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1.
Am J Geriatr Psychiatry ; 32(2): 137-147, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37770349

RESUMEN

OBJECTIVES: Late life depression (LLD) and hoarding disorder (HD) are common in older adults and characterized by executive dysfunction and disability. We aimed to determine the frequency of co-occurring HD in LLD and examine hoarding severity as an additional contributor to executive dysfunction, disability, and response to psychotherapy for LLD. DESIGN: Cross-sectional. SETTING: Outpatient psychiatry program. PARTICIPANTS: Eighty-three community-dwelling adults ages 65-90 with LLD. INTERVENTION: Problem-solving therapy. MEASUREMENTS: Measures of executive function, disability, depression, and hoarding severity were completed at post-treatment. Pearson's chi-squared tests evaluated group differences in rates of cognitive impairment, disability, and depression treatment response between participants with HD (LLD+HD) and LLD only. Separate linear regressions assessed associations between hoarding severity and executive function, disability, and psychotherapy response. Covariates included age, education, gender, and depression severity. RESULTS: 30.1% (25/83) of LLD participants met HD criteria. Relative to LLD, LLD+HD participants demonstrated greater impairment rates on measures of executive function (Letter-Number-Sequencing, X2(1)=4.0, p = 0.045; Stroop-Interference, X2(1) = 4.8, p = 0.028). Greater hoarding severity was associated with poorer executive functioning performance (Letter-Number-Sequencing (t[70] = -2.1, ß = -0.05, p = 0.044), Digit-Span (t[71] = -2.4, ß = -0.07, p = 0.019), Letter-Fluency (t[ 71] = -2.8, ß = -0.24, p = 0.006)). Rates of disability were significantly higher for LLD+HD (88.0%) than LLD (62.3%), (X2[1] = 5.41, p = 0.020) and higher hoarding severity was related to greater disability (t[72] = 2.97, ß = 0.13, p = 0.004). Depression treatment response rates were significantly lower for LLD+HD (24.0%) compared to LLD (48.3%), X2(1) = 4.26, p = 0.039, and HD status predicted psychotherapy response, t(67) = -2.15, ß = -15.6, p = 0.035. CONCLUSIONS: We found 30.1% co-occurrence of HD in LLD, which was accompanied by greater executive dysfunction, disability, and poorer response to depression treatment. Results underscore the need for increased screening of hoarding behaviors in LLD and tailored interventions for this LLD+HD group.


Asunto(s)
Disfunción Cognitiva , Trastorno de Acumulación , Acaparamiento , Humanos , Anciano , Depresión/complicaciones , Depresión/epidemiología , Depresión/terapia , Estudios Transversales , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/terapia , Conducta Compulsiva , Trastorno de Acumulación/terapia , Trastorno de Acumulación/psicología
2.
Am J Geriatr Psychiatry ; 32(4): 497-508, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38092621

RESUMEN

Hoarding disorder (HD) is a debilitating neuropsychiatric condition that affects 2%-6% of the population and increases in incidence with age. Major depressive disorder (MDD) co-occurs with HD in approximately 50% of cases and leads to increased functional impairment and disability. However, only one study to date has examined the rate and trajectory of hoarding symptoms in older individuals with a lifetime history of MDD, including those with current active depression (late-life depression; LLD). We therefore sought to characterize this potentially distinct phenotype. We determined the incidence of HD in two separate cohorts of participants with LLD (n = 73) or lifetime history of MDD (n = 580) and examined the reliability and stability of hoarding symptoms using the Saving Inventory-Revised (SI-R) and Hoarding Rating Scale-Self Report (HRS), as well as the co-variance of hoarding and depression scores over time. HD was present in 12% to 33% of participants with MDD, with higher rates found in those with active depressive symptoms. Hoarding severity was stable across timepoints in both samples (all correlations >0.75), and fewer than 30% of participants in each sample experienced significant changes in severity between any two timepoints. Change in depression symptoms over time did not co-vary with change in hoarding symptoms. These findings indicate that hoarding is a more common comorbidity in LLD than previously suggested, and should be considered in screening and management of LLD. Future studies should further characterize the interaction of these conditions and their impact on outcomes, particularly functional impairment in this vulnerable population.


Asunto(s)
Trastorno Depresivo Mayor , Trastorno de Acumulación , Acaparamiento , Humanos , Anciano , Depresión/psicología , Trastorno Depresivo Mayor/epidemiología , Acaparamiento/epidemiología , Reproducibilidad de los Resultados , Conducta Compulsiva , Trastorno de Acumulación/diagnóstico
3.
Behav Cogn Psychother ; 52(1): 65-77, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37699703

RESUMEN

BACKGROUND: Anxiety disorders are the most frequently diagnosed psychiatric conditions in children and adolescents. Cognitive behavioural therapy (CBT) is a well-established and effective treatment for anxiety and related disorders across the lifespan. Expectations of psychotherapy have been demonstrated to affect outcomes, yet there is sparse existing literature on adolescent patient and parent perspectives of CBT prior to engagement with treatment. AIMS: This study aimed to qualitatively explore the expectations and perceptions of CBT for anxiety and related disorders among adolescent patients and parents. METHOD: Fourteen adolescent patients and 16 parents participated in semi-structured individual interviews or focus groups consisting of 2-3 participants. Interview transcripts were analysed using inductive analysis. RESULTS: Three themes were identified: worries about CBT, expectations and knowledge of the CBT process, and the role of parents and families. Overall, we found that adolescents and parents had generally positive views of CBT. The outset of CBT saw adolescents and parents express concern about stigma as well as the ambiguity of CBT. Parents continued to express a lack of understanding of what CBT entailed during their child's treatment course. CONCLUSION: These results suggest that both adolescents and parents would benefit from early discussion and reinforcement of expectations for CBT treatment. Further research efforts are warranted and should be directed towards determining appropriate expectations for parental involvement in a child's CBT course and effective communication of treatment expectations to both adolescents and parents.


Asunto(s)
Terapia Cognitivo-Conductual , Motivación , Adolescente , Humanos , Niño , Trastornos de Ansiedad/terapia , Trastornos de Ansiedad/psicología , Padres/psicología , Terapia Cognitivo-Conductual/métodos , Ansiedad
4.
Neurobiol Dis ; 185: 106252, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37536382

RESUMEN

Gilles de la Tourette syndrome (GTS) is a neuropsychiatric movement disorder with reported abnormalities in various neurotransmitter systems. Considering the integral role of iron in neurotransmitter synthesis and transport, it is hypothesized that iron exhibits a role in GTS pathophysiology. As a surrogate measure of brain iron, quantitative susceptibility mapping (QSM) was performed in 28 patients with GTS and 26 matched controls. Significant susceptibility reductions in the patients, consistent with reduced local iron content, were obtained in subcortical regions known to be implicated in GTS. Regression analysis revealed a significant negative association of tic scores and striatal susceptibility. To interrogate genetic mechanisms that may drive these reductions, spatially specific relationships between susceptibility and gene-expression patterns from the Allen Human Brain Atlas were assessed. Correlations in the striatum were enriched for excitatory, inhibitory, and modulatory neurochemical signaling mechanisms in the motor regions, mitochondrial processes driving ATP production and iron­sulfur cluster biogenesis in the executive subdivision, and phosphorylation-related mechanisms affecting receptor expression and long-term potentiation in the limbic subdivision. This link between susceptibility reductions and normative transcriptional profiles suggests that disruptions in iron regulatory mechanisms are involved in GTS pathophysiology and may lead to pervasive abnormalities in mechanisms regulated by iron-containing enzymes.


Asunto(s)
Trastornos del Movimiento , Síndrome de Tourette , Humanos , Síndrome de Tourette/diagnóstico por imagen , Síndrome de Tourette/genética , Transcriptoma , Encéfalo/diagnóstico por imagen , Homeostasis
5.
Psychol Med ; 53(7): 3021-3035, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35243971

RESUMEN

BACKGROUND: Clinical, epidemiological, and genetic findings support an overlap between eating disorders, obsessive-compulsive disorder (OCD), and anxiety symptoms. However, little research has examined the role of genetics in the expression of underlying phenotypes. We investigated whether the anorexia nervosa (AN), OCD, or AN/OCD transdiagnostic polygenic scores (PGS) predict eating disorder, OCD, and anxiety symptoms in a large developmental cohort in a sex-specific manner. METHODS: Using summary statistics from Psychiatric Genomics Consortium AN and OCD genome-wide association studies, we conducted an AN/OCD transdiagnostic genome-wide association meta-analysis. We then calculated AN, OCD, and AN/OCD PGS in participants from the Avon Longitudinal Study of Parents and Children to predict eating disorder, OCD, and anxiety symptoms, stratified by sex (combined N = 3212-5369 per phenotype). RESULTS: The PGS prediction of eating disorder, OCD, and anxiety phenotypes differed between sexes, although effect sizes were small. AN and AN/OCD PGS played a more prominent role in predicting eating disorder and anxiety risk than OCD PGS, especially in girls. AN/OCD PGS provided a small boost over AN PGS in the prediction of some anxiety symptoms. All three PGS predicted higher compulsive exercise across different developmental timepoints [ß = 0.03 (s.e. = 0.01) for AN and AN/OCD PGS at age 14; ß = 0.05 (s.e. = 0.02) for OCD PGS at age 16] in girls. CONCLUSIONS: Compulsive exercise may have a transdiagnostic genetic etiology, and AN genetic risk may play a role in the presence of anxiety symptoms. Converging with prior twin literature, our results also suggest that some of the contribution of genetic risk may be sex-specific.


Asunto(s)
Anorexia Nerviosa , Trastornos de Alimentación y de la Ingestión de Alimentos , Trastorno Obsesivo Compulsivo , Masculino , Femenino , Humanos , Anorexia Nerviosa/epidemiología , Estudios Longitudinales , Estudio de Asociación del Genoma Completo , Comorbilidad , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/genética , Trastorno Obsesivo Compulsivo/diagnóstico , Ansiedad/genética
6.
Mol Psychiatry ; 27(12): 5020-5027, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36224258

RESUMEN

Tourette Syndrome (TS) is a heritable, early-onset neuropsychiatric disorder that typically begins in early childhood. Identifying rare genetic variants that make a significant contribution to risk in affected families may provide important insights into the molecular aetiology of this complex and heterogeneous syndrome. Here we present a whole-genome sequencing (WGS) analysis from the 11-generation pedigree (>500 individuals) of a densely affected Costa Rican family which shares ancestry from six founder pairs. By conducting an identity-by-descent (IBD) analysis using WGS data from 19 individuals from the extended pedigree we have identified putative risk haplotypes that were not seen in controls, and can be linked with four of the six founder pairs. Rare coding and non-coding variants present on the haplotypes and only seen in haplotype carriers show an enrichment in pathways such as regulation of locomotion and signal transduction, suggesting common mechanisms by which the haplotype-specific variants may be contributing to TS-risk in this pedigree. In particular we have identified a rare deleterious missense variation in RAPGEF1 on a chromosome 9 haplotype and two ultra-rare deleterious intronic variants in ERBB4 and IKZF2 on the same chromosome 2 haplotype. All three genes play a role in neurodevelopment. This study, using WGS data in a pedigree-based approach, shows the importance of investigating both coding and non-coding variants to identify genes that may contribute to disease risk. Together, the genes and variants identified on the IBD haplotypes represent biologically relevant targets for investigation in other pedigree and population-based TS data.


Asunto(s)
Neurogénesis , Síndrome de Tourette , Preescolar , Humanos , Costa Rica , Haplotipos , Linaje , Transducción de Señal , Síndrome de Tourette/genética , Neurogénesis/genética , Polimorfismo Genético , Secuenciación Completa del Genoma , Factor 2 Liberador de Guanina Nucleótido/genética
7.
Mol Psychiatry ; 26(12): 7522-7529, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34526668

RESUMEN

Tourette syndrome (TS) is a highly heritable neuropsychiatric disorder with complex patterns of genetic inheritance. Recent genetic findings in TS have highlighted both numerous common variants with small effects and a few rare variants with moderate or large effects. Here we searched for genetic causes of TS in a large, densely-affected British pedigree using a systematic genomic approach. This pedigree spans six generations and includes 122 members, 85 of whom were individually interviewed, and 53 of whom were diagnosed as "cases" (consisting of 28 with definite or probable TS, 20 with chronic multiple tics [CMT], and five with obsessive-compulsive behaviors [OCB]). A total of 66 DNA samples were available (25 TS, 15 CMT, 4 OCB cases, and 22 unaffecteds) and all were genotyped using a dense single nucleotide polymorphism (SNP) array to identify shared segments, copy number variants (CNVs), and to calculate genetic risk scores. Eight cases were also whole genome sequenced to test whether any rare variants were shared identical by descent. While we did not identify any notable CNVs, single nucleotide variants, indels or repeat expansions of near-Mendelian effect, the most distinctive feature of this family proved to be an unusually high load of common risk alleles for TS. We found that cases within this family carried a higher load of TS common variant risk similar to that previously found in unrelated TS cases. Thus far, the strongest evidence from genetic data for contribution to TS risk in this family comes from multiple common risk variants rather than one or a few variants of strong effect.


Asunto(s)
Trastornos de Tic , Síndrome de Tourette , Humanos , Linaje , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Síndrome de Tourette/genética
8.
BMC Psychiatry ; 22(1): 647, 2022 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-36241971

RESUMEN

BACKGROUND: Hoarding symptoms are associated with functional impairment, though investigation of disability among individuals with hoarding disorder has largely focused on clutter-related impairment to home management activities and difficulties using space because of clutter. This analysis assesses disability among individuals with hoarding symptoms in multiple domains of everyday functioning, including cognition, mobility, self-care, interpersonal and community-level interactions, and home management. The magnitude of the association between hoarding and disability was compared to that of medical and psychiatric disorders with documented high disability burden, including major depressive disorder (MDD), diabetes, and chronic pain. METHODS: Data were cross-sectionally collected from 16,312 adult participants enrolled in an internet-based research registry, the Brain Health Registry. Pearson's chi-square tests and multivariable logistic regression models were used to quantify the relationship between hoarding and functional ability relative to MDD, diabetes, and chronic pain. RESULTS: More than one in ten participants endorsed clinical (5.7%) or subclinical (5.7%) hoarding symptoms (CHS and SCHS, respectively). After adjusting for participant demographic characteristics and psychiatric and medical comorbidity, CHS and SCHS were associated with increased odds of impairment in all domains of functioning. Moderate to extreme impairment was endorsed more frequently by those with CHS or SCHS compared to those with self-reported MDD, diabetes, and/or chronic pain in nearly all domains (e.g., difficulty with day-to-day work or school: CHS: 18.7% vs. MDD: 11.8%, p < 0.0001) except mobility and self-care. While those with current depressive symptoms endorsed higher rates of impairment than those with hoarding symptoms, disability was most prevalent among those endorsing both hoarding and comorbid depressive symptoms. CONCLUSIONS: Hoarding symptoms are associated with profound disability in all domains of functioning. The burden of hoarding is comparable to that of other medical and psychiatric illnesses with known high rates of functional impairment. Future studies should examine the directionality and underlying causality of the observed associations, and possibly identify target interventions to minimize impairment associated with hoarding symptomatology.


Asunto(s)
Dolor Crónico , Trastorno Depresivo Mayor , Diabetes Mellitus , Acaparamiento , Trastornos Mentales , Adulto , Humanos
9.
Planta Med ; 88(14): 1348-1359, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34839465

RESUMEN

There are several forms of kava (Piper methysticum) products available for human consumption, and many factors are known to influence their chemical compositions and therefore their pharmacological properties. Because of the increased popularity of kava intake, a rigorous characterization of their content diversity is prerequisite, particularly due to its known potential to cause hepatotoxicity. To understand the composition diversity of kavalactones and flavokavains in commercial kava products, we developed a UPLC-MS/MS-based analytical method for the quantification of six kavalactones (kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin and desmethoxyyangonin) and two flavokavains (flavokavains A and B) and analyzed their contents in 28 different kava products in the form of capsules, tinctures, traditional aqueous suspensions and dried powders. Our results demonstrated a great variation in terms of the total and relative abundance of the analyzed kavalactones and flavokavains among the analyzed kava preparations. More importantly, the kavalactone abundance in the product label could differ up to 90% from our experimental measurements. Therefore, more rigorous and comprehensive quality control of kava products is required with respect to the content of individual kavalactones and flavokavains. Accurate content information is essential to understand the pharmacological properties and safety of different kava products.


Asunto(s)
Kava , Humanos , Kava/química , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida , Lactonas/farmacología , Lactonas/química , Extractos Vegetales/farmacología , Extractos Vegetales/química
10.
J Clin Nurs ; 2022 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-35949164

RESUMEN

AIMS AND OBJECTIVES: (1) To investigate the vulnerability of nurses to experiencing professional burnout and low fulfilment across 5 months of the COVID-19 pandemic. (2) To identify modifiable variables in hospital leadership and individual vulnerabilities that may mitigate these effects. BACKGROUND: Nurses were at increased risk for burnout and low fulfilment prior to the COVID-19 pandemic. Hospital leadership factors such as organisational structure and open communication and consideration of employee opinions are known to have positive impacts on work attitudes. Personal risk factors for burnout include symptoms of depression and anxiety. METHODS: Healthcare workers (n = 406 at baseline, n = 234 longitudinal), including doctors (n = 102), nurses (n = 94), technicians (n = 90) and non-clinical administrative staff (n = 120), completed 5 online questionnaires, once per month, for 5 months. Participants completed self-report questionnaires on professional fulfilment and burnout, perceptions of healthcare leadership, and symptoms of anxiety and depression. Participants were recruited from various healthcare settings in the southeastern United States. The STROBE checklist was used to report the present study. RESULTS: Both at baseline and across the 5 months, nurses working during the COVID-19 pandemic reported increased burnout and decreased fulfilment relative to doctors. For all participants, burnout remained largely steady and fulfilment decreased slightly. The strongest predictors of both burnout and fulfilment were organisational structure and depressive symptoms. Leadership consideration and anxiety symptoms had smaller, yet significant, relationships to burnout and fulfilment in longitudinal analyses. CONCLUSIONS: Burnout and reduced fulfilment remain a problem for healthcare workers, especially nurses. Leadership styles and employee symptoms of depression and anxiety are appropriate targets for intervention. RELEVANCE TO CLINICAL PRACTICE: Leadership wishing to reduce burnout and increase fulfilment among employees should increase levels of organisational support and consideration and expand supports to employees seeking treatment for depression and anxiety.

11.
Mov Disord ; 36(8): 1899-1910, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33942911

RESUMEN

BACKGROUND: Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation. OBJECTIVE: The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT. METHODS: We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature. RESULTS: Rates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates. CONCLUSIONS: Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno Obsesivo Compulsivo , Trastornos de Tic , Tics , Síndrome de Tourette , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Comorbilidad , Humanos , Trastorno Obsesivo Compulsivo/epidemiología , Trastornos de Tic/epidemiología , Tics/epidemiología , Síndrome de Tourette/epidemiología
12.
Mol Psychiatry ; 25(9): 2036-2046, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-30087453

RESUMEN

Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a cross-disorder GWAS meta-analysis of 3495 AN cases, 2688 OCD cases, and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 ± 0.13, p = 9.07 × 10-7) and a sizable SNP heritability (SNP h2 = 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., rg = 0.36 with bipolar disorder and 0.34 with neuroticism) and negative genetic correlations with metabolic phenotypes (e.g., rg = -0.25 with body mass index and -0.20 with triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN-OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted.


Asunto(s)
Anorexia Nerviosa , Trastorno Obsesivo Compulsivo , Anorexia Nerviosa/genética , Índice de Masa Corporal , Comorbilidad , Estudio de Asociación del Genoma Completo , Humanos , Trastorno Obsesivo Compulsivo/genética , Fenotipo
13.
J Neural Transm (Vienna) ; 128(11): 1757-1765, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34389898

RESUMEN

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Tics , Síndrome de Tourette , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno del Espectro Autista/genética , Femenino , Interacción Gen-Ambiente , Estudio de Asociación del Genoma Completo , Humanos , Embarazo , Índice de Severidad de la Enfermedad
14.
Br J Clin Psychol ; 59(1): 1-21, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31271462

RESUMEN

OBJECTIVES: Hoarding disorder (HD) was recognized as a psychiatric disorder in 2013. Existing literature suggests room for improvement in its treatment. The current pilot study aimed to provide an initial evaluation on the potential of compassion-focused therapy (CFT) as an intervention for HD, with the primary aim being assessing its feasibility and acceptability, and the secondary being evaluating its effects. DESIGN: Both CFT and a second round of the current standard of treatment and cognitive behavioural therapy (CBT) were investigated in the current study as follow-up treatment options for individuals who had completed CBT but were still significantly symptomatic. METHODS: Forty eligible individuals were enrolled (20 in each treatment). Treatment feasibility and acceptability were assessed by quantitative and qualitative measures. To explore treatment effects, HD symptom severity, HD-related dysfunctions, and their underlying mechanisms were assessed pre-treatment and post-treatment. RESULTS: Retention rates were 72% for CFT and 37% for CBT. All participants and 79% of the participants rated CFT and CBT, respectively, as good or excellent. After receiving CFT as a follow-up treatment, HD symptom severity dropped below the cut-off point for clinically significant HD for 77% of the treatment completers, and 62% achieved clinically significant reduction in symptom severity. In contrast, after completing a second course of CBT, 23% had HD symptom severity dropped below the cut-off threshold, and 29% achieved clinically significant symptom reduction. CONCLUSIONS: The current study showed satisfactory feasibility and acceptability of CFT. Moreover, it also found promising effects of CFT in addressing hoarding-related mechanisms that may not have been sufficiently addressed by CBT. The results suggest promising potential of CFT as a treatment for HD. Further investigation on this intervention is needed. PRACTITIONER POINTS: CFT may be a promising treatment option, particularly for those who do not respond well to CBT. Improving emotion regulation and negative self-perception by applying CFT interventions may help relieve hoarding symptoms. Generalization of the findings should be applied with caution given the small convenience sample of the current study. Statistical comparison on treatment effect measures between CFT and CBT as follow-up treatments was not available due to small sample size. Therefore, the comparative conclusions based on this pilot study should be made with caution.


Asunto(s)
Terapia Cognitivo-Conductual/métodos , Empatía/fisiología , Trastorno de Acumulación/psicología , Adulto , Anciano , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto
15.
Genet Med ; 21(10): 2264-2274, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30926959

RESUMEN

PURPOSE: Incorporating a patient's genotype into the clinical decision-making process is one approach to precision medicine. The University of Florida (UF) Health Precision Medicine Program is a pharmacist-led multidisciplinary effort that has led the clinical implementation of six gene-drug(s) pairs to date. This study focuses on the challenges encountered and lessons learned with implementing pharmacogenetic testing for three of these: CYP2D6-opioids, CYP2D6/CYP2C19-selective serotonin reuptake inhibitors, and CYP2C19-proton pump inhibitors within six pragmatic clinical trials at UF Health and partners. METHODS: We compared common measures collected within each of the pharmacogenetic implementations as well as solicited feedback from stakeholders to identify challenges, successes, and lessons learned. RESULTS: We identified several challenges related to trial design and implementation, and learned valuable lessons. Most notably, case discussions are effective for prescriber education, prescribers need clear concise guidance on genotype-based actions, having genotype results available at the time of the patient-prescriber encounter helps optimize the ability to act on them, children prefer noninvasive sample collection, and study participants are willing to answer patient-reported outcomes questionnaires if they are not overly burdensome, among others. CONCLUSION: The lessons learned from implementing three gene-drug pairs in ambulatory care settings will help shape future pharmacogenetic clinical trials and clinical implementations.


Asunto(s)
Farmacogenética/métodos , Pruebas de Farmacogenómica/métodos , Medicina de Precisión/métodos , Atención Ambulatoria , Ensayos Clínicos como Asunto/métodos , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Florida , Genotipo , Humanos
16.
Depress Anxiety ; 36(6): 552-564, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30958911

RESUMEN

Hoarding disorder is present in 2-6% of the population and can have an immense impact on the lives of patients and their families. Before its inclusion the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, pathological hoarding was often characterized as a symptom of obsessive-compulsive disorder, and several different diagnostic assessment methods were used to identify and characterize it. Although the age of onset of pathological hoarding is an important epidemiological measure, as clarifying the age of onset of hoarding symptoms may allow for early identification and implementation of evidence-based treatments before symptoms become clinically significant, the typical age of onset of hoarding is still uncertain. To that end, this study is a systematic review and meta-analysis of research published in English between the years 1900 and 2016 containing information on age of onset of hoarding symptoms. Twenty-five studies met inclusion criteria. The mean age of onset of hoarding symptoms across studies was 16.7 years old, with evidence of a bimodal distribution of onset. The authors conclude by discussing practice implications for early identification and treatment.


Asunto(s)
Trastorno de Acumulación/epidemiología , Adolescente , Distribución por Edad , Edad de Inicio , Trastorno de Acumulación/diagnóstico , Trastorno de Acumulación/terapia , Humanos , Incertidumbre
17.
Eur Child Adolesc Psychiatry ; 27(5): 569-579, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29098466

RESUMEN

Trichotillomania/hair pulling disorder (HPD) and excoriation/skin picking disorder (SPD) are childhood-onset, body-focused repetitive behaviors that are thought to share genetic susceptibility and underlying pathophysiology with obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). We sought to determine the prevalence of DSM-5 HPD and SPD in TS patients, and to identify clinical factors most associated with their co-morbidity with TS. Participants included 811 TS patients recruited from TS specialty clinics for a multi-center genetic study. Patients were assessed using standardized, validated semi-structured interviews. HPD and SPD diagnoses were determined using a validated self-report questionnaire. HPD/SPD prevalence rates were calculated, and clinical predictors were evaluated using regression modeling. 3.8 and 13.0% of TS patients met DSM-5 criteria for HPD and SPD, respectively. In univariable analyses, female sex, OCD, and both tic and obsessive-compulsive symptom severity were among those associated with HPD and/or SPD. In multivariable analyses, only lifetime worst-ever motor tic severity remained significantly associated with HPD. Female sex, co-occurring OCD, ADHD, and motor tic severity remained independently associated with SPD. This is the first study to examine HPD and SPD prevalence in a TS sample using semi-structured diagnostic instruments. The prevalence of HPD and SPD in TS patients, and their association with increased tic severity and co-occurring OCD, suggests that clinicians should screen children with TS and related disorders for HPD/SPD, particularly in females and in those with co-occurring OCD. This study also helps set a foundation for subsequent research regarding HPD/SPD risk factors, pathophysiology, and treatment models.


Asunto(s)
Trastorno Obsesivo Compulsivo/etiología , Conducta Autodestructiva/etiología , Síndrome de Tourette/diagnóstico , Tricotilomanía/etiología , Niño , Comorbilidad , Femenino , Humanos , Masculino , Prevalencia , Encuestas y Cuestionarios , Síndrome de Tourette/patología
18.
Am J Geriatr Psychiatry ; 25(3): 245-255, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27939851

RESUMEN

OBJECTIVE: Little is known about the age-specific prevalence of hoarding and obsessive compulsive symptoms (OCS), particularly in older age groups. The objectives of this study were to estimate the age-specific prevalence, severity, and relationships between hoarding and OCS in males and females using a large population-based sample. METHODS: We assessed the age-specific prevalence rates of hoarding disorder (HD) and OC disorder (OCD) in males and females (at various age ranges between 15 and 97 years) from the Netherlands Twins Register (N = 15,194). Provisional HD and OCD diagnoses were made according to Diagnostic and Statistical Manual of Mental Health Disorders, 5th Edition, criteria using self-report measures. We also assessed hoarding and OCS severity in the various age groups and explored specific hoarding and OCS patterns (e.g., difficulty discarding, excessive acquisition, clutter, checking, washing, perfectionism, and obsessions) with age. RESULTS: Prevalence of provisional HD diagnoses (2.12%) increased linearly by 20% with every 5 years of age (z = 13.8, p < 0.0001) and did not differ between males and females. Provisional OCD diagnoses were most common in younger individuals and in individuals over age 65. Co-occurring OCD increased hoarding symptom severity (coefficient: 4.5; SE: 0.2; 95% CI: 4.1-4.9; t = 22.0, p < 0.0001). Difficulty discarding for HD and checking behaviors for OCD appeared to drive most increases in these diagnoses in older ages. CONCLUSION: Increased prevalence and severity of HD with age appears to be primarily driven by difficulties with discarding. Increases in OCD prevalence with older age were unexpected and of potential clinical relevance.


Asunto(s)
Trastorno Obsesivo Compulsivo/epidemiología , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Trastorno de Acumulación/epidemiología , Trastorno de Acumulación/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/fisiopatología , Prevalencia , Adulto Joven
20.
JAMA ; 317(13): 1358-1367, 2017 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-28384832

RESUMEN

Importance: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder associated with significant impairment and a lifetime prevalence of 1% to 3%; however, it is often missed in primary care settings and frequently undertreated. Objective: To review the most current data regarding screening, diagnosis, and treatment options for OCD. Evidence Review: We searched PubMed, EMBASE, and PsycINFO to identify randomized controlled trials (RCTs), meta-analyses, and systematic reviews that addressed screening and diagnostic and treatment approaches for OCD among adults (≥18 years), published between January 1, 2011, and September 30, 2016. We subsequently searched references of retrieved articles for additional reports. Meta-analyses and systematic reviews were prioritized; case series and reports were included only for interventions for which RCTs were not available. Findings: Among 792 unique articles identified, 27 (11 RCTs, 11 systematic reviews or meta-analyses, and 5 reviews/guidelines) were selected for this review. The diagnosis of OCD was revised for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, which addresses OCD separately from anxiety disorders and contains specifiers to delineate the presence of tics and degree of insight. Treatment advances include increasing evidence to support the efficacy of online-based dissemination of cognitive behavioral therapies, which have demonstrated clinically significant decreases in OCD symptoms when conducted by trained therapists. Current evidence continues to support the use of selective serotonin reuptake inhibitors as first-line pharmacologic interventions for OCD; however, more recent data support the adjunctive use of neuroleptics, deep-brain stimulation, and neurosurgical ablation for treatment-resistant OCD. Preliminary data suggest safety of other agents (eg, riluzole, ketamine, memantine, N-acetylcysteine, lamotrigine, celecoxib, ondansetron) either in combination with selective serotonin reuptake inhibitors or as monotherapy in the treatment of OCD, although their efficacy has not yet been established. Conclusions and Relevance: The dissemination of computer-based cognitive behavioral therapy and improved evidence supporting it represent a major advancement in treatment of OCD. Although cognitive behavioral therapy with or without selective serotonin reuptake inhibitors remains a preferred initial treatment strategy, increasing evidence that supports the safety and efficacy of neuroleptics and neuromodulatory approaches in treatment-resistant cases provides alternatives for patients whose condition does not respond to first-line interventions.


Asunto(s)
Trastorno Obsesivo Compulsivo , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Antipsicóticos/uso terapéutico , Estimulación Encefálica Profunda , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Humanos , Metaanálisis como Asunto , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto
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