A consideração da idade de início de sintomas, como parte do diagnóstico de TDAH, é controversa e tem sido um tema revisitado com o surgimento das novas classificações de Psiquiatria. O objetivo deste estudo é comparar pacientes com sintomas de TDAH de início precoce e tardio em termos de características neuropsicológicas e de personalidade. Pacientes adultos com TDAH (n = 415) foram avaliados no ambulatório de TDAH do Hospital de Clínicas de Porto Alegre, Brasil. O processo de diagnóstico de TDAH e comorbidades foi baseado nos critérios do DSM-IV. A comparação entre os dois grupos de idade de início (antes de 7; n = 209 e de 7 a 12 anos; n = 206) foi realizada com ANOVA, seguido de análises de regressão Stepwise forward para restringir o número de comparações e acessar o possível efeito de confundidores múltiplos. Adultos com TDAH de início precoce apresentam escores mais altos em busca de novidade em ambas as análises (respectivamente p = 0,016 e p = 0,002), mas as características cognitivas e de atenção são similares em comparação com o grupo de início tardio. Estes dados acrescentam evidências anteriores de que apesar de um perfil mais externalizante do TDAH de início precoce, o desempenho geral é semelhante, reforçando a necessidade da conscientização e inclusão deste grupo nos critérios diagnósticos do DSM-V. / The consideration of age of onset of impairment as part of the ADHD diagnosis is controversial and has been a revisited issue with the emergence of the new classifications in Psychiatry. The aim of this study is to compare patients with early and late onset of ADHD impairment in terms of neuropsychological and personality characteristics. Adult patients with ADHD (n=415) were evaluated in the ADHD outpatient program at Hospital de Clínicas de Porto Alegre, Brazil. The diagnostic process for ADHD and comorbidities was based on DSM-IV criteria. The comparison between the two age of onset groups (before 7; n=209 or from 7 to 12 years; n=206) was performed with ANOVA, followed by Stepwise forward regression analyses to restrict the number of comparisons and access the possible effect of multiple confounders. Patients with early onset ADHD present higher scores in novelty seeking in both analyses (respectively p = 0.016 and p = 0.002), but similar cognitive and attention features as compared with the late onset group. These data add to previous evidence that despite a more externalizing profile of early onset ADHD, the overall performance is similar reinforcing the need for awareness and inclusion of the late onset group in DSM-V diagnostic criteria.

A consideração da idade de início de sintomas, como parte do diagnóstico de TDAH, é controversa e tem sido um tema revisitado com o surgimento das novas classificações de Psiquiatria. O objetivo deste estudo é comparar pacientes com sintomas de TDAH de início precoce e tardio em termos de características neuropsicológicas e de personalidade. Pacientes adultos com TDAH (n = 415) foram avaliados no ambulatório de TDAH do Hospital de Clínicas de Porto Alegre, Brasil. O processo de diagnóstico de TDAH e comorbidades foi baseado nos critérios do DSM-IV. A comparação entre os dois grupos de idade de início (antes de 7; n = 209 e de 7 a 12 anos; n = 206) foi realizada com ANOVA, seguido de análises de regressão Stepwise forward para restringir o número de comparações e acessar o possível efeito de confundidores múltiplos. Adultos com TDAH de início precoce apresentam escores mais altos em busca de novidade em ambas as análises (respectivamente p = 0,016 e p = 0,002), mas as características cognitivas e de atenção são similares em comparação com o grupo de início tardio. Estes dados acrescentam evidências anteriores de que apesar de um perfil mais externalizante do TDAH de início precoce, o desempenho geral é semelhante, reforçando a necessidade da conscientização e inclusão deste grupo nos critérios diagnósticos do DSM-V. / The consideration of age of onset of impairment as part of the ADHD diagnosis is controversial and has been a revisited issue with the emergence of the new classifications in Psychiatry. The aim of this study is to compare patients with early and late onset of ADHD impairment in terms of neuropsychological and personality characteristics. Adult patients with ADHD (n=415) were evaluated in the ADHD outpatient program at Hospital de Clínicas de Porto Alegre, Brazil. The diagnostic process for ADHD and comorbidities was based on DSM-IV criteria. The comparison between the two age of onset groups (before 7; n=209 or from 7 to 12 years; n=206) was performed with ANOVA, followed by Stepwise forward regression analyses to restrict the number of comparisons and access the possible effect of multiple confounders. Patients with early onset ADHD present higher scores in novelty seeking in both analyses (respectively p = 0.016 and p = 0.002), but similar cognitive and attention features as compared with the late onset group. These data add to previous evidence that despite a more externalizing profile of early onset ADHD, the overall performance is similar reinforcing the need for awareness and inclusion of the late onset group in DSM-V diagnostic criteria.

A consideração da idade de início de sintomas, como parte do diagnóstico de TDAH, é controversa e tem sido um tema revisitado com o surgimento das novas classificações de Psiquiatria. O objetivo deste estudo é comparar pacientes com sintomas de TDAH de início precoce e tardio em termos de características neuropsicológicas e de personalidade. Pacientes adultos com TDAH (n = 415) foram avaliados no ambulatório de TDAH do Hospital de Clínicas de Porto Alegre, Brasil. O processo de diagnóstico de TDAH e comorbidades foi baseado nos critérios do DSM-IV. A comparação entre os dois grupos de idade de início (antes de 7; n = 209 e de 7 a 12 anos; n = 206) foi realizada com ANOVA, seguido de análises de regressão Stepwise forward para restringir o número de comparações e acessar o possível efeito de confundidores múltiplos. Adultos com TDAH de início precoce apresentam escores mais altos em busca de novidade em ambas as análises (respectivamente p = 0,016 e p = 0,002), mas as características cognitivas e de atenção são similares em comparação com o grupo de início tardio. Estes dados acrescentam evidências anteriores de que apesar de um perfil mais externalizante do TDAH de início precoce, o desempenho geral é semelhante, reforçando a necessidade da conscientização e inclusão deste grupo nos critérios diagnósticos do DSM-V. / The consideration of age of onset of impairment as part of the ADHD diagnosis is controversial and has been a revisited issue with the emergence of the new classifications in Psychiatry. The aim of this study is to compare patients with early and late onset of ADHD impairment in terms of neuropsychological and personality characteristics. Adult patients with ADHD (n=415) were evaluated in the ADHD outpatient program at Hospital de Clínicas de Porto Alegre, Brazil. The diagnostic process for ADHD and comorbidities was based on DSM-IV criteria. The comparison between the two age of onset groups (before 7; n=209 or from 7 to 12 years; n=206) was performed with ANOVA, followed by Stepwise forward regression analyses to restrict the number of comparisons and access the possible effect of multiple confounders. Patients with early onset ADHD present higher scores in novelty seeking in both analyses (respectively p = 0.016 and p = 0.002), but similar cognitive and attention features as compared with the late onset group. These data add to previous evidence that despite a more externalizing profile of early onset ADHD, the overall performance is similar reinforcing the need for awareness and inclusion of the late onset group in DSM-V diagnostic criteria.

BACKGROUND: Idiopathic psychotic disorders, which include schizophrenia, schizoaffective and bipolar disorder with psychosis, are debilitating disorders affecting about 3% of the world’s population. Neurodevelopmental and neurodegenerative hypotheses have been proposed in psychosis, but the literature is mixed in regards to whether psychosis pathogenesis involves one or both of these processes. Since the visual system matures early in development, studying visual pathway abnormalities stratified by disease onset may further inform our understanding of psychosis pathogenesis. OBJECTIVE: The objective of this thesis is to determine whether disease onset, independent of illness duration, has a differential effect on visual cortical abnormalities in psychosis. We examined visual cortical measures for thickness, surface area, and volume using a pseudo-longitudinal study design of first episode psychosis-schizophrenia (FEP-SZ), FEP-non-schizophrenia (FEP-NSZ), early onset psychosis (EOP, <15 years of age), adult onset psychosis (OP, >15 and <30 years of age), and late onset psychosis (LOP, >30 years of age) groups. Relationships between visual cortical metrics and clinical or functional outcomes were performed. METHODS: The FEP sample (n= 102) included healthy controls (n= 44), FEP-SZ (n= 36), and FEP-NSZ (n= 22). The chronic psychosis data included healthy controls (n= 311) and psychosis probands (n=510). Psychosis probands was stratified by disease onset: EOP (n=213), OP (n=257), and LOP (n=40). Propensity matching was performed to match healthy controls (HC) according to age, sex and race. Linear regression models were performed comparing the means of visual cortical measures between groups. Partial Spearman correlations controlling for confounding factors were performed between visual cortical regions and clinical data. For FEP, clinical outcomes were assessed using Clinical Global Impression scale (CGI), Scale of Positive Symptoms (SAPS), and Scale of Negative Symptoms (SANS). For onset groups, clinical and functional outcomes were assessed using Positive and Negative Syndrome Scale (PANSS), Montgomery–Åsberg Depression Rating Scale (MADRS), Brief Assessment of Cognition (BACS), Wecshler Memory Scale (WMS) spatial span, anti-saccade error rates, dot expectancy pattern test, emotion recognition test, and Birchwood Social Functioning Scale (SFS). Multiple comparisons were performed using the Benjamini-Hochberg procedure. RESULTS: FEP-SZ was associated with smaller V1 and V2 areas, higher MT area and lower MT thickness compared to HCs. Lower MT thickness was associated with worse negative symptoms. Compared to HC, patients with chronic psychosis had lower V1, V2, and MT areas, as well as smaller MT thickness. V1 and V2 area and MT thickness were lower in the EOP group in comparison to matched HC. OP and LOP had a thinner MT region compared to matched HC. Of particular note, it was observed that EOP had greater area differences as compared to thickness reductions in the LOP group. Increased hallucinations and delusions were associated with a thinner MT region in the EOP group. CONCLUSION: When stratified by disease onset, FEP, EOP, OP, and LOP appear to have different pathogenic mechanisms and the severity of visual cortex neuroanatomical abnormalities are dependent on when the disease onset occurs. EOP occurs earlier in neurodevelopment resulting in greater severity in symptom and visual cortical measures as compared to OP. On the contrary, LOP appears to have a neurodegenerative mechanism which is evidenced by accelerated visual cortical thinning. / 2022-06-01T00:00:00Z

Bipolar affective disorder is a very dynamic disease, which is influenced by numerous factors. One of these factors is the age at onset. The age at onset of bipolar affective disorder may play a major role in its course, severity and number of relapses, number of hospitalizations or response to mood stabilizers. Other factors influenced by the age at onset are suicide thoughts or attempted suicide. The aim of this work is to investigate and demonstrate the effect of age of the first symptom on the course of bipolar disorder. In the framework of quantitative research, 116 respondents completed a questionnaire on the course of bipolar affective disorder. Early age at onset (≤ 19 years) correlated significantly with the longer interval between the first symptom and the visit to the doctor, the first symptom and the first diagnosis and the first symptom and the diagnosis of bipolar affective disorder. There were no statistically significant relationships between the age at onset and the number of hospitalizations or the severity of the disease. Although the effect of age at onset on the course and severity of the disease has not been proven, this area should be further explored as it may help to better management the treatment of the disorder.

The purposes of this study were to describe the characteristics of the changing male voice in 4th, 5th and 6th grade students using Cooksey's maturation stages and, to compare the age-of-onset of the male voice change in African American, White, and Hispanic male students. Participants included volunteer 4th (n = 61), 5th (n = 73), and 6th grade male students (n = 63) from 2 urban elementary schools, 5 suburban elementary schools, 1 suburban middle school and 1 urban middle school in the North Texas region. The three ethnic groups represented in this study were: African American (n = 62), White (n = 58), and Hispanic (n = 77). Results indicated that approximately 46% of 4th grade participants, 62% of 5th grade participants, and 67% of 6th grade participants were classified as changing voices. A descriptively larger percentage of African American participants were classified as changing voices than Hispanic and White participants. Also, a larger percentage of African American and Hispanic participants were descriptively classified in the more advanced stages of the voice change than White participants. Urban African American, White, and Hispanic participants had a larger percentage of males classified as changing voices than suburban African American, White, and Hispanic participants. Results of a one-way, between subjects ANOVA revealed no significant main effect for ethnicity, F (2, 51) = .42, p = .66, η2 = .02. The overall mean age-of-onset for participants in this study was approximately 11.20 years of age.

Alzheimer’s disease (AD) is a multifactorial neurological condition associated with genetic profiles that are still not completely understood. We performed a family-based low-density genome-wide association analysis of age at onset (AAO) in AD (244 patients and their relatives) using Illumina 6 K single-nucleotide polymorphisms (SNPs) panel and the FBAT-logrank statistic. We observed 10 SNPs associated with AAO in AD with p < 2 × 10−3. The most significant hit within a known gene, the neuronal protein astrotactin 2 (ASTN2), was SNP rs1334071 (p = 8.74 × 10−4). ASTN2 has been implicated in several neuropsychiatric disorders, including cognitive disorders, autism and schizophrenia. We then conducted a replication study focusing on ASTN2 gene in a Canadian sample of 791 AD patients and 782 controls using the logrank test. Five ASTN2 SNPs (highest association is rs16933774 with p = 0.0053) showed associations with AAO in this Canadian sample (p < 0.05). Furthermore, Kaplan–Meier survival analysis of SNP rs16933774 showed that the AAO of AD in individuals heterozygous for AG genotype of rs16933774 (median of AAO = 68.5 years) was approximately 4.5 years earlier than those individuals having the AA genotype (median of AAO = 73 years). In conclusion, a significant association of ASTN2 genetic variants with AAO of AD in two independent samples demonstrates a role for ASTN2 in the pathogenesis of AD. Future functional studies of this gene may help to characterize the genetic architecture of the AAO of AD. Genetic factors in AAO may be a critical factor for early AD intervention and prevention efforts.

The Neuregulin 3 (NRG3) gene at 10q22-q24 has been implicated in multiple psychiatric traits such as cognitive impairment. We therefore hypothesized that NRG3 gene polymorphisms may play a role in Alzheimer disease (AD). This present study explored the association of NRG3 with the age at onset (AAO) of AD and the risk of developing AD. Secondary data analysis of 257 single-nucleotide polymorphisms (SNPs) in NRG3 gene was performed in 806 Alzheimer's disease patients and 782 controls using logistic regression and linear regression analyses. Eight SNPs were associated with the risk of AD (p < 0.05), while linear regression analysis showed 33 SNPs associated with the AAO of AD (p < 0.05). Two-SNP haplotype analyses based on UNPHASED revealed that the G-C haplotype from rs17685233 and rs17101017 was significantly associated with AD (p = 0.0031) and the A-G haplotype from rs504522 and rs474018 as well as the A-G haplotype from rs504522 and rs2483295 were more significantly associated with the AAO of AD (p = 6.72 × 10-5). Using an independent family-based sample, we found one SNP rs11192423 associated with AAO both in the case-control sample (p = 0.0155) and in the family sample (p = 0.0166). In addition, we observed nominally significant associations with AD and AAO for several flanking SNPs (p < 0.05). This is the first study demonstrating that genetic variants in the NRG3 gene play a role in AD. Our results also revealed that SNPs in the NRG3 genes were more strongly associated with AAO of AD.

We performed a genome-wide association analysis to identify genetic variants influencing age at onset (AAO) and examine gene×gender interactions for AAO in schizophrenia (SCZ) using a European-American sample (1,162 cases). Linear regression model in PLINK was used to test for associations with AAO while the GxE option was chosen to test for the influence of gene×gender interactions. The most significant association with AAO was observed with SNP rs7819815 (P=3.10×10-7) at 8q24.22. The next best signal was at 4q25 in COL25A1 gene (rs17039583, P=4.30×10-6) and the third region was at 4p16.1 (rs17407555, P=4.56×10-6, near RAF1P1, and rs4697924, P=1.23×10-5 within WDR1 gene). Conditional analysis on chromosome 4 indicated that 4p16.1 and 4q25 loci were independent. Furthermore, 2 SNPs (rs16834822 and rs16834824) at 1q43 in RYR2 showed strong associations in the female sample (P=2.10×10-6 and 2.33×10-6, respectively) and strong gene×gender interactions in influencing AAO (P=9.23×10-7 and 1.15×10-6, respectively) while the second best region showing gene×gender interaction was at 7q22.3 (rs179863, P=2.33×10-6). Using an independent sample of 1,068 cases, we could not replicate the associations for above top SNPs; however, we found nominal significance associations for their flanking SNPs (P<0.05). These findings provide evidence of several genetic variants influencing AAO of SCZ.

The MAPT gene has been shown to be associated with several neurodegenerative disorders, including forms of parkinsonism and Parkinson disease (PD), but the results reveal population differences. We investigated the association of 10 single-nucleotide polymorphisms (SNPs) in the region of MAPT on chromosome 17q21 with PD and age at onset, by using 443 discordant sib pairs in PD from a public dataset (Mayo-Perlegen LEAPS Collaboration). Association with PD was assessed by the FBAT using generalized estimating equations (FBAT-GEE), while the association with age at onset as a quantitative trait was evaluated using the FBAT-logrank statistic. Five SNPs were significantly associated with PD (P < 0.05) in an additive model, and 9 SNPs were associated with PD (P < 0.05) in dominant and recessive models. Interestingly, 8 PD-associated SNPs were also associated with age at onset of PD (P < 0.05) in dominant and recessive models. The SNP most significantly associated with PD and age at onset was rs17649641 (P = 0.015 and 0.021, respectively). Two-SNP haplotypes inferred from rs17563965 and rs17649641 also showed association with PD (P = 0.018) and age at onset (P = 0.026). These results provide further support for the role of MAPT in development of PD.