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In a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors.
In a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models.
A lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (β = −0.09, t = −3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (β = 0.09, t = 3.04, p = 0.002).
In this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD.
There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.
To investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls.
Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls.
Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest.
Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.
Declaration of interest
R.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
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.
Disaster responders are frequently emergency physicians (EPs). Effective response is enhanced by the strong support of home institutions and clear policies for backfill of regular duties. A group of disaster medicine responders and researchers worked with an academic department of emergency medicine to create a policy that addresses concerns of deploying physicians, colleagues remaining at the home institution, and administrators. This article describes the process and content of this policy development work.
KahnCA, KoenigKL, SchultzCH. Emergency Physician Disaster Deployment: Issues to Consider and a Model Policy. Prehosp Disaster Med. 2017;32(4):462–464.
Public health interest in norovirus (NoV) has increased in recent years following improved diagnostics, global burden estimates and the development of NoV vaccine candidates. This study aimed to describe the detection rate, clinical characteristics and environmental features associated with NoV detection in hospitalized children <5 years with diarrhoea in South Africa (SA). Between 2009 and 2013, prospective diarrhoeal surveillance was conducted at four sites in SA. Stool specimens were collected and screened for NoVs and other enteric pathogens using molecular and serological assays. Epidemiological and clinical data were compared in patients with or without detection of NoV. The study detected NoV in 15% (452/3103) of hospitalized children <5 years with diarrhoea with the majority of disease in children <2 years (92%; 417/452). NoV-positive children were more likely to present with diarrhoea and vomiting (odds ratio (OR) 1·3; 95% confidence interval (CI) 1·1–1·7; P = 0·011) with none-to-mild dehydration (adjusted OR 0·5; 95% CI 0·3–0·7) compared with NoV-negative children. Amongst children testing NoV positive, HIV-infected children were more likely to have prolonged hospitalization and increased mortality compared with HIV-uninfected children. Continued surveillance will be important to consider the epidemic trends and estimate the burden and risk of NoV infection in SA.
Africa is experiencing a rapid increase in adult obesity and associated cardiometabolic diseases (CMDs). The H3Africa AWI-Gen Collaborative Centre was established to examine genomic and environmental factors that influence body composition, body fat distribution and CMD risk, with the aim to provide insights towards effective treatment and intervention strategies. It provides a research platform of over 10 500 participants, 40–60 years old, from Burkina Faso, Ghana, Kenya and South Africa. Following a process that involved community engagement, training of project staff and participant informed consent, participants were administered detailed questionnaires, anthropometric measurements were taken and biospecimens collected. This generated a wealth of demographic, health history, environmental, behavioural and biomarker data. The H3Africa SNP array will be used for genome-wide association studies. AWI-Gen is building capacity to perform large epidemiological, genomic and epigenomic studies across several African counties and strives to become a valuable resource for research collaborations in Africa.
Poor educational achievement is associated with a range of psychiatric disorders. Several studies suggest that this underperformance is due to cognitive deficits that commence before disease onset and reflect a genetic risk for this disorder. However, the specificity and the familial contribution of this cognitive deficit are not clear. We analysed lifetime educational achievement of psychiatric patients diagnosed with schizophrenia, bipolar or depressive disorder and their unaffected siblings.
In a register-based case-control study, 1561 patients with schizophrenia, 813 patients with bipolar disorder, 8112 patients with depression, and their siblings were each matched with eight population controls. Patients, siblings and controls were compared on the highest educational stream they completed.
Lower educational achievement was present in schizophrenia patients from primary school onwards [completing primary school: odds ratio (OR) 0.69; completing secondary school: OR 0.69; completing academic education: OR 0.46], compared to patients with bipolar disorder or depression. Siblings of schizophrenia, bipolar or depressed patients showed no underachievement at primary or secondary school, but siblings of schizophrenia patients as well as siblings of depressed patients were less successful in their educational achievement after secondary school (completing academic education, schizophrenia siblings: OR 0.90; depressive disorder siblings: OR 0.91).
Educational underachievement from primary school onwards is specifically related to schizophrenia and not to bipolar disorder or depression. Moreover, it appears to be a harbinger of the illness, since it is not found in their siblings. These results add to evidence that early cognitive deficits are a distinct feature of the schizophrenia phenotype.
Although additional surveys with large Schmidt telescopes continue to yield small catches of additional planetaries (Kohoutek) one cannot escape the conclusion that most planetaries available to existing equipment have been detected. Much remains to be done with powerful Schmidt equipment in the southern hemisphere, especially in the Magellanic Clouds. A vast body of photometric and spectroscopic observation needs to be garnered for the numerous faint nebulae so far discovered.
Spectroscopic and spectrophotometric studies have been carried out for most bright planetaries (λ < 5800) but much remains to be done in the red and near infrared. Important advances have been made in the far infrared (~10μ) (Gillett, Low, Stein, Woolf) where a number of planetaries seem to show abnormally strong continua. This abnormally intense radiation has been attributed to non-thermal emission, effects of many faint lines, and to thermal emission by dust grains (Krishna Swamy, O’Dell) with perhaps the bulk of the evidence favoring the last-mentioned hypothesis. An increasing number of radio observations from 9·5 mm to 73 cm (Thompson, Colvin, Stanley, LeMarne, Kaftan-Kassim, Babieri and Ficarra, Terzian, L. Aller and Milne, Hughes) all indicate that planetaries are thermal sources.
The X-ray transient 4U1543-47 was observed in 1983 by the EXOSAT observatory near the maximum of an outburst. The X-ray spectrum was measured using a gas scintillation proportional counter (GSPC) and a transmission grating spectrometer (TGS). Two emission line features are resolved. A broad (FWHM ~2.7 keV) line at 5.9 keV is detected in the GSPC, which we interprete as a redshifted and broadened iron Kα line. The Une broadening and redshift may arise from either Compton scattering in a cool plasma with small optical depth (τ ≈ 5), or from Doppler and relativistic effects in the vicinity of a compact object. The spectrum below 2 keV, obtained with the TGS, shows evidence for a broad emission line feature at 0.74 keV, which may be an iron L-transition complex. However, we find that such an emission feature could be an artifact caused by an anomalously low interstellar absorption by neutral Oxygen. The continuum emission is extremely soft and is well described by an unsaturated Comptonized spectrum from a very cool plasma (kT = 0.84 keV) with large scattering depth (τ ≈ 27). The continuum spectrum is strikingly similar to that of black hole candidate LMC X-3.
We have initiated an extensive atomic modeling effort applicable to X-ray line emission in high-temperature astrophysical plasmas. The emphasis of our program is on the detailed accounting of the mechanisms which populate excited states of highly ionized atoms over a wide range of electron temperatures and densities. As a first demonstration we have calculated spectra for the important L -shell ions Fe XVI-XIX in a complete collisional-radiative model under conditions appropriate to solar coronal plasmas. Using methods presented here, we have synthesized the X-ray spectra of solar flares and active regions over the wavelength interval 13 – 18 Ǡ. The atomic model, which includes 705 atomic energy levels, is the largest and most detailed of its kind. In this introductory paper, we discuss the effects of dielectronic recombination on the spectrum of Fe XVII and present a new technique whereby the 3s lines can be used as a diagnostic of the electron temperature. Also included are new values for the rate of resonance excitation of the n=3 Fe XVII excited states. These rates are lower than those previously obtained and suggest that resonance excitation does not contribute significantly to the population kinetics. Finally, we present a direct comparison of our a calculated model spectrum with data from a solar flare.
A multi-faceted, multi-institutional laboratory astrophysics program is carried out at the Livermore electron beam ion trap facility, which is a mature spectroscopic source with unsurpassed controls and capabilities, and an unparalleled assortment of spectroscopic equipment, including a full complement of grating and crystal spectrometers and a 6x6 micro-calorimeter array. Recent results range from the calibration of x-ray diagnostics, including the Fe XVII and Fe XXV emission lines, extensive lists of L-shell ions, the first laboratory simulation and fit of a cometary x-ray emission spectrum, and the discovery of new spectral diagnostics for measuring magnetic field strengths.
Schizophrenia is a severe mental disorder with a typical onset in adolescence or young adulthood. Global lifetime prevalence is about 0.3–0.7% (van Os and Kapur, 2009). Symptoms can be divided into positive symptoms (e.g., delusions and hallucinations), negative (deficit) symptoms (e.g., anhedonia, blunted affect, and avolition), and disorganization symptoms (e.g. disorganized speech). In addition, the majority of schizophrenia patients show cognitive dysfunctioning. In general, schizophrenia patients have deficits in most cognitive domains (e.g., attention, memory, and executive functioning) approximately one standard deviation below the normative mean (Mesholam-Gately et al., 2009). However, there is no specific cognitive profile that distinguishes schizophrenia patients from patients with other Diagnostic and Statistical Manual of Mental Disorders (DSM) (American Psychiatric Association, 2000) diagnoses. Schizophrenia is often preceded by a prodromal period of months to years in which mild psychotic and other symptoms can occur and psycho-social functioning deteriorates.
A short case example:
Michael is a 20-year-old philosophy student who has been skipping a lot of classes lately. In the class room he hears his name being whispered by fellow students in the front row, although the distance is too far to be able to hear them. During the breaks, he hears other students talk and laugh about him. Sometimes he thinks they are conspiring to kill him, especially because he also hears them talking about how they are going to get him when he is alone in his room. He is unable to concentrate on what the professor says in the classroom. It is as if he cannot extract the meaning of what is being said. He has suffered from that problem for several years. His grades have decreased during this period and he will probably drop out from university. He also experiences a feeling of emptiness, which started years ago. Nothing seems to get through to him. Even the birth of his niece left him cold. He experiences a loss of identity. Lately, he sometimes has the feeling that someone else is putting thoughts in his head or moves his limbs outside his own will.
Schizophrenia has remained a mental disorder with an unknown etiology, unchanged prevalence, and disabling outcomes for the vast majority of the patients. Sustained recovery occurs in less than 14% within the first five years following a psychotic episode and in an additional 16% in a later phase (Harrison et al., 2001; Robinson et al., 2004).
Antibiotic treatment for asymptomatic bacteriuria (ASB) is prevalent but often contrary to published guidelines.
To evaluate risk factors for treatment of ASB.
Retrospective observational study.
A tertiary academic hospital, county hospital, and community hospital.
Hospitalized adults with bacteriuria.
Patients without documented symptoms of urinary tract infection per Infectious Diseases Society of America (IDSA) criteria were classified as ASB. We examined ASB treatment risk factors as well as broad-spectrum antibiotic usage and quantified diagnostic concordance between IDSA and National Healthcare Safety Network criteria.
Among 300 patients with bacteriuria, ASB was present in 71% by IDSA criteria. By National Healthcare Safety Network criteria, 71% of patients had ASB; within-patient diagnostic concordance with IDSA was moderate (kappa, 0.52). After excluding those given antibiotics for nonurinary indications, antibiotics were given to 38% (62/164) with ASB. Factors significantly associated with ASB treatment were elevated urine white cell count (65 vs 24 white blood cells per high-powered field, P<.01), hospital identity (hospital C vs A, odds ratio, 0.34 [95% CI, 0.14–0.80], P =.01), presence of leukocyte esterase (5.48 [2.35–12.79], P<.01), presence of nitrites (2.45 [1.11–5.41], P=.03), and Escherichia coli on culture (2.4 [1.2–4.7], P=.01). Of patients treated for ASB, broad-spectrum antibiotics were used in 84%.
ASB treatment was prevalent across settings and contributed to broad-spectrum antibiotic use. Associating abnormal urinalysis results with the need for antibiotic treatment regardless of symptoms may drive unnecessary antibiotic use.
Infect. Control Hosp. Epidemiol. 2016;37(3):319–326
Smaller hippocampal volume has often been observed in patients with post-traumatic stress disorder (PTSD). However, there is no consensus whether this is a result of stress/trauma exposure, or constitutes a vulnerability factor for the development of PTSD. Second, it is unclear whether hippocampal volume normalizes with successful treatment of PTSD, or whether a smaller hippocampus is a risk factor for the persistence of PTSD.
Magnetic resonance imaging (MRI) scans and clinical interviews were collected from 47 war veterans with PTSD, 25 healthy war veterans (combat controls) and 25 healthy non-military controls. All veterans were scanned a second time with a 6- to 8-month interval, during which PTSD patients received trauma-focused therapy. Based on post-treatment PTSD symptoms, patients were divided into a PTSD group who was in remission (n = 22) and a group in whom PTSD symptoms persisted (n = 22). MRI data were analysed with Freesurfer.
Smaller left hippocampal volume was observed in PTSD patients compared with both control groups. Hippocampal volume of the combat controls did not differ from healthy controls. Second, pre- and post-treatment analyses of the PTSD patients and combat controls revealed reduced (left) hippocampal volume only in the persistent patients at both time points. Importantly, hippocampal volume did not change with treatment.
Our findings suggest that a smaller (left) hippocampus is not the result of stress/trauma exposure. Furthermore, hippocampal volume does not increase with successful treatment. Instead, we demonstrate for the first time that a smaller (left) hippocampus constitutes a risk factor for the persistence of PTSD.
Post-traumatic stress disorder (PTSD) is thought to be characterized by general heightened amygdala activation. However, this hypothesis is mainly based on specific studies presenting fear or trauma-related stimuli, hence, a thorough investigation of trauma-unrelated emotional processing in PTSD is needed.
In this study, 31 male medication-naive veterans with PTSD, 28 male control veterans (combat controls; CC) and 25 non-military men (healthy controls; HC) were included. Participants underwent functional MRI while trauma-unrelated neutral, negative and positive emotional pictures were presented. In addition to the group analyses, PTSD patients with and without major depressive disorder (MDD) were compared.
All groups showed an increased amygdala response to negative and positive contrasts, but amygdala activation did not differ between groups. However, a heightened dorsal anterior cingulate cortex (dACC) response for negative contrasts was observed in PTSD patients compared to HC. The medial superior frontal gyrus was deactivated in the negative contrast in HC, but not in veterans. PTSD+MDD patients showed decreased subgenual ACC (sgACC) activation to all pictures compared to PTSD–MDD.
Our findings do not support the hypothesis that increased amygdala activation in PTSD generalizes to trauma-unrelated emotional processing. Instead, the increased dACC response found in PTSD patients implicates an attentional bias that extends to trauma-unrelated negative stimuli. Only HC showed decreased medial superior frontal gyrus activation. Finally, decreased sgACC activation was related to MDD status within the PTSD group.
The risk of developing bipolar disorder (BD) has been linked to structural brain abnormalities. The degree to which genes and environment influence the association of BD with cortical surface area remains to be elucidated. In this twin study, genetic and environmental contributions to the association between liability to develop BD and surface area, thickness and volume of the cortex were examined.
The study cohort included 44 affected monozygotic (nine concordant, 12 discordant) and dizygotic (four concordant, 19 discordant) twin pairs, and seven twins from incomplete discordant monozygotic and dizygotic discordant twin pairs. In addition, 37 monozygotic and 24 dizygotic healthy control twin pairs, and six twins from incomplete monozygotic and dizygotic control pairs were included.
Genetic liability to develop BD was associated with a larger cortical surface in limbic and parietal regions, and a thicker cortex in central and parietal regions. Environmental factors related to BD were associated with larger medial frontal, parietal and limbic, and smaller orbitofrontal surfaces. Furthermore, thinner frontal, limbic and occipital cortex, and larger frontal and parietal, and smaller orbitofrontal volumes were also associated with environmental factors related to BD.
Our results suggest that unique environmental factors play a prominent role in driving the associations between liability to develop BD and cortical measures, particularly those involving cortical thickness. Further evaluation of their influence on the surface and thickness of the cortical mantle is recommended. In addition, cortical volume appeared to be primarily dependent on surface and not thickness.
We investigated electronic structure of one-dimensional biradical molecular chain which is constructed by exploiting the covalency between organic molecules of a diphenyl derivative of s-indacenodiphenalene (Ph2-IDPL). To control the crystallinity, we used gas deposition method. Ultraviolet photoelectron spectroscopy (UPS) revealed developed band structure with wide dispersion of the one-dimensional biradical molecular chain.