Correlates of obsessive-compulsive and related disorders symptom severity during the COVID-19 pandemic.
Journal of psychiatric research
We investigated changes in the severity of obsessive-compulsive and related disorders (OCRDs) symptoms as a result of the COVID-19 pandemic. An Amazon Mechanical Turk sample of 829 individuals was evaluated with a series of instruments assessing the severity of the OCRDs before and during the pandemic. Additional questionnaires about sociodemographic factors, personal and family histories of OCRD, COVID-19 related events, compulsivity and impulsivity traits, schizotypal symptoms, and the severity of depression, anxiety and stress levels, were also used. Participants reported that OCD, hoarding disorder (HD) and skin picking disorder (SPD) symptoms significantly worsened during the pandemic along with increased disability, more affective symptoms and reduced quality of life. Female gender, a higher number of COVID-19 related stressful events, and higher pre-COVID-19 fear of harm and symmetry symptoms predicted more severe OCD symptoms during the pandemic, whereas lack of a HD diagnosis by a mental health professional and more severe schizotypal symptoms predicted worsened hoarding symptoms. Greater compulsivity traits were associated with more severe COVID-19 pandemic obsessive-compulsive and hoarding symptoms. These data indicate that the immense distress resulting from the COVID-19 included significant deterioration of OCRDs' symptoms, particularly of OCD, HD and SPD. It was also possible to identify a pre-pandemic profile of people most at risk of pandemic-related deterioration in OCRDs' symptoms, which may prove valuable for preventative initiatives in relation to the likely future waves of COVID-19 or of other communicable diseases. Future studies should follow up these findings longitudinally.
10.1016/j.jpsychires.2021.03.046
Prevalence, comorbidity, and predictors of obsessive-compulsive disorder in Iranian children and adolescents.
Mohammadi Mohammad Reza,Ahmadi Nastaran,Hooshyari Zahra,Khaleghi Ali,Rismanian Yazdi Fatemeh,Mehrparvar Amir Houshang
Journal of psychiatric research
BACKGROUND AND OBJECTIVES:Obsessive-compulsive disorder (OCD) is a disease that causes personal distress or social dysfunction, especially in childhood. The present study aimed to provide the prevalence, comorbidity, and predictors of OCD among children and adolescents. METHODS:This was a cross-sectional national project conducted on 29,858 children and adolescents using the multi-stage cluster random sampling in Iran. There were both genders in each cluster and three age groups (6-9, 10-14, and 15-18 years) within each cluster. The tools used in this research included a demographic questionnaire and K-SADS-PL. To analyze the data, logistic regression and cross-tab tests were used. RESULTS:According to the results, the prevalence of OCD in children and adolescents was 3.1 in boys and 3.8 in girls. Also, gender, age, place of residence, and history of psychiatric hospitalization of parents could predict OCD. OCD had comorbidity with behavioral disorders (OR = 0.60, 95%CI: 0.39-0.92), elimination disorders (OR = 0.50, 95%CI: 0.30-0.83), mood disorders (OR = 2.92, 95%CI: 1.43-5.94), and smoking and alcohol disorders (OR = 4.33, 95%CI: 1.28-14.63). CONCLUSION:In the development of the obsessive-compulsive disorder, other disorders and symptoms also environmental factors can play a role and are important. Based on our findings, given the prevalence rate of OCD was higher in the age groups of 10-14 and 15-18 years, are one of the most important stages of development for the prevention and treatment of mental disorders, especially OCD, clinical specialists can design appropriate clinical trials or modify existing interventions based on the results of such research.
10.1016/j.jpsychires.2021.06.018
A prospective longitudinal investigation of the trajectory of obsessive-compulsive symptoms during adolescence.
Psychiatry research
Obsessive-compulsive symptoms (OCS) increase with age during childhood and adolescence, and subthreshold OCS in childhood associate with a higher probability of obsessive-compulsive disorder (OCD) diagnosis in adulthood. Additionally, average age of onset for OCD is in adolescence, with the majority of OCD cases emerging by early adulthood. Despite these trends, the specific course of OCS development in adolescence is relatively unknown. To this end, the present prospective longitudinal study used latent growth mixture modeling and a diverse community sample of 3,335 high schoolers to identify and characterize growth trajectories of OCS across middle to late adolescence. Results identified three trajectories: High-but-Remitting, Moderate-but-Escalating, and Low-and-Stable. Results also indicated age, gender, anxiety sensitivity, and distress tolerance as significant predictors of trajectory group membership, such that younger age and being female predicted classification in the High-but Remitting group, greater anxiety sensitivity predicted classification in both the High-but-Remitting and Moderate-but Escalating groups, and greater distress tolerance predicted a lower likelihood of classification in the High-but-Remitting and Moderate-but-Escalating groups. Taken together, these trajectories have illustrated the temporal course and development of OCS across key developmental years. Moreover, the trajectories and their corresponding predictors may help identify adolescents who are particularly vulnerable to developing OCD.
10.1016/j.psychres.2024.116155
The Relationship Between Trauma Exposure and Obsessive-Compulsive Disorder in Youth: A Systematic Review.
Child psychiatry and human development
Extant literature suggests a possible relationship between childhood trauma exposure and the development and trajectory of obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD); however, this relationship is poorly understood. We conducted a systematic review that examined trauma exposure and OCS/OCD in youth. Primary inclusion criteria were English-language articles that addressed a sample with participants under 18 years of age. 46 articles met criteria for review, and were categorized into three groups of overlap: Post-traumatic Stress Disorder (PTSD) and OCS or OCD (n = 3), clearly defined Criterion A event trauma exposure and OCS or OCD (n = 30), and less well-defined potential trauma exposure and OCS or OCD (n = 13). There was mixed evidence linking trauma exposure and the development of OCS or OCD in youth. Major methodological limitations preclude formal conclusions. More research on co-occurring trauma exposure and OCD/OCS in youth is needed to advance research and improve treatment.
10.1007/s10578-022-01352-5
The Relationship Between Adverse Childhood Experiences, Symptom Severity, Negative Thinking, Comorbidity, and Treatment Response in Youth with Obsessive-Compulsive Disorder.
Child psychiatry and human development
Although youth and adults with obsessive-compulsive disorder (OCD) endorse elevated incidence of exposure to traumatic life events during childhood, the existing literature on adverse childhood experiences (ACEs) and OCD is mixed and studies focusing on pediatric OCD are limited. The present study examines the relationship between ACEs and OCD onset, symptom severity, negative cognitive patterns, comorbidity, and cognitive-behavioral therapy (CBT) response in 142 children and adolescents with OCD. ACEs were ascertained from parent reports. Most parents reported child exposure to ACEs. Out of the parents who reported ACEs, 50% reported ACE exposure prior to OCD diagnosis and 50% reported ACE exposure after OCD diagnosis. No significant associations between ACEs and comorbidity or CBT response were found, suggesting that CBT for pediatric OCD is effective regardless of ACE exposure. Family financial problems were associated with increased obsessive-compulsive symptom severity and negative thinking. Implications for research and practice are discussed.
10.1007/s10578-022-01488-4
Predictors of the 6-year outcome of obsessive-compulsive disorder: Findings from the Netherlands Obsessive-Compulsive Disorder Association study.
The Australian and New Zealand journal of psychiatry
OBJECTIVE:Obsessive-compulsive disorder is characterized by a chronic course that can vary between patients. The knowledge on the naturalistic long-term outcome of obsessive-compulsive disorder and its predictors is surprisingly limited. The present research was designed to identify clinical and psychosocial predictors of the long-term outcome of obsessive-compulsive disorder. METHODS:We included 377 individuals with a current diagnosis of obsessive-compulsive disorder, who participated in the Netherlands Obsessive Compulsive Disorder Association study, a multicenter naturalistic cohort study. Predictors were measured at baseline using self-report questionnaires and clinical interviews. Outcome was assessed using the Yale-Brown Obsessive Compulsive Scale at 2-, 4- and 6-year follow-up. RESULTS:The overall course of obsessive-compulsive disorder was characterized by two prominent trends: the first reflected an improvement in symptom severity, which was mitigated by the second, worsening trend in the long term. Several determinants affected the course variations of obsessive-compulsive disorder, namely, increased baseline symptom severity, late age of onset, history of childhood trauma and autism traits. CONCLUSION:The long-term outcome of obsessive-compulsive disorder in naturalistic settings was characterized by an overall improvement in symptom severity, which was gradually halted to the point of increased worsening. However, after 6 years, the severity of symptoms remained below the baseline level. While certain determinants predicted a more favorable course, their effect diminished over time in correspondence to the general worsening trend. The results highlight the importance of a regular and continuous monitoring for symptom exacerbations as part of the management of the obsessive-compulsive disorder, regardless of the presence of putative predictors.
10.1177/00048674231173342
The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication.
Ruscio A M,Stein D J,Chiu W T,Kessler R C
Molecular psychiatry
Despite significant advances in the study of obsessive-compulsive disorder (OCD), important questions remain about the disorder's public health significance, appropriate diagnostic classification, and clinical heterogeneity. These issues were explored using data from the National Comorbidity Survey Replication, a nationally representative survey of US adults. A subsample of 2073 respondents was assessed for lifetime Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) OCD. More than one quarter of respondents reported experiencing obsessions or compulsions at some time in their lives. While conditional probability of OCD was strongly associated with the number of obsessions and compulsions reported, only small proportions of respondents met full DSM-IV criteria for lifetime (2.3%) or 12-month (1.2%) OCD. OCD is associated with substantial comorbidity, not only with anxiety and mood disorders but also with impulse-control and substance use disorders. Severity of OCD, assessed by an adapted version of the Yale-Brown Obsessive Compulsive Scale, is associated with poor insight, high comorbidity, high role impairment, and high probability of seeking treatment. The high prevalence of subthreshold OCD symptoms may help explain past inconsistencies in prevalence estimates across surveys and suggests that the public health burden of OCD may be greater than its low prevalence implies. Evidence of a preponderance of early onset cases in men, high comorbidity with a wide range of disorders, and reliable associations between disorder severity and key outcomes may have implications for how OCD is classified in DSM-V.
10.1038/mp.2008.94
Women Are at Greater Risk of OCD Than Men: A Meta-Analytic Review of OCD Prevalence Worldwide.
Fawcett Emily J,Power Hilary,Fawcett Jonathan M
The Journal of clinical psychiatry
OBJECTIVE:To estimate the worldwide prevalence of obsessive-compulsive disorder (OCD), examine whether women are at greater risk than men, and explore other potential moderators of OCD prevalence to explain variability in community-based epidemiologic studies. DATA SOURCES:An electronic search of PsycINFO and PubMed was conducted until January 2017, without date or language restrictions, using the keywords OCD, epidemiology, and prevalence. The search was supplemented by articles referenced in the obtained sources and relevant reviews. STUDY SELECTION:Studies were included if they reported current, period, and/or lifetime OCD prevalence (diagnosed according to an interview based on DSM or ICD criteria) in representative community samples of adults aged 18 years or older. A total of 4,045 studies were retrieved, with 34 studies ultimately included. DATA EXTRACTION:OCD prevalence was extracted from each study alongside 9 moderators: gender, year, response rate, region, economic status, diagnostic criteria, diagnostic interview, interviewer, and age. RESULTS:The overall aggregate current, period, and lifetime OCD prevalence estimates were 1.1%, 0.8%, and 1.3%, respectively. In a typical sample, women were 1.6 times more likely to experience OCD compared to men, with lifetime prevalence rates of 1.5% in women and 1.0% in men. There was also a trend toward younger adults' being more likely to experience OCD in their lifetime than older adults. All findings demonstrated moderate heterogeneity. CONCLUSIONS:Women are typically at greater risk of experiencing OCD in their lifetime than men.
10.4088/JCP.19r13085
Association between bullying victimization and obsessive-compulsive disorder: a population-based, genetically informative study.
Molecular psychiatry
The extent to which bullying victimization is associated with an increased risk of obsessive-compulsive disorder (OCD) has received little empirical attention. This longitudinal, population-based, genetically informative study examined whether self-reported bullying victimization at age 15 was associated with a clinical diagnosis of OCD in the Swedish National Patient Register and with self-reported obsessive-compulsive symptoms (OCS) at ages 18 and 24 in 16,030 twins from the Child and Adolescent Twin Study in Sweden. Using a discordant twin design, including monozygotic (MZ) and dizygotic (DZ) twins, each twin was compared with their co-twin, allowing a strict control of genetic and environmental confounding. At the population level, adjusting for birth year and sex, each standard deviation (SD) increase in bullying victimization was associated with a 32% increase in the odds of an OCD diagnosis (OR, 1.32; 95% CI, 1.21-1.44), of 0.13 SD in OCS at age 18 (β, 0.13; 95% CI, 0.11-0.16), and of 0.11 SD in OCS at age 24 (β, 0.11; 95% CI, 0.07-0.16). While associations tended to persist in the within DZ-twin comparison models, the estimates attenuated and were no longer statistically significant in the within MZ-twin comparisons. These results suggest that the association between bullying victimization and OCD/OCS is likely due to genetic confounding and therefore incompatible with a strong causal effect. Other mechanisms, such as evocative gene-environment correlations, are more plausible explanations for the observed associations.
10.1038/s41380-024-02849-2
Incidence Rates and Cumulative Incidences of the Full Spectrum of Diagnosed Mental Disorders in Childhood and Adolescence.
Dalsgaard Søren,Thorsteinsson Erla,Trabjerg Betina B,Schullehner Jörg,Plana-Ripoll Oleguer,Brikell Isabell,Wimberley Theresa,Thygesen Malene,Madsen Kathrine Bang,Timmerman Allan,Schendel Diana,McGrath John J,Mortensen Preben Bo,Pedersen Carsten B
JAMA psychiatry
Importance:Knowledge about the epidemiology of mental disorders in children and adolescents is essential for research and planning of health services. Surveys can provide prevalence rates, whereas population-based registers are instrumental to obtain precise estimates of incidence rates and risks. Objective:To estimate age- and sex-specific incidence rates and risks of being diagnosed with any mental disorder during childhood and adolescence. Design:This cohort study included all individuals born in Denmark from January 1, 1995, through December 31, 2016 (1.3 million), and followed up from birth until December 31, 2016, or the date of death, emigration, disappearance, or diagnosis of 1 of the mental disorders examined (14.4 million person-years of follow-up). Data were analyzed from September 14, 2018, through June 11, 2019. Exposures:Age and sex. Main Outcomes and Measures:Incidence rates and cumulative incidences of all mental disorders according to the ICD-10 Classification of Mental and Behavioral Disorders: Diagnostic Criteria for Research, diagnosed before 18 years of age during the study period. Results:A total of 99 926 individuals (15.01%; 95% CI, 14.98%-15.17%), including 41 350 girls (14.63%; 95% CI, 14.48%-14.77%) and 58 576 boys (15.51%; 95% CI, 15.18%-15.84%), were diagnosed with a mental disorder before 18 years of age. Anxiety disorder was the most common diagnosis in girls (7.85%; 95% CI, 7.74%-7.97%); attention-deficit/hyperactivity disorder (ADHD) was the most common in boys (5.90%; 95% CI, 5.76%-6.03%). Girls had a higher risk than boys of schizophrenia (0.76% [95% CI, 0.72%-0.80%] vs 0.48% [95% CI, 0.39%-0.59%]), obsessive-compulsive disorder (0.96% [95% CI, 0.92%-1.00%] vs 0.63% [95% CI, 0.56%-0.72%]), and mood disorders (2.54% [95% CI, 2.47%-2.61%] vs 1.10% [95% CI, 0.84%-1.21%]). Incidence peaked earlier in boys than girls in ADHD (8 vs 17 years of age), intellectual disability (5 vs 14 years of age), and other developmental disorders (5 vs 16 years of age). The overall risk of being diagnosed with a mental disorder before 6 years of age was 2.13% (95% CI, 2.11%-2.16%) and was higher in boys (2.78% [95% CI, 2.44%-3.15%]) than in girls (1.45% [95% CI, 1.42%-1.49%]). Conclusions and Relevance:This nationwide population-based cohort study provides a first comprehensive assessment of the incidence and risks of mental disorders in childhood and adolescence. By 18 years of age, 15.01% of children and adolescents in this study were diagnosed with a mental disorder. The incidence of several neurodevelopmental disorders peaked in late adolescence in girls, suggesting possible delayed detection. The distinct signatures of the different mental disorders with respect to sex and age may have important implications for service planning and etiological research.
10.1001/jamapsychiatry.2019.3523
Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies.
Molecular psychiatry
Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.
10.1038/s41380-021-01161-7
Obsessive-compulsive disorder.
Nature reviews. Disease primers
Obsessive-compulsive disorder (OCD) is a highly prevalent and chronic condition that is associated with substantial global disability. OCD is the key example of the 'obsessive-compulsive and related disorders', a group of conditions which are now classified together in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the International Classification of Diseases, 11th Revision, and which are often underdiagnosed and undertreated. In addition, OCD is an important example of a neuropsychiatric disorder in which rigorous research on phenomenology, psychobiology, pharmacotherapy and psychotherapy has contributed to better recognition, assessment and outcomes. Although OCD is a relatively homogenous disorder with similar symptom dimensions globally, individualized assessment of symptoms, the degree of insight, and the extent of comorbidity is needed. Several neurobiological mechanisms underlying OCD have been identified, including specific brain circuits that underpin OCD. In addition, laboratory models have demonstrated how cellular and molecular dysfunction underpins repetitive stereotyped behaviours, and the genetic architecture of OCD is increasingly understood. Effective treatments for OCD include serotonin reuptake inhibitors and cognitive-behavioural therapy, and neurosurgery for those with intractable symptoms. Integration of global mental health and translational neuroscience approaches could further advance knowledge on OCD and improve clinical outcomes.
10.1038/s41572-019-0102-3
Association of Obsessive-Compulsive Disorder With Objective Indicators of Educational Attainment: A Nationwide Register-Based Sibling Control Study.
JAMA psychiatry
Importance:To our knowledge, the association of obsessive-compulsive disorder (OCD) and academic performance has not been objectively quantified. Objective:To investigate the association of OCD with objectively measured educational outcomes in a nationwide cohort, adjusting for covariates and unmeasured factors shared between siblings. Design, Setting, And Participants:This population-based birth cohort study included 2 115 554 individuals who were born in Sweden between January 1, 1976, and December 31, 1998, and followed up through December 31, 2013. Using the Swedish National Patient Register and previously validated International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, we identified persons with OCD; within the cohort, we identified 726 198 families with 2 or more full siblings, and identified 11 482 families with full siblings discordant for OCD. Data analyses were conducted from October 1, 2016, to September 25, 2017. Main Outcomes and Measures:The study evaluates the following educational milestones: eligibility to access upper secondary school after compulsory education, finishing upper secondary school, starting a university degree, finishing a university degree, and finishing postgraduate education. Results:Of the 2 115 554 individuals in the cohort, 15 120 were diagnosed with OCD (59% females). Compared with unexposed individuals, those with OCD were significantly less likely to pass all core and additional courses at the end of compulsory school (adjusted odds ratio [aOR] range, 0.35-0.60) and to access a vocational or academic program in upper secondary education (aOR, 0.47; 95% CI, 0.45-0.50 and aOR, 0.61; 95% CI, 0.58-0.63, for vocational and academic programs, respectively). People with OCD were also less likely to finish upper secondary education (aOR, 0.43; 95% CI, 0.41-0.44), start a university degree (aOR, 0.72; 95% CI, 0.69-0.75), finish a university degree (aOR, 0.59; 95% CI, 0.56-0.62), and finish postgraduate education (aOR, 0.52; 95% CI, 0.36-0.77). The results were similar in the sibling comparison models. Individuals diagnosed with OCD before age 18 years showed worse educational attainment across all educational levels compared with those diagnosed at or after age 18 years. Exclusion of patients with comorbid neuropsychiatric disorders, psychotic, anxiety, mood, substance use, and other psychiatric disorders resulted in attenuated estimates, but patients with OCD were still impaired across all educational outcomes. Conclusions and Relevance:Obsessive-compulsive disorder, particularly when it has an early onset, is associated with a pervasive and profound decrease in educational attainment, spanning from compulsory school to postgraduate education.
10.1001/jamapsychiatry.2017.3523
Maternal Effects as Causes of Risk for Obsessive-Compulsive Disorder.
Biological psychiatry
BACKGROUND:While genetic variation has a known impact on the risk for obsessive-compulsive disorder (OCD), there is also evidence that there are maternal components to this risk. Here, we partitioned sources of variation, including direct genetic and maternal effects, on risk for OCD. METHODS:The study population consisted of 822,843 individuals from the Swedish Medical Birth Register, born in Sweden between January 1, 1982, and December 31, 1990, and followed for a diagnosis of OCD through December 31, 2013. Diagnostic information about OCD was obtained using the Swedish National Patient Register. RESULTS:A total of 7184 individuals in the birth cohort (0.87%) were diagnosed with OCD. After exploring various generalized linear mixed models to fit the diagnostic data, genetic maternal effects accounted for 7.6% (95% credible interval: 6.9%-8.3%) of the total variance in risk for OCD for the best model, and direct additive genetics accounted for 35% (95% credible interval: 32.3%-36.9%). These findings were robust under alternative models. CONCLUSIONS:Our results establish genetic maternal effects as influencing risk for OCD in offspring. We also show that additive genetic effects in OCD are overestimated when maternal effects are not modeled.
10.1016/j.biopsych.2020.01.006