Publicaciones científicas sobre TOC

Publicaciones científicas sobre TOC

  • juanwalker
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    El propósito de este hilo es dejar reseñas de publicaciones científicas ( no opiniones sobre las mismas) de investigaciones que buscan investigar la causa raíz del TOC, su patogénesis y la búsqueda de una solución permanente sobre el trastorno a futuro.

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    juanwalker
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    Title: Psychiatric and neuropsychiatric syndromes and COVID-19

    Source: https://www.thelancet.com/action/showPdf?pii=S2215-0366%2820%2930317-5

    Description: During the COVID-19 pandemic when uncertainty is on the rise, preliminary evidence suggests that people with obsessive-compulsive disorder might be showing relapse and worsening of symptoms. Chat bot mobile application to address compulsions and a web application to address compulsion though a threshold for each person.

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    juanwalker
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    Title:A Clinical Staging Model for Obsessive–Compulsive Disorder: Is It Ready for Prime Time?

    Source: https://www.thelancet.com/action/showPdf?pii=S2589-5370%2819%2930020-3

    Description:

    In this investigation the authors proposed a staging as a mechanism to avoid the progression the illness to people who could be vulnerable to OCD generation. In the article they refer to some biomarkers like family histories, environmental risks and some OCD symptoms that normal people can have in order to classify the patients according with the staging. In each staging they also proposed as treatment likes SRIs, EX/RP, deep brain stimulation, transcanial magnetic devices,  psychiatric surgery)

    How to diagnose OCD?

     

    Adult: Y-BOCS 

    Children: CY-BOCS

     Very young children 2-4 years:  Parent’s Report Childhood Routines Inventory

     

    Perinatal complications, reproductive cycle, stressful life are main risk factors:

     

    “128 studies met inclusion criteria. Potential environmental risk factors for OCD have been identified in the broad areas of perinatal complications, reproductive cycle, and stressful life events. There is limited evidence regarding other potential risk factors, such as parental age, season of birth, socioeconomic status, parental rearing practices, infections, traumatic brain injury, substance use or vitamin deficiency. In general, studies were of limited methodological quality.” 

     

    Systematic review of environmental risk factors for Obsessive-Compulsive Disorder: A proposed roadmap from association to causation

     

    28.2% of population can have obsessive episodes in one moment of their lives:

     

    “28.2% of population despite having OCD subthreshold symptoms at some part of their lives  not meet the criteria for OCD while OCD prevalence of 12 months is around 2,3% and 1.2%.” The Epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication

     

    “Treatment and follow-up studies of patients with diagnosed OCD have shown that duration of untreated illness is associated with worse treatment response.” CLINICAL PREDICTORS OF LONG‐TERM OUTCOME IN OBSESSIVE‐COMPULSIVE DISORDER

     

    Children at age of 11 can develop OCD 20 years later:

     

    “Epidemiological studies suggest that only few adults with subthreshold OCD (≈3%) will develop OCD on the long term , one follow-up study found that children reporting obsessions/compulsions at age 11 were significantly more likely to meet diagnostic criteria for OCD 20 years later.” 

     

    Obsessions and Compulsions in the Community: Prevalence, Interference, Help-Seeking, Developmental Stability, and Co-Occurring Psychiatric Conditions

     

    Severy of OCD increases over time:

     

    “A number of studies showed that, as severity of OCD increases, so does duration of illness and the ensuing clinical complexity, including the number of associated physical [26] and psychiatric comorbidities  and the rates of depressive disorders (major depressive disorder or dysthymia) and social phobia.” 

     

    Clinical features associated with increased severity of illness in tertiary clinic referred patients with obsessive compulsive disorder

     

    Family participation:

     

    “Similarly, a meta-analysis found increased severity of OCD leads to increased “family accommodation” (or “participation” of family members in OCD individual’s rituals) [29]. These studies attest the importance of illness progression, and of an early intervention in OCD.” 

     

    Wu MS, McGuire JF, Martino C, Phares V, Selles RR, Storch EA. A meta-analysis of family accommodation and OCD symptom severity. Clin Psychol Rev 2016;45: 34–44

     

    Tics comorbid during familial OCD onset:

     

    “It has been suggested that there may be at least four different types of OCD, three of which are familial forms of the disorder. These familial forms include an early on set type of OCD that is comorbid with tics (expressed as Tourette syndrome and/or chronic tics), an early-onset type of OCD without tics, and a later-onset form of OCD without tics. The non-familial type (that is, sporadic OCD) also does not seem to be associated with tics.” 

     

    Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective

     

    One twin can have OCD, other just don’t:

     

    “A recent meta-analysis found that additive genetic factors (the influence of many genes) and non-shared environment effects (e.g. a stressful life event experience by just one twin) explain most of the variance (37–41% and 50–52%, respectively) in obsessive– compulsive symptoms, while shared environment (e.g. upbringing styles, affecting both twins) and non-additive genetic effects (epistatic or dominance effects) made little or no contribution (5–6% and 9–10%, respectively)” .

     

    Etiology of obsessions and compulsions: A meta-analysis and narrative review of twin studies

     

    Neurotransmitters   increase OCD:

    “It is now clear that the occurrence of certain genetic variants associated with the major neurotransmitter systems increase the risk for OCD. Candidate genes involved in brain functional [e.g. serotonergic (5HTT and SLC6A4), dopaminergic (COMT, DAT1, and DRD3), and glutamatergic (SLC1A1) neurotransmission”.

    Se presentan alteraciones en los neurotransmisores, los medicamentos regular los neurotansmisores dopamina cerotonina, gkutamato. La fluxoamina regula la concetracion de la serotonina, por eso el OCD ayuda en este aspecto

    5htt receptor de serotonina

    COMT Encima que metaboliza la dopamina

    DAT transportador

    DRD3 gen similar al SL6A4

    Molecular genetics of obsessive–compulsive disorder: a comprehensive meta-analysis of genetic association studies

    Complex Genetic Architecture of Obsessive-Compulsive Disorder:

    “While these findings are difficult to synthesise, a recent metaanalysis of the two existing GWAS  reported associations between OCD and variants located in or near the genes ASB13, RSPO4, DLGAP1, PTPRD, GRIK2, FAIM2 and CDH20. The results of these approaches converge with association studies at the level of the biological pathways (e.g. glutamate signalling) rather than at the level of specific genes.”

     

    Revealing the Complex Genetic Architecture of Obsessive-Compulsive Disorder Using Meta-Analysis

     

    Neuroinflamation:

     

    “For instance, a handful of studies have found inflammatory markers (e.g. proinflammatory cytokines) to be increased in OCD samples compared to controls, and to correlate positively with severity of OCD symptoms , negatively with age at onset, and positively with duration of illness.” 

     

    A cytokine study of adult patients with obsessive-compulsive disorder

     

    Neuroimaging brain structures:

     

    “Accordingly, a few studies have reported correlations between the volumes of different brain structures to progression of illness, either in relation to severity or to duration of illness. For instance, one study described that enlargement of striatal regions in OCD patients was driven by longer duration of and higher age.” 

     

    Pujol J, Soriano-Mas C, Alonso P, et al. Mapping structural brain alterations in obsessive-compulsive disorder. Arch Gen Psychiatry 2004;61(7):720–30.

     

    “A mega-analysis reported the lack of ageing-related reductions in the volumes of parts of the striatum and inferior frontal lobe in OCD patients, which were interpreted as resulting from chronic compulsive behaviours “increasing” putamen and striatum volumes or compensatory activation induced neuroplasticity preserving inferior frontal cortex and anterior insula. The same study found (para) limbic parts of the medial and lateral temporal cortex (regions that are relatively preserved in healthy ageing) to show greater ageing-related volume loss in OCD.”

     

    de Wit SJ, Alonso P, Schweren L, et al. Multicenter voxel-based morphometry megaanalysis of structural brain scans in obsessive-compulsive disorder. Am J Psychiatry 2014;171(3):340–9

     

    “The Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium found adult early onset OCD patients to exhibit larger pallidum than controls.”

     

     Boedhoe PS, Schmaal L, Abe Y, et al. Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and mega-analysis. Am J Psychiatry 2017; 174(1):60–9.

     

    “Paediatric OCD to show decreased thickness of the parietal cortex, which tended to normalise with illness progression.”  

     

    Boedhoe PSW, Schmaal L, Abe Y, et al. Cortical abnormalities associated with pediatric and adult obsessive-compulsive disorder: findings from the ENIGMA ObsessiveCompulsive Disorder Working Group. The American Journal of Psychiatry 2018;175 (5):453–62

     

    “Grey matter density and duration of OCD correlated negatively in left hemisphere structures (including the post-central gyrus, the supra-marginal gyrus the pre-central gyrus, the middle and superior temporal gyrus, the inferior frontal gyrus) and the right inferior parietal lobule, while the insular and post-central gyrus correlated positively with the severity of OCD [60]” 

     

    Yoo SY, Roh MS, Choi JS, et al. Voxel-based morphometry study of gray matter abnormalities in obsessive-compulsive disorder. J Korean Med Sci 2008;23(1):24–30.

     

    !A study on treatment refractory OCD found duration of illness to be negatively correlated with bilateral hippocampal and left amygdala volumes and severity of OCD with the left hippocampus [61]” 

     

    Atmaca M, Yildirim H, Ozdemir H, et al. Hippocampus and amygdalar volumes in patients with refractory obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2008;32(5):1283–6.

     

    “A recent DTI study found duration of illness to correlate with greater white matter changes in the anterior cingulate bundle bilaterally.” Andrade J, Meirelles F, Suo C, et al. Metabolic and structural abnormalities in obsessive-compulsive disorder: a multimodal neuroimaging and clinical approach. Paper presented at: 31st European College of Neuropsychopharmacology Congress 2018; Barcelona; 2019

     

    “Finally, from the neurochemical point-of-view, increased duration of OCD correlated with decreased glutamate concentration in the anterior cingulate cortex.” 

     

    Odolescent obsessive-compulsive disorder: a case-control study. European Neuropsychopharmacology 2015;25(1):60–8rtiz AE, Ortiz AG, Falcon C, et al. 1H-MRS of the anterior cingulate cortex in childhood and a

     

    “instead to focus on larger-scale studies (like the ENIGMA and other mega-analysis) or smaller investigations felt to be more relevant for our staging model of OCD. As such, the available evidence suggests that increased duration of illness is related to perturbation on structures related to the corticostriato-thalamo-cortical circuits, and tends to increase striatal volumes and to decrease the volumes of other (e.g. hippocampus) structures. It is difficult to speculate on the significance of these findings in light of the recent developments on the RDoC systems [31],but

    It seems that the more OCD is left untreated, the more likely OCD behaviours and cognitions are to be “entrenched” in habit systems”. 

     

    From the current article

     

    Conventional treatment:

     

    “A follow-up study of participants drawn from the general population of Zurich, Switzerland, who participated in a series of seven interviews over a period of 30 years [12] confirmed the links between earlier interventions and better outcomes”.

     

    Remission of obsessive-compulsive disorders and syndromes; evidence from a prospective community cohort study over 30 years

     

    “In untreated illness from 7 to 8 years, the perception that OCD is caused by “stress” (including the threat of or an actual recent very unpleasant event, family or marital conflict or difficulty, grief or separation, or physical illness,) seem to shorten contact with mental health professions.”

     

    Vigne P, Fortes P, Dias RV, et al. Duration of untreated illness in a cross-diagnostic sample of obsessive-compulsive disorder, panic disorder, and social anxiety disorder. CNS Spectr 2018:1–7

     

    OCD stages definition:

     

    One of the ultimate objectives of any clinical staging is avoiding progression of illness.

     

    Stage 0: Healthy individuals with family history and/or tics. Treatment psycoeducation

     

    Stage 1:Substhreshold (1-13 YBOCS score)  Some obsessive symptoms.Treatment: A 3-hour cognitive behavioural workshop, which in one clinical trial reduced number of OCD symptoms at 5-month follow-up, and the extent of thought action fusion (TAF) at 1 and 5-month follow-up [80]. In another trial, eight sessions of a mindfulness based meditation program showed decreases in Obsessive–Compulsive Inventory-Revised and TAF scores at the end of two months [81]. Based on research performed in clinical OCD samples (as reviewed by [82]) lifestyle interventions focusing on decreasing stress (e.g. kundalini yoga, acceptance and commitment therapy), eliminating sedentarism (physical exercise), improving diet, minimising alcohol ingestion, and ameliorating sleep need to be tested in this latter population in future trials

     

    Stage 2 Mild to moderate (14-34 YBOCS Score) . Suggested treatment High dose SRI treatments for at least 12 weeks or a total of 20 h EX/RP sessions

     

    Stage 3 : Servere symptoms (35-40 YBOCS score). Suggested treatment High dose SRI treatments for at least 12 weeks or a total of 20 h EX/RP sessions. Consider deep brain stimulation or psychiatric surgery

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    juanwalker
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    Title:Harmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis

    Source:https://www.thelancet.com/action/showPdf?pii=S2215-0366%2816%2930069-4

    Description:

    In this study the investigator compared the efficiency of different treatments available as treatment to OCD,describe in the below image:

     

    “Behavioural therapy (meandiff erence –14·48 [95% credible interval –18·61 to –10·23]; 11 trials and 287 patients), cognitive therapy (–13·36 [–18·40 to –8·21]; six trials and 172 patients), behavioural therapy and clomipramine (–12·97 [–19·18 to –6·74]; one trial and 31 patients), cognitive behavioural therapy and fluvoxamine (–7·50 [–13·89 to –1·17]; one trial and six patients), cognitive behavioural therapy (–5·37 [–9·10 to –1·63]; nine trials and 231 patients), clomipramine (–4·72 [–6·85 to –2·60]; 13 trials and 831 patients), and all SSRIs (class eff ect –3·49 [95% credible interval –5·12 to –1·81]; 37 trials and 3158 patients) had greater eff ects than did drug placebo. Clomipramine was not better than were SSRIs (–1·23 [–3·41 to 0·94]). Psychotherapeutic interventions had a greater eff ect than did medications, but a serious limitation was that most psychotherapeutic trials included patients who were taking stable doses of antidepressants (12 [80%] of the 15 psychotherapy trials explicitly allowed antidepressants

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    juanwalker
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    Title: Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis

    Source:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660151/#SD2

    Description:

    This investigation compared two genome-wide association studies (GWAS) addressed by the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS) using meta analysis technique (Indivual studies compared in a statistical way).No SNPs reached genome-wide significance. However, in comparison to the two individual GWASs, the distribution of p-values shifted towards significance. The top haplotypic blocks (SNPs) were tagged with rs4733767 (p=7.1×10−7; OR=1.21;(CI: 1.12,1.31); genes CASC8/CASC11), rs1030757 (p=1.1×10−6; OR=1.18;CI:1.10,1.26, gen GRID2) and rs12504244 (p=1.6×10−6; OR=1.18;CI: 1.11,1.27, KIT). Variants located in or near the genes ASB13, RSPO4, DLGAP1, PTPRD, GRIK2, FAIM2, and CDH20, identified in linkage peaks and the original GWASs, were amongst the top signals.The common SNP heritability in the combined OCGAS and IOCDF-GC sample was estimated to be 0.28 (s.e. = 0.04).This joint analysis constituting the largest single OCD genome-wide study to date represents a major integrative step in elucidating the genetic causes of OCD.

     

    Polygenic Risk Score (PRS) and LD score regression (LDSC) analyses confirm that the two samples share genetic risk factors for OCD, and are thus appropriate for combined GWAS analyses. With LDSC we observed a strong genetic correlation between the IOCDF-GC and OCGAS samples (rg = 0.83, s.e. = 0.28; p = 0.003).

     

    The investigation was done using different softwares as PLINK and GCTA

     

    Twins can share obsessive compulsive disorder:

     

    “Population-based twin studies estimate the heritability of dimensional measures of obsessive-compulsive symptoms (OCS) to be 40 −50%, with a similar contribution from non-shared environment, and no significant contribution from a shared environment” 

     

    Taylor S Etiology of obsessions and compulsions: a meta-analysis and narrative review of twin studies. Clin Psychol Rev 2011; 31(8): 1361–1372.

     

    Heritage:

     

    “Genome wide association study (GWAS) provided heritability estimates of 0.37 (se = 0.07, p = 1.5 × 10−07) for OCD. In the same sample, the estimate of heritability for childhood-onset OCD (symptoms before the age of 1715) was 0.43 (se = 0.10, p = 1 × 10−05).”

     

     Davis LK, Yu D, Keenan CL, Gamazon ER, Konkashbaev AI, Derks EM et al. Partitioning the heritability of tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genet 2013; 9(10): e1003864.

     

    Gnome studies of OCD:

     

    “To date, eight whole-genome studies of OCD or OCS have been published, including five linkage studies1622, two genome-wide association studies (GWAS) of OCD23, 24, and one GWAS of obsessive compulsive symptoms (OCS).”

     

    “the first OCD GWAS, comprising 1,465 cases and 5,557 ancestry-matched controls, as well as 400 complete trios, from 22 sites worldwide 26. The top signal from the combined trio-case-control sample was rs297941 on chromosome 19p13.2, near FAIM2 (p =4.99 × 10−7). Although no SNPs were found to be associated with OCD at a genome-wide significance level, a significant enrichment of methylation quantitative trait loci (p<0.001) and frontal lobe expression quantitative trait loci (p=0.001) were observed within the top-ranked SNPs, providing evidence, consistent with other disease reports”

    “A second GWAS, conducted by six research centers in the United States23. In this study, 1,065 families (containing 1,406 patients with OCD), combined with population-based control samples (resulting in a total sample of 5,061 individuals), were studied. The smallest p-value (p=4.13 × 10−7) was detected for a SNP on chromosome 9p23, in close proximity to the protein tyrosine phosphate receptor D gene (PTPRD). The second smallest p-value was 1.76 × 10−6 near the cadherin type 9 and 10 (CDH9 and CDH10) genes on chromosome 5p15.”

     

    “A third GWAS, this one examining quantitative obsessive compulsive symptoms (OCS), was conducted in 6,931 individuals from the Netherlands Twin Registry (NTR)25. This study identified one gene that met criteria for genome-wide significance, the myocyte enhancer factor 2B neighbor (MEF2BNB) (p=2.56 × 10−8), on chromosome 19p13. The total SNP-based heritability for OCS in this sample was 0.14 (se=0.05, p=0.003), and the polygenic risk score (PRS) derived from the IOCDF-GC GWAS was significantly associated with OCS, explaining 0.2% of the variance.”

     

     Mathews CA, Badner JA, Andresen JM, Sheppard B, Himle JA, Grant JE et al. Genome-wide Linkage Analysis of Obsessive-Compulsive Disorder Implicates Chromosome 1p36. Biol Psychiatry 2012.

     

    den Braber A, Zilhao NR, Fedko IO, Hottenga JJ, Pool R, Smit DJ et al. Obsessive-compulsive symptoms in a large population-based twin-family sample are predicted by clinically based polygenic scores and by genome-wide SNPs. Translational psychiatry 2016; 6: e731

     

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    juanwalker
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    Title: Molecular genetics of obsessive–compulsive disorder: a comprehensive meta-analysis of genetic association studies

    Source:https://www.nature.com/articles/mp201276.pdf

    Description:Twin studies indicate that obsessive–compulsive disorder (OCD) is strongly influenced by additive genetic factors. Yet, molecular genetic association studies have yielded inconsistent results, possibly because of differences across studies in statistical power. Meta-analysis can yield greater power. This study reports the first comprehensive meta-analysis of the relationship between OCD and all previously examined polymorphisms for which there was sufficient information in the source studies to compute odds ratios (ORs). A total of 230 polymorphisms from 113 genetic association studies were identified. A full meta-analysis was conducted for 20 polymorphisms that were examined in 5 or more data sets, and a secondary meta-analysis (limited to the computation of mean effect sizes) was conducted for 210 polymorphisms that were examined in fewer than 5 data sets. In the main meta-analysis, OCD was associated with serotonin-related polymorphisms (5-HTTLPR and HTR2A) and, in males only, with polymorphisms involved in catecholamine modulation (COMT and MAOA). Nonsignificant trends were identified for two dopamine-related polymorphisms (DAT1 and DRD3) and a glutamate-related polymorphism (rs3087879). The secondary meta-analysis identified another 18 polymorphisms with significant ORs that merit further investigation. This study demonstrates that OCD is associated with multiple genes, with most having a modest association with OCD. This suggests a polygenic model of OCD, consistent with twin studies, in which multiple genes make small, incremental contributions to the risk of developing the disorder. Future studies, with sufficient power to detect small effects, are needed to investigate the genetic basis of OCD subtypes, such as early vs late onset OCD

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