Implications of Extending the ADHD Age-of-Onset Criterion to Age 12: Results from a Prospectively Studied Birth Cohort

Objective: To evaluate whether including children with onset of symptoms between ages 7 and 12 years in the ADHD diagnostic category would: (a) increase the prevalence of the disorder at age 12, and (b) change the clinical and cognitive features, impairment profile, and risk factors for ADHD compared with findings in the literature based on the DSM-IV definition of the disorder. Method: A birth cohort of 2,232 British children was prospectively evaluated at ages 7 and 12 years for ADHD using information from mothers and teachers. The prevalence of diagnosed ADHD at age 12 was evaluated with and without the inclusion of individuals who met DSM-IV age-of-onset criterion through mothers` or teachers` reports of symptoms at age 7. Children with onset of ADHD symptoms before versus after age 7 were compared on their clinical and cognitive features, impairment profile, and risk factors for ADHD. Results: Extending the age-of-onset criterion to age 12 resulted in a negligible increase in ADHD prevalence by age 12 years of 0.1%. Children who first manifested ADHD symptoms between ages 7 and 12 did not present correlates or risk factors that were significantly different from children who manifested symptoms before age 7. Conclusions: Results from this prospective birth cohort might suggest that adults who are able to report symptom onset by age 12 also had symptoms by age 7, even if they are not able to report them. The data suggest that the prevalence estimate, correlates and risk factors of ADHD will not be affected if the new diagnostic scheme extends the age-of-onset criterion to age 12. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(3):210-216.

Older age of onset in child L2 acquisition can be facilitative: evidence from the acquisition of English passives by Spanish natives

We report a longitudinal comprehension study of (long) passive constructions in two native-Spanish child groups differing by age of initial exposure to L2 English (young group: 3;0-4;0 years; older group: 6;0-7;0 years); where amount of input, L2 exposure environment, and socio-economic status are controlled. Data from a forced-choice task show that both groups comprehend active sentences, not passives, initially (after 3.6 years of exposure). One year later, both groups improve, but only the older group reaches ceiling on both actives and passives. Two years from initial testing, the younger group catches up. Input alone cannot explain why the younger group takes 5 years to accomplish what the older group does in 4. We claim that some properties take longer to acquire at certain ages because language development is partially constrained by general cognitive and linguistic development (e.g. de Villiers, 2007; Long & Rothman, 2014; Paradis, 2008, 2010, 2011; Tsimpli, 2014).

Symptom dimensions are associated with age of onset and clinical course of obsessive-compulsive disorder

Meta-analysis of the heterogeneous symptoms of obsessive-compulsive disorder (OCD) has found a four-factor structure of symptom dimensions consisting of cleaning, forbidden thoughts, symmetry, and hoarding. Research into age of onset of symptom dimensions has yielded inconsistent results, and it is unknown whether symptoms along these dimensions differ in their clinical course. We assessed age of onset and clinical course of different OCD symptom dimensions in a large cohort of adult patients. Nine-hundred fifty-five subjects were assessed using the Dimensional Yale-Brown Obsessive-Compulsive Scale. For age of onset analysis, we tested across three methods of classification: (1) primary (more severe) symptom dimension (2) clinically significant symptoms within a dimension or (3) any symptoms within a dimension. Age of onset was defined as the earliest age of onset reported for any individual item within a symptom dimension. For analysis of different types of clinical course, we used chi-square tests to assess for differences between primary symptom dimensions. OCD symptoms in the symmetry dimension had an earlier age of onset than other OCD symptom dimensions. These findings remained significant across all three methods of classification and controlling for gender and comorbid tics. No significant differences were found between the other dimensions. Subjects with primary OCD symptoms in the forbidden thoughts dimension were more likely to report a waxing-and-waning course, whereas symmetry symptoms were less likely to be associated with a waxing-and-waning course. © 2013.

Impact of sunlight on the age of onset of bipolar disorder

Bauer M, Glenn T, Alda M, Andreassen OA, Ardau R, Bellivier F, Berk M, Bjella TD, Bossini L, Del Zompo M, Dodd S, Fagiolini A, Frye MA, Gonzalez-Pinto A, Henry C, Kapczinski F, Kliwicki S, Konig B, Kunz M, Lafer B, Lopez-Jaramillo C, Manchia M, Marsh W, Martinez-Cengotitabengoa M, Melle I, Morken G, Munoz R, Nery FG, ODonovan C, Pfennig A, Quiroz D, Rasgon N, Reif A, Rybakowski J, Sagduyu K, Simhandl C, Torrent C, Vieta E, Zetin M, Whybrow PC. Impact of sunlight on the age of onset of bipolar disorder. Bipolar Disord 2012: 14: 654663. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objective: Although bipolar disorder has high heritability, the onset occurs during several decades of life, suggesting that social and environmental factors may have considerable influence on disease onset. This study examined the association between the age of onset and sunlight at the location of onset. Method: Data were obtained from 2414 patients with a diagnosis of bipolar I disorder, according to DSM-IV criteria. Data were collected at 24 sites in 13 countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data from both hemispheres. The age of onset and location of onset were obtained retrospectively, from patient records and/or direct interviews. Solar insolation data, or the amount of electromagnetic energy striking the surface of the earth, were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database for each location of onset. Results: The larger the maximum monthly increase in solar insolation at the location of onset, the younger the age of onset (coefficient= -4.724, 95% CI: -8.124 to -1.323, p = 0.006), controlling for each countrys median age. The maximum monthly increase in solar insolation occurred in springtime. No relationships were found between the age of onset and latitude, yearly total solar insolation, and the maximum monthly decrease in solar insolation. The largest maximum monthly increases in solar insolation occurred in diverse environments, including Norway, arid areas in California, and Chile. Conclusion: The large maximum monthly increase in sunlight in springtime may have an important influence on the onset of bipolar disorder.

Lifetime Prevalence, Age and Gender Distribution and Age-of-Onset of Psychiatric Disorders in the Sao Paulo Metropolitan Area, Brazil: Results from the Sao Paulo Megacity Mental Health Survey

Objectives: To estimate prevalence, age-of-onset, gender distribution and identify correlates of lifetime psychiatric disorders in the Sao Paulo Metropolitan Area (SPMA). Methods: The Sao Paulo Megacity Mental Health Survey assessed psychiatric disorders on a probabilistic sample of 5,037 adult residents in the SPMA, using the World Mental Health Survey Version of the Composite International Diagnostic Interview. Response rate was 81.3%. Results: Lifetime prevalence for any disorder was 44.8%; estimated risk at age 75 was 57.7%; comorbidity was frequent. Major depression, specific phobias and alcohol abuse were the most prevalent across disorders; anxiety disorders were the most frequent class. Early age-of-onset for phobic and impulse-control disorders and later age-of-onset for mood disorders were observed. Women were more likely to have anxiety and mood disorders, whereas men, substance use disorders. Apart from conduct disorders, more frequent in men, there were no gender differences in impulse-control disorders. There was a consistent trend of higher prevalence in the youngest cohorts. Low education level was associated to substance use disorders. Conclusions: Psychiatric disorders are highly prevalent among the general adult population in the SPMA, with frequent comorbidity, early age-of-onset for most disorders, and younger cohorts presenting higher rates of morbidity. Such scenario calls for vigorous public health action.

Lifetime Prevalence, age and gender distribution and age-of-onset of psychiatric disorders in the São Paulo Metropolitan Area, Brazil: results from the São Paulo Megacity Mental Health Survey

OBJECTIVES: To estimate prevalence, age-of-onset, gender distribution and identify correlates of lifetime psychiatric disorders in the São Paulo Metropolitan Area (SPMA). METHODS: The São Paulo Megacity Mental Health Survey assessed psychiatric disorders on a probabilistic sample of 5,037 adult residents in the SPMA, using the World Mental Health Survey Version of the Composite International Diagnostic Interview. Response rate was 81.3%. RESULTS: Lifetime prevalence for any disorder was 44.8%; estimated risk at age 75 was 57.7%; comorbidity was frequent. Major depression, specific phobias and alcohol abuse were the most prevalent across disorders; anxiety disorders were the most frequent class. Early age-of-onset for phobic and impulse-control disorders and later age-of-onset for mood disorders were observed. Women were more likely to have anxiety and mood disorders, whereas men, substance use disorders. Apart from conduct disorders, more frequent in men, there were no gender differences in impulse-control disorders. There was a consistent trend of higher prevalence in the youngest cohorts. Low education level was associated to substance use disorders. CONCLUSIONS: Psychiatric disorders are highly prevalent among the general adult population in the SPMA, with frequent comorbidity, early age-of-onset for most disorders, and younger cohorts presenting higher rates of morbidity. Such scenario calls for vigorous public health action.

Age-of-onset-dependent influence of NOD2 gene variants on disease behaviour and treatment in Crohn's disease

BACKGROUND: Influence of genetic variants in the NOD2 gene may play a more important role in disease activity, behaviour and treatment of pediatric- than adult-onset Crohn's disease (CD). METHODS: 85 pediatric- and 117 adult-onset CD patients were tested for the three main NOD2 CD-associated variants (p.R702W, p.G908R and p.10007fs) and clinical data of at least two years of follow-up were compared regarding disease behaviour and activity, response to therapy and bone mineral density (BMD). RESULTS: Chronic active and moderate to severe course of CD is associated in patients with pediatric-onset (p=0.0001) and NOD2 variant alleles (p=0.0001). In pediatric-onset CD the average PCDAI-Score was significantly higher in patients carrying NOD2 variants (p=0.0008). In addition, underweight during course of the disease (p=0.012) was associated with NOD2 variants. Interestingly, osteoporosis was found more frequently in patients carrying NOD2 variant alleles (p=0.033), especially in pediatric-onset CD patients with homozygous NOD2 variants (p=0.037). Accordingly, low BMD in pediatric-onset CD is associated with a higher PCDAI (p=0.0092), chronic active disease (p=0.0148), underweight at diagnosis (p=0.0271) and during follow-up (p=0.0109). Furthermore, pediatric-onset CD patients with NOD2 variants are more frequently steroid-dependent or refractory (p=0.048) and need long-term immunosuppressive therapy (p=0.0213). CONCLUSIONS: These data suggests that the presence of any of the main NOD2 variants in CD is associated with osteoporosis and an age of onset dependent influence towards underweight, higher disease activity and a more intensive immunosuppressive therapy. This observation supports the idea for an early intensive treatment strategy in children and adolescent CD patients with NOD2 gene variants.

The Maudsley Early Onset Schizophrenia Study:The effect of age of onset and illness duration on fronto-parietal gray matter

Objective: In Early Onset Schizophrenia (EOS; onset before the 18th birthday) late brain maturational changes may interact with disease mechanisms leading to a wave of back to front structural changes during adolescence. To further explore this effect we examined the relationship between age of onset and duration of illness on brain morphology in adolescents with EOS. Subjects and methods: Structural brain magnetic resonance imaging scans were obtained from 40 adolescents with EOS. We used Voxel Based Morphometry and multiple regressions analyses, implemented in SPM, to examine the relationship between gray matter volume with age of onset and illness duration. Results: Age of onset showed a positive correlation with regional gray matter volume in the right superior parietal lobule (Brodmann Area 7). Duration of illness was inversely related to regional gray matter volume in the left inferior frontal gyrus (BA 11/47). Conclusions: Parietal gray matter loss may contribute to the onset of schizophrenia while orbitofrontal gray matter loss is associated with illness duration. © 2008 Elsevier Masson SAS. All rights reserved.

Relationship between sunlight and the age of onset of bipolar disorder:an international multisite study

Background - The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. Methods - Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. Results - There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. Limitations - Recall bias for onset and family history data. Conclusions - A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.

Influence of birth cohort on age of onset cluster analysis in bipolar I disorder

PURPOSE: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. METHODS: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. RESULTS: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. CONCLUSION: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.

Influence of light exposure during early life on the age of onset of bipolar disorder

Background: Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. Methods: Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4N and 70.7N, and 1.2S and 41.3S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. Results: More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. Conclusions: Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.

Evaluation of RET polymorphisms in a six-generation family with G533C RET mutation: specific RET variants may modulate age at onset and clinical presentation

P>Context We previously described a six-generation family with G533C RET mutation and medullary thyroid carcinoma, in the largest family reported do date. Of particular interest, phenotype variability regarding the age of onset and clinical presentation of the disease, was observed. Objective We evaluate whether single SNPs within RET oncogene or haplotype comprising the RET variants (defined by Haploview) could predispose to early development of MTC in this family and influence the clinical manifestation. Design Eight SNPs were selected based on their previous association with the clinical course of hereditary or sporadic MTC, in particular promoting an early onset of disease. The variants were initially tested in 77 G533C-carriers and 100 controls using either PCR-direct sequencing or PCR-RFLP. Association between a SNP or haplotype and age at diagnosis or presence of lymph node metastasis was tested in 34 G533C-carries with MTC. Different bioinformatic tools were used to evaluate the potential effects on RNA splicing. Results An association was found between IVS1-126G > T and age at diagnosis. The variant [IVS8 +82A > G; 85-86 insC] was associated with the presence of lymph node metastases at diagnosis. In silico analysis suggested that this variant may induce abnormal splicing. This in silico analysis predicted that the [IVS8 +82A > G; 85-86 insC] could alter the splicing by disrupting and/or creating exonic splicing enhancer motifs. Conclusions We here identified two RET variants that were associated with phenotype variability in G533C-carriers, which highlights the fact that the modifier effect of a variant might depend on the type of mutation.

Obsessive-compulsive disorder: Influence of age at onset on comorbidity patterns

Purpose: This study investigates the influence of age at onset of OCS on psychiatric comorbidities, and tries to establish a cut-off point for age at onset. Methods: Three hundred and thirty OCD patients were consecutively recruited and interviewed using the following structured interviews: Yale-Brown Obsessive Compulsive Scale; Yale Global Tic Severity Scale and the Structured Clinical Interview for DSM-IV. Data were analyzed with regression and cluster analysis. Results: Lower age at onset was associated with a higher probability of having comorbidity with tic, anxiety, somatoform, eating and impulse-control disorders. Longer illness duration was associated with lower chance of having tics. Female gender was associated with anxiety, eating and impulse-control disorders. Tic disorders were associated with anxiety disorders and attention-deficit/hyperactivity disorder. No cut-off age at onset was found to clearly divide the sample in homogeneous subgroups. However, cluster analyses revealed that differences started to emerge at the age of 10 and were more pronounced at the age of 17, suggesting that these were the best cut-off points on this sample. Conclusions: Age at onset is associated with specific comorbidity patterns in OCD patients. More prominent differences are obtained when analyzing age at onset as an absolute value. © 2008 Elsevier Masson SAS. All rights reserved.