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Expert Consensus Statement for Telepsychiatry and Attention Deficit Hyperactivity Disorder
- Jennifer Hong, Gregory W. Mattingly, Julie A. Carbray, Takesha V. Cooper, Robert L. Findling, Martin Gignac, Paul E. Glaser, Frank A. Lopez, Vladamir Maletic, Roger S. McIntyre, Adelaide S. Robb, Manpreet K. Singh, Mark Stein, Stephen M. Stahl
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- CNS Spectrums / Accepted manuscript
- Published online by Cambridge University Press:
- 20 May 2024, pp. 1-34
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Physiological and biochemical processes underlying the differential sucrose yield and biomass production in sugarcane varieties
- Tamires Da Silva Martins, José R. Magalhães Filho, Larissa Prado Cruz, Daniela F. S. P. Machado, Norma M. Erismann, Rose M. A. Gondim-Tomaz, Paulo E. R. Marchiori, André L. B. O. Silva, Eduardo Caruso Machado, Rafael Vasconcelos Ribeiro
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- Experimental Agriculture / Volume 60 / 2024
- Published online by Cambridge University Press:
- 14 May 2024, e13
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Sucrose yield in sugarcane is a complex process regulated by both environmental and endogenous factors. However, the metabolic balance driving vegetative growth and sucrose accumulation remains poorly understood. Herein, we carried out a comprehensive assessment of carbohydrate dynamics throughout the crop cycle in two sugarcane varieties varying in biomass production, evaluating the carbon metabolism in both leaves and stalks. Our data revealed that the decline in photosynthetic rates during sugarcane maturation is associated not only to accumulation of sugars in leaves but also due to stomatal and non-stomatal limitations. We found that metabolic processes in leaves and stalks were intrinsically linked. While IACSP94-2094 had higher stalk sucrose concentration than IACSP95-5000, this latter produced more biomass. Compared to IACSP95-5000, IACSP94-2094 showed higher sucrose phosphate synthase (SPS) activity in leaves and stalks, along with lower soluble acid invertase (SAI) activity in leaves during the maximum growth stage. Interestingly, IACSP94-2094 also exhibited higher stalk SPS activity and lower stalk SAI activity than IACSP95-5000 during maturation. High biomass production by IACSP95-5000 was associated with higher sucrose synthase (SuSy) and SAI activity in leaves and higher SuSy and soluble neutral invertase (SNI) activity in stalks when compared to IACSP94-2094 during the maximum growth. Despite the contrasting strategies, both varieties displayed similar total sucrose yield, a balance between sucrose concentration and biomass production. This phenomenon implies the presence of a compensatory mechanism in sugarcane, with high biomass production compensating low sucrose accumulation and vice versa.
Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score associations
- Sarah E. Paul, David A.A. Baranger, Emma C. Johnson, Joshua J. Jackson, Aaron J. Gorelik, Alex P. Miller, Alexander S. Hatoum, Wesley K. Thompson, Michael Strube, Danielle M. Dick, Chella Kamarajan, John R. Kramer, Martin H. Plawecki, Grace Chan, Andrey P. Anokhin, David B. Chorlian, Sivan Kinreich, Jacquelyn L. Meyers, Bernice Porjesz, Howard J. Edenberg, Arpana Agrawal, Kathleen K. Bucholz, Ryan Bogdan
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 09 May 2024, pp. 1-14
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Background
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
MethodsData came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
ResultsExternalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
ConclusionsBehavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
Let's move forward: Image-computable models and a common model evaluation scheme are prerequisites for a scientific understanding of human vision – CORRIGENDUM
- James J. DiCarlo, Daniel L. K. Yamins, Michael E. Ferguson, Evelina Fedorenko, Matthias Bethge, Tyler Bonnen, Martin Schrimpf
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- Journal:
- Behavioral and Brain Sciences / Volume 47 / 2024
- Published online by Cambridge University Press:
- 02 February 2024, e66
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4 Evaluating Plasma GFAP for the Detection of Alzheimer’s Disease Dementia
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Ann C. McKee, Thor D. Stein, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Michael L. Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 408-409
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Objective:
Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.
Participants and Methods:This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.
Results:The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).
Conclusions:Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.
4 Risk Factor and Biomarker Correlates of FLAIR White Matter Hyperintensities in Former American Football Players
- Monica T Ly, Fatima Tuz-Zahra, Yorghos Tripodis, Charles H Adler, Laura J Balcer, Charles Bernick, Elaine Peskind, Megan L Mariani, Rhoda Au, Sarah J Banks, William B Barr, Jennifer V Wethe, Mark W Bondi, Lisa Delano-Wood, Robert C Cantu, Michael J Coleman, David W Dodick, Michael D McClean, Jesse Mez, Joseph N Palmisano, Brett Martin, Kaitlin Hartlage, Alexander P Lin, Inga K Koerte, Jeffrey L Cummings, Eric M Reiman, Martha E Shenton, Robert A Stern, Sylvain Bouix, Michael L Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 608-610
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Objective:
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
5 Antemortem Plasma GFAP Predicts Alzheimer’s Disease Neuropathological Changes
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Bertran R. Huber, Ann C. McKee, Thor D. Stein, Michael L. Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 409-410
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Objective:
Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).
Participants and Methods:This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.
Results:Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.
Conclusions:The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.
Selected rock powders as sources of nutrients for soil fertilization and maize-wheat grain production in southern Brazil
- A. L. Bamberg, R. Martinazzo, C. A. P. Silveira, C. N. Pillon, L. Stumpf, M. Bergmann, P. van Straaten, E. S. Martins
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- The Journal of Agricultural Science / Volume 161 / Issue 5 / October 2023
- Published online by Cambridge University Press:
- 07 December 2023, pp. 654-668
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The current study evaluated alternative sources of nutrients to improve the soil fertility status and yield of maize-wheat succession in Southern Brazil. The treatments were: T1: no fertilization; T2: liming with dolomitic marble; T3: alternative liming (AL) with limestone interbedded with shale; T4: AL + 50% P - with Arad natural phosphate (P-ANP) + 50% P – triple superphosphate (P-TSP); T5: AL + 100% P-ANP; T6: AL + 100% P-ANP + 100% K-rich monzogranite; T7: AL + 100% P-ANP + 100% N (50% N from tung pressed cake (N-TPC) + 50% N-urea); T8: AL + 100% P-ANP + 100% K-rich monzogranite + 100% N (50% N-TPC + 50% N-Urea) + 100% S; T9: AL + regional average rate of NPK (5-20-20) formulation. Except for T7 and T8, all treatments received the full recommended rate of N through Urea. Immediate and residual effects were evaluated over 2.5 years (90, 360 and 900 days) on soil fertility and maize - wheat yield. The limestone interbedded with shale released Ca, Mg and corrected soil acidity similarly to dolomitic marble. The fertilization strategies used in T4, T7 and T8 presented the highest cumulative productivities while T3 (U$ = 1223), T9 (U$ = 1174) and T4 (U$ = 1122) resulted in higher profits than the other evaluated fertilization strategies. The limestone interbedded with shale (T3), alone or combined with 50% of P-ANP + 50% of P – TSP (T4) provided the best economical and technical results, highlighting the potential of selected alternative regional sources for soil fertility improvement and plant-nutrients supply.
Let's move forward: Image-computable models and a common model evaluation scheme are prerequisites for a scientific understanding of human vision
- James J. DiCarlo, Daniel L. K. Yamins, Michael E. Ferguson, Evelina Fedorenko, Matthias Bethge, Tyler Bonnen, Martin Schrimpf
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- Behavioral and Brain Sciences / Volume 46 / 2023
- Published online by Cambridge University Press:
- 06 December 2023, e390
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In the target article, Bowers et al. dispute deep artificial neural network (ANN) models as the currently leading models of human vision without producing alternatives. They eschew the use of public benchmarking platforms to compare vision models with the brain and behavior, and they advocate for a fragmented, phenomenon-specific modeling approach. These are unconstructive to scientific progress. We outline how the Brain-Score community is moving forward to add new model-to-human comparisons to its community-transparent suite of benchmarks.
Ten new insights in climate science 2023
- Mercedes Bustamante, Joyashree Roy, Daniel Ospina, Ploy Achakulwisut, Anubha Aggarwal, Ana Bastos, Wendy Broadgate, Josep G. Canadell, Edward R. Carr, Deliang Chen, Helen A. Cleugh, Kristie L. Ebi, Clea Edwards, Carol Farbotko, Marcos Fernández-Martínez, Thomas L. Frölicher, Sabine Fuss, Oliver Geden, Nicolas Gruber, Luke J. Harrington, Judith Hauck, Zeke Hausfather, Sophie Hebden, Aniek Hebinck, Saleemul Huq, Matthias Huss, M. Laurice P. Jamero, Sirkku Juhola, Nilushi Kumarasinghe, Shuaib Lwasa, Bishawjit Mallick, Maria Martin, Steven McGreevy, Paula Mirazo, Aditi Mukherji, Greg Muttitt, Gregory F. Nemet, David Obura, Chukwumerije Okereke, Tom Oliver, Ben Orlove, Nadia S. Ouedraogo, Prabir K. Patra, Mark Pelling, Laura M. Pereira, Åsa Persson, Julia Pongratz, Anjal Prakash, Anja Rammig, Colin Raymond, Aaron Redman, Cristobal Reveco, Johan Rockström, Regina Rodrigues, David R. Rounce, E. Lisa F. Schipper, Peter Schlosser, Odirilwe Selomane, Gregor Semieniuk, Yunne-Jai Shin, Tasneem A. Siddiqui, Vartika Singh, Giles B. Sioen, Youba Sokona, Detlef Stammer, Norman J. Steinert, Sunhee Suk, Rowan Sutton, Lisa Thalheimer, Vikki Thompson, Gregory Trencher, Kees van der Geest, Saskia E. Werners, Thea Wübbelmann, Nico Wunderling, Jiabo Yin, Kirsten Zickfeld, Jakob Zscheischler
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- Journal:
- Global Sustainability / Volume 7 / 2024
- Published online by Cambridge University Press:
- 01 December 2023, e19
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Non-technical summary
We identify a set of essential recent advances in climate change research with high policy relevance, across natural and social sciences: (1) looming inevitability and implications of overshooting the 1.5°C warming limit, (2) urgent need for a rapid and managed fossil fuel phase-out, (3) challenges for scaling carbon dioxide removal, (4) uncertainties regarding the future contribution of natural carbon sinks, (5) intertwinedness of the crises of biodiversity loss and climate change, (6) compound events, (7) mountain glacier loss, (8) human immobility in the face of climate risks, (9) adaptation justice, and (10) just transitions in food systems.
Technical summaryThe Intergovernmental Panel on Climate Change Assessment Reports provides the scientific foundation for international climate negotiations and constitutes an unmatched resource for researchers. However, the assessment cycles take multiple years. As a contribution to cross- and interdisciplinary understanding of climate change across diverse research communities, we have streamlined an annual process to identify and synthesize significant research advances. We collected input from experts on various fields using an online questionnaire and prioritized a set of 10 key research insights with high policy relevance. This year, we focus on: (1) the looming overshoot of the 1.5°C warming limit, (2) the urgency of fossil fuel phase-out, (3) challenges to scale-up carbon dioxide removal, (4) uncertainties regarding future natural carbon sinks, (5) the need for joint governance of biodiversity loss and climate change, (6) advances in understanding compound events, (7) accelerated mountain glacier loss, (8) human immobility amidst climate risks, (9) adaptation justice, and (10) just transitions in food systems. We present a succinct account of these insights, reflect on their policy implications, and offer an integrated set of policy-relevant messages. This science synthesis and science communication effort is also the basis for a policy report contributing to elevate climate science every year in time for the United Nations Climate Change Conference.
Social media summaryWe highlight recent and policy-relevant advances in climate change research – with input from more than 200 experts.
GWAS of Dizygotic Twinning in an Enlarged Australian Sample of Mothers of DZ Twins
- Scott D. Gordon, David L. Duffy, David C. Whiteman, Catherine M. Olsen, Kerrie McAloney, Jessica M. Adsett, Natalie A. Garden, Simone M. Cross, Susan E. List-Armitage, Joy Brown, Jeffrey J. Beck, Hamdi Mbarek, Sarah E. Medland, Grant W. Montgomery, Nicholas G. Martin
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- Journal:
- Twin Research and Human Genetics / Volume 26 / Issue 6 / December 2023
- Published online by Cambridge University Press:
- 23 November 2023, pp. 327-338
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Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).
How can genetic factors be best leveraged to explain individual differences in risk to onset, course of illness and response to treatment in depression and other mood disorders?
- Ian B. Hickie, Sarah E. Medland, Naomi R. Wray, Brittany L. Mitchell, Jacob J. Crouse, Nicholas G. Martin
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- Research Directions: Depression / Volume 1 / 2024
- Published online by Cambridge University Press:
- 11 October 2023, e11
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The clinical field of depression and other mood disorders is characterised by the vast heterogeneity between those who present for care, and the highly variable degree of response to the range of psychological, pharmacological and physical treatments currently provided. These individual differences likely have a genetic component, and leveraging genetic risk is appealing because genetic risk factors point to causality. The possibility that individual genotyping at entry to health care may be a key way forward is worthy of discussion (Torkamani et al., 2018).
A causal roadmap for generating high-quality real-world evidence
- Lauren E. Dang, Susan Gruber, Hana Lee, Issa J. Dahabreh, Elizabeth A. Stuart, Brian D. Williamson, Richard Wyss, Iván Díaz, Debashis Ghosh, Emre Kıcıman, Demissie Alemayehu, Katherine L. Hoffman, Carla Y. Vossen, Raymond A. Huml, Henrik Ravn, Kajsa Kvist, Richard Pratley, Mei-Chiung Shih, Gene Pennello, David Martin, Salina P. Waddy, Charles E. Barr, Mouna Akacha, John B. Buse, Mark van der Laan, Maya Petersen
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue 1 / 2023
- Published online by Cambridge University Press:
- 22 September 2023, e212
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Increasing emphasis on the use of real-world evidence (RWE) to support clinical policy and regulatory decision-making has led to a proliferation of guidance, advice, and frameworks from regulatory agencies, academia, professional societies, and industry. A broad spectrum of studies use real-world data (RWD) to produce RWE, ranging from randomized trials with outcomes assessed using RWD to fully observational studies. Yet, many proposals for generating RWE lack sufficient detail, and many analyses of RWD suffer from implausible assumptions, other methodological flaws, or inappropriate interpretations. The Causal Roadmap is an explicit, itemized, iterative process that guides investigators to prespecify study design and analysis plans; it addresses a wide range of guidance within a single framework. By supporting the transparent evaluation of causal assumptions and facilitating objective comparisons of design and analysis choices based on prespecified criteria, the Roadmap can help investigators to evaluate the quality of evidence that a given study is likely to produce, specify a study to generate high-quality RWE, and communicate effectively with regulatory agencies and other stakeholders. This paper aims to disseminate and extend the Causal Roadmap framework for use by clinical and translational researchers; three companion papers demonstrate applications of the Causal Roadmap for specific use cases.
Agricultural Research Service Weed Science Research: Past, Present, and Future
- Stephen L. Young, James V. Anderson, Scott R. Baerson, Joanna Bajsa-Hirschel, Dana M. Blumenthal, Chad S. Boyd, Clyde D. Boyette, Eric B. Brennan, Charles L. Cantrell, Wun S. Chao, Joanne C. Chee-Sanford, Charlie D. Clements, F. Allen Dray, Stephen O. Duke, Kayla M. Eason, Reginald S. Fletcher, Michael R. Fulcher, John F. Gaskin, Brenda J. Grewell, Erik P. Hamerlynck, Robert E. Hoagland, David P. Horvath, Eugene P. Law, John D. Madsen, Daniel E. Martin, Clint Mattox, Steven B. Mirsky, William T. Molin, Patrick J. Moran, Rebecca C. Mueller, Vijay K. Nandula, Beth A. Newingham, Zhiqiang Pan, Lauren M. Porensky, Paul D. Pratt, Andrew J. Price, Brian G. Rector, Krishna N. Reddy, Roger L. Sheley, Lincoln Smith, Melissa C. Smith, Keirith A. Snyder, Matthew A. Tancos, Natalie M. West, Gregory S. Wheeler, Martin M. Williams, Julie Wolf, Carissa L. Wonkka, Alice A. Wright, Jing Xi, Lew H. Ziska
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- Journal:
- Weed Science / Volume 71 / Issue 4 / July 2023
- Published online by Cambridge University Press:
- 16 August 2023, pp. 312-327
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The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
Off-label use of atypical antipsychotics- Where are we?
- R. P. Vaz, J. Martins, A. L. Costa, J. Brás, R. Sousa, E. Almeida, J. Abreu, N. Castro, R. Andrade, N. Gil
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S305
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Introduction
Nowadays, In the exercise of psychiatric clinical activity, the prescription of atypical antipsychotics is a widespread practice.
However, despite the approval in the treatment of psychoses and bipolar affective disorder, where its effectiveness is clearly demonstrated, these drugs are off-label prescribed in most of the clinical situations.
ObjectivesThis work aims to clarify which atypical antipsychotics are most frequent prescribed and the clinical conditions where their off-label prescription is more common.
MethodsBibliographic research in the Pubmed® database using the terms “atypical antipsychotics and off-label use”
ResultsAccording to the scientific literature consulted, the off-label prescription of atypical antipsychotics may represent about 70% of the total prescription of these psychotropic drugs.
Risperidone, olanzapine, quetiapine and aripiprazole are the most off-label prescribed among the atypical antipsychotics.
The psychiatric conditions where atypical antipsychotics are most often off-label prescribed are addictive disorders, anxiety disorders, post-traumatic stress disorder, personality disorders, eating disorders, insomnia and dementia, where therapeutic benefits are demonstrated when carefully selected.
ConclusionsThe off-label prescription can be interpreted from two points of view. On the one hand, it can guide innovation in clinical practice and improve symptoms in patients who do not respond to standard treatments. On the other hand, it may be associated with negative consequences due to the lack of data on safety and efficacy in these situations.
Despite widespread prescribing of atypical antipsychotics, there is no evidence-based recommendation beyond psychoses and bipolar affective disorder.
Thus, when prescribed, we must proceed with careful monitoring and consider the risks and benefits in relation to off-label prescription.
Disclosure of InterestNone Declared
Knocking on the Doors of Perception: the role of psilocybin in substance use disorder treatment
- R. Sousa, L. Costa, J. Brás, R. Vaz, J. Martins, J. Abreu, E. Almeida, N. Castro, R. Andrade, N. Cunha
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S270
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Introduction
Substance use disorders(SUDs) are a major health concern and current treatment interventions have proven only limited success. Despite increasing effectiveness, still about 50–60% relapse within 6–12 months after treatment [Cornelius et al., Addict Behav. 2003;28 381-386]. SUDs are defined as chronic disorders of brain reward system, motivation, and memory processes that have gone awry. Medication reducing craving and substance use is mainly available for alcohol dependence and to a lesser extent for other substances.
Hallucinogens may represent a group of agents with potential anti-craving properties subsequently reducing substance use in SUD patients. For instance, lysergic acid diethylamide(LSD) and psilocybin have previously been shown to effectively alleviate symptoms of alcohol and nicotine dependence.
ObjectivesNew treatments preferably focusing on reducing craving and subsequent substance use are therefore urgently needed. The hallucinogen psilocybin may provide a new treatment option for SUD patients, given the beneficial results observed in recent studies
MethodsSystematic revision of literature.
ResultsIn the 1950s, a group of drugs with potential to alter consciousness were discovered (hallucinogens). Several studies suggested their anti-SUD potential, improving self-acceptance and interpersonal relationships, reducing craving and alcohol use. As a result of its recreational popularity during the 1960s, they were banned in 1967, greatly hampering scientific research in this field. Recently, psilocybin, an hallucinogenic substance in psilocybin-containing mushrooms has gained popularity in neuropsychological research, showing to increase trait openness, cognitive and behavioral flexibility, and ratings of positive attitude, mood, social effects, and behavior and even reported persistent positive changes in attitude and behavior. These findings might suggest a valuable compound for the treatment of psychiatric conditions with several additional studies providing supportive evidence for the therapeutic potential of psilocybin for SUD treatment and relapse prevention.
ConclusionsWith the reported limited amount of side effects and potential beneficial effects of psilocybin in SUD, there are valid reasons to further investigate the therapeutic efficacy and safety of psilocybin as a potential SUD treatment. On the one hand, psilocybin may exert its anti-addictive properties by beneficial effects on negative emotional states and stress. On the other hand, psilocybin may improve cognitive inflexibility and compulsivity. Research on the efficacy of psilocybin on SUD is still limited to a handful of published studies to date. As a result, many important questions related to the use of psilocybin as a complement to current treatment of SUD and its working mechanisms remain unanswered. Before psilocybin can be implemented as a treatment option for SUD, more extensive research is needed.
Disclosure of InterestNone Declared
Suicide among physicians: what do we know about it?
- R. P. Vaz, J. Martins, A. L. Costa, J. Brás, R. Sousa, E. Almeida, J. Abreu, N. Castro, R. Andrade, N. Gil
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S1115-S1116
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Introduction
The prevalence of mental illness has increased worldwide over the past few years. At the same time, and even in the sense, there is also an increase in suicide rates with special incidence in certain risk groups, among which health professionals stand out.
In this particular group, physicians seem to represent a class particularly vulnerable by the stress and demand associated with it, but also by access and knowledge about potentially lethal means.
For this very part, they have a higher risk of suicide than the general population.
ObjectivesThis paper aims to better understand the phenomenon of suicide among physicians and identify which medical specialties are most vulnerable.
MethodsBibliographic research in the Pubmed® database using the terms “suicide and physicians”.
ResultsThe data obtained from the scientific literature consulted indicate that physicians have a higher risk of suicide than the general population, with greater emphasis on females who have higher rates compared to males.
Work factors that translate into higher levels of demand and stress combined with easy access and knowledge about the use of potentially lethal means seem to contribute very significantly to this phenomenon. Perfectionist personality traits with a high sense of responsibility and duty are also important characteristics that place these professionals in a position of greater vulnerability.
With regard to the different medical specialties, anesthesiology, psychiatry and general and family medicine are the ones with higher suicide rates among the medical class.
ConclusionsThe risk of suicide, although admittedly high in the medical class, is not homogeneous among different countries, being naturally influenced by the satisfaction/gratification obtained in the performance of their profession. In this sense, countries such as Switzerland and Canada show higher levels of professional satisfaction. In the opposite direction, dissatisfaction in the exercise of clinical activity is associated with higher levels of fatigue and burnout.
Medical women, due to the need to combine the responsibility of family tasks with professional responsibility, are at greater risk.
In this sense, it is necessary to develop strategies that are more appropriate for the prevention and early identification of suicide risk situations that can be experienced not only by improving working conditions but also by better addressing professionals suffering from mental disorders.
Disclosure of InterestNone Declared
Psychosis in Parkinson’s Disease: a Case Report of Diagnosis and Management
- R. P. L. Andrade, N. P. Gil, A. L. Costa, J. Brás, N. Castro, R. Sousa, R. P. Vaz, J. Martins, E. Almeida, J. Abreu, H. Afonso
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S1085
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Introduction
Psychosis is a frequent complication in patients diagnosed with Parkinson’s Disease (PD). Characterized mainly by visual hallucinations and paranoid delusions, it occurs most frequently, but not exclusively, as an adverse effect of antiparkinson medications. Nevertheless, cognitive impairment and dementia, as a frequent feature of PD, needs to be considered for differential diagnosis.
ObjectivesOur main objective is to report a case of PD Psychosis, its diagnosis and management and complement it with a non-systematic review of literature.
MethodsPatient file consultation and an additional research, based on the key words “Psychosis” and “Parkinson’s Disease”, using Pubmed as database.
ResultsA 53-year-old female, diagnosed with Juvenile Parkinson’s Disease since age 45 and, as expected, polimedicated with antiparkinson medication. Without any relevant psychiatric background, she was admitted to the emergency department for disorganized behaviour, with 2 weeks of evolution. There, it was also possible to determine the presence of auditive hallucinations and persecutory delusions, associated with marked anguish.
After exclusion of any underlying cause for this symptomatology, inpatient treatment was proposed and accepted by the patient. In collaboration with the Neurology Department, a gradual reduction and optimization of antiparkinson drugs was conducted, associated with introduction of low doses of antipsychotic drugs, in this case Olanzapine. With this medication adjustments, clinical improvement was accomplished, with eventual fading and cessation of psychotic symptoms. Additionally, an irregularly intake of antiparkinson drugs was considered the most probably cause of this clinical decompensation.
ConclusionsAs present in literature, due to the chronicity and complexity of PD, stopping all antiparkinson drugs is not an option, even when psychotic symptoms, that could be a consequence of these drugs, are present. Therefore, a rigorous evaluation and management are mandatory, including the exclusion of other underlying causes and a careful therapeutic adjustment, with gradual reduction of antiparkinson drugs, addressing an eventual temporal relationship between the beginning of a specific drug and the onset of symptoms, and verification of therapeutic compliance, including an involuntary overdose. In cases of refractory symptoms, and after a risk-benefit assessment, pharmacologic treatment directed at these symptoms, low doses of anti-psychotics, may be necessary.
Disclosure of InterestNone Declared
The Suicidal Physician: When the Doctor Wants to Die
- D. O. Martins, M. Pinho, P. S. Martins, L. Gomes, E. G. Pereira
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S1109
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Introduction
Medical-related professions are at high suicide risk. Suicide is a major cause of premature death among physicians, but the prevalence of suicide-related behaviors is inconsistent across studies.
ObjectivesPresenting a review of the prevalence and risk factors of suicide among physicians.
MethodsSearch on Pubmed® and Medscape® databases with the following keywords: “physicians” and “suicide”. We focused on data from systematic reviews and meta-analyzes. The articles were selected by the authors according to their relevance.
ResultsFemale and US physicians were at higher risk of suicidal behavior. Suicide decreased over time, especially in Europe. Some specialties might be at higher risk such as anesthesiologists, psychiatrists, general practitioners and general surgeons. It is well established that anesthesiologists tend to have much higher rates of substance abuse than other physicians. Psychiatrists are also known to have more mental distress, mental illness and burnout compared with other physician groups and have concerning rates of depression and psychotropic. Physicians are less likely to seek mental health services out of career concerns, culture and/ or a predisposition toward self-reliance. Additionally, retrospective toxicology screening of suicide data finds that physicians are more likely than nonphysicians to have positive results for antipsychotics, benzodiazepines, and barbiturates but not antidepressants.
ConclusionsPhysicians are an at-risk profession of suicide, with women particularly at risk. The rate of suicide in physicians decreased over time, especially in Europe. The high prevalence of physicians who committed suicide attempt as well as those with suicidal ideation should benefits for preventive strategies at the workplace. Physician suicides are multifactorial, and further research into these factors is critical. Appropriate preventive and treatment measures should be implemented to reduce the risk of suicide-related behaviors in this population.
Disclosure of InterestNone Declared
European Journal of Psychiatric Trainees - a new scientific peer-reviewed Journal in Psychiatry
- F. Santos Martins, M. J. Santos, L. Afonso Fernandes, D. Cavaleri, M. Pinto da Costa, N. Žaja, K. Markin, L. Tomašić, H. Ryland, J. D King, L. E Stirland, A. Seker
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S1118-S1119
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Introduction
Psychiatry training programs vary in the degree to which they offer trainees with an opportunity to get involved in research. Exposure to research during the training period is critical, as this is usually when trainees start their own scientific research projects and gain their first experiences in academic publishing.
ObjectivesWe present the European Journal of Psychiatric Trainees (EJPT) (ejpt.scholasticahq.com), the official journal of the European Federation of Psychiatric Trainees (EFPT), including its scope, mission and vision and practical considerations.
MethodsReflecting on the foundation and operation of the European Journal of Psychiatric Trainees.
ResultsThe European Journal of Psychiatric Trainees is an Open Access, double blind peer-reviewed journal which aims to publish original and innovative research as well as clinical, theory, perspective and policy articles, and reviews in the field of psychiatric training, psychiatry and mental health. Its mission is to encourage research on psychiatric training and inspire scientific engagement by psychiatric trainees. Work conducted by psychiatric trainees and studies of training in psychiatry are prioritized. The journal is open to submissions, and while articles from psychiatric trainees are prioritized, submissions within scope from others are also encouraged. The article processing fee is very low and waivable. It is planned to publish two issues yearly.
The first article was published in July 2022, titled “Fluoxetine misuse by snorting in a teenager: a case report” and it received 218 views as of 17 October 2022, which confirms the journal’s potential for visibility.
ConclusionsThe European Journal of Psychiatric Trainees is a non-profit initiative designed to offer psychiatric trainees a platform to publish and gain experience in publishing. Thanks to its robust double blind peer reviewing system, it has the potential to contribute to scientific excellence.
Disclosure of InterestNone Declared