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1.
Curr Psychiatry Rep ; 22(5): 26, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32377970

RESUMO

PURPOSE OF REVIEW: This paper aims to acquaint child and adolescent psychiatrists with the field of pharmacogenomics (PGX) and review the most up-to-date evidence-based practices to guide the application of this field in clinical care. RECENT FINDINGS: Despite much research being done in this area, the field of PGX continues to yield controversial findings. In the adult world, studies have focused on the impact of combinatorial gene panels that guide medication selection by providing reports that estimate the impact of multiple pharmacodynamic and pharmacokinetic genes, but to date, these have not been directly examined in younger patient populations. Pharmacokinetic genes, CYP2D6 and CYP2C19, and hypersensitivity genes, HLA-A and HLA-B, have the strongest evidence base for application to pharmacotherapy in children. Although the field is evolving, and the evidence is mixed, there may be a role for PGX testing in children to help guide dosing and monitoring strategies. However, evidence-based medicine, rather than PGX testing, continues to play the lead role in guiding medication selection in pediatric psychopharmacology.

2.
J Am Med Inform Assoc ; 27(4): 539-548, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32068839

RESUMO

OBJECTIVE: To build a knowledge base of dietary supplement (DS) information, called the integrated DIetary Supplement Knowledge base (iDISK), which integrates and standardizes DS-related information from 4 existing resources. MATERIALS AND METHODS: iDISK was built through an iterative process comprising 3 phases: 1) establishment of the content scope, 2) development of the data model, and 3) integration of existing resources. Four well-regarded DS resources were integrated into iDISK: The Natural Medicines Comprehensive Database, the "About Herbs" page on the Memorial Sloan Kettering Cancer Center website, the Dietary Supplement Label Database, and the Natural Health Products Database. We evaluated the iDISK build process by manually checking that the data elements associated with 50 randomly selected ingredients were correctly extracted and integrated from their respective sources. RESULTS: iDISK encompasses a terminology of 4208 DS ingredient concepts, which are linked via 6 relationship types to 495 drugs, 776 diseases, 985 symptoms, 605 therapeutic classes, 17 system organ classes, and 137 568 DS products. iDISK also contains 7 concept attribute types and 3 relationship attribute types. Evaluation of the data extraction and integration process showed average errors of 0.3%, 2.6%, and 0.4% for concepts, relationships and attributes, respectively. CONCLUSION: We developed iDISK, a publicly available standardized DS knowledge base that can facilitate more efficient and meaningful dissemination of DS knowledge.

3.
Annu Rev Pharmacol Toxicol ; 60: 311-331, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31283429

RESUMO

Pharmacogenetics is a key component of precision medicine. Genetic variation in drug metabolism enzymes can lead to variable exposure to drugs and metabolites, potentially leading to inefficacy and drug toxicity. Although the evidence for pharmacogenetic associations in children is not as extensive as for adults, there are several drugs across diverse therapeutic areas with robust pediatric data indicating important, and relatively common, drug-gene interactions. Guidelines to assist gene-based dose optimization are available for codeine, thiopurine drugs, selective serotonin reuptake inhibitors, atomoxetine, tacrolimus, and voriconazole. For each of these drugs, there is an opportunity to clinically implement precision medicine approaches with children for whom genetic test results are known or are obtained at the time of prescribing. For many more drugs that are commonly used in pediatric patients, additional investigation is needed to determine the genetic factors influencing appropriate dose.

4.
Neuropsychopharmacology ; 45(4): 666-674, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31812151

RESUMO

Abnormal neuroanatomic brain networks have been reported in schizophrenia, but their characterization across patients with psychotic disorders, and their potential alterations in nonpsychotic relatives, remain to be clarified. Participants recruited by the Bipolar and Schizophrenia Network for Intermediate Phenotypes consortium included 326 probands with psychotic disorders (107 with schizophrenia (SZ), 87 with schizoaffective disorder (SAD), 132 with psychotic bipolar disorder (BD)), 315 of their nonpsychotic first-degree relatives and 202 healthy controls. Single-subject gray matter graphs were extracted from structural MRI scans, and whole-brain neuroanatomic organization was compared across the participant groups. Compared with healthy controls, psychotic probands showed decreased nodal efficiency mainly in bilateral superior temporal regions. These regions had altered morphological relationships primarily with frontal lobe regions, and their network-level alterations were associated with positive symptoms of psychosis. Nonpsychotic relatives showed lower nodal centrality metrics in the prefrontal cortex and subcortical regions, and higher nodal centrality metrics in the left cingulate cortex and left thalamus. Diagnosis-specific analysis indicated that individuals with SZ had lower nodal efficiency in bilateral superior temporal regions than controls, probands with SAD only exhibited lower nodal efficiency in the left superior and middle temporal gyrus, and individuals with psychotic BD did not show significant differences from healthy controls. Our findings provide novel evidence of clinically relevant disruptions in the anatomic association of the superior temporal lobe with other regions of whole-brain networks in patients with psychotic disorders, but not in their unaffected relatives, suggesting that it is a disease-related trait. Network disorganization primarily involving frontal lobe and subcortical regions in nonpsychotic relatives may be related to familial illness risk.

6.
Pharmacotherapy ; 40(2): 142-152, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31884695

RESUMO

OBJECTIVES: Implementing pharmacogenetics for very important pharmacogenes (VIPs) holds the promise of improving clinical outcomes through optimal medication selection and dosing. However, significant differences in the frequency of actionable variants in VIPs may exist within subpopulations of a given ancestral group. Furthermore, these differences can potentially impact drug selection and dosing. The purpose of this study was to ascertain allele frequencies for VIPs and to predict medication requirements using Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines in Hmong and compare with published data for East Asians. METHODS: Using a community-based participatory action research approach, DNA collected from 194 Hmong adults living in the United States was analyzed for 22 genetic variants within eight VIPs (CYP2C9, CYP2C19, CYP4F2, DPYD, G6PD, SLCO1B1, TPMT, VKORC1). Allele frequencies for VIPs and predicted medication requirements using CPIC guidelines were compared between Hmong participants and East Asians. RESULTS: Significant differences in allele frequencies between the Hmong and East Asians were found for 23% (5/22) of the CPIC-actionable variants tested. Allele frequencies for VIPs in Hmong versus East Asians were 16.6% versus 3.4% in CYP2C9*3A, 42.2% versus 29.0% for CYP2C19*2, 0.3% versus 8.3% in CYP2C19*3, 6.5% versus 22.1% in CYP4F2*3, and 3.6% versus 0.1% in SLCO1B1*5, respectively. These differences significantly influenced predicted medication usage recommendations in warfarin, simvastatin, and phenytoin between Hmong and East Asians. CONCLUSIONS: Important differences in allele frequencies for key genetic variants influencing selection of medications and dosages were found between the Hmong and East Asians. The magnitude and nature of these differences can be expected to result in different medication recommendations for the Hmong relative to East Asians.

7.
Transl Psychiatry ; 9(1): 230, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530798

RESUMO

Schizophrenia, Schizoaffective, and Bipolar disorders share behavioral and phenomenological traits, intermediate phenotypes, and some associated genetic loci with pleiotropic effects. Volumetric abnormalities in brain structures are among the intermediate phenotypes consistently reported associated with these disorders. In order to examine the genetic underpinnings of these structural brain modifications, we performed genome-wide association analyses (GWAS) on 60 quantitative structural brain MRI phenotypes in a sample of 777 subjects (483 cases and 294 controls pooled together). Genotyping was performed with the Illumina PsychChip microarray, followed by imputation to the 1000 genomes multiethnic reference panel. Enlargement of the Temporal Horns of Lateral Ventricles (THLV) is associated with an intronic SNP of the gene NRXN1 (rs12467877, P = 6.76E-10), which accounts for 4.5% of the variance in size. Enlarged THLV is associated with psychosis in this sample, and with reduction of the hippocampus and enlargement of the choroid plexus and caudate. Eight other suggestively significant associations (P < 5.5E-8) were identified with THLV and 5 other brain structures. Although rare deletions of NRXN1 have been previously associated with psychosis, this is the first report of a common SNP variant of NRXN1 associated with enlargement of the THLV in psychosis.

8.
Am J Cardiol ; 124(7): 1038-1043, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31375243

RESUMO

Guideline-recommended anticoagulation is frequently omitted in high-risk patients with atrial fibrillation (AF) for reasons not fully understood, which may result in suboptimal care. A nationally representative, expert group of physicians (cardiology, neurology, and general medicine), and clinical pharmacists participated in a consensus-seeking, modified Delphi method to identify key clinical decision-making factors driving anticoagulant prescribing in real-world AF patients. Representing >2,500 anticoagulation-related patient encounters per month, 27 of 30 participants completed the study (90% overall response rate). In Round-1, experts rated their level of agreement with factors and suggested modifications or additional factors. Of 66 factors entering Round-1, 21 met and 4 partially met consensus, 41 did not meet consensus, and 7 were newly suggested. Of 32 factors advanced for scoring in Round-2, 16 met consensus criteria. In Round-3, experts were given the option to rescue up to 2 of the 16 nonconsensus factors from Round-2. Including a concomitant need for dual antiplatelet therapy, no factor was successfully rescued into consensus. The most important factors related to risk of infarction rather than bleeding risk or other patient-specific considerations. Among factors not independently addressed in current guidelines, these included baseline hematologic indicators of potential bleeding risk, previous bleeding episodes by specific type, other risk factors for bleeding, and adherence. In conclusion, when determining anticoagulation strategies in AF, there is a need for further research on the clinical implications of these emerging factors as well as the reasons behind divergent opinions toward nonconsensus factors.

10.
Am J Psychiatry ; 176(7): 564-572, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31164007

RESUMO

OBJECTIVE: The choroid plexus is an important physiological barrier and produces CSF and neurotrophic, angiogenic, and inflammatory factors involved in brain development. Choroid plexus abnormalities have been implicated in both schizophrenia and bipolar disorder. A previous choroid plexus transcriptomic analysis of schizophrenia identified an upregulation of immune and inflammatory genes that correlated with peripheral inflammatory markers. The purpose of this study was to examine choroid plexus volume in probands across the psychosis spectrum and in their first-degree and axis II cluster A relatives, as well as choroid plexus familiality and choroid plexus covariance with clinical, cognitive, brain, and peripheral marker measures. METHODS: Choroid plexus volume was quantified (using FreeSurfer) in psychosis probands, their first-degree and axis II cluster A relatives, and healthy control subjects, organized by DSM-IV-TR diagnosis. Analyte, structural connectivity, and genotype data were collected from a subset of study subjects. RESULTS: Choroid plexus volume was significantly larger in probands compared with first-degree relatives or healthy control subjects; first-degree relatives had intermediate enlargement compared with healthy control subjects; and total choroid plexus volume was significantly heritable. Larger volume was associated with worse cognition, smaller total gray matter and amygdala volume, larger lateral ventricle volume, and lower structural connectivity in probands. Associations between larger volume and higher levels of interleukin 6 in probands was also observed. CONCLUSIONS: These findings suggest the involvement of the choroid plexus across the psychosis spectrum with a potential pathophysiological mechanism involving the neuroimmune axis, which functions in maintaining brain homeostasis and interacting with the peripheral immune and inflammatory system. The choroid plexus may be an important target in future research.


Assuntos
Plexo Corióideo/patologia , Cognição , Inflamação/patologia , Transtornos Psicóticos/patologia , Adulto , Estudos de Casos e Controles , Plexo Corióideo/diagnóstico por imagem , Plexo Corióideo/fisiopatologia , Cognição/fisiologia , Feminino , Humanos , Inflamação/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Neuroimagem , Tamanho do Órgão , Fenótipo , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/fisiopatologia
11.
Pharmacogenomics ; 20(4): 291-306, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30883267

RESUMO

Clinical symptom response to antipsychotic medications is highly variable. Genome-wide association studies (GWAS) provide a 'hypothesis-free' method of interrogating the genome for biomarkers of antipsychotic response. We performed a systematic review of GWAS findings for antipsychotic efficacy or effectiveness. 14 studies met our inclusion criteria, ten of which examined antipsychotic response using quantitative rating scales to measure symptom improvement. 15 genome-wide significant loci were identified, seven of which were replicated in other antipsychotic GWAS publications: CNTNAP5, GRID2, GRM7, 8q24 (KCNK9), PCDH7, SLC1A1 and TNIK. Notably, four replicated loci are involved in glutamatergic pathways. Additional validation and evaluation of the biological significance of these markers is warranted. These markers should also be evaluated for clinical utility, especially in the context of other validated pharmacogenomic variants (e.g., CYP450 genes). These findings may generate new avenues for development of novel antipsychotic treatments.

12.
Genet Med ; 21(10): 2255-2263, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30894703

RESUMO

PURPOSE: A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers. METHODS: We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption. Data were collected on testing approaches, return of results procedures, applications of genotype results, challenges faced, and lessons learned. RESULTS: Among early adopters, CYP2D6 testing was most commonly ordered to assist with opioid and antidepressant prescribing. Key differences among programs included test ordering and genotyping approaches, result reporting, and clinical decision support. However, all sites tested for copy-number variation and nine common variants, and reported results in the medical record. Most sites provided automatic consultation and had designated personnel to assist with genotype-informed therapy recommendations. Primary challenges were related to stakeholder support, CYP2D6 gene complexity, phenotype assignment, and sustainability. CONCLUSION: There are specific challenges unique to CYP2D6 testing given the complexity of the gene and its relevance to multiple medications. Consensus lessons learned may guide those interested in pursuing similar clinical pharmacogenetic programs.

13.
Clin Pharmacol Ther ; 106(1): 94-102, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30801677

RESUMO

Atomoxetine is a nonstimulant medication used to treat attention-deficit/hyperactivity disorder (ADHD). Cytochrome P450 (CYP)2D6 polymorphisms influence the metabolism of atomoxetine thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for atomoxetine based on CYP2D6 genotype (updates at www.cpicpgx.org).

14.
Am J Pharm Educ ; 83(10): 7276, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-32001873

RESUMO

Objective. To examine the feasibility and effectiveness of combining whole-task and guided reflection educational design principles with cloud-based learning technologies to simulate the clinical psychiatric advanced pharmacy practice experience (APPE) in the classroom to begin to close the theory to practice gap. Methods. Components of the typical student experience while completing an APPE were integrated into the course experience, ie, patient case work-ups, facilitated sessions with a preceptor, personal statement of goals and progress with feedback, and intentional interaction with peer-learners. Multiple sources of quantitative and qualitative data were collected and analyzed. Results. Twelve third-year pharmacy students from two campuses participated in and successfully completed this one-credit elective advanced psychiatric pharmacotherapy course. Eleven board-certified psychiatric pharmacists (BCPP) served as visiting experts, some participating for multiple weeks, and provided preceptor-like feedback to the case presentations in spring 2017. All BCPP pharmacists plus an additional geriatric pharmacist specialist participated in the course in spring 2018. Results of the quantitative and qualitative analyses demonstrated that students progressed in their readiness for APPEs and gained additional psychiatric pharmacy knowledge and evidence-based medicine decision making skills. Conclusion. Pharmacy programs are challenged to find additional ways to improve student readiness for APPEs and expand psychiatric learning opportunities to meet the increasing mental health needs across clinical settings. This example provides a feasible and effective strategy to do both without the requirement to create extensive new learning materials or add significant faculty workload.

15.
Schizophr Res ; 202: 173-179, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30539769

RESUMO

BACKGROUND: Oxytocin (OT) and arginine vasopressin (AVP) exert sexually dimorphic effects on cognition and emotion processing. Abnormalities in these hormones are observed in schizophrenia and may contribute to multiple established sex differences associated with the disorder. Here we examined sex-dependent hormone associations with resting brain activity and their clinical associations in schizophrenia patients. METHODS: OT and AVP serum concentrations were assayed in 35 individuals with schizophrenia (23 men) and 60 controls (24 men) from the Chicago BSNIP study site. Regional cerebral function was assessed with resting state fMRI by measuring the amplitude of low-frequency fluctuations (ALFF) which are believed to reflect intrinsic spontaneous neuronal activity. RESULTS: In female patients, lower OT levels were associated with lower ALFF in frontal and cerebellar cortices (p's < 0.05) and in female controls AVP levels were inversely associated with ALFF in the frontal cortex (p = 0.01). In male patients, lower OT levels were associated with lower ALFF in the posterior cingulate and lower AVP levels were associated with lower ALFF in frontal cortex (p's < 0.05). In male controls, lower OT levels were associated with lower ALFF in frontal cortex and higher ALFF in the thalamus (p's < 0.05). There were some inverse ALFF-behavior associations in patients. CONCLUSIONS: Alterations in peripheral hormone levels are associated with resting brain physiology in a sex-dependent manner in schizophrenia. These effects may contribute to sex differences in psychiatric symptom severity and course of illness in schizophrenia.


Assuntos
Encéfalo/fisiopatologia , Neurofisinas/sangue , Ocitocina/sangue , Precursores de Proteínas/sangue , Esquizofrenia/fisiopatologia , Caracteres Sexuais , Vasopressinas/sangue , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Estudos Transversais , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Descanso , Esquizofrenia/diagnóstico por imagem
16.
Front Psychiatry ; 9: 418, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30279666

RESUMO

Mindfulness Based Stress Reduction (MBSR) is an effective non-pharmacologic treatment for veterans with PTSD. Extensive work has identified epigenetic factors related to PTSD disease risk and pathophysiology, but how these factors influence treatment response is unclear. Serotonin signaling and hypothalamic-pituitary-adrenal (HPA) axis functioning may be perturbed in PTSD and are molecular pathways targeted by PTSD treatments. To identify potential biomarkers for treatment response, we utilized genomic DNA isolated from peripheral blood samples from veterans with PTSD who were responders (n = 11) or non-responders (n = 11) to MBSR as part of a clinical trial. We assessed methylation levels at CpG sites in regions of the serotonin transporter (SLC6A4) previously associated with expression and depression outcomes, as well as the Intron 7 region of the FK506 binding protein 5 (FKBP5) containing known glucocorticoid response elements suggested to regulate this gene. Selected subjects were matched across MBSR responder status by baseline symptoms, age, sex, current smoking status, and current antidepressant use. Percent methylation was compared between responders and non-responders at baseline (pre-MBSR treatment). Additionally, percent change in methylation from baseline to post-treatment was compared between responders and non-responders. There was a significant time x responder group interaction for methylation in FKBP5 intron 7 bin 2 [F (1, 19) = 7.492, p = 0.013] whereby responders had a decrease in methylation and non-responders had an increase in methylation from before to after treatment in this region. Analyses of the three CpG sites within bin 2 revealed a significant time x responder group interaction for CpG_35558513 [F (1, 19) = 5.551, p = 0.029] which resides in a known glucocorticoid response element (GRE). Decreases in FKBP5 methylation after treatment in responders as compared to increases in non-responders suggest that effective meditation intervention may be associated with stress-related pathways at the molecular level. These preliminary findings suggest that DNA methylation signatures within FKBP5 are potential indicators of response to meditation treatment in PTSD and require validation in larger cohorts.

17.
AMIA Jt Summits Transl Sci Proc ; 2017: 207-216, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29888074

RESUMO

Dietary supplements, often considered as food, are widely consumed despite of limited knowledge around their safety/efficacy and any well-established regulatory policies, unlike their drug counterparts. Informatics methods may be useful in filling this knowledge gap, however, the lack of standardized representation of DS hinders this progress. In this pilot study, five electronic DS resources, i.e., NM, DSID & NHPID (ingredient level) and DSLD & LNHPD (product level), were evaluated and compared both quantitatively and qualitatively employing four phases. Essential data elements needed for comprehensive DS representation were compiled based on LanguaL code (food) & AHFSA (drugs) guidelines and employed as a check-list. We further investigated the completeness of DS representation by incorporating Ginseng and Fish oil as examples. We found fragmented and inconsistent distribution of DS representation in terms of essential data elements across five resources. This study provides a preliminary platform for development of standardized DS terminology/ontology model.

18.
Schizophr Res ; 202: 212-216, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29941295

RESUMO

This study evaluated the ability to flexibly shift cognitive set and to consistently maintain a new response preference using the Penn Conditional Exclusion Test (PCET). The relationship of performance errors with catechol-O-methyltransferase (COMT) rs4680 (Val158Met) genotype (Met carriers vs. Val homozygotes) on test performance before and after antipsychotic treatment in 32 first episode psychosis (FEP) patients was examined. After treatment, patients demonstrated a mixture of beneficial and adverse cognitive outcomes that varied in relation to COMT genotype. Met carriers showed decreased perseverative and regressive errors, reflecting improved cognitive flexibility and enhanced stability of behavioral preferences, respectively. In contrast, Val homozygotes exhibited an increase in regressive errors after treatment. These findings suggest that Val homozygotes may be vulnerable to adverse effects of antipsychotic medication on cognitive processes that maintain consistent adaptive response preferences, an ability linked to the striatum in rodent models.


Assuntos
Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Catecol O-Metiltransferase/genética , Função Executiva/efeitos dos fármacos , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/genética , Adulto , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/enzimologia , Transtorno Bipolar/genética , Transtorno Bipolar/psicologia , Cognição/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/enzimologia , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/psicologia , Feminino , Heterozigoto , Humanos , Masculino , Variantes Farmacogenômicos , Transtornos Psicóticos/enzimologia , Transtornos Psicóticos/psicologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/enzimologia , Esquizofrenia/genética , Psicologia do Esquizofrênico
19.
J Acquir Immune Defic Syndr ; 79(1): 83-91, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29781879

RESUMO

OBJECTIVE: The aging HIV population has increased comorbidity burden and consequently non-antiretroviral medication utilization. Many non-antiretroviral medications have known neurocognitive-adverse effects ("NC-AE medications"). We assessed the cognitive effects of NC-AE medications in HIV+ and HIV- women. METHODS: One thousand five hundred fifty-eight participants (1037 HIV+; mean age 46) from the Women's Interagency HIV Study completed a neuropsychological test battery between 2009 and 2011. The total number of NC-AE medications and subgroups (eg, anticholinergics) were calculated based on self-report. Generalized linear models for non-normal data were used to examine the cognitive burden of medications and factors that exacerbate these effects. RESULTS: HIV+ women reported taking more NC-AE medications vs. HIV- women (P < 0.05). NC-AE medication use altogether was not associated with cognitive performance. However, among NC-AE medication subgroups, anticholinergic-acting medications, but not opioids or anxiolytics/anticonvulsants, were negatively associated with performance. HIV status moderated the association between these NC-AE medication subgroups and performance (P's < 0.05). HIV-serostatus differences (HIV- < HIV+) in global, learning, fluency, and motor function were greatest among women taking >1 anticholinergic medications. HIV-serostatus differences in performance on learning and psychomotor speed were also greatest among women taking 1 or more anxiolytics/anticonvulsants and 1 or more opioids, respectively. CONCLUSIONS: HIV+ women have increased cognitive vulnerabilities to anticholinergic, anxiolytic/anticonvulsant, and opioid medications. Potential synergy between these medications and HIV may explain some HIV-related cognitive impairments. It may be important clinically to consider these specific types of medications as a contributor to impaired cognitive performance in HIV+ women and assess the cost/benefit of treatment dosage for underlying conditions.


Assuntos
Disfunção Cognitiva/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Adulto , Analgésicos Opioides/efeitos adversos , Ansiolíticos/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Antidepressivos/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Comorbidade , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Infecções por HIV/complicações , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Adesão à Medicação , Pessoa de Meia-Idade , Testes Neuropsicológicos
20.
Transl Psychiatry ; 8(1): 78, 2018 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-29643358

RESUMO

Psychotic disorders including schizophrenia are commonly accompanied by cognitive deficits. Recent studies have reported negative genetic correlations between schizophrenia and indicators of cognitive ability such as general intelligence and processing speed. Here we compare the effect of polygenetic risk for schizophrenia (PRSSCZ) on measures that differ in their relationships with psychosis onset: a measure of current cognitive abilities (the Brief Assessment of Cognition in Schizophrenia, BACS) that is greatly reduced in psychotic disorder patients, a measure of premorbid intelligence that is minimally affected by psychosis onset (the Wide-Range Achievement Test, WRAT); and educational attainment (EY), which covaries with both BACS and WRAT. Using genome-wide single nucleotide polymorphism (SNP) data from 314 psychotic and 423 healthy research participants in the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) Consortium, we investigated the association of PRSSCZ with BACS, WRAT, and EY. Among apparently healthy individuals, greater genetic risk for schizophrenia (PRSSCZ) was significantly associated with lower BACS scores (r = -0.17, p = 6.6 × 10-4 at PT = 1 × 10-4), but not with WRAT or EY. Among individuals with psychosis, PRSSCZ did not associate with variations in any of these three phenotypes. We further investigated the association between PRSSCZ and WRAT in more than 4500 healthy subjects from the Philadelphia Neurodevelopmental Cohort. The association was again null (p > 0.3, N = 4511), suggesting that different cognitive phenotypes vary in their etiologic relationship with schizophrenia.


Assuntos
Predisposição Genética para Doença , Herança Multifatorial , Transtornos Psicóticos/genética , Esquizofrenia/genética , Psicologia do Esquizofrênico , Adulto , Cognição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Polimorfismo de Nucleotídeo Único , Transtornos Psicóticos/complicações , Fatores de Risco , Esquizofrenia/complicações
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