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Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
Regionalizing pre-colonial Africa aids in the collection and interpretation of primary sources as data for further analysis. This article includes a map with six broad regions and 34 sub-regions, which form a controlled vocabulary within which researchers may geographically organize and classify disparate pieces of information related to Africa’s past. In computational terms, the proposed African regions serve as data containers in order to consolidate, link, and disseminate research among a growing trend in digital humanities projects related to the history of the African diasporas before c. 1900. Our naming of regions aims to avoid terminologies derived from European slave traders, colonialism, and modern-day countries.
We evaluated the risk of patients contracting coronavirus disease 2019 (COVID-19) during their hospital stay to inform the safety of hospitalization for a non–COVID-19 indication during this pandemic.
A case series of adult patients hospitalized for 2 or more nights from May 15 to June 15, 2020 at large tertiary-care hospital in the midwestern United States was reviewed. All patients were screened at admission with the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) test. Selected adult patients were also tested by IgG serology. After dismissal, patients with negative serology and PCR at admission were asked to undergo repeat serologic testing at 14–21 days after discharge. The primary outcome was healthcare-associated COVID-19 defined as a new positive SARS-CoV-2 PCR test on or after day 4 of hospital stay or within 7 days of hospital dismissal, or seroconversion in patients previously established as seronegative.
Of the 2,068 eligible adult patients, 1,778 (86.0%) completed admission PCR testing, while 1,339 (64.7%) also completed admission serology testing. Of the 1,310 (97.8%) who were both PCR and seronegative, 445 (34.0%) repeated postdischarge serology testing. No healthcare-associated COVID-19 cases were detected during the study period. Of 1,310 eligible PCR and seronegative adults, no patients tested PCR positive during hospital admission (95% confidence interval [CI], 0.0%–0.3%). Of the 445 (34.0%) who completed postdischarge serology testing, no patients seroconverted (0.0%; 95% CI, 0.0%–0.9%).
We found low likelihood of hospital-associated COVID-19 with strict adherence to universal masking, physical distancing, and hand hygiene along with limited visitors and screening of admissions with PCR.
Realizing packaged state-of-the-art performance of monolithic microwave integrated circuits (MMICs) operating at millimeter wavelengths presents significant challenges in terms of electrical interface circuitry and physical construction. For instance, even with the aid of modern electromagnetic simulation tools, modeling the interaction between the MMIC and its package embedding circuit can lack the necessary precision to achieve optimum device performance. Physical implementation also introduces inaccuracies and requires iterative interface component substitution that can produce variable results, is invasive and risks damaging the MMIC. This paper describes a novel method for in situ optimization of packaged millimeter-wave devices using a pulsed ultraviolet laser to remove pre-selected areas of interface circuit metallization. The method was successfully demonstrated through the optimization of a 183 GHz low noise amplifier destined for use on the MetOp-SG meteorological satellite series. An improvement in amplifier output return loss from an average of 12.9 dB to 22.7 dB was achieved across an operational frequency range of 175–191 GHz and the improved circuit reproduced. We believe that our in situ tuning technique can be applied more widely to planar millimeter-wave interface circuits that are critical in achieving optimum device performance.
Firearm injuries are a significant public health problem. Prior studies have analyzed firearm death data or adult firearm injury data, but few studies have analyzed firearm injury data specifically among youth. To inform the current debate surrounding gun policy in the United States, this study aims to provide an estimate of the immense burden of youth firearm injury and its associated risk factors. Therefore, we performed a descriptive analysis of the Nationwide Emergency Department Sample (NEDS), the largest all-payer emergency department database in the United States, from January 2006 to September 2015. All patients age < 21 who presented with any diagnosis of firearm-related injuries were included.
There were an estimated 198,839 incidents of firearm-related emergency department visits for patients age < 21 from 2006 through 2015. After presenting to the ED, an estimated 11,909 cases resulted in death. The population adjusted rate of firearm-related emergency department visits was highest in the South and Midwest. This study demonstrates the significant burden of firearm injury among youth. Having a reliable estimate of the number of children harmed by firearms each year is a critical tool for policymakers — and may make common-sense gun safety measures more politically possible.
Twenty-four new optically stimulated luminescence (OSL) and radiocarbon ages from sediment cores in nine lakes associated with the Shipshewana and Sturgis moraines in northern Indiana and southern Michigan estimate when recession of the Saginaw Lobe of the Laurentide Ice Sheet was underway in the southern Great Lakes region, USA. Average OSL ages of 23.4 ± 2.2 ka for the Shipshewana Moraine and 19.7 ± 2.2 ka for the Sturgis Moraine are considered minimum limiting deglacial ages for these recessional moraines. The much younger radiocarbon ages are consistent with other regional radiocarbon ages from lakes, and record climate amelioration around ~16.5 cal ka BP. Early recession of the interlobate Saginaw Lobe was well underway by 23.4 ± 2.2 ka, when the adjacent Lake Michigan and Huron-Erie lobes were a few hundred kilometers farther south and near their maximum southerly limits. The results provide the first time constraints when sediment from the Lake Michigan and Huron-Erie lobes began filling the accommodation space left by the Saginaw Lobe. The difference between the oldest radiocarbon and OSL age is 7400 yr for the Shipshewana Moraine and 3400 yr for the Sturgis Moraine.
Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.
The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.
There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.
These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
Obesity and excess bodyweight are highly prevalent in individuals with bipolar disorders (BD) and are associated with adverse consequences. Multiple factors may explain increased bodyweight in BD including side effects of psychotropic medications, and reduced physical activity. Research in the general population demonstrates that sleep disturbances may also contribute to metabolic burden. We present a cross-sectional study of the associations between body mass index (BMI) and sleep parameters in patients with BD as compared with healthy controls (HC).
Twenty-six French outpatients with remitted BD and 29 HC with a similar BMI completed a 21-day study of sleep parameters using objective (actigraphy) and subjective (PSQI: Pittsburgh Sleep Quality Index) assessments.
In BD cases, but not in HC, higher BMI was significantly correlated with lower sleep efficiency (P = 0.009) and with several other sleep parameters: shorter total sleep time (P = 0.01), longer sleep onset latency (P = 0.05), higher fragmentation index (P = 0.008), higher inter-day variability (P = 0.05) and higher PSQI total score (P = 0.004).
The findings suggest a link between a high BMI and several sleep disturbances in BD, including lower sleep efficiency. Physiological mechanisms in BD cases may include an exaggeration of phenomena observed in non-clinical populations. However, larger scale studies are required to clarify the links between metabolic and sleep-wake cycle disturbances in BD.
Antidepressants may induce manic or hypomanic episodes. The identification of predictors of antidepressant- induced mania (AIM) is essential to improve the management of bipolar disorder (BD). However, the rare studies on AIM are generally characterized by small sample sizes, varying definitions of AIM and heterogeneous groups of patients, thus leading to conflicting results.
To compare a population of AIM(+) to AIM(-) patients in order to identify specific clinical factors associated with AIM.
All 252 participants met the DSM-IV criteria for BD. Only patients who reported AIM in the 90 days after the beginning of an antidepressant (with or without a mood stabilizer) were diagnosed as AIM (+) and those without any lifetime history of AIM despite lifetime antidepressant prescription were considered AIM (-). Sociodemographic and clinical factors were collected using the DIGS, ALS, AIS BIS and WURS.
AIM(+) (N=74) and AIM(-) (N=178) patients did not differ significantly in terms of age, gender distribution, bipolar disorder duration and age of onset, ALS, BIS and WURS score. However, the rates of rapid cyclers, lifetime history of suicidal acts, alcohol use disorder and AIS score were significantly higher in the AIM(+)group. The type of polarity of onset was significantly different in both groups.
A history of rapid cycling, of suicidal acts and of alcohol use disorder could be considered as risk factors of AIM in BD. Patients with these factors could therefore be identified as a vulnerable subgroup prone to manic switch with antidepressant.
The brain-derived neurotrophic factor (BDNF) is a neurotrophin fundamentally involved in the differentiation and growth during brain development. BDNF has pathogenically been linked to the schizophrenia neurodevelopmental hypothesis. Several studies have found lower BDNF blood levels in chronic schizophrenia than controls. Few studies suggest that BDNF levels in first-episode psychosis (FEP) are lower than in healthy controls (HC).
Comparing serum BDNF levels in a group of antipsychotic-naive FEP with HC and determining the serum BDNF pattern during the first year illness evolution.
Serum BDNF levels at admission of 28 inpatients with FEP were compared with 28 age/gender matched HC. BDNF was also measured at discharge, three, six, nine and twelve months. After discharge, antipsychotics were gradually decreased. Results are presented as mean±sd. and BDNF levels in ng./ml.
At admission, patients BDNF levels were significantly lower than controls (18.06±4.06 vs 26.55±3.22, p>0.001). At discharge FEP levels increase until HC levels without significant differences between gropus (25.95±3.93 vs 26.55±3.22, p=0.539). Upon the following determinations, BDNF FEP levels progressively decreased, reaching the admission values, and being significantly lower than the controls and that levels at discharge (patients: three months: 19.68±3.88; six months: 19.02±4.13; nine months: 17.64±5.24; twelve months: 17.51±3.45 vs controls: 26.55±3.22, all p>0.001).
Our results confirm the studies that found lower BDNF levels in chronic schizophrenia. Serum BDNF levels could be considered as a biological marker of treatment and evolution of FEP. Further studies with FEP patients with and without treatment are warranted.
Although investigation have demonstrated that stimulants are effective medication for the treatment of the symptoms on the ADHD, a commonly described but quite slightly studied side effect of this type of medication, is the effect on the emotional expression of patients.
evaluate the effect of the treatment with Methylphenidate on the affective/emotional expression in children diagnosed with ADHD.
It's a descriptive study of several cases series, from a center and about a unique group, where 'n” will be 15 children diagnosed with ADHD at the University Hospital, who were required beginning treatment with methylphenidate, with a daily dose of at least 0,3mg/Kg. In this study it will be evaluated the emotional expression of the group, according to the scale Expression and Emotion Scale for Children (EESC) making a comparison between the previous moment to the treatment and a subsequent month from its beginning.
The evaluation of the total result of the EESC conducted by the parent didn't show statistically significant differences between scores previously of the treatment and results after a month with it. The dominions (positive emotions, emotional flatness and emotional lability) didn't show differences between both periods of time, nevertheless, the positive emotions showed a tendency of reduction more showy than the rest, without getting to be statistically significant (p=0.0638).
Statistically there haven't been significant changes in the emotional expression of the children caused by the treatment with methylphenidate. Nevertheless, the data show that there is a tendency to an improvement in it.
Large population based studies demonstrate a link between childhood trauma (CT) and increased prevalence of a wide range of psychiatric disorders, including mood disorders and psychosis. The identification of CT as an environmental risk factor for bipolar disorders (BD) and schizophrenia is of crucial importance to move to GxE interaction studies. In this presentation, we will mainly use the example of bipolar disorders (BD) and draw some parallels with psychosis. First we have demonstrated that CT were associated to BD using case-control studies (with a dose-effect of emotional abuse), as this has been previously demonstrated in psychosis by meta-analytic approaches. We also have shown that CT (mainly emotional and sexual abuses) influenced the clinical expression and course of BD, with associations between CT, earlier age at onset, rapid cycling and suicidal behavior. Some of these associations were also observed in schizophrenia and thus appeared as relatively non-specific. Moreover some cumulative effects of CT and cannabis misuse on the age at onset of BD or on the transition to psychosis have been suggested. Using psychopathological dimensions as outputs, we have been able to demonstrate that CT influence affective regulation and impulsivity-related dimensions, that could mediate the links between CT and clinical categorical outputs. Disentangling these pathways from CT, through dimensions, to clinical expression could shed some light on the clinical and dimensional aspects to could be incorporated in future GenexCT interaction studies. As an example, we will present preliminary data on the interaction between CT and serotonin transporter gene variants but also dysimmunity-related genes variants on the age at onset in BD.
Lithium remains the gold standard of prophylactic treatment in bipolar disorder. However 10–40% of patients are not responder to lithium and there is still no operational predictive markers of lithium response. Moreover, previous studies relate some conflicting results due to the absence of an unanimous definition and evaluation of prophylactic lithium response. Our objective was to identify clinical factors associated with prophylactic lithium response assessed by Alda questionnaire that includes 6 categories of prophylactic response from no response for at least two years of treatment to no relapse for three years.
To study characteristics associated with lithium response.
All 516 participants met the DSM-IV criteria for bipolar disorder. They all received at least once in their life lithium (for at least two years) and all completed the Alda questionnaire. They were compared on several sociodemographic and clinical factors which were collected using the DIGS. Psychological dimensions were assessed with the ALS and AIS (for affective lability and instability), the BIS (for impulsivity) and the WURS (for ADHD screening) and history of childhood trauma.
Among the 516 subjects, 132 (25,6%) were lithium responders with no relapse during at least two years of treatment; 106 (20,5%) were poor lithium responders. These groups were compared for clinical, dimensional and childhood trauma characteristics, using both univariate and multivariate analyses.
Characteristics associated with lithium response may help to define personalized strategies.
Immune dysfunction is thought to play a critical role in the pathophysiology of bipolar disorder (BD). Better insight into the genetic control of innate immune responses is of importance due to possible interactions with environmental risk factors such as infectious agents, particularly early in life.
Given the importance of Toll-like receptors (TLRs) in innate immunity, we analysed the association of selected genetic variants of TLR-2 and TLR-4, both major sensors of pathogenic infectious and non-infectious structures, with BD.
Explore possible implications of the innate arm of the immune response in BD.
Genomic DNAs from 572 BD patients and 202 controls were analyzed for the distribution of polymorphisms on the TLR-2 and TLR-4 loci using TaqMan®. Associations were examined using Chi-square test.
We found that TLR-4 rs1927914 AA and rs11536891 TT genotypes were more frequent in BD patients than in controls (corrected p; pc = .02 and .02 respectively) particularly in early-onset BD (EOBD) patients (pc = .004 and .006) born during the summer season (pc = 02 and .002 respectively). We also found that TLR-2 rs3804099 TT and rs4696480 TT genotypes were significantly more prevalent in EOBD group as compared to the late-onset BD (LOBD) subset, the latter only after excluding patients with positive family history of psychiatric disorders (pc=0.024 and 0.002 respectively).
We report an association between BD and TLR-2 and TLR-4 genetic variants suggesting an important role for pathogens in disease development.
Bipolar disorders (BD) are characterized by sleep disturbances and emotional dysregulation both during acute episodes and remission periods. We hypothesized that sleep quality (SQ) and emotional reactivity (ER) defined clusters of patients with no or abnormal SQ and ER and we studied the association with functioning.
We performed a bi-dimensional cluster analysis using SQ and ER measures in a sample of 533 outpatients patients with BD (in remission or with subsyndromal mood symptoms). Clusters were compared for mood symptoms, sleep profile and functioning.
We identified three clusters of patients: C1 (normal ER and SQ, 54%), C2 (hypo-ER and low SQ, 22%) and C3 (hyper-ER and low SQ, 24%). C1 was characterized by minimal mood symptoms, better sleep profile and higher functioning than other clusters. Although highly different for ER, C2 and C3 had similar levels of subsyndromal mood symptoms as assessed using classical mood scales. When exploring sleep domains, C2 showed poor sleep efficiency and a trend for longer sleep latency as compared to C3. Interestingly, alterations in functioning were similar in C2 and C3, with no difference in any of the sub-domains.
Abnormalities in ER and SQ delineated three clusters of patients with BD and significantly impacted on functioning.
Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania.
The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points.
There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition.
Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.
Addiction to psychoactive substances (PAS) can lead to cardiovascular complications. Cardiotoxicity of drugs is known but it is rarely documented by toxicology.
We conducted a prevalence study on PAS use among patients with cardiac symptoms, with an analysis of diagnosis and a description of PAS user's characteristics.
To improve the therapeutic management in addictology for cardiac patients.
Prospective observational study performed during 3 months. Patients admitted in cardiology had to complete a hetero-questionnaire about his PAS consumption and a qualitative toxicological research in urine and/or blood (immunochemical/GC–MS detection).
One hundred and sixty-one patients were included: 86% men, aged 24–68 years (Table 1). Results show a high level of PAS use in our population: 8.7%. A significant PAS use is observed among patients aged 40–70 years, with a prevalence of 22% for the 40–49, 15% for the 50–59 and 7% for the 60–69. PAS detected were mainly cannabis and cocaine. Clinical diagnoses of patients positive to PAS were acute coronary syndromes and severe cardiac arrhythmias.
In patients admitted in cardiology, toxicological screening is rarely done. Our study shows a significant PAS use among patients aged 40–70 years. According to data of the French Health Barometer, there is regular use of cannabis and cocaine at respectively 3% and 1.1% among people aged 18–64. These results invite us to achieve a more systematic identification of PAS use among patients with cardiovascular disorders and to optimize the therapeutic management by a systematic orientation in addictology.
Disclosure of interest
The authors have not supplied their declaration of competing interest.