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SCN2A-Related Disorders
- Edited by Alfred L. George, Jr.
- Megan Abbott, Kevin J. Bender, Andreas Brunklaus, Scott Demarest, Shawn Egan, Isabel Haviland, Jennifer A. Kearney, Leah Schust Myers, Heather E. Olson, Stephan J. Sanders, Christina SanInocencio, Joseph Symonds, Christopher H. Thompson
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- July 2024
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- 31 July 2024
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SCN2A encodes a voltage-gated sodium channel (designated NaV1.2) vital for generating neuronal action potentials. Pathogenic SCN2A variants are associated with a diverse array of neurodevelopmental disorders featuring neonatal or infantile onset epilepsy, developmental delay, autism, intellectual disability and movement disorders. SCN2A is a high confidence risk gene for autism spectrum disorder and a commonly discovered cause of neonatal onset epilepsy. This remarkable clinical heterogeneity is mirrored by extensive allelic heterogeneity and complex genotype-phenotype relationships partially explained by divergent functional consequences of pathogenic variants. Emerging therapeutic strategies targeted to specific patterns of NaV1.2 dysfunction offer hope to improving the lives of individuals affected by SCN2A-related disorders. This Element provides a review of the clinical features, genetic basis, pathophysiology, pharmacology and treatment of these genetic conditions authored by leading experts in the field and accompanied by perspectives shared by affected families. This title is also available as Open Access on Cambridge Core.
Domain-specific associations between psychopathology and neurocognitive functioning
- Eirini Zoupou, Tyler M. Moore, Monica E. Calkins, Raquel E. Gur, Ruben C. Gur, J. Cobb Scott
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 03 June 2024, pp. 1-11
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Background
Neurocognitive dysfunction is a transdiagnostic finding in psychopathology, but relationships among cognitive domains and general and specific psychopathology dimensions remain unclear. This study aimed to examine associations between cognition and psychopathology dimensions in a large youth cohort.
MethodThe sample (N = 9350; age 8–21 years) was drawn from the Philadelphia Neurodevelopmental Cohort. Data from structured clinical interviews were modeled using bifactor confirmatory factor analysis (CFA), resulting in an overall psychopathology (‘p’) factor score and six orthogonal psychopathology dimensions: dysphoria/distress, obsessive-compulsive, behavioral/externalizing, attention-deficit/hyperactivity, phobias, and psychosis. Neurocognitive data were aggregated using correlated-traits CFA into five factors: executive functioning, memory, complex cognition, social cognition, and sensorimotor speed. We examined relationships among specific and general psychopathology dimensions and neurocognitive factors.
ResultsThe final model showed both overall and specific associations between cognitive functioning and psychopathology, with acceptable fit (CFI = 0.91; TLI = 0.90; RMSEA = 0.024; SRMR = 0.054). Overall psychopathology and most psychopathology dimensions were negatively associated with neurocognitive functioning (phobias [p < 0.0005], behavioral/externalizing [p < 0.0005], attention-deficit/hyperactivity [p < 0.0005], psychosis [p < 0.0005 to p < 0.05]), except for dysphoria/distress and obsessive-compulsive symptoms, which were positively associated with complex cognition (p < 0.05 and p < 0.01, respectively).
ConclusionBy modeling a broad range of cognitive and psychopathology domains in a large, diverse sample of youth, we found aspects of neurocognitive functioning shared across clinical phenotypes, as well as domain-specific patterns. Findings support transdiagnostic examination of cognitive performance to parse variability in the link between neurocognitive functioning and clinical phenotypes.
Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study
- Stephanie Haering, Antonia V. Seligowski, Sarah D. Linnstaedt, Vasiliki Michopoulos, Stacey L. House, Francesca L. Beaudoin, Xinming An, Thomas C. Neylan, Gari D. Clifford, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Jr., Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Robert A. Swor, Nina T. Gentile, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Brian J. O'Neil, Leon D. Sanchez, Steven E. Bruce, Steven E. Harte, Samuel A. McLean, Ronald C. Kessler, Karestan C. Koenen, Jennifer S. Stevens, Abigail Powers
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 22 May 2024, pp. 1-11
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Background
Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.
MethodsAs part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.
ResultsWomen reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.
ConclusionsOur findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.
Endothall and 2,4-D Activity in Milfoil Hybrid (Myriophyllum spicatum × M. sibiricum) when Applied Alone and in Combination
- Mirella F. Ortiz, Scott J. Nissen, Franck E. Dayan
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- Journal:
- Weed Science / Accepted manuscript
- Published online by Cambridge University Press:
- 08 May 2024, pp. 1-16
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Eurasian watermilfoil (Myriophyllum spicatum L.) is an invasive aquatic plant that can hybridize with the native Northern watermilfoil (Myriophyllum sibiricum Kom.). These milfoil hybrids (M. spicatum × M. sibiricum) are becoming more prevalent in many lakes where the invasive and the native milfoil co-occur. Hybrid plants are more vigorous than either parent with a faster growth rate and lower sensitivity to some herbicides. The aquatic herbicides, endothall and 2,4-D, provide two effective modes of action (MOA) for management of the hybrids. For more than a decade, these two herbicides have been used in combination as an effective control option and a resistance management strategy. How this combination impacts herbicide movement and efficacy is unknown. Therefore, the objective of this research was to determine the activity of endothall and 2,4-D combined compared to activity applied alone. Absorption and translocation of endothall, 2,4-D and the combination was determined in hybrid plants over a 96-h time course. Endothall bioaccumulation was not impacted when these herbicides were applied in combination; however, 2,4-D accumulation increased by 80%, relative to when 2,4-D was applied alone. Endothall translocation from shoots to roots decreased by almost 50% when applied in combination with 2,4-D (alone = 16.7% ± 2.6; combination = 9.2% ± 1.2). Shoot-to-root translocation of 2,4-D also decreased when the two herbicides were applied in combination (24.8% ± 2.6 when applied alone to only 3.93% ± 0.4 when in the presence of endothall). This research demonstrates that combining herbicides can significantly impact herbicide activity in plants. Future research is needed to determine if this reduced translocation negatively impacts operational effectiveness when these herbicides applied in combination.
Chapter 12 - Politics
- from Part III - Culture and Society
- Edited by Julian Onderdonk, West Chester University, Pennsylvania, Ceri Owen, University of Birmingham
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- Vaughan Williams in Context
- Published online:
- 28 March 2024
- Print publication:
- 04 April 2024, pp 105-111
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Summary
The general outlines of Vaughan Williams’s politics are encapsulated in a remark to Rutland Boughton: ‘Ever since I had a vote I have voted either Radical or Labour’. He was born into considerable financial security, in a family broadly of religiously Nonconformist and politically liberal bent. Despite living as rentier capitalists (with a private income produced from a landed estate, and in the composer’s own case, later, from music royalties), the family and Vaughan Williams himself felt that sensitivity to class difference, and to a harmonious coming together of the classes, were the bedrock of a progressive politics. Hence his musical style, which blends ‘low’ and ‘high’ aesthetics, and ‘folk’ and ‘cosmopolitan’ styles. And hence, too, his professional work with amateurs, both as a composer and conductor, and also as an advocate for the highest quality of musical production (which he felt to be to the benefit of all), both in broadcasting and in competitions he helped to adjudicate. At the national level his was also an important voice on the panels of both the British Council and the Arts Council of Great Britain (as well as its predecessor, the Council for the Encouragement of Music and the Arts).
DISCUSSION: PRESENTATION OF ATMOSPHERIC 14CO2 DATA
- Stephen E Schwartz, Quan Hua, David E Andrews, Ralph F Keeling, Scott J Lehman, Jocelyn C Turnbull, Paula J Reimer, John B Miller, Harro A J Meijer
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- Journal:
- Radiocarbon / Volume 66 / Issue 2 / April 2024
- Published online by Cambridge University Press:
- 27 March 2024, pp. 386-399
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- April 2024
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Observations of radiocarbon (14C) in Earth’s atmosphere and other carbon reservoirs are important to quantify exchanges of CO2 between reservoirs. The amount of 14C is commonly reported in the so-called Delta notation, i.e., Δ14C, the decay- and fractionation-corrected departure of the ratio of 14C to total C from that ratio in an absolute international standard; this Delta notation permits direct comparison of 14C/C ratios in the several reservoirs. However, as Δ14C of atmospheric CO2, Δ14CO2 is based on the ratio of 14CO2 to total atmospheric CO2, its value can and does change not just because of change in the amount of atmospheric14CO2 but also because of change in the amount of total atmospheric CO2, complicating ascription of change in Δ14CO2 to change in one or the other quantity. Here we suggest that presentation of atmospheric 14CO2 amount as mole fraction relative to dry air (moles of 14CO2 per moles of dry air in Earth’s atmosphere), or as moles or molecules of 14CO2 in Earth’s atmosphere, all readily calculated from Δ14CO2 and the amount of atmospheric CO2 (with slight dependence on δ13CO2), complements presentation only as Δ14CO2, and can provide valuable insight into the evolving budget and distribution of atmospheric 14CO2.
The effect of older age on outcomes of rTMS treatment for treatment-resistant depression
- Michael K. Leuchter, Cole Citrenbaum, Andrew C. Wilson, Tristan D. Tibbe, Nicholas J. Jackson, David E. Krantz, Scott A. Wilke, Juliana Corlier, Thomas B. Strouse, Gil D. Hoftman, Reza Tadayonnejad, Ralph J. Koek, Aaron R. Slan, Nathaniel D. Ginder, Margaret G. Distler, Hewa Artin, John H. Lee, Adesewa E. Adelekun, Evan H. Einstein, Hanadi A. Oughli, Andrew F. Leuchter
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- Journal:
- International Psychogeriatrics , First View
- Published online by Cambridge University Press:
- 25 March 2024, pp. 1-6
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Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.
Head and Neck Cancer: United Kingdom National Multidisciplinary Guidelines, Sixth Edition
- Jarrod J Homer, Stuart C Winter, Elizabeth C Abbey, Hiba Aga, Reshma Agrawal, Derfel ap Dafydd, Takhar Arunjit, Patrick Axon, Eleanor Aynsley, Izhar N Bagwan, Arun Batra, Donna Begg, Jonathan M Bernstein, Guy Betts, Colin Bicknell, Brian Bisase, Grainne C Brady, Peter Brennan, Aina Brunet, Val Bryant, Linda Cantwell, Ashish Chandra, Preetha Chengot, Melvin L K Chua, Peter Clarke, Gemma Clunie, Margaret Coffey, Clare Conlon, David I Conway, Florence Cook, Matthew R Cooper, Declan Costello, Ben Cosway, Neil J A Cozens, Grant Creaney, Daljit K Gahir, Stephen Damato, Joe Davies, Katharine S Davies, Alina D Dragan, Yong Du, Mark R D Edmond, Stefano Fedele, Harriet Finze, Jason C Fleming, Bernadette H Foran, Beth Fordham, Mohammed M A S Foridi, Lesley Freeman, Katherine E Frew, Pallavi Gaitonde, Victoria Gallyer, Fraser W Gibb, Sinclair M Gore, Mark Gormley, Roganie Govender, J Greedy, Teresa Guerrero Urbano, Dorothy Gujral, David W Hamilton, John C Hardman, Kevin Harrington, Samantha Holmes, Jarrod J Homer, Deborah Howland, Gerald Humphris, Keith D Hunter, Kate Ingarfield, Richard Irving, Kristina Isand, Yatin Jain, Sachin Jauhar, Sarra Jawad, Glyndwr W Jenkins, Anastasios Kanatas, Stephen Keohane, Cyrus J Kerawala, William Keys, Emma V King, Anthony Kong, Fiona Lalloo, Kirsten Laws, Samuel C Leong, Shane Lester, Miles Levy, Ken Lingley, Gitta Madani, Navin Mani, Paolo L Matteucci, Catriona R Mayland, James McCaul, Lorna K McCaul, Pádraig McDonnell, Andrew McPartlin, Valeria Mercadante, Zoe Merchant, Radu Mihai, Mufaddal T Moonim, John Moore, Paul Nankivell, Sonali Natu, A Nelson, Pablo Nenclares, Kate Newbold, Carrie Newland, Ailsa J Nicol, Iain J Nixon, Rupert Obholzer, James T O'Hara, S Orr, Vinidh Paleri, James Palmer, Rachel S Parry, Claire Paterson, Gillian Patterson, Joanne M Patterson, Miranda Payne, L Pearson, David N Poller, Jonathan Pollock, Stephen Ross Porter, Matthew Potter, Robin J D Prestwich, Ruth Price, Mani Ragbir, Meena S Ranka, Max Robinson, Justin W G Roe, Tom Roques, Aleix Rovira, Sajid Sainuddin, I J Salmon, Ann Sandison, Andy Scarsbrook, Andrew G Schache, A Scott, Diane Sellstrom, Cherith J Semple, Jagrit Shah, Praveen Sharma, Richard J Shaw, Somiah Siddiq, Priyamal Silva, Ricard Simo, Rabin P Singh, Maria Smith, Rebekah Smith, Toby Oliver Smith, Sanjai Sood, Francis W Stafford, Neil Steven, Kay Stewart, Lisa Stoner, Steve Sweeney, Andrew Sykes, Carly L Taylor, Selvam Thavaraj, David J Thomson, Jane Thornton, Neil S Tolley, Nancy Turnbull, Sriram Vaidyanathan, Leandros Vassiliou, John Waas, Kelly Wade-McBane, Donna Wakefield, Amy Ward, Laura Warner, Laura-Jayne Watson, H Watts, Christina Wilson, Stuart C Winter, Winson Wong, Chui-Yan Yip, Kent Yip
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- Journal:
- The Journal of Laryngology & Otology / Volume 138 / Issue S1 / April 2024
- Published online by Cambridge University Press:
- 14 March 2024, pp. S1-S224
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- April 2024
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Attitudes, subjective norms and perceived behavioural control factors influencing Canadian secondary school students’ milk and milk alternatives consumption
- Carise M Thompson, Susan J Elliott, Samantha Meyer, Scott T Leatherdale, Shannon E Majowicz
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- Journal:
- Public Health Nutrition / Volume 27 / Issue 1 / 2024
- Published online by Cambridge University Press:
- 08 March 2024, e92
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Objective:
The research objectives were to evaluate factors that influence Canadian secondary school students’ milk and milk alternatives (MMA) consumption and to explore associations through age and gender lenses.
Design:A qualitative design was used, consisting of semi-structured interviews and photo-elicitation methods. Analysis was guided by the Theory of Planned Behaviour (TPB). Deductive and inductive thematic analyses were used to generate themes, charting data based on attributes such as gender and age.
Setting:Interviews were held virtually or via telephone.
Participants:Participants were twenty-eight high school students from Ontario, Canada, diverse in terms of gender and age.
Results:Both desirable and undesirable beliefs about the health outcomes of consuming MMA were commonly discussed. These included health benefits such as strong bones, muscular strength, and growth, and health consequences like unwanted skin conditions, weight gain, and diseases. While boys and girls associated MMA consumption with muscular strength, boys predominantly considered this favourable, while girls discussed outcomes like unwanted skin conditions and weight gain more often. Adolescents’ perspectives on taste/perceived enjoyment, environmentally friendly choices and animal welfare also influenced their MMA preferences. Parental influences were most cited among social factors, which appeared to be stronger during early adolescence. Factors involving cost, time and accessibility affected adolescents’ beliefs about how difficult it was to consume MMA.
Conclusions:Recommendations for shifting attitudes towards MMA are provided to address unfavourable beliefs towards these products. Interventions to increase MMA consumption among adolescents should include parents and address cost barriers.
Changes in evening-shifted loss of control eating severity following treatment for binge-eating disorder
- Angeline R. Bottera, Elizabeth N. Dougherty, Glen Forester, Carol B. Peterson, Ross D. Crosby, Scott G. Engel, Scott J. Crow, Jennifer E. Wildes, Stephen A. Wonderlich
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 28 February 2024, pp. 1-8
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Background
Loss of control eating is more likely to occur in the evening and is uniquely associated with distress. No studies have examined the effect of treatment on within-day timing of loss of control eating severity. We examined whether time of day differentially predicted loss of control eating severity at baseline (i.e. pretreatment), end-of-treatment, and 6-month follow-up for individuals with binge-eating disorder (BED), hypothesizing that loss of control eating severity would increase throughout the day pretreatment and that this pattern would be less pronounced following treatment. We explored differential treatment effects of cognitive-behavioral guided self-help (CBTgsh) and Integrative Cognitive-Affective Therapy (ICAT).
MethodsIndividuals with BED (N = 112) were randomized to receive CBTgsh or ICAT and completed a 1-week ecological momentary assessment protocol at baseline, end-of-treatment, and 6-month follow-up to assess loss of control eating severity. We used multilevel models to assess within-day slope trajectories of loss of control eating severity across assessment periods and treatment type.
ResultsWithin-day increases in loss of control eating severity were reduced at end-of-treatment and 6-month follow-up relative to baseline. Evening acceleration of loss of control eating severity was greater at 6-month follow-up relative to end-of-treatment. Within-day increases in loss of control severity did not differ between treatments at end-of-treatment; however, evening loss of control severity intensified for individuals who received CBTgsh relative to those who received ICAT at 6-month follow-up.
ConclusionsFindings suggest that treatment reduces evening-shifted loss of control eating severity, and that this effect may be more durable following ICAT relative to CBTgsh.
Synthesis of Al-PILC Assisted by Ultrasound: Reducing the Intercalation Time and the Amount of Synthesis Water
- M. Josefina Pérez-Zurita, Gabriela J. Pérez-Quintana, Alfonso J. Hasblady, Adriana Maldonado, Caribay Urbina de Navarro, Ander De Abrisqueta, Carlos E. Scott
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- Journal:
- Clays and Clay Minerals / Volume 53 / Issue 5 / October 2005
- Published online by Cambridge University Press:
- 01 January 2024, pp. 528-535
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Of all the known pillared layered clays (PILC), Al-PILC is the most studied. In spite of that, its use on a commercial scale is not yet possible due to the large amount of water required for its synthesis. The aim of the present work was to take advantage of the beneficial effects of ultrasound radiation for reducing intercalation time, and to optimize the synthesis parameters in order to find a viable industrial means of preparing Al-PILC.
A comprehensive study of the effect of ultrasonic radiation on the parameters which have a direct effect on the amount of water used in the synthesis was conducted, specifically on the effects of: (1) mmol of Al/g of clay ratio (R) by decreasing the volume of A1 solution and keeping the amount of clay constant, (2) the concentration of clay in the initial suspension (or not suspending the clay at all), and (3) the concentration of the A1 precursor solution. The use of ultrasonic radiation produced the expected reduction in exchange time which was attributed to a decrease of the clay-particle size. This decrease of particle size gave rise to an improvement in the diffusion of the A1 precursor towards the core of the clay grain leading to solids with increased surface areas, basal spacing and X-ray diffraction peak definition. By optimizing the synthesis parameters directly involved in the consumption of water, it was possible to decrease the amount used by >60%.
57 CSF Markers of AD-Related Pathology Relate to aMCI among People with HIV
- Judith D. Lobo, Erin E. Sundermann, Laura M. Campbell, Ben Gouaux, Scott Letendre, Mark W. Bondi, David J. Moore
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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. 53-54
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Objective:
Older people with HIV (PWH) are at-risk for Alzheimer’s disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). Identifying aMCI among PWH is challenging because memory impairment is also common in HIV-associated neurocognitive disorders (HAND). The neuropathological hallmarks of aMCI/AD are amyloid-ß42 (Aß42) plaque and phosphorylated tau (p-tau) accumulation. Neurofilament light chain protein (NfL) is a marker of neuronal injury in AD and other neurodegenerative diseases. In this study, we assessed the prognostic value of the CSF AD pathology markers of lower Aß42, and higher p-tau, p-tau/Aß42 ratio, and NfL levels to identify an aMCI-like profile among older PWH and differentiating it from HAND. We assessed the relationship between aMCI and HAND diagnosis and AD biomarker levels
Participants and Methods:Participants included 74 PWH (Mean age=48 [SD=8.5]; 87.4% male, 56.5% White) from the National NeuroAIDS Tissue Consortium (NNTC). CSF Aß42, Aß40, p-tau and NfL were measured by commercial immunoassay. Participants completed a neurocognitive evaluation assessing the domains of learning, recall, executive function, speed of information processing, working memory, verbal fluency, and motor. Memory domains were assessed with the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised, and aMCI was defined as impairment (<1.0 SD below normative mean) on two or more memory outcomes among HVLT-R and BVMT-R learning, delayed recall and recognition with at-least one recognition impairment required. HAND was defined as impairment (<1.0 SD below normative mean) in 2 or more cognitive domains. A series of separate linear regression models were used to examine how the levels of CSF p-tau, Aß42, p-tau/Aß42 ratio, and NfL relate to aMCI and HAND status while controlling for demographic variables (age, gender, race and education). Covariates were excluded from the model if they did not reach statistical significance.
Results:58% percent of participants were diagnosed with HAND, 50.5% were diagnosed with aMCI. PWH with aMCI had higher levels of CSF p-tau/Aß42 ratio compared to PWH without aMCI (ß=.222, SE=.001, p=.043) while controlling for age (ß=.363, p=.001). No other AD biomarker significantly differed by aMCI or HAND status.
Conclusions:Our results indicate that the CSF p-tau/Aß42 ratio relates specifically to an aMCI-like profile among PWH with high rates of cognitive impairment across multiple domains in this advanced HIV disease cohort. Thus, the p-tau/Aß42 ratio may have utility in disentangling aMCI from HAND and informing the need for further diagnostic procedures and intervention. Further research is needed to fully identify, among a broader group of PWH, who is at greatest risk for aMCI/AD and whether there is increased risk for aMCI/AD among PWH as compared to those without HIV.
3 Development of a Computerized Neurocognitive Battery for Children and Adolescents Affected by Human Immunodeficiency Virus in Botswana
- J. Cobb Scott, Tyler M Moore, Amelia E Van Pelt, Mogomotsi Matshaba, Ontibile Tshume, Onkemetse Phoi, Boitumelo Thuto, Ruben C Gur, Elizabeth D Lowenthal
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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. 211-212
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Objective:
Children born to mothers infected with human immunodeficiency virus (HIV) during pregnancy experience increased risk of neurocognitive impairment. In Botswana, HIV infection is common, but standardized cognitive testing is limited. The Penn Computerized Neurocognitive Battery (PennCNB) is a widely used cognitive test battery that streamlines evaluation of neurocognitive functioning. Our group translated and culturally adapted the PennCNB for use among children and adolescents in this high-burden, low-resource setting. The current study examined the construct validity and sensitivity to HIV infection and exposure of the culturally adapted PennCNB among a cohort of HIV-affected children and adolescents in Gaborone, Botswana.
Participants and Methods:628 school-aged children aged 7-17 years (n=223 children living with HIV [HIV+]; n=204 HIV exposed, uninfected [HEU]; and 201 HIV unexposed, uninfected [HUU]) completed the PennCNB. Participants were recruited from a clinic specializing in the care and treatment of HIV+ children and adolescents in Gaborone, Botswana, as well as from local schools. Confirmatory factor analyses were performed on efficiency measures for 13 PennCNB tests. Multiple regressions examined associations between HIV and neurocognitive functioning while controlling for age and sex. Multivariate normative comparisons were used to examine rates of overall cognitive impairment by comparing individual profiles of test scores to the multivariate distribution of test scores using age-normed data from the HUU group.
Results:Confirmatory factor analysis supported four hypothesized neurocognitive domains: executive functioning, episodic memory, complex cognition, and sensorimotor/processing speed. As expected, there were main effects of age on cognitive performance across all domains (ps < .001), and there were small sex differences, with females performing better in executive functioning and males performing better on visuospatial processing. Children and adolescents living with HIV performed significantly worse than HUU across all domains (ps < .001), with the largest effect sizes on measures of abstraction, working memory, and processing speed. HEU also performed worse than HUU across several domains, with smaller effect sizes. Multivariate normative comparisons indicated that 27% of the HIV+ group evidenced global neurocognitive impairment.
Conclusions:Overall, results support the validity of a neurocognitive battery adapted for use in Botswana, a non-Western, resource-limited setting. Results indicated that the adapted battery applied to children and adolescents with limited computer familiarity had a similar factor structure as in Western settings, indicating that the PennCNB appeared to assess the hypothesized neurocognitive domains. Hypothesized associations with age and sex supported the battery’s construct validity. Moreover, the battery appears to be sensitive to cognitive impairments associated with perinatally-acquired HIV and in utero HIV-related exposures, as it discriminated between the HUU, HIV+, and HEU groups. Differences were found in specific domains and in detection of overall impairment, including approximately one quarter of children and adolescents living with HIV in this cohort evidencing global neurocognitive impairment. Together, these results provide evidence that the PennCNB could serve as a useful tool for the assessment of neurocognitive functioning in school-aged children and adolescents from Botswana and, potentially, other resource-limited settings.
4 Methamphetamine, cannabis, HIV, and their combined effects on neurocognition
- Jeffrey M Rogers, Igor Grant, Maria Cecilia Marcondes, Erin E Morgan, Mariana Cherner, Ronald J Ellis, Scott L Letendre, Robert K Heaton, Jennifer E Iudicello
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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. 797-798
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Objective:
Methamphetamine and cannabis are two widely used substances with possibly opposing effects on aspects of central nervous system functioning. Use of these substances is prevalent among people with HIV (PWH), though their combined effects on HIV-associated neurocognitive impairment (NCI) are unknown. Adverse effects of methamphetamine use on cognition are well documented. Cannabis may disturb cognition acutely, though its longer-term effects in PWH are not well understood. Our prior analysis of people without HIV (PWoH) found that cotemporaneous cannabis use was associated with better neurocognitive outcomes among methamphetamine users. The aim of this study was to assess how lifetime cannabis and methamphetamine use disorder relate to neurocognitive outcomes in PWH.
Participants and Methods:HIV-positive participants (n=472) were on average 45.6±11.5 years of age, male (86.4%), White (60.6%), and educated 13.9±2.5 years. Most participants were on ART (81.9%) and virally suppressed (70%). Participants were stratified by lifetime methamphetamine (M-/M+) and cannabis (C-/C+) DSM-IV abuse/dependence disorder into four groups: M-C- (n=187), M-C+ (n=68), M+C-, (n=82) and M+C+ (n=135) and completed a comprehensive neurobehavioral assessment. Demographically corrected T-scores and deficit scores were used for analyses. Group differences in global and domain NC performances (i.e., T-scores) were examined using multiple linear regression, holding constant covariates that were associated with study groups and/or cognition. Specifically, M+ participants displayed higher rates of Hepatitis C infection (p=.004), higher current depressive symptom scores (p<.001), and higher rates of detectable plasma HIV RNA (p=.014). Multiple logistic regression was used to test for group differences in probability of neurocognitive impairment (i.e., deficit scores>0.5), including the same covariates. Pooling data with a sample of HIV-negative participants (n=423), we used generalized linear mixed effect models to examine how neurocognitive performance and impairment profiles varied by methamphetamine and/or cannabis use group, HIV disease characteristics, and their interactions.
Results:Compared to M+C+, M+C- performed worse on measures of executive functions (ß=-3.17), learning (ß=-3.95), memory (ß=-5.58), and working memory (ß=-4.05) and were more likely to be classified as impaired in the learning (OR=2.93), memory (OR=5.24), and working memory (OR=2.48) domains. M-C- performed better than M+C+ on measures of learning (ß=3.46) and memory (ß=5.19), but worse than M-C+ on measures of executive functions (ß=-3.90), learning (ß=-3.32), memory (ß=-3.38), and working memory (ß=-3.38). Generalized linear mixed effect models indicate that detectable plasma HIV RNA (ß=-1.85) and low nadir CD4 T-cell counts (nadir CD4<200; ß=-1.07) were associated with worse neurocognitive performance, and these effects did not differ in size or direction by substance use group.
Conclusions:In PWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. Cannabis use disorder does not appear to exacerbate methamphetamine-related deficits in PWH. Instead, results are consistent with findings from preclinical studies that cannabis use may protect against methamphetamine’s deleterious effects. Profile analysis models showed that participants with a history of cannabis use disorder display better overall neurocognitive performance than comparison (M-C-) participants. Mechanisms underlying a potential protective effect of cannabis may be elucidated by examining the temporal relationship between cannabis and methamphetamine consumption and neurocognitive performance.
3 The Relationship Between Apolipoprotein-E4 Genotype, Memory, and the Medial Temporal Lobe and How These Relationships Vary by Race in Middle-Aged Persons with HIV
- Laura M Campbell, Maulika Kohli, Erin E Sundermann, Christine Fennema-Notestine, Averi Barrett, Cinnamon Bloss, Mark W Bondi, David B Clifford, Ronald J Ellis, Donald Franklin, Benjamin Gelman, Igor Grant, Robert K Heaton, Scott Letendre, Payal B Patel, David J Moore, Susan Morgello, Raeanne C Moore
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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. 683-684
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Objective:
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.
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).
Patterns, predictors, and patient-reported reasons for antidepressant discontinuation in the WHO World Mental Health Surveys
- Alan E. Kazdin, Meredith G. Harris, Irving Hwang, Nancy A. Sampson, Dan J. Stein, Maria Carmen Viana, Daniel V. Vigo, Chi-Shin Wu, Sergio Aguilar-Gaxiola, Jordi Alonso, Corina Benjet, Ronny Bruffaerts, José Miguel Caldas-Almeida, Graça Cardoso, Elisa Caselani, Stephanie Chardoul, Alfredo Cía, Peter de Jonge, Oye Gureje, Josep Maria Haro, Elie G. Karam, Viviane Kovess-Masfety, Fernando Navarro-Mateu, Marina Piazza, José Posada-Villa, Kate M. Scott, Juan Carlos Stagnaro, Margreet ten Have, Yolanda Torres, Cristian Vladescu, Ronald C. Kessler
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- Psychological Medicine / Volume 54 / Issue 1 / January 2024
- Published online by Cambridge University Press:
- 14 September 2023, pp. 67-78
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Background
Despite their documented efficacy, substantial proportions of patients discontinue antidepressant medication (ADM) without a doctor's recommendation. The current report integrates data on patient-reported reasons into an investigation of patterns and predictors of ADM discontinuation.
MethodsFace-to-face interviews with community samples from 13 countries (n = 30 697) in the World Mental Health (WMH) Surveys included n = 1890 respondents who used ADMs within the past 12 months.
Results10.9% of 12-month ADM users reported discontinuation-based on recommendation of the prescriber while 15.7% discontinued in the absence of prescriber recommendation. The main patient-reported reason for discontinuation was feeling better (46.6%), which was reported by a higher proportion of patients who discontinued within the first 2 weeks of treatment than later. Perceived ineffectiveness (18.5%), predisposing factors (e.g. fear of dependence) (20.0%), and enabling factors (e.g. inability to afford treatment cost) (5.0%) were much less commonly reported reasons. Discontinuation in the absence of prescriber recommendation was associated with low country income level, being employed, and having above average personal income. Age, prior history of psychotropic medication use, and being prescribed treatment from a psychiatrist rather than from a general medical practitioner, in comparison, were associated with a lower probability of this type of discontinuation. However, these predictors varied substantially depending on patient-reported reasons for discontinuation.
ConclusionDropping out early is not necessarily negative with almost half of individuals noting they felt better. The study underscores the diverse reasons given for dropping out and the need to evaluate how and whether dropping out influences short- or long-term functioning.
Vegetation dynamics in Dhofar, Oman, from the Late Holocene to present inferred from rock hyrax middens
- Kaitlyn E. Horisk, Sarah J. Ivory, Joy McCorriston, Molly McHale, Ali Al Mehri, Andrew Anderson, R. Scott Anderson, Ali Ahmad Al Kathiri
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- Quaternary Research / Volume 116 / November 2023
- Published online by Cambridge University Press:
- 30 August 2023, pp. 12-29
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Arid regions are especially vulnerable to climate change and land use. More than one-third of Earth's population relies on these ecosystems. Modern observations lack the temporal depth to determine vegetation responses to climate and human activity, but paleoecological and archaeological records can be used to investigate these relationships. Decreasing rainfall across the Late Holocene provides a case study for vegetation response to changing hydroclimate. Rock hyrax (Procavia capensis) middens preserve paleoenvironmental indicators in arid environments where traditional archives are unavailable. Pollen from modern middens collected in Dhofar, Oman, demonstrates the reliability of this archive. Pollen, stable isotope (δ13C, δ15N), and microcharcoal data from fossil middens reveal changes in vegetation, relative moisture, and fire from 4000 cal yr BP to the present. Trees limited to moister areas (e.g., Terminalia) today existed farther inland at ~3100 cal yr BP. After ~2900 cal yr BP, taxa with more xeric affiliations (e.g., Senegalia) had increased. Coprophilous fungal spores (Sporormiella) and grazing indicator pollen revealed an amplified signal of domesticate grazing at ~1000 cal yr BP. This indicates that trees associated with semiarid environments were maintained in the interior desert during ~3000–4000 yr of decreasing rainfall and that impacts of human activity intensified after the transition to a drier environment.
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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- 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.
Cannabis use may attenuate neurocognitive performance deficits resulting from methamphetamine use disorder
- Jeffrey M. Rogers, Igor Grant, Maria Cecilia G. Marcondes, Erin E. Morgan, Mariana Cherner, Ronald J. Ellis, Scott L. Letendre, Robert K. Heaton, Jennifer E. Iudicello
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- Journal:
- Journal of the International Neuropsychological Society / Volume 30 / Issue 1 / January 2024
- Published online by Cambridge University Press:
- 09 August 2023, pp. 84-93
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Objective:
Methamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders.
Method:423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M−/M+) and/or cannabis (C−/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition.
Results:Globally, M+C+ performed worse than M−C− but better than M+C−. M+C+ outperformed M+C− on measures of verbal fluency, information processing speed, learning, memory, and working memory. M−C+ did not display lower performance than M−C− globally or on any domain measures, and M−C+ even performed better than M−C− on measures of learning, memory, and working memory.
Conclusions:Our findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.