RESUMO
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.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno Obsessivo-Compulsivo , Transtornos de Tique , Tiques , Síndrome de Tourette , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Comorbidade , Humanos , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtornos de Tique/epidemiologia , Tiques/epidemiologia , Síndrome de Tourette/epidemiologiaRESUMO
OBJECTIVES: Repetitive transcranial magnetic stimulation (TMS) is a promising treatment for suicidality, but it is underlying neural mechanisms remain poorly understood. Our prior findings indicated that frontostriatal functional connectivity correlates with the severity of suicidal thoughts and behaviors. In this secondary analysis of data from an open label trial, we evaluated whether changes in frontostriatal functional connectivity would accompany suicidality reductions following TMS. We also explored the relationship between frontostriatal connectivity change and underlying white matter (WM) organization. MATERIALS AND METHODS: We conducted seed-based functional connectivity analysis on participants (N = 25) with comorbid post-traumatic stress disorder and depression who received eight weeks of 5 Hz TMS to left dorsolateral prefrontal cortex. We measured clinical symptoms with the Inventory of Depressive Symptomatology-Self Report (IDS-SR) and the PTSD Checklist for DSM-5 (PCL-5). We derived suicidality from IDS-SR item 18. Magnetic resonance imaging data were collected before TMS, and at treatment end point. These data were entered into analyses of covariance, evaluating the effect of suicidality change across treatment on striatal and thalamic functional connectivity. Changes in other PTSD and depression symptoms were included as covariates and results were corrected for multiple comparisons. Diffusion connectometry in a participant subsample (N = 17) explored the relationship between frontal WM integrity at treatment baseline and subsequent functional connectivity changes correlated with differences in suicidality. RESULTS: Suicidal ideation decreased in 65% of participants. Reductions in suicidality and functional connectivity between the dorsal striatum and frontopolar cortex were correlated (p-False Discover Rate-corrected < 0.001), after covariance for clinical symptom change. All other results were nonsignificant. Our connectometry results indicated that the integrity of frontostriatal WM may circumscribe functional connectivity response to TMS for suicide. CONCLUSIONS: Targeted reduction of fronto-striatal connectivity with TMS may be a promising treatment for suicidality. Future research can build on this multimodal approach to advance individualized stimulation approaches in high-risk patients.
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Transtornos de Estresse Pós-Traumáticos , Suicídio , Humanos , Imageamento por Ressonância Magnética , Córtex Pré-Frontal/diagnóstico por imagem , Estimulação Magnética TranscranianaRESUMO
INTRODUCTION: Anger is an important clinical feature of posttraumatic stress disorder (PTSD) that can hamper recovery. We recently reported that intermittent theta burst stimulation (iTBS) demonstrated preliminary efficacy to reduce symptoms of posttraumatic stress disorder and major depression; here, we performed a secondary analysis testing whether iTBS reduced symptoms of anger over the course of iTBS treatment and compared to sham stimulation. MATERIALS AND METHODS: Fifty veterans with chronic PTSD received ten daily sessions of sham-controlled, double-blind iTBS (1800 pulses/session, once per weekday) targeting the right dorsolateral prefrontal cortex (intent-to-treat = 25 per group). Participants who completed the double-blind phase were offered another ten sessions of unblinded iTBS. Participants completed the Dimensions of Anger Reactions scale at pre-iTBS baseline, treatment midpoints, and endpoints of the blinded and unblinded phases, and at one-month after the last stimulation session. Correlations between anger, PTSD, depression, and sleep were also explored. RESULTS: After the first week, during the double-blind phase, participants randomized to active stimulation reported significantly reduced anger compared to sham stimulation (p = 0.04). Participants initially randomized to sham appeared to catch-up to the point they no longer differed from those initially randomized to active iTBS when they received iTBS during the unblinded phase (p = 0.14). Anger reduction was maintained at one-month after iTBS in participants initially randomized to active stimulation (i.e., total of four weeks of iTBS). CONCLUSIONS: This secondary analysis suggests that iTBS might reduce anger in veterans with PTSD. Future studies focused on more granular level anger outcomes and effects of number of stimulation sessions are needed.
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Transtorno Depressivo Maior , Transtornos de Estresse Pós-Traumáticos , Veteranos , Ira , Método Duplo-Cego , Humanos , Córtex Pré-Frontal , Transtornos de Estresse Pós-Traumáticos/terapia , Estimulação Magnética TranscranianaRESUMO
BACKGROUND: Chronic pain and associated symptoms are debilitating for veterans. Medical costs of treatments are high and current treatment options, most notably with opioid medications, have been associated with significant risk. Mindfulness-based interventions appear promising for chronic pain, but require additional testing in veteran care settings. OBJECTIVE: This project was designed to test the feasibility of engaging and retaining veterans with chronic lower back pain in a new mindfulness protocol tailored for veterans, mindfulness-based care for chronic pain (MBCP). Clinical outcomes were also assessed. DESIGN: An open pilot trial of an 8-week MBCP course that included meditation, gentle yoga, and psychoeducation. SUBJECTS: Twenty-two veterans (mean age=49.77; 18% women) were recruited from a VA Medical Center in the Northeastern US. After screening for inclusion/exclusion criteria, 20 were eligible at baseline. MEASURES: Veterans were assessed at baseline and postintervention for functional impairment, pain intensity and bothersomeness, depression, and mindfulness. RESULTS: The average number of sessions completed was 5; only 4 (20%) attended all sessions. Eleven of the 20 participants (55%) attended 5 or more sessions and had complete preintervention and postintervention visits. Five of the 11 had a clinically meaningful decrease in pain intensity and in depressive symptoms, while 6 of 11 had a meaningful decrease in pain bothersomeness and functional impairment. CONCLUSIONS: It was challenging to enroll and retain participants in this study, even with our intervention designed for veterans. We discuss possible adaptations and refinements in MBCP for veterans with chronic pain to enhance feasibility and improve upon these interventions.
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Dor Lombar/terapia , Terapias Mente-Corpo/métodos , Adulto , Idoso , Doença Crônica , Protocolos Clínicos , Depressão/epidemiologia , Depressão/terapia , Avaliação da Deficiência , Feminino , Nível de Saúde , Humanos , Dor Lombar/epidemiologia , Masculino , Meditação/métodos , Pessoa de Meia-Idade , Atenção Plena/métodos , Medição da Dor , Educação de Pacientes como Assunto/métodos , Desempenho Físico Funcional , Projetos Piloto , Índice de Gravidade de Doença , Fatores Socioeconômicos , Veteranos , Saúde dos Veteranos , YogaRESUMO
For more than half a century, stereotactic neurosurgical procedures have been available to treat patients with severe, debilitating symptoms of obsessive-compulsive disorder (OCD) that have proven refractory to extensive, appropriate pharmacological, and psychological treatment. Although reliable predictors of outcome remain elusive, the establishment of narrower selection criteria for neurosurgical candidacy, together with a better understanding of the functional neuroanatomy implicated in OCD, has resulted in improved clinical efficacy for an array of ablative and non-ablative intervention techniques targeting the cingulum, internal capsule, and other limbic regions. It was against this backdrop that gamma knife capsulotomy (GKC) for OCD was developed. In this paper, we review the history of this stereotactic radiosurgical procedure, from its inception to recent advances. We perform a systematic review of the existing literature and also provide a narrative account of the evolution of the procedure, detailing how the procedure has changed over time, and has been shaped by forces of evidence and innovation. As the procedure has evolved and adverse events have decreased considerably, favorable response rates have remained attainable for approximately one-half to two-thirds of individuals treated at experienced centers. A reduction in obsessive-compulsive symptom severity may result not only from direct modulation of OCD neural pathways but also from enhanced efficacy of pharmacological and psychological therapies working in a synergistic fashion with GKC. Possible complications include frontal lobe edema and even the rare formation of delayed radionecrotic cysts. These adverse events have become much less common with new radiation dose and targeting strategies. Detailed neuropsychological assessments from recent studies suggest that cognitive function is not impaired, and in some domains may even improve following treatment. We conclude this review with discussions covering topics essential for further progress of this therapy, including suggestions for future trial design given the unique features of GKC therapy, considerations for optimizing stereotactic targeting and dose planning using biophysical models, and the use of advanced imaging techniques to understand circuitry and predict response. GKC, and in particular its modern variant, gamma ventral capsulotomy, continues to be a reliable treatment option for selected cases of otherwise highly refractory OCD.
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Cápsula Interna/cirurgia , Transtorno Obsessivo-Compulsivo/cirurgia , Transtorno Obsessivo-Compulsivo/terapia , Lobo Frontal/fisiopatologia , Humanos , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Procedimentos Neurocirúrgicos/métodos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Radiocirurgia/métodos , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: Chronic low back pain (CLBP) is highly prevalent, with a substantial psychosocial burden. Pain has both sensory and affective components. The latter component is a significant driver of disability and psychiatric comorbidity but is often inadequately treated. Previously we reported that noninvasive transcranial direct current stimulation (tDCS) may modulate pain-associated affective distress. Here we tested whether 10 daily tDCS sessions aimed to inhibit the left dorsal anterior cingulate cortex (dACC), a region strongly implicated in the affective component of pain, would produce selective reduction in pain-related symptoms. METHODS: In this multisite, double-blinded, randomized placebo-controlled trial (RCT), 21 CLBP patients received 10 weekday sessions of 2-mA active tDCS or sham (20 minutes/session). A cathodal electrode was placed over FC1 (10-20 electroencephalography coordinates), and an identical anodal return electrode was placed over the contralateral mastoid. Participants rated pain intensity, acceptance, interference, disability, and anxiety, plus general anxiety and depression. RESULTS: Regression analysis noted significantly less pain interference (P =0.002), pain disability (P =0.001), and depression symptoms (P =0.003) at six-week follow-up for active tDCS vs sham. Omnibus tests suggested that these improvements were not merely due to baseline (day 1) group differences. CONCLUSIONS: To our knowledge, this is the first double-blinded RCT of multiple tDCS sessions targeting the left dACC to modulate CLBP's affective symptoms. Results are encouraging, including several possible tDCS-associated improvements. Better-powered RCTs are needed to confirm these effects. Future studies should also consider different stimulation schedules, additional cortical targets, high-density multi-electrode tDCS arrays, and multimodal approaches.
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Sintomas Afetivos/diagnóstico , Sintomas Afetivos/terapia , Dor Lombar/diagnóstico , Dor Lombar/terapia , Manejo da Dor/métodos , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Sintomas Afetivos/psicologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Dor Lombar/psicologia , Masculino , Adulto JovemRESUMO
BACKGROUND: This study addresses the strength of associations between trichotillomania (TTM) and other DSM-IV Axis I conditions in a large sample (nâ¯=â¯2606) enriched for familial obsessive-compulsive disorder (OCD), to inform TTM classification. METHODS: We identified participants with TTM in the Johns Hopkins OCD Family Study (153 families) and the OCD Collaborative Genetics Study, a six-site genetic linkage study of OCD (487 families). We used logistic regression (with generalized estimating equations) to assess the strength of associations between TTM and other DSM-IV disorders. RESULTS: TTM had excess comorbidity with a number of conditions from different DSM-IV chapters, including tic disorders, alcohol dependence, mood disorders, anxiety disorders, impulse-control disorders, and bulimia nervosa. However, association strengths (odds ratios) were highest for kleptomania (6.6), pyromania (5.8), OCD (5.6), skin picking disorder (4.4), bulimia nervosa (3.5), and pathological nail biting (3.4). CONCLUSIONS: TTM is comorbid with a number of psychiatric conditions besides OCD, and it is strongly associated with other conditions involving impaired impulse control. Though DSM-5 includes TTM as an OCD-related disorder, its comorbidity pattern also emphasizes the impulsive, appetitive aspects of this condition that may be relevant to classification.
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Transtornos Disruptivos, de Controle do Impulso e da Conduta/epidemiologia , Transtorno Obsessivo-Compulsivo/epidemiologia , Tricotilomania/epidemiologia , Adulto , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtornos Disruptivos, de Controle do Impulso e da Conduta/genética , Feminino , Ligação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/genética , Tricotilomania/genética , Adulto JovemRESUMO
BACKGROUND: Hoarding behavior may distinguish a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Little is known about the relationship between executive dysfunction and hoarding in individuals with OCD. METHODS: The study sample included 431 adults diagnosed with DSM-IV OCD. Participants were assessed by clinicians for Axis I disorders, personality disorders, indecision, and hoarding. Executive functioning domains were evaluated using a self-report instrument, the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). We compared scores on these domains in the 143 hoarding and 288 non-hoarding participants, separately in men and women. We used logistic regression to evaluate relationships between executive function scores and hoarding, and correlation and linear regression analyses to evaluate relationships between executive function scores and hoarding severity, in women. RESULTS: In men, the hoarding group had a significantly higher mean score than the non-hoarding group only on the shift dimension. In contrast, in women, the hoarding group had higher mean scores on the shift scale and all metacognition dimensions, i.e., those that assess the ability to systematically solve problems via planning and organization. The relationships in women between hoarding and scores on initiating tasks, planning/organizing, organization of materials, and the metacognition index were independent of other clinical features. Furthermore, the severity of hoarding in women correlated most strongly with metacognition dimensions. CONCLUSIONS: Self-reported deficits in planning and organization are associated with the occurrence and severity of hoarding in women, but not men, with OCD. This may have implications for elucidating the etiology of, and developing effective treatments for, hoarding in OCD.
Assuntos
Função Executiva , Colecionismo/epidemiologia , Colecionismo/psicologia , Transtorno Obsessivo-Compulsivo/epidemiologia , Transtorno Obsessivo-Compulsivo/psicologia , Autorrelato , Adolescente , Adulto , Idoso , Manual Diagnóstico e Estatístico de Transtornos Mentais , Função Executiva/fisiologia , Feminino , Colecionismo/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico , Adulto JovemRESUMO
BACKGROUND: Hoarding behavior may indicate a clinically and possibly etiologically distinct subtype of obsessive-compulsive disorder (OCD). Empirical evidence supports a relationship between hoarding and emotional over-attachment to objects. However, little is known about the relationship between hoarding and parental attachment in OCD. METHOD: The study sample included 894 adults diagnosed with DSM-IV OCD who had participated in family and genetic studies of OCD. Participants were assessed for Axis I disorders, personality disorders, and general personality dimensions. The Parental Bonding Instrument (PBI) was used to assess dimensions of perceived parental rearing (care, overprotection, and control). We compared parental PBI scores in the 334 hoarding and 560 non-hoarding participants, separately in men and women. We used logistic regression to evaluate the relationship between parenting scores and hoarding in women, adjusting for other clinical features associated with hoarding. RESULTS: In men, there were no significant differences between hoarding and non-hoarding groups in maternal or paternal parenting scores. In women, the hoarding group had a lower mean score on maternal care (23.4 vs. 25.7, p<0.01); a higher mean score on maternal protection (9.4 vs. 7.7, p<0.001); and a higher mean score on maternal control (7.0 vs. 6.2, p<0.05), compared to the non-hoarding group. The magnitude of the relationships between maternal bonding dimensions and hoarding in women did not change after adjustment for other clinical features. Women who reported low maternal care/high maternal protection had significantly greater odds of hoarding compared to women with high maternal care/low maternal protection (OR=2.54, 95% CI=1.60-4.02, p<0.001). CONCLUSIONS: Perceived poor maternal care, maternal overprotection, and maternal overcontrol are associated with hoarding in women with OCD. Parenting dimensions are not related to hoarding in men. These findings provide further support for a hoarding subtype of OCD and for sex-specific differences in etiologic pathways for hoarding in OCD.
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Colecionismo/psicologia , Apego ao Objeto , Transtorno Obsessivo-Compulsivo/psicologia , Poder Familiar/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Adulto JovemRESUMO
BACKGROUND: Clinicians have long considered doubt to be a fundamental characteristic of obsessive-compulsive disorder (OCD). However, the clinical relevance of doubt in OCD has not been addressed. METHODS: Participants included 1182 adults with OCD who had participated in family and genetic studies of OCD. We used a clinical measure of the severity of doubt, categorized as none, mild, moderate, severe, or extreme. We evaluated the relationship between doubt and OCD clinical features, Axis I disorders, personality and personality disorder dimensions, impairment, and treatment response. RESULTS: The severity of doubt was inversely related to the age at onset of OCD symptoms. Doubt was strongly related to the number of checking symptoms and, to a lesser extent, to the numbers of contamination/cleaning and hoarding symptoms. Doubt also was related to the lifetime prevalence of recurrent major depression and generalized anxiety disorder; to the numbers of avoidant, dependent, and obsessive-compulsive personality disorder traits; and to neuroticism and introversion. Moreover, doubt was strongly associated with global impairment and poor response to cognitive behavioral treatment (CBT), even adjusting for OCD severity and other correlates of doubt. CONCLUSIONS: Doubt is associated with important clinical features of OCD, including impairment and cognitive-behavioral treatment response.
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Emoções , Transtorno Obsessivo-Compulsivo/psicologia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Transtornos de Ansiedade/psicologia , Terapia Cognitivo-Comportamental , Transtorno da Personalidade Compulsiva/psicologia , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroticismo , Transtornos da Personalidade/psicologia , Adulto JovemRESUMO
OBJECTIVES: Several studies have found impaired response inhibition, measured by a stop-signal task (SST), in individuals who are currently symptomatic for obsessive-compulsive disorder (OCD). The aim of this study was to assess stop-signal reaction time (SSRT) performance in individuals with a lifetime diagnosis of OCD, in comparison to a healthy control group. This is the first study that has examined OCD in participants along a continuum of OCD severity, including approximately half of whom had sub-syndromal symptoms at the time of assessment. METHODS: OCD participants were recruited primarily from within the OCD clinic at a psychiatric hospital, as well as from the community. Healthy controls were recruited from the community. We used the stop signal task to examine the difference between 21 OCD participants (mean age, 42.95 years) and 40 healthy controls (mean age, 35.13 years). We also investigated the relationship between SST and measures of OCD, depression, and anxiety severity. RESULTS: OCD participants were significantly slower than healthy controls with regard to mean SSRT. Contrary to our prediction, there was no correlation between SSRT and current levels of OCD, anxiety, and depression severity. CONCLUSIONS: Results support prior studies showing impaired response inhibition in OCD, and extend the findings to a sample of patients with lifetime OCD who were not all currently above threshold for diagnosis. These findings indicate that response inhibition deficits may be a biomarker of OCD, regardless of current severity levels. (JINS, 2016, 22, 785-789).
Assuntos
Função Executiva/fisiologia , Inibição Psicológica , Transtorno Obsessivo-Compulsivo/fisiopatologia , Desempenho Psicomotor/fisiologia , Adulto , Humanos , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/psicologiaRESUMO
BACKGROUND: To determine possible dimensions that underlie obsessive-compulsive personality disorder (OCPD) and to investigate their clinical correlates, familiality, and genetic linkage. METHODS: Participants were selected from 844 adults assessed with the Structured Instrument for the Diagnosis of DSM-IV Personality Disorders (SIDP) in the OCD Collaborative Genetics Study (OCGS) that targeted families with obsessive-compulsive disorder (OCD) affected sibling pairs. We conducted an exploratory factor analysis, which included the eight SIDP-derived DSM-IV OCPD traits and the indecision trait from the DSM-III, assessed clinical correlates, and estimated sib-sib correlations to evaluate familiality of the factors. Using MERLIN and MINX, we performed genome-wide quantitative trait locus (QTL) linkage analysis to test for allele sharing among individuals. RESULTS: Two factors were identified: Factor 1: order/control (perfectionism, excessive devotion to work, overconscientiousness, reluctance to delegate, and rigidity); and Factor 2: hoarding/indecision (inability to discard and indecisiveness). Factor 1 score was associated with poor insight, whereas Factor 2 score was associated with task incompletion. A significant sib-sib correlation was found for Factor 2 (rICC = .354, P < .0001) but not Factor 1 (rICC = .129, P = .084). The linkage findings were different for the two factors. When Factor 2 was analyzed as a quantitative trait, a strong signal was detected on chromosome 10 at marker d10s1221: KAC LOD = 2.83, P = .0002; and marker d10s1225: KAC LOD = 1.35, P = .006. CONCLUSIONS: The results indicate two factors of OCPD, order/control and hoarding/indecision. The hoarding/indecision factor is familial and shows modest linkage to a region on chromosome 10.
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Transtorno da Personalidade Compulsiva/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno da Personalidade Compulsiva/classificação , Transtorno da Personalidade Compulsiva/genética , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: Current chronic pain treatments target nociception rather than affective "suffering" and its associated functional and psychiatric comorbidities. The left dorsolateral prefrontal cortex (DLPFC) has been implicated in affective, cognitive, and attentional aspects of pain and is a primary target of neuromodulation for affective disorders. Transcranial direct current stimulation (tDCS) can non-invasively modulate cortical activity. The present study tests whether anodal tDCS targeting the left DLPFC will increase tolerability of acute painful stimuli vs cathodal tDCS. METHODS: Forty tDCS-naive healthy volunteers received anodal and cathodal stimulation targeting the left DLPFC in two randomized and counterbalanced sessions. During stimulation, each participant performed cold pressor (CP) and breath holding (BH) tasks. We measured pain intensity with the Defense and Veterans Pain Rating Scale (DVPRS) before and after each task. RESULTS: Mixed ANOVA revealed no main effect of stimulation polarity for mean CP threshold, tolerance, or endurance, or mean BH time (allP > 0.27). However, DVPRS rise associated with CP was significantly smaller with anodal vs cathodal tDCS (P = 0.024). We further observed a significant tDCS polarity × stimulation order interaction (P = 0.042) on CP threshold, suggesting task sensitization. CONCLUSIONS: Although our results do not suggest that polarity of tDCS targeting the left DLPFC differentially modulates the tolerability of CP- and BH-related pain distress in healthy volunteers, there was a significant effect on DVPRS pain ratings. This contrasts with our previous findings that tDCS targeting the left dorsal anterior cingulate cortex showed a trend toward higher mean CP tolerance with cathodal vs anodal stimulation. The present results may suggest tDCS-related effects on nociception or DLPFC-mediated attention, or preferential modulation of the affective valence of pain as captured by the DVPRS. Sham-controlled clinical studies are needed.
Assuntos
Dor Aguda/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Estimulação Transcraniana por Corrente Contínua/métodos , Adolescente , Adulto , Idoso , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Limiar da Dor , Adulto JovemRESUMO
The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
Assuntos
Transtorno Obsessivo-Compulsivo/genética , Característica Quantitativa Herdável , Síndrome de Tourette/genética , Frequência do Gene , Estudo de Associação Genômica Ampla , Humanos , Transtorno Obsessivo-Compulsivo/patologia , Fenótipo , Polimorfismo de Nucleotídeo Único , Síndrome de Tourette/patologiaRESUMO
OBJECTIVE: Pain remains a critical medical challenge. Current treatments target nociception without addressing affective symptoms. Medically intractable pain is sometimes treated with cingulotomy or deep brain stimulation to increase tolerance of pain-related distress. Transcranial direct current stimulation (tDCS) may noninvasively modulate cortical areas related to sensation and pain representations. The present study aimed to test the hypothesis that cathodal ("inhibitory") stimulation targeting left dorsal anterior cingulate cortex (dACC) would increase tolerance to distress from acute painful stimuli vs anodal stimulation. METHODS: Forty healthy volunteers received both anodal and cathodal stimulation. During stimulation, we measured pain distress tolerance with three tasks: pressure algometer, cold pressor, and breath holding. We measured pain intensity with a visual-analog scale before and after each task. RESULTS: Mixed ANOVA revealed that mean cold pressor tolerance tended to be higher with cathodal vs anodal stimulation (P = 0.055) for participants self-completing the task. Pressure algometer (P = 0.81) and breath holding tolerance (P = 0.19) did not significantly differ. The pressure algometer exhibited a statistically significant order effect irrespective of stimulation polarity (all P < 0.008). Pain intensity ratings increased acutely after cold pressor and pressure algometer tasks (both P < 0.01), but not after breath holding (P = 0.099). Cold pressor pain ratings tended to rise less after cathodal vs anodal tDCS (P = 0.072). CONCLUSIONS: Although our primary results were nonsignificant, there is a preliminary suggestion that cathodal tDCS targeting left dACC may increase pain distress tolerance to cold pressor. Pressure algometer results are consistent with task-related sensitization. Future studies are needed to refine this novel approach for pain neuromodulation.
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Manejo da Dor/métodos , Dor/psicologia , Estresse Psicológico/psicologia , Estimulação Transcraniana por Corrente Contínua , Adolescente , Adulto , Suspensão da Respiração , Temperatura Baixa , Eletrodos , Feminino , Giro do Cíngulo , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Limiar da Dor , Pressão , Adulto JovemRESUMO
The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.
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Estimulação Encefálica Profunda/métodos , Cooperação Internacional , Doença de Parkinson/terapia , Síndrome de Tourette/terapia , Animais , Encéfalo/fisiologia , HumanosRESUMO
A few patients with obsessive-compulsive disorder (OCD) remain severely impaired despite exhausting best-practice treatments. For them, neurosurgery (stereotactic ablation or deep brain stimulation) might be considered. The authors investigated the proportion of treatment-seeking OCD patients, in a naturalistic clinical sample, who met contemporary neurosurgery selection criteria. Using comprehensive baseline data on diagnosis, severity, and treatment history for adult patients from the NIMH-supported Brown Longitudinal OCD Study, only 2 of 325 patients met screening criteria for neurosurgery. This finding prompts consideration of new models for clinical trials with limited samples as well as methods of refining entry criteria for such invasive treatments.
Assuntos
Estimulação Encefálica Profunda/métodos , Transtorno Obsessivo-Compulsivo/terapia , Seleção de Pacientes , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Multicêntricos como Assunto , Observação , Escalas de Graduação Psiquiátrica , Índice de Gravidade de DoençaRESUMO
We report the case of a patient requiring gamma ventral capsulotomy (GVC), a neurosurgical intervention to address severe refractory obsessive-compulsive disorder (OCD). GVC involves stereotactic lesions in the ventral anterior limb of the internal capsule and adjacent ventral striatum. This study details the course of an extinction-based behavioral therapy, namely exposure and response prevention (ERP). The patient experienced significant changes in motivation and ability to tolerate ERP post-surgery. Furthermore, he was better able to absorb and remember exposure sessions. GVC surgery may affect the neural mechanisms involved in the extinction learning process, the same process implicated in ERP treatment.
Assuntos
Terapia Comportamental , Cápsula Interna/cirurgia , Transtorno Obsessivo-Compulsivo/terapia , Radiocirurgia , Adulto , Terapia Combinada , Extinção Psicológica , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: This study assesses the long-term course of treatment-seeking youth with a primary diagnosis of DSM-IV OCD. METHOD: Sixty youth and their parents completed intake interviews and annual follow-up interviews for 3 years using the youth version of the Longitudinal Interval Follow-up Evaluation (Y-LIFE) and Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Remission was defined as no longer meeting DSM-IV criteria for OCD for 8 weeks or more, and recurrence was defined as meeting full criteria for OCD for 4 consecutive weeks after having achieved symptom remission. Remission rates for youth were compared to rates of adults participating in the same study. RESULTS: The probability of achieving partial remission of OCD was 0.53 and the probability of achieving full remission was 0.27. Among the 24 youth participants who achieved remission, 79% stayed in remission throughout the study (mean of 88 weeks of follow-up) and 21% experienced a recurrence of symptoms. Better functioning at intake and a shorter latency to initial OCD treatment were associated with faster onset of remission (P<.001). CONCLUSIONS: Remission is more likely among youth versus adults with OCD. Treatment early in the course of illness and before substantial impact on functioning predicted a better course.
Assuntos
Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/psicologia , Adolescente , Adulto , Idade de Início , Criança , Terapia Cognitivo-Comportamental , Feminino , Humanos , Estudos Longitudinais , Masculino , Massachusetts , Transtorno Obsessivo-Compulsivo/terapia , Determinação da Personalidade , Prognóstico , Estudos Prospectivos , Recidiva , Rhode Island , Adulto JovemRESUMO
Some individuals with obsessive-compulsive disorder (OCD) have autistic-like traits, including deficits in social and communication behaviors (pragmatics). The objective of this study was to determine if pragmatic impairment aggregates in OCD families and discriminates a clinically and genetically distinct subtype of OCD. We conducted clinical examinations on, and collected DNA samples from, 706 individuals with OCD in 221 multiply affected OCD families. Using the Pragmatic Rating Scale (PRS), we compared the prevalence of pragmatic impairment in OCD-affected relatives of probands with and without pragmatic impairment. We also compared clinical features of OCD-affected individuals in families having at least one, versus no, individual with pragmatic impairment, and assessed for linkage to OCD in the two groups of families. The odds of pragmatic impairment were substantially greater in OCD-affected relatives of probands with pragmatic impairment. Individuals in high-PRS families had greater odds of separation anxiety disorder and social phobia, and a greater number of schizotypal personality traits. In high-PRS families, there was suggestive linkage to OCD on chromosome 12 at marker D12S1064 and on chromosome X at marker DXS7132 whereas, in low-PRS families, there was suggestive linkage to chromosome 3 at marker D3S2398. Pragmatic impairment aggregates in OCD families. Separation anxiety disorder, social phobia, and schizotypal personality traits are part of a clinical spectrum associated with pragmatic impairment in these families. Specific regions of chromosomes 12 and X are linked to OCD in high-PRS families. Thus, pragmatic impairment may distinguish a clinically and genetically homogeneous subtype of OCD.