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PubMed1996

Subgrouping of bovine respiratory syncytial virus strains detected in lung tissue.

Bovine respiratory syncytial virus is an important respiratory pathogen in cattle. Recently, subgroups of BRSV have been identified, based on antigenic differences. However, little is known about subgroups of BRSV that circulate in the cattle population. Therefore, we determined the reactivity of monoclonal antibodies (mAbs), directed against the G, F, or P protein of BRSV, with lung tissue from 47 calves, that suffered from severe respiratory disease. Fourteen animals (30%) proved to be infected with BRSV, because they all reacted with mAbs against the P or F protein, as detected by fluorescent antibody tests. Monoclonal antibodies against the G protein were able to discriminate between the BRSV-positive specimens: 7 strains were identified as subgroup A strains, and 5 strains as subgroup AB, which is introduced as BRSV subgroup in this paper. Two strains could not be identified unambiguously. It is concluded that BRSV subgroup A and AB were associated with severe respiratory disease, and that strains belonging to either subgroup circulated concurrently in the cattle population in the Netherlands.

Animals↗
PubMed1998

A bovine respiratory syncytial virus strain with mutations in subgroup-specific antigenic domains of the G protein induces partial heterologous protection in cattle.

Bovine respiratory syncytial virus (BRSV) strains are tentatively divided in subgroups A, AB and B, based on antigenic differences of the G protein. A Dutch BRSV strain (Waiboerhoeve: WBH), could not be assigned to one of the subgroups, because the strain did not react with any monoclonal antibody against the G protein. We describe here that the WBH strain has accumulated critical mutations in subgroup-specific domains of the G protein gene, which also occur but then independently in G protein genes of BRSV subgroup A or B strains. Although the comparison of nucleotide residues 256-792 of the G gene of the WBH strain with those of subgroup A and B strains showed that the G gene of the WBH strain is different from that of BRSV subgroup A and B strains, the sequence divergence was not more than observed within the G genes of human respiratory syncytial virus subgroup A or B strains. The WBH strain did not induce severe disease after experimental infection of calves, and induced partial protection against a heterologous challenge. Despite the dissimilarity of the conserved central regions of the G protein of the WBH strain and that of the challenge strain, a secondary antibody response against this region was induced in WBH-infected calves after challenge. We conclude that complete BRSV virus can partially protect against a BRSV infection with a strain that contains an antigenic dissimilar G protein.

Amino Acid Sequence↗
PubMed2001

Do logistic regression and signal detection identify different subgroups at risk? Implications for the design of tailored interventions.

Identifying subgroups of high-risk individuals can lead to the development of tailored interventions for those subgroups. This study compared two multivariate statistical methods (logistic regression and signal detection) and evaluated their ability to identify subgroups at risk. The methods identified similar risk predictors and had similar predictive accuracy in exploratory and validation samples. However, the 2 methods did not classify individuals into the same subgroups. Within subgroups, logistic regression identified individuals that were homogeneous in outcome but heterogeneous in risk predictors. In contrast, signal detection identified individuals that were homogeneous in both outcome and risk predictors. Because of the ability to identify homogeneous subgroups, signal detection may be more useful than logistic regression for designing distinct tailored interventions for subgroups of high-risk individuals.

Adult↗
PubMed2003

A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma.

To classify cancer specimens by their gene expression profiles, we created a statistical method based on Bayes' rule that estimates the probability of membership in one of two cancer subgroups. We used this method to classify diffuse large B cell lymphoma (DLBCL) biopsy samples into two gene expression subgroups based on data obtained from spotted cDNA microarrays. The germinal center B cell-like (GCB) DLBCL subgroup expressed genes characteristic of normal germinal center B cells whereas the activated B cell-like (ABC) DLBCL subgroup expressed a subset of the genes that are characteristic of plasma cells, particularly those encoding endoplasmic reticulum and golgi proteins involved in secretion. We next used this predictor to discover these subgroups within a second set of DLBCL biopsies that had been profiled by using oligonucleotide microarrays [Shipp, M. A., et al. (2002) Nat. Med. 8, 68-74]. The GCB and ABC DLBCL subgroups identified in this data set had significantly different 5-yr survival rates after multiagent chemotherapy (62% vs. 26%; P < or = 0.0051), in accord with analyses of other DLBCL cohorts. These results demonstrate the ability of this gene expression-based predictor to classify DLBCLs into biologically and clinically distinct subgroups irrespective of the method used to measure gene expression.

B-Lymphocytes↗
PubMed1980

OK10, an avian acute leukemia virus of the MC 29 subgroup with a unique genetic structure.

The RNA of defective avian acute leukemia virus OK10 was isolated from a defective virus particle, released by OK10-transformed nonproducer avian fibroblasts, as a 60S complex consisting of 8.6-kilobase subunits. Oligonucleotide fingerprinting and RNA.cDNA hybridization identified two sets of sequences in OK10 RNA: group-specific sequences, which are related to all nondefective members of the avian tumor virus group, and a sequence closely related to the subgroup-specific sequences (mcv) of the myelocytomatosis virus (MC29) subgroup of avian acute leukemia viruses. Hence, OK10 is classified as a member of the MC29 subgroup of avian tumor viruses, in agreement with classification based on its oncogenic spectrum. The group-specific sequences of OK10 RNA include partial (Delta) pol and env genes, a c-region, and, unlike those of all other members of the MC29 subgroup, a complete gag gene. Oligonucleotide mapping revealed 5'-gag-Deltapol-mcv-Deltaenv-c-3' as the order of the subgroup-specific and group-specific elements of OK10 RNA. The genetic unit gag-Deltapol-mcv, measuring approximately 6.4 kilobases, codes for the nonstructural, presumably transforming, 200,000-dalton OK10-specific protein and also includes the gag gene coding for the internal virion proteins. Because gag is the only intact virion gene shared in addition to regulatory RNA sequences between OK10 and nondefective avian tumor viruses, it is concluded that the gag gene is sufficient for the formation of a defective virus particle. Comparisons among the RNAs and gene products of different viruses of the MC29 subgroup show that they share 5'-terminal gag-related and internal mcv sequences but differ from each other in intervening gag-, pol-, and mcv-related sequences. It follows that the probable transforming genes and their protein products have two essential domains, one consisting of conserved 5' gag-related and the other of 3' mcv-related sequence elements. In the light of this and previous knowledge we can now distinguish two designs among five different transforming onc genes of avian tumor viruses: onc genes with coding sequences unrelated to virion genes, like those of Rous sarcoma virus and avian myeloblastosis virus, and onc genes with coding sequences that are hybrids of virion genes and specific sequences, like those of the MC29 subgroup viruses, of avian erythroblastosis virus, and of Fujinami sarcoma virus.

Animals↗
PubMed1996

Neuropsychological subgroups of patients with Alzheimer's disease.

Neuropsychological data from 134 patients diagnosed with probable Alzheimer's disease (AD) were studied retrospectively to investigate whether subgroups of patients with qualitatively distinct profiles could be identified. Three empirical classification approaches were undertaken in this regard: Q-type factor analysis, hierarchical agglomerative cluster analysis, and iterative partitioning. Three subgroups were consistently identified across the clustering methods. Subgroup 1, the largest of the groups, was marked by moderate to severe anomia and constructional dyspraxia. Individuals in subgroup 2 displayed relatively spared visual-perceptual/constructional functioning but severe anomia. Members of subgroup 3 exhibited intact naming and nonverbal reasoning and moderate difficulty in copying overlapping figures. The three subgroups did not differ with respect to age, age at disease onset, duration of illness, educational level, or Hamilton depression rating. Detailed description of the data analyses are provided as a tutorial outlining subtyping methodology. Results are discussed in terms of the subgroup and the stage model approaches to the conceptualization of AD.

Aged↗
PubMed1996

Cognitive inhibition and schizophrenic symptom subgroups.

Subgroups of patients with schizophrenia were examined in relation to repetition and semantic priming under conditions in which the prime stimulus was to be either attended to or ignored (unattended). Attended conditions normally would produce positive priming; and unattended conditions, negative priming (i.e., a delayed reaction resulting from inhibition of target information previously presented as to-be-ignored stimulus). Cluster analysis of participants' ratings on the Schedule for the Assessment of Positive Symptoms and the Schedule for the Assessment of Negative Symptoms revealed three subgroups that aligned broadly previous research citing with disorganization, reality distortion, and psychomotor poverty syndromes, and a fourth episodic subgroup. The Disorganization, Reality Distortion, and Episodic subgroups were associated with reduced, indeed reversed, negative priming in unattended priming conditions, whereas the Psychomotor Poverty subgroup exhibited the usual negative priming effect. Participants in the former three subgroups also exhibited reversed positive priming for the repetition condition, while the Psychomotor Poverty group displayed the expected positive priming effect. These results indicate that weakening of inhibitory processes may underlie both the reality distortion and disorganization dimensions of positive schizophrenic symptomatology, including the latent presence of these symptoms. In contrast, negative symptoms contributing to the psychomotor poverty dimension of schizophrenia are not linked to reduced inhibition. The association of positive symptom subgroups with reversed positive priming suggested that, for these participants, stimuli and task differences have an impact on the preattentive activation of information underlying such priming. It is proposed that a "reduced inhibition" model of schizophrenic symptomatology may need to be extended to account for influences on preattentive processing.

Adolescent↗
PubMed2006

Outcomes in subgroups of hypertensive patients treated with regimens based on valsartan and amlodipine: An analysis of findings from the VALUE trial.

BACKGROUND: In the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial the primary outcome (cardiac morbidity and mortality) did not differ between valsartan and amlodipine-based treatment groups, although systolic blood pressure (SBP) and diastolic blood pressure reductions were significantly more pronounced with amlodipine. Stroke incidence was non-significantly, and myocardial infarction was significantly lower in the amlodipine-based regimen, whereas cardiac failure was non-significantly lower on valsartan. OBJECTIVES: The study protocol specified additional analyses of the primary endpoint according to: sex; age; race; geographical region; smoking status; type 2 diabetes; total cholesterol; left ventricular hypertrophy; proteinuria; serum creatinine; a history of coronary heart disease; a history of stroke or transient ischemic attack; and a history of peripheral artery disease. Additional subgroups were isolated systolic hypertension and classes of antihypertensive agents used immediately before randomization. METHODS: The 15,245 hypertensive patients participating in VALUE were divided into subgroups according to baseline characteristics. Treatment by subgroup interaction analyses were carried out by a Cox proportional hazard model. Within each subgroup, treatment effects were assessed by hazard ratios and 95% confidence intervals. RESULTS: For cardiac mortality and morbidity, the only significant subgroup by treatment interaction was of sex (P = 0.016), with the hazard ratio indicating a relative excess of cardiac events with valsartan treatment in women but not in men, but SBP differences in favour of amlodipine were distinctly greater in women. No other subgroup showed a significant difference in the composite cardiac outcome between valsartan and amlodipine-based treatments. For secondary endpoints, a sex-related significant interaction was found for heart failure (P < 0.0001), with men but not women having a lower incidence of heart failure with valsartan. CONCLUSION: As in the whole VALUE cohort, in no subgroup of patients were there differences in the incidence of the composite cardiac endpoint with valsartan and amlodipine-based treatments, despite a greater blood pressure decrease in the amlodipine group. The only exception was sex, in which the amlodipine-based regimen was more effective than valsartan in women, but not in men, whereas the valsartan regimen was more effective in preventing cardiac failure in men than in women.

Aged↗
PubMed1995

VP6 from porcine rotavirus strain CN86: amino acid sequence divergence with conservation of subgroup II specificity.

A porcine rotavirus strain, CN86, originally isolated from rotavirus-infected piglets in Argentina, has been shown to possess unique characteristics. It was the first animal strain described to be antigenically related to human serotype G1 and the standard counterpart of another porcine strain showing rearrangement of genome segment 11. Owing to these features, molecular characterization of this virus seemed relevant. The gene encoding the major inner capsid protein, VP6, was cloned and its nucleotide sequence was determined. Comparative analysis of the deduced amino acid sequence of CN86 VP6 with those representing the four different subgroups showed that it is more closely related to subgroup II human Wa and porcine Gottfried strains, albeit to a lesser extent than they are to each other. Despite exhibiting sequence divergence, CN86 VP6 has 12 out of the 14 residues expected to be conserved in strains bearing subgroup II specificity. Interestingly, CN86 VP6 shows a high degree of homology with VP6 of porcine strain YM rotavirus which, although being closely related to subgroup II strains, has been serologically characterized as subgroup I. Subgroup II reactivity of CN86 strain, predicted by sequence analysis, was confirmed by ELISA with subgroup-specific monoclonal antibodies. Taken together, our results provide evidence for the existence of a human-pig lineage for rotavirus gene 6.

Amino Acid Sequence↗
PubMed2004

Restriction in the repertoire of the immunoglobulin light chain subgroup in pathological cold agglutinins with anti-Pr specificity.

BACKGROUND AND OBJECTIVES: In cold agglutinin disease, monoclonal red blood cell autoantibodies, termed cold agglutinins, induce haemolysis in patients exposed to the cold. Commonly, these autoantibodies are directed against the developmentally regulated I/i blood groups. A second blood group system, the Pr system (located on glycophorins), is involved less frequently. Anti-Pr cold agglutinins recognize either alpha 2,3- or alpha 2,6-linked N-acetylneuraminic acid as the immunodominant group. Cold agglutinins of anti-I/i specificity show a remarkable restriction in their genomic repertoire of the immunoglobulin heavy and light-chain immunoglobulin-variable domain (i.e. exclusive use of VH4-34 in heavy chains). For anti-Pr cold agglutinins, preliminary data on the repertoire of the light-chain variable domain indicate a preference for the subgroup Vkappa IV. To elucidate restrictions in the light-chain variable-domain subgroup repertoire of anti-Pr cold agglutinins systematically, and to discuss these results in the context of their anti-Pr(1-3) subclassification and immunodominant sialic acid, light chains in 13 anti-Pr cold agglutinins were investigated. MATERIALS AND METHODS: The anti-Pr light chains were isolated using temperature-dependent absorption/elution techniques. Subsequently, they were subjected to N-terminal Edman degradation, and the light chain Vkappa subgroup was affiliated using the Kabat database. RESULTS: Five of 13 (38%) light chains belonged to Vkappa IV, five of 13 (38%) to Vkappa I and three of 13 (23%) to Vkappa III. Anti-Pr with Vkappa IV subgroup light chains exclusively recognized alpha 2,3-linked N-acetylneuraminic acid. CONCLUSIONS: Including data from the literature, the repertoire of the light-chain variable domain in pathological anti-Pr cold agglutinins exhibits a clear bias towards the use of the single germline gene-derived subgroup, Vkappa IV (eight of 17 or 47%). The association of Vkappa IV subgroup light chain-containing anti-Pr cold agglutinins with binding to alpha 2,3-, but not alpha 2,6-linked N-acetyneuraminic acid raises speculations about a possible role of subgroup-derived determinants in anti-Pr binding.

Adult↗
PubMed1984

Relative frequency of rotavirus subgroups 1 and 2 in Venezuelan children with gastroenteritis as assayed with monoclonal antibodies.

Monoclonal antibodies recently developed against the 42,000-dalton protein of two rotavirus strains were used in an enzyme-linked immunosorbent assay to determine the subgroup specificity of 252 specimens collected during a 45-month period from Venezuelan children with rotavirus gastroenteritis. Subgroup 2 rotavirus was shed by 85% of the children, whereas only 14% shed subgroup 1 rotavirus (one-half of them in a 3-month period). No differences were found in the occurrence of fever and vomiting between children shedding either rotavirus subgroup, but it appeared that the syndrome tended to last longer in children shedding subgroup 2 rotavirus. The monoclonal subgrouping enzyme-linked immunosorbent assay seemed to be more sensitive than an immune adherence hemagglutination assay, an enzyme-linked immunosorbent assay with polyclonal antibodies, or the electrophoretic analysis of RNA extracted from the virus. Overall, 99% of the specimens could be subgrouped by this assay.

Antibodies, Monoclonal↗
PubMed1988

Rotavirus epidemiology in Vellore, south India: group, subgroup, serotype, and electrophoretype.

Rotaviruses were detected in 163 of 916 (17.8%) specimens collected from children under 3 years of age with gastroenteritis in Vellore, South India, between August 1983 and July 1985. Rotaviruses were detected throughout the study period, with a peak prevalence in December to February (winter) and June to August (southwest monsoon season). A total of 117 rotavirus strains were tested for subgroup, serotype, and rotavirus double-stranded RNA electrophoretic migration pattern; 24.8% of the strains were subgroup I, 69.2% were subgroup II, and 6.0% were neither subgroup I nor subgroup II. Subgroup I and II strains were circulating concurrently throughout the study. Of the 117 rotavirus strains, 32 (27.4%) were serotyped; 15 were serotype 1, 3 were serotype 2, 2 were serotype 3, and 12 were serotype 4. Three serotypes were circulating concurrently during the periods of peak rotavirus prevalence. In 100 of the 117 strains (85.4%) an RNA pattern was detected. One unusual subgroup I group A rotavirus with a long migration pattern and four atypical rotaviruses serologically related to group C were also detected.

Child↗
PubMed1999

Rearrangements in the 5' nontranslated region and phylogenetic analyses of cucumber mosaic virus RNA 3 indicate radial evolution of three subgroups.

Cucumber mosaic virus (CMV) has been divided into two subgroups based on serological data, peptide mapping of the coat protein, nucleic acid hybridization, and nucleotide sequence similarity. Analyses of a number of recently isolated strains suggest a further division of the subgroup I strains. Alignment of the 5' nontranslated regions of RNA 3 for 26 strains of CMV suggests the division of CMV into subgroups IA, IB, and II and suggests that rearrangements, deletions, and insertions in this region may have been the precursors of the subsequent radiation of each subgroup. Phylogeny analyses of CMV using the coat protein open reading frame of 53 strains strongly support the further division of subgroup I into IA and IB. In addition, strains within each subgroup radiate from a single point of origin, indicating that they have evolved from a single common ancestor for each subgroup.

5' Untranslated Regions↗
PubMed2006

Comparison of warfarin versus aspirin for the prevention of recurrent stroke or death: subgroup analyses from the Warfarin-Aspirin Recurrent Stroke Study.

BACKGROUND AND PURPOSE: We performed a combination of prespecified and exploratory subgroup analyses to detect any treatment differences among various baseline subgroups in the Warfarin-Aspirin Recurrent Stroke Study (WARSS) cohort. METHODS: The WARSS compared the efficacy of adjusted-dose warfarin (INR 1.4-2.8) to aspirin (325 mg/day) for recurrent ischemic stroke or death within 2 years. The effect of warfarin and aspirin was compared among prespecified and exploratory subgroups with respect to sociodemographic and vascular risk factors, stroke subtype, arterial territory, and infarct topography. Hazard ratios and 95% confidence intervals comparing warfarin to aspirin were calculated using Cox proportional hazards models. Differences in hazard ratios were tested using interaction terms. RESULTS: No treatment differences between warfarin and aspirin were found across multiple prespecified subgroups. In a multivariate model, warfarin was associated with greater hazard among patients with moderate stroke severity (HR 1.63, 95% CI 1.005-2.64, p = 0.047) and a greater benefit among those with posterior circulation location without brainstem infarction (HR 0.54, 95% CI 0.33-0.88, p = 0.013). In post-hoc analyses of the cryptogenic subgroup, warfarin was associated with worse outcomes among patients with moderate stroke severity and better outcomes among those without baseline hypertension or with posterior circulation infarcts sparing the brainstem. CONCLUSIONS: In the WARSS, the majority of subgroup analyses showed no benefit of warfarin over aspirin. Warfarin benefit was limited to brainstem-sparing posterior circulation infarcts and select cryptogenic stroke subgroups. Pending future clinical trial evidence to the contrary, antiplatelets are recommended for survivors of noncardioembolic stroke.

Aged↗
PubMed2006

FDA and CPMP rulings on subgroup analyses.

The extent to which subgroup analyses should affect the interpretation and conclusions in a trial report is a contentious matter, and guidelines regarding this issue have been established by the US Food and Drug Administration (FDA) and the EU Committee for Proprietary Medicinal Products (CPMP). Subgroup analyses should be set out in the protocol of clinical trials. The treatment effect itself may vary within a subgroup or covariate. In some cases, interactions are anticipated or are of particular a priori interest; hence a subgroup analysis or a statistical model including interactions is part of the planned analysis. However, subgroup or interaction analyses are often merely exploratory and should be clearly identified as such in the protocol. When exploratory, these analyses should be interpreted cautiously. Market approval of a compound is based on the overall trial results, and, importantly, no drug has so far been approved or not-approved either in the US or in the EU on the basis of subgroup analysis. However, subgroup analysis can influence the approval or can even be required, and therefore it can influence the labelling of the Summary Characteristics of a Product. Two examples in heart failure are given by the Val-HeFT trial comparing valsartan to placebo and the MERIT-HF trial comparing metoprolol to placebo, from which some remarkable regulatory issues arose that were debated by the FDA and CPMP.

Clinical Trials as Topic↗
PubMed1970

Gamma G globulin subgroup composition of the glomerular deposits in human renal diseases.

36 renal biopsies from patients with nephritis were studied for glomerular localization of the heavy chain subgroups of immunoglobulin G (IgG or gammaG). The deposition pattern of these subgroups was selective and did not reflect the normal serum concentration of these proteins. gammaG2, which comprises 18% of normal serum gammaG, was the predominant or unique subgroup deposited in five cases of lupus nephritis and four biopsies with other forms of nephritis associated with granular gammaG deposits. gammaG3, which normally makes up only 8% of the serum gammaG, was the dominant subgroup seen in one biopsy of lobular glomerulonephritis. Patients with linear gammaG deposits generally had a selective absence of gammaG3 and often had large amounts of gammaG4 (normally 3% of the serum gammaG) deposited. The deposition of complement components C1q, C4, and C3 was variable. One biopsy had only gammaG2 and no complement components in the deposits and had no neutrophile leukocyte infiltration. This latter observation correlates well with the poor ability of gammaG2 to fix complement in vitro. Similarly, deposits containing large amounts of gammaG4, which does not fix complement, also tended to have less inflammatory infiltrate than deposits devoid of this subgroup. The selective deposition of monotypic or restricted gammaG subgroups on the glomerulus supports the likelihood that the gammaG represents antibody. The nature of the subgroup involved in the deposit may represent one variable in the determination of the inflammatory and morphological picture that evolves in human glomerulonephritis.

Anti-Glomerular Basement Membrane Disease↗
PubMed1970

Imbalances of gamma globulin subgroups and gene defects in patients with primary hypogammaglobulinemia.

Analysis of immunoglobulin classes, gammaG subgroups, and Gm genetic markers from 59 patients with various types of immune deficiencies was undertaken to assess the function of the several cistrons concerned with synthesis of gamma globulins. 13 patients including two sibling pairs were found to have gammaG subgroup imbalances. All of these patients had non sex-linked disease. 11 of the 13 had preponderance of the gammaG3 subgroup. In most instances of gammaG3 preponderance it was the Gm(b) type of gammaG3 that was selectively retained; the Gm(g) type, controlled by the allelic gene was markedly depressed but not absent in the cases where it could be studied. Other imbalances, either seen concomitantly with gammaG3 preponderance or independently, included predominance of the gammaG2 subgroup and selective absence of single gammaG subgroups.One family was encountered with probable structural gene abnormalities in the autosomal Gm loci. Both parents had different abnormal gene complexes detectable by absence of specific Gm markers and the propositus received both types from the parents. Similar gene complexes have been seen previously in rare instances through population screening but only in the heterozygous state and were not associated with clinically evident hypogammaglobulinemia. Of several other families of patients with subgroup imbalance, two were informative in that structural gene defects could be excluded. Studies on 22 first degree relatives of patients with subgroup imbalances indicated that the most common abnormality detected was in gammaA which was absent in 3 and markedly decreased in 2 others; other abnormalities included decreased levels of specific genetic types of gammaG globulin. It is concluded that gammaG subgroup imbalances are frequently found in non sex-linked immunoglobulin deficiency disorders and in some instances may be associated with family abnormalities suggesting either regulator or structural gene defects.

Adolescent↗
PubMed2003

Age at onset in bipolar I affective disorder: further evidence for three subgroups.

OBJECTIVE: Preliminary data suggested that there are three subgroups of bipolar affective disorder based on age at onset. The authors sought to replicate those findings and determine the cut-off age of each subgroup. METHOD: Admixture analysis was used to determine the best-fitting model for the observed ages at onset of 368 consecutively admitted patients. The results obtained were compared with those of the previously described model. The authors also investigated whether affected siblings are more likely to belong to the same theoretical age-at-onset subgroup as identified by admixture analysis. RESULTS: The existence of three subgroups defined by age at onset was confirmed. The mean ages estimated in this model were 17.4 years (SD=2.3), 25.1 years (SD=6.2), and 40.4 years (SD=11.3). Affected siblings were more likely to belong to the same theoretical subgroup. CONCLUSIONS: There are three age-at-onset subgroups of bipolar patients, and specific familial vulnerability factors might underlie each subgroup.

Adolescent↗