-months were 22.6(12.4) and 20.6(13.5), respectively. Cronbach's alpha coefficients were 0.8 and 0.77 for the PDI and PDEQ, respectively. The 1-month test-retest correlation coefficient (n=33) was 0.77 for both measures. The PDI demonstrated a 2-factor structure while the PDEQ displayed a 1-factor structure. As with adults, the two measures were inter-correlated (r=0.52) and correlated with subsequent PTSD symptoms (r=0.21−0.56; p< 0.05).
The PDI and PDEQ are reliable and valid in school-aged children, and predict PTSD symptoms.
It remains unknown whether peritraumatic reactions predict PTSD symptoms in younger populations. To prospectively investigated the power of self-reported peritraumatic distress and dissociation to predict the development of PTSD symptoms at 1-month in school-aged children.
A sample of 103 school-aged children (8-15 years old) admitted to an Emergency Department after a road traffic accident were consecutively enrolled. Peritraumatic distress was assessed using the Peritraumatic Distress Inventory (range 0-52) and peritraumatic dissociation was assessed using the Peritraumatic Dissociative Experiences Questionnaire (PDEQ) (range 10-50). PTSD symptoms were measured at 1-month by both the child version of the clinician-administered PTSD Scale (CAPS-CA) (range: 0-136) and the Child Post-traumatic Stress Reaction Index (CPTS-RI) (range 0-80).
Mean(SD) participants’ age was 11.7(2.2) and 53.4% (n=55) of them were of male gender. At baseline, mean PDI and PDEQ scores were 21.4 (SD=7.8) and 19.2 (SD=10.2), respectively. At 1-month, mean self-reported (CPTS-RI) and interviewer-based (CAPS-CA) PTSD symptom scores were 23.2 (SD=12.1) and 19 (SD=16.9), respectively. According to the CAPS-CA, 5 children (4.9%) suffered from full PTSD. Bivariate analyses demonstrated a significant association between peritraumatic variables (PDI and PDEQ) and both CAPS-CA and CPTS-RI (r=0.22-0.57; all p< 0.05). However, in a multivariate analysis, PDI was the only significant predictor of acute PTSD symptoms (Beta=0.33, p< 0.05).
As has been found in adults, peritraumatic distress is a robust predictor of who will develop PTSD symptoms among school-aged children.
Violent behaviors in psychiatric emergency departments are a common problem. The aim is to study characteristics of patients who need intense preventive care measures and who act violently.
The study was conducted in a locked short term psychiatric inpatient unit and involved 172 patients admitted in a 8 months period. Sociodemographic and clinical data were obtained through a review of the medical records. Secclusion, restraint and agressive behaviors were noted on specific nurse sheets.
Aggressive behaviors or intense preventive measures concerned 34% (n=59) of the 172 patients. Among these 59 patients, 61% (n=36) are men and the mean age is 34,9 years, 28 had seclusion, 51 had restraint and 11 had physical aggression or against object aggression. The diagnosis are schizophrenic disorders for 63% (n=37), dependence or substance abuse for 11% (n=7), mania for 10% (n=6), depression for 3,5% (n=2). For 27% (n=16) of them it was first time in Emergency Department and 30,5% (n=18) were intoxicated at admission. The mean neuroleptic treatments dosis of these patients at admission were 656mg (equivalent chlorpromazine).
Patients concerned by seclusion, restraint and aggressive behavior are more frequently men with schizophrenic disorders, high neuroleptic dosis, and various past admissions in the Emergency Department.
Les mécanismes pharmacodynamiques à l’origine des diabètes médicamenteux sous neuroleptiques ne sont pas clairement établis . Des données pharmacodynamiques expérimentales nous ont conduits à faire l’hypothèse d’une implication du récepteur sérotoninergique 5HT2 C [2,3].
Évaluer une association entre le niveau d’affinité pour le récepteur 5HT2 C de certains psychotropes et la notification d’un diabète avec ces médicaments.
À partir de la base de données de pharmacovigilance de l’OMS, Vigibase®, nous avons identifié les observations enregistrées durant la période du 01/01/1994 au 29/03/2013, correspondant à une liste de 15 médicaments psychotropes d’affinité 5HT2 C connue. Nous avons recherché une disproportionnalité entre le niveau d’affinité 5HT2 C et la notification de diabète à l’aide de modèles de régression logistique. Le premier modèle ajustait sur les facteurs cliniques de confusion (modèle A) et le deuxième intégrait, en plus, les autres affinités réceptorielles (5HT2A, 5HT1A, D2, D3, Δ1et Δ2).
Parmi les 100 966 notifications, 1 790 (1,77 %) correspondaient à un effet indésirable de type diabète médicamenteux. Nous avons retrouvé une association significative et croissante entre le niveau d’affinité 5HT2 C et les notifications de diabète. Dans le modèle A, par rapport à une affinité 5HT2 C faible (référence), le rapport de cote (RC) pour une affinité 5HT2 C moyenne était de 2,98 (IC 95 % [2,54–3,48]) et celui pour une affinité 5HT2 C importante de 5,85 (IC 95 % [5,03–6,80]). Ces résultats étaient renforcés par le modèle B : RC = 3,15 (IC 95 % [2,54–3,91]) pour une affinité moyenne, RC = 7,07 [5,79–8,64] pour une affinité importante.
Ce travail illustre une méthode d’étude de type pharmacovigilance-pharmacodynamique (étude PV-PD). Il établit une association entre le niveau d‘affinité 5HT2 C et les notifications de diabète dans Vigibase®. Des études intégrant le niveau d’activité pour le récepteur 5HT2 C sont nécessaires pour compléter ces résultats.
Most patients (70%) discontinuing tobacco smoking will relapse within 6 months. A major challenge is the understanding of the processes involved in relapse. High cigarette craving has been proposed as a predictor of relapse. A recent study suggests that low inhibitory control capacities (low ability to inhibit prepotent responses) were correlated with high nicotine dependence. In this study, we focused on the link between inhibition capacity, craving, tobacco dependence and relapse.
134 smokers willing to quit smoking were consecutively included and followed prospectively. Tobacco dependence was assessed with the Fagerstorm test. We used the Hayling task to measure their inhibitory capacity and a specific questionnaire to measure tobacco craving (TCQ 12). Assessments were performed at baseline, 1, 3 and 6 months after smoking cessation. Any relapse in smoking during the follow-up was evaluated.
There was an association between lower inhibition capacities and higher dependance level at baseline. Low inhibition capacities were an independent predictor of relapse at 6 months (logit R 2 = .08, F (2,134) = 10.851, p <. 004). In contrast, although level of tobacco dependence and craving predicted relapse in the short term (first month), they did not predict relapse at 6 months.
These results suggest that inhibition capacities may predict smoking relapse in the long term (6 months) better than usual measures of craving. In clinical practice, an inhibition test, which is short and feasible, could be of interest to identify smokers at higher risk of relapse.
Increasing evidence suggests that clock genes may be implicated in a spectrum of psychiatric diseases, including sleep and mood related disorders as well as schizophrenia. The bHLH transcription factors SHARP1/DEC2/BHLHE41 and SHARP2/DEC1/BHLHE40 are modulators of the circadian system and SHARP1/DEC2/BHLHE40 has been shown to regulate homeostatic sleep drive in humans.
In this study, we characterized Sharp1 and Sharp2 double mutant mice (S1/2-/-) using online EEG recordings in living animals, behavioral assays, global gene expression profiling and bioinformatic modeling. Gene expression in human brains samples was performed with qRT-PCR.
EEG recordings revealed attenuated sleep/wake amplitudes and alterations of theta oscillations. Increased sleep in the dark phase is paralleled by reduced voluntary activity and cortical gene expression signatures reveal associations with psychiatric diseases. S1/2-/- mice display alterations in novelty induced activity, anxiety and curiosity. Moreover, mutant mice exhibit impaired working memory and deficits in prepulse inhibition resembling symptoms of psychiatric diseases. Network modeling indicates a connection between neural plasticity and clock genes, particularly for SHARP1 and PER1, which are also significantly downregulated in the frontal cortex of schizophrenic patients.
Our findings support the hypothesis that abnormal sleep and certain (endo)phenotypes of psychiatric diseases may be caused by common mechanisms involving components of the molecular clock including SHARP1 and SHARP2
Suicide is a major public health issue, and a critical step in its prevention is a psychiatric assessment of individuals following suicide attempts (NICE 2008). In cases where patients attempt suicide through substance overdose, the central nervous system and consciousness are altered in significant ways. This is problematic, given that patients must have recovered sufficient cognitive capacity if a psychiatric assessment is to yield a meaningful and suitable care plan that the patient will recall and follow (Lukens 2006). Currently, there is no validated tool to assess whether sufficient cognitive recovery has occurred in such patients to ensure their memory of the assessment. Therefore, our goal was to identify indicators that predict preserved memory of undergoing a psychiatric assessment. We carried out a prospective study with 41 patients recruited from an emergency department. We collected data on cognitive tests (including WAIS coding test), memory self-assessment, plasma benzodiazepine levels, age, gender, and educational level at the time of psychiatric assessment. We then assessed patients’ memory for undergoing a psychiatric interview 24 hours post-assessment, using an episodic memory score. Whereas memory self-assessment did not predict the episodic memory score, age, plasma benzodiazepine level, and cognitive test scores significantly influenced it, predicting 70% of memory score variation. Among these factors, the WAIS coding test predicted 57% of the memory score variation. To improve clinical practice, it may be useful to assess visual scanning, processing speed, and attentional function prior to psychiatric interview to ensure later patient recall.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Serum BDNF levels are decreased in major depressive disorder (MDD) and tend to normalize under antidepressant treatment, serving as a treatment outcome predictor. BDNF is initially synthetized as precursor protein proBDNF and is cleaved to mature BDNF (mBDNF) while only the latter exerts neurotrophic activity.
The aim was to explore if a specific enzyme-linked immunosorbent assay (ELISA) kit for mBDNF in serum would be superior to the unspecific assessment of total serum BDNF in predicting treatment response in MDD.
Twenty-five patients with MDD underwent standardized treatment with duloxetine. Severity of depression was measured by Hamilton Depression Rating Scale (HDRS) at baseline (BL), after one (W1), two (W2) and six weeks (W6) of treatment. Treatment response was defined as a HDRS ≥ 50% reduction of BL score at W6. mBDNF and total BDNF serum levels were determined at BL, W1 and W2.
A high and stable correlation was found between mBDNF and total BDNF serum levels over all measurements. The predictive value of mBDNF BL levels and mBDNFΔW1 to response was similar to that of total BDNF BL and total BDNFΔW1. The assessment of serum mBDNF was not superior to total BDNF in prediction of treatment outcome.
Not only baseline total BDNF but also mBDNF is predictive to treatment outcome. The later might represent the main player in this respect, which supports the idea of a functional link between neuroplasticity and MDD.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
We present results of a multiwavelength study of the isolated dual AGN system Was 49. Observations show that the dominant component in this interacting system, Was 49a, is a spiral galaxy, while Was 49b is hosted in a dwarf galaxy located at 8 kpc from the nucleus of Was 49a, at the edge of its disk. The intriguing fact about this system is the luminosity of their corresponding AGNs. While Was 49a hosts a low luminosity Seyfert 2 with Lbol˜1043erg s–1, Was 49b has a Seyfert 2 with Lbol ˜ 1045erg s–1, in the luminosity range of Quasars. Furthermore, estimates of the black hole and host galaxy masses of Was 49b indicate a black hole significantly more massive than one would expect from scaling relations. This result is in contrast with findings that the most luminous merger-triggered AGNs are found in major mergers and that minor mergers predominantly enhance AGN activity in the primary galaxy.
We have analyzed Chandra/High Energy Transmission Grating spectra of the X-ray emission line gas in the Seyfert galaxy NGC 4151. The zeroth-order spectral images show extended H- and He-like O and Ne, up to a distance r ˜ 200 pc from the nucleus. Using the 1st-order spectra, we measure an average line velocity ˜230 km s–1, suggesting significant outflow of X-ray gas. We generated Cloudy photoionization models to fit the 1st-order spectra; the fit required three distinct emission-line components. To estimate the total mass of ionized gas (M) and the mass outflow rates, we applied the model parameters to fit the zeroth-order emission-line profiles of Ne IX and Ne X. We determined an M ≍ 5.4 × 105Mʘ. Assuming the same kinematic profile as that for the [O III] gas, derived from our analysis of Hubble Space Telescope/Space Telescope Imaging Spectrograph spectra, the peak X-ray mass outflow rate is approximately 1.8 Mʘ yr–1, at r ˜ 150 pc. The total mass and mass outflow rates are similar to those determined using [O III], implying that the X-ray gas is a major outflow component. However, unlike the optical outflows, the X-ray emitting mass outflow rate does not drop off at r > 100pc, which suggests that it may have a greater impact on the host galaxy.
Stellarator configurations with reactor relevant energetic particle losses are constructed by simultaneously optimizing for quasisymmetry and an analytically derived metric (
), which attempts to align contours of the second adiabatic invariant,
with magnetic surfaces. Results show that with this optimization scheme it is possible to generate quasihelically symmetric equilibria on the scale of ARIES-CS which completely eliminate all collisionless alpha particle losses within normalized radius
. We show that the best performance is obtained by reducing losses at the trapped–passing boundary. Energetic particle transport can be improved even when neoclassical transport, as calculated using the metric
, is degraded. Several quasihelically symmetric equilibria with different aspect ratios are presented, all with excellent energetic particle confinement.
Flaviviruses include many viruses causing encephalitis, including West Nile encephalitis, St. Louis encephalitis, tick-borne encephalitis and Japanese encephalitis. Human pegivirus genotype-1 (HPgV-1) is a lesser known member of the Flaviviridae family and has been identified in human serum, cerebrospinal fluid and brain tissue. Here, we describe two adult patients with fatal HPgV-1-associated encephalitis. Neuroimaging revealed multifocal lesions, initially present in the periventricular and brain stem white matter, then one year later throughout the corona radiata bilaterally with marked involvement of the brainstem and cervical spinal cord. Phylogenetic analyses of HPgV-1 showed clustering of brain-derived sequences from both patients with other human pegiviruses. In both patients, a novel 87-nucleotide deletion in the viral NS2 gene was detected. The presence of positive and negative strand HPgV-1 RNA and viral antigens in both patients indicated viral persistence and replication in the CNS. Autopsy showed lymphocyte infiltration and gliosis predominantly in white matter of the brain and brain stem but, to a lesser extent, also in grey matter. Immunofluorescence revealed HPgV-1 NS5A antigen in lymphocytes as well as in astrocytes and oligodendrocytes. Thus, we hypothesize that the novel deletion in the NS2 coding region may have caused HPgV-1 neuroadaptation or might represent a yet unrecognized genotype of human pegivirus.
This presentation will enable the learner to:
1. Describe the clinical and neuropathological features of fatal human pegivirus-associated encephalitis
2. Recognize the importance of molecular analysis in encephalitis cases with unknown etiology