Onset Subgroup Research Articles

Four-Year Longitudinal Investigation of the Relationship Between Myopia and Retinal Shape in Chinese Children: The Anyang Childhood Eye Study

Purpose To investigate the longitudinal relationship between myopia and retinal shape in Chinese children. Methods A total of 2471 seven-year-old Chinese children were measured for axial length, anterior corneal radius of curvature, anterior chamber depth, lens thickness, central spherical equivalent, and peripheral refractions along the horizontal meridian (±15°, ±30°) under cycloplegia. Retinal shape was fitted using vertex radius of curvature, asphericity, and an offset. The areas under the horizontal retinal curve, the nasal side of areas under the horizontal retinal curve and the temporal side of areas under the horizontal retinal curve, were calculated. Children were tested annually for 5 years from year 0 to 4, with 1123 newly developed myopes divided into eight subgroups based on relative time to myopia onset. Results In follow-up subgroups, vertex radius of curvature showed positive correlations with central spherical equivalent from years 1 to 4. Smaller temporal side of areas under the horizontal retinal curve was associated with negative central spherical equivalent each year. Myopic shift (Δcentral spherical equivalent) was negatively correlated with baseline central spherical equivalent and with greater change in areas under the horizontal retinal curve from year 0 to 4. The absolute change in temporal side of areas under the horizontal retinal curve (0.39 ± 1.15 mm2) was significantly larger than the absolute change in nasal side of areas under the horizontal retinal curve (0.05 ± 1.11 mm2) over the 4 years. In myopia onset subgroups, temporal side of areas under the horizontal retinal curve was significantly smaller than nasal side of areas under the horizontal retinal curve. The ratio of temporal side of areas under the horizontal retinal curve/nasal side of areas under the horizontal retinal curve was closest to 1 in the year before myopia onset and decreased as myopia developed. Vertex radius of curvature, areas under the horizontal retinal curve, and temporal side of areas under the horizontal retinal curve decreased linearly as myopia progressed. Conclusion A progressive steepening of the horizontal posterior retina was associated with myopia progression. Myopia shift was negatively correlated with baseline central spherical equivalent and with greater change in posterior retinal shape. As myopia progressed, the horizontal retina shape displayed increased asymmetry.

Abstract P155: Elevated Long-Term Triglyceride-to-High Density Lipoprotein Cholesterol Ratio Variability From Childhood Is Linked To Higher Risk Of Early-Onset Hypertension: The Bogalusa Heart Study

Background: Early-onset hypertension is linked to higher risk of hypertensive organ damage compared to late-onset hypertension. Insulin resistance has been shown to be associated with greater risk of hypertension. Greater triglyceride-to-high density lipoprotein cholesterol ratio (TG/HDL-C), a surrogate marker of insulin resistance, has been linked to higher risk of hypertension. However, whether elevated long-term TG/HDL-C variability from childhood is associated with higher risk of early-onset hypertension is unclear. Methods: We studied 1271 participants of the Bogalusa Heart Study (age at enrollment: 9.9 ± 4.0 years, follow-up : 38.3 ± 3.8 years, age at last exam: 48.2 ± 5.2 years, 59.5% women, 34.4% Black participants) with ≥3 lipid measurements during follow-up. TG/HDL-C was obtained as TG (mg/dL) divided by HDL-C (mg/dL). Onset of hypertension was defined as blood pressure ≥140/90 mmHg or taking antihypertensive medications detected during follow-up. According to age at onset of hypertension, 4 subgroups were formed: <35 years (early-onset hypertension), 35-44 years, ≥45 years, and people without hypertension. Long-term TG/HDL-C variability from childhood was calculated as the deviation from age predicted values (DEV) and residual SD (RSD). DEV and RSD were obtained from the growth curves derived from linear mixed effect models, as the mean and SD of the residuals of observed and predicted TG/HDL-C levels. Associations between TG/HDL-C variability and hypertension onset subgroups were evaluated using multinomial logistic regression models. People who did not have hypertension during follow-up were the reference group. Interactions by race and sex were performed. Results: Among the 1271 participants, 585 (46.0%) had hypertension at last exam; among the 585, 124 (21.2%) had early-onset hypertension. For 1 SD increase in DEV and RSD of TG/HDL-C, the odds of early-onset hypertension increased by 30.6% (95% CI 1.06, 1.61) and 28.8% (95% CI 1.06,1.57), compared to people without hypertension, after adjusting for race, sex, diabetes, obesity, and smoking status, education, and TG/HDL-C at last exam. No significant associations were observed between DEV and RSD of TG/HDL-C and other hypertension onset subgroups. No significant interactions were found between both DEV and RSD and race and sex. Conclusions: Our results suggest that individuals with higher long-term variability in insulin resistance may be at a greater risk of having early-onset hypertension.

Abstract P372: Greater Long-Term Non-High Density Lipoprotein Cholesterol Variability From Childhood Is Associated With Higher Risk Of Early-Onset Hypertension: The Bogalusa Heart Study

Background: Early-onset hypertension is associated with greater risk of cardiovascular mortality and hypertension associated organ damage, compared to late-onset hypertension. Non-high-density lipoprotein cholesterol (non-HDL-C) is known to better predict future cardiovascular event risk, compared to low-density lipoprotein cholesterol. Whether higher long-term non-HDL-C variability from childhood is associated with higher risk of early-onset hypertension is unclear. Methods: We included 1271 participants of the Bogalusa Heart Study (age at enrollment: 9.9 ± 4.0 years, follow-up: 38.3 ± 3.8 years, age at last exam: 48.2 ± 5.2 years, 59.5 % women, 34.4 % Black participants) with ≥3 lipid measurements during follow-up. Non-HDL-C was calculated as total cholesterol (mg/dL) - HDL-C (mg/dL). Onset of hypertension was defined as having blood pressure ≥140/90 mmHg or using antihypertensive medications during follow-up. Participants were categorized according to age at hypertension onset (years) into 4 subgroups: <35 (early-onset), 35-44, ≥45, and people without hypertension. Long-term non-HDL-C variability was obtained from the deviation from age predicted values (DEV) and residual SD (RSD). DEV and RSD were calculated from growth curves derived from linear mixed effect models, as the mean and SD of the residuals of observed and predicted non-HDL-C levels. Associations between non-HDL-C variability and hypertension onset subgroups were analyzed using multinomial logistic regression models. Interactions by race and sex were performed. Results: For 1-SD increase in DEV and RSD of non-HDL-C, the odds of hypertension increased for all hypertension onset subgroups compared to people without hypertension, after adjusting for race, sex, diabetes, obesity, and smoking status, education, and non-HDL-C at last exam. The odds of hypertension was highest in the early-onset subgroup (Table). No significant interactions were found between both DEV and RSD and race and sex. Conclusions: Our findings suggest that individuals with higher long-term non-HDL-C variability may be at a greater risk of having early-onset hypertension.

Association between COMMD1 gene polymorphism rs11125908 and rheumatoid arthritis in the Cuban population.

To evaluate the association of the rs11125908 polymorphism in the COMMD1 gene in the Cuban population with rheumatoid arthritis (RA). In this case-control study, 161 RA patients and 150 control subjects were genotyped for rs11125908 by the allele-specific polymerase chain reaction method. DNA sequencing was used to verify the assignation of the polymorphism. The odds ratios (OR) and their 95% confidence interval were calculated by logistic regression to determine the associations between genotypes and RA using the SNPStats software. An association of the single nucleotide polymorphism with the disease was found in the overdominant model (p=0.025; OR=1.91) for the AG genotype. Our analyses revealed an association between rs11125908 and the subgroup of patients with swollen joints < median under the codominant model for AG (p=0.034; OR=2.30) and GG genotype (p=0.034; OR=0.82) and with the overdominant model (p=0.01; OR=2.38). The subgroup of patients with an age of onset lower than the mean and AG genotype showed an association in the overdominant model (p=0.027; OR=2.27). Disease activity score 28 with erythrocyte sedimentation rate and disease duration variables were not associated with the rs11125908 polymorphism. rs11125908 was associated with RA and with the number of swollen joints and age of onset subgroup analyses. We provide concepts for treatments for RA, based on pharmacological management of COMMD1 expression.

Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes after Acute Ischemic Stroke: An Analysis of the DAWN Trial.

We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. The association between every 1-h treatment delay with 90-day functional independence (modified Rankin Scale [mRS] score 0-2), symptomatic intracranial hemorrhage, and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs. witnessed vs. unwitnessed). Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0-2 1-hour delay OR 1.07; 95% CI 0.93-1.24; mRS 6 OR 0.84; 95% CI 0.65-1.03) or medical management (mRS 0-2 1-hour delay OR 0.98; 95% CI 0.80-1.14; mRS 6 1-hour delay OR 0.94; 95% CI 0.79-1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake-up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024;96:356-364.

Upper motor neuron signs in primary lateral sclerosis and hereditary spastic paraplegia.

The frequency and distribution of upper motor neuron (UMN) signs in primary lateral sclerosis (PLS) are unknown. We aimed to study the spectrum of UMN signs in PLS and compare it with hereditary spastic paraplegia (HSP). We retrospectively analyzed the frequency of different UMN signs, including hyperreflexia (limbs and jaw), limb and tongue spasticity, Babinski, and Hoffman signs, in PLS patients at first observation and compared this respect to onset region and symptom duration. We also compared PLS versus HSP patients. We included 34 PLS and 20 HSP patients, with a median symptom duration at first visit of 3.0 (interquartile range, IQR = 4.0) and 19.0 (IQR = 22.0) years, respectively. In PLS patients, hyperreflexia of upper (UL) (88.2%) and lower (LL) (91.2%) limbs, and LL spasticity (79.4%) were the most common findings. Spasticity of LL was significantly (p = .012) more frequent in LL-spinal onset subgroup, tongue spasticity in bulbar-onset subgroup (p = .021), and Hoffman sign in UL-spinal onset subgroup (p = .024). The PLS subgroup with shorter disease duration had a higher frequency of abnormal jaw jerk reflex (p = .037). Compared with HSP, PLS patients had a higher frequency of UL hyperreflexia (88.2% vs. 42.1%, p < .001) and UL spasticity (44.1% vs. 0.0%, p < .001). Asymmetric distribution of UMN signs was present in PLS and not in HSP. In PLS, UL UMN signs are nearly always present and UMN sign distribution appears to be associated with onset region. At first observation, bulbar involvement, asymmetrical distribution of UMN signs and UL spasticity may indicate PLS versus HSP.

Abstract WMP92: Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes After Acute Ischemic Stroke: An Analysis of the DAWN Trial

Introduction: In the early window, time to treatment with endovascular thrombectomy (EVT) is inversely associated with favorable clinical outcomes but this remains unclear in the extended window. We aimed to assess the impact of time to EVT on clinical outcomes in the DAWN trial. Methods: The association between every 1-hour treatment delay with 90-day functional independence (modified Rankin Scale [mRS] 0-2), symptomatic intracranial hemorrhage (SICH), and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs witnessed vs unwitnessed) considering both time from last seen well (TLSW) and time from symptoms first observed (TSFO). Results: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6-12-hour and 12-24-hour time window, respectively. Considering all three modes of onset together, there was no statistically significant association between TLSW to randomization with either functional independence or mortality at 90 days in either the EVT (mRS0-2 OR 1-hour-delay:1.07;95%CI[0.93-1.24]; mRS6 OR:0.84;95%CI[0.65-1.03]) or medical management (mRS0-2 OR1-hour-delay:0.98;95%CI[0.80-1.14]; mRS6 OR 1-hour-delay:0.94;95%CI[0.79-1.09]) groups. Moreover, there was no significant interaction between treatment effect and time (p=0.439 and p=0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between TLSW to successful reperfusion (mTICI≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p=0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p=0.018) negative slope in wake-up patients. There was no association between treatment times and SICH. Comparable analysis using TSFO yielded similar results. Conclusion: In extended window patients, the association between time to treatment and clinical outcomes seems to be primarily driven by successfully perfused patients with wake-up rather than witnessed or unwitnessed strokes suggesting that wake-up strokes do not behave as “slow-progressors”.

Electrodiagnostic findings in amyotrophic lateral sclerosis: Variation with region of onset and utility of thoracic paraspinal muscle examination.

Limited data exist regarding variation of electrodiagnostic (EDX) findings in amyotrophic lateral sclerosis (ALS) patients with different onset regions and specificity of thoracic paraspinal muscle (TPSP) examination for confirming a diagnosis of ALS. We aimed to demonstrate the variation of EDX features and characterize the utility of TPSP muscle examination in the electrodiagnosis of ALS. This is a retrospective study of a large cohort of ALS patients who had a comprehensive EDX evaluation. The study included 448 patients; all fulfilled the Gold Coast criteria for ALS. The average age at the time of EDX study was 64 years, and 41.1% were women. The onset region was identified as follows: bulbar (N = 149), cervical (N = 127), lumbosacral (N = 162), and other (N = 10). In contrast to limb onset, bulbar-onset patients more frequently demonstrated a pattern of normal or near normal needle electromyography (EMG) (p < .0001) and less frequently had abnormalities on EMG of TPSP (p = .002). Clinical or EDX diagnosis of sensory polyneuropathy was present in 12.6% patients, more frequently in the lumbosacral onset subgroup (p < .03). EMG showed active denervation in 9.6% and chronic denervation in 59% of craniobulbar muscles examined, without observed difference among different onset regions. TPSP showed higher frequencies of active and chronic denervation in ALS than a group of patients with non-ALS neuromuscular disorders. EDX features may differ among ALS patients of different onset regions. TPSP EMG is highly useful in differentiating ALS from non-ALS neuromuscular disorders while the yield of craniobulbar muscles, especially for active denervation, is low.

Excessive weight gain onset-age and risk of developing diabetes mellitus: a large, prospective Chinese cohort study.

Excessive weight gain and obesity are widely accepted as risk factors for diabetes mellitus, and the age at which obesity onsets may be related to the development of cardiovascular diseases and certain cancers. Here, we aimed to investigate associations between the onset-age of overweight/obesity and risk of developing diabetes mellitus in China. 42,144 people with the normal weight range and without diabetes at baseline, were enrolled from the Kailuan cohort which began on the 1st June 2006. All participants were followed-up, biennially, until 31st December 2017. During follow-up, 11,220 participants had become overweight/obese. For each case, one normal-weight control was matched according to age ( ± 1 year) and sex. Our final analysis included 10,858 case-control pairs. An age-scaled Cox model was implemented to estimate hazard ratios (HR) with corresponding 95% confidence intervals (CI) for diabetes mellitus incidence across age-groups. At a median follow-up of 5.46 years, 1,403 cases of diabetes mellitus were identified. After multivariate adjustments, age-scaled Cox modelling suggested that risk gradually attenuated with every 10 year increase in age of onset of overweight/obesity. Diabetes mellitus adjusted HRs (aHRs) for new-onset overweight/obesity at <45years, 45-54 years, and 55-64 years were 1.47 (95%CI, 1.12-1.93), 1.38 (95%CI, 1.13-1.68), 1.32 (95%CI, 1.09-1.59), respectively. However, new-onset of overweight/obesity at ≥65 years did not relate to diabetes mellitus (aHR, 1.20; 95%CI, 0.92-1.57). This trend was not observed in women or the new-onset obesity subgroup but was evident in men and the new overweight onset subgroup. Participants with early onset of excessive weight gain issues are at considerably higher risk of developing diabetes mellitus compared to those who maintain a normal weight.

Relevance between age of onset and hospitalization characteristics of Major Depressive Disorders: A 16 years retrospective cohort study

BackgroundAge of onset (AOO) influences the prognosis of many diseases and even serves as potential driver. But in Major Depressive Disorder, there is no consensus regarding the effect of AOO on the course. MethodsIn this study, a total of 38,671 inpatients were surveyed over 16 years, and 6113 inpatients were eventually included in the statistical analysis after applying rigorous data criteria. Inpatients were divided into four AOO subgroups: adolescent onset, early adult onset, middle adult onset, and late adult onset. ResultsIn the subset of first hospitalization (n = 4884), the differences in the length of stay between several AOO subgroups were statistically significant (F = 56.852, df1 = 3, df2 = 4880, P < 0.001, ω2 = 0.033). Similarly, this difference was also significant in the subset of relapse hospitalization (n = 1229, F = 5.985, df1 = 3, df2 = 1225, P < 0.001, ω2 = 0.012). The Bonferroni post hoc test suggested a longer length of stay in the adolescent onset group (P < 0.001). Besides, in the adolescent onset subgroup, the proportion with 2 or more relapses hospitalization within one year was higher than those without relapses (6.7 % Vs 2.7 %, χ2 = 12.685, df = 6, P < 0.001). Logistic regression suggests that patients with adolescent onset are at higher risk for 2 or more relapses hospitalization within one year (B = 0.881, OR = 2.41, 95 % CI 1.37–4.23, P = 0.002). LimitationsRetrospective design may have recall bias. ConclusionsThis is the first large sample size study to examine age at onset and risk of relapse at the individual level in a Chinese population. Our study found that adolescent onset is more susceptible to the chronicity of MDD. These findings will contribute to the accurate typing of MDD, as well as customized individualized prevention and treatment options.

Patterns of allergic sensitization in adults with severe asthma: the ATLAS non-interventional study

Objectives Severe asthma is heterogeneous, with childhood-onset asthma believed more likely to be allergic, whereas adult-onset asthma is considered typically non-allergic. However, the allergic diagnosis is typically by exclusion: if patients do not react to an allergen panel, which is not standardized and often limited to few allergens, they are considered non-allergic. The overall aim of the ATLAS study was to characterize the sensitization to allergens in severe asthma (independent of phenotype). Methods Single-visit, cross-sectional, non-interventional study in adults with severe asthma. Analyses were conducted for total and specific immunoglobulin E against 53 allergens, overall and in subgroups, including age at asthma onset (<20 [childhood-onset] and >40 years of age). Results Among 1010 recruited patients, 28.4% reported childhood-onset asthma and 33.6% onset >40 years of age. After excluding patients receiving omalizumab/anti-IL5 therapy, 27.6% were not sensitized to any tested allergens, whereas 19.1% were sensitized to >10 allergens. All allergens triggered sensitization in some patients. Baseline characteristics in the two onset subgroups were similar; 23.2% with childhood-onset asthma were not sensitized to any allergen, compared to 32.0% with onset >40 years of age. Conclusion When a broad panel of allergens is used for sensitization testing, as many as three quarters of patients with severe asthma display sensitivity to at least one allergen, with substantial overlaps in all characteristics between the two age-at-onset subgroups. All of the tested allergens triggered a response in at least some patients, emphasizing the importance of including a broad range of allergens in any testing panel.

A biomarker-validated time scale in years of disease progression has identified early- and late-onset subgroups in sporadic Alzheimer’s disease

BackgroundIt is possible to calculate the number of years to the expected clinical onset (YECO) of autosomal-dominant Alzheimer’s disease (adAD). A similar time scale is lacking for sporadic Alzheimer’s disease (sAD). The purpose was to design and validate a time scale in YECO for patients with sAD in relation to CSF and PET biomarkers.MethodsPatients diagnosed with Alzheimer’s disease (AD, n = 48) or mild cognitive impairment (MCI, n = 46) participated in the study. They underwent a standardized clinical examination at the Memory clinic, Karolinska University Hospital, Stockholm, Sweden, which included present and previous medical history, laboratory screening, cognitive assessment, CSF biomarkers (Aβ42, total-tau, and p-tau), and an MRI of the brain. They were also assessed with two PET tracers, 11C-Pittsburgh compound B and 18F-fluorodeoxyglucose. Assuming concordance of cognitive decline in sAD and adAD, YECO for these patients was calculated using equations for the relationship between cognitive performance, YECO, and years of education in adAD (Almkvist et al. J Int Neuropsychol Soc 23:195-203, 2017).ResultsThe mean current point of disease progression was 3.2 years after the estimated clinical onset in patients with sAD and 3.4 years prior to the estimated clinical onset in patients with MCI, as indicated by the median YECO from five cognitive tests. The associations between YECO and biomarkers were significant, while those between chronological age and biomarkers were nonsignificant. The estimated disease onset (chronological age minus YECO) followed a bimodal distribution with frequency maxima before (early-onset) and after (late-onset) 65 years of age. The early- and late-onset subgroups differed significantly in biomarkers and cognition, but after control for YECO, this difference disappeared for all except the APOE e4 gene (more frequent in early- than in late-onset).ConclusionsA novel time scale in years of disease progression based on cognition was designed and validated in patients with AD using CSF and PET biomarkers. Two early- and late-disease onset subgroups were identified differing with respect to APOE e4.

Identification of an inflammation-associated psychosis onset subgroup by applying unsupervised machine learning to whole-blood expression levels of immune gene transcripts

Identification of an inflammation-associated psychosis onset subgroup by applying unsupervised machine learning to whole-blood expression levels of immune gene transcripts

A machine learning approach on whole blood immunomarkers to identify an inflammation associated psychosis onset subgroups

AbstractPsychosis onset is a transdiagnostic event that leads to a range of psychiatric disorders, which are currently diagnosed through clinical observation. Since several years, the role of immune system in the pathophysiology of psychosis has been well-recognized, showing differences from the onset to chronic phases. In this lecture, I will show the results of our recent study that tested the hypothesis of the existence of subgroups of first-episode psychosis (FEP) patients identified by distinct peripheral immunomarkers’ profiles, possibly underpinning a subgroup-specific immunopathogenesis. More in detail, I will show the results obtained by the unsupervised machine learning model that we applied to the set of 12 peripheral blood immune gene transcripts, which we recently demonstrated to classify with high accuracy a cohort of FEP patients and HC. Also, I will report the results obtained by performing post-hoc univariate analyses using selective clinical, cognitive, and brain structural phenotypes of FEP patients and HC belonging to each subgroup identified by the computational model. I will extensively discuss two key clusters identified and validated by our model: 1) a FEP cluster characterized by the high expression of inflammatory and immune-activating genes; 2) a cluster consisting of an equal number of FEP and HC subjects, which did not show a relative over or under expression of any immune marker (balanced subgroup). Therefore, in this lecture I will emphasize that our study has been the first to demonstrate the existence of a psychosis onset subgroup identified by a peculiar multivariate pattern of immunomarkers, independently of clinical features or categorical diagnosis. This is paramount as if validated in independent samples, our clustering model could enable the sample selection in clinical trials aiming to test the efficacy of novel immunomodulant or anti-inflammatory therapies tailored to the specific inflammatory subgroup of psychotic patients.Disclosure of InterestNone Declared

A machine learning approach on whole blood immunomarkers to identify an inflammation-associated psychosis onset subgroup.

Psychosis onset is a transdiagnostic event that leads to a range of psychiatric disorders, which are currently diagnosed through clinical observation. The integration of multimodal biological data could reveal different subtypes of psychosis onset to target for the personalization of care. In this study, we tested the existence of subgroups of patients affected by first-episode psychosis (FEP) with a possible immunopathogenic basis. To do this, we designed a data-driven unsupervised machine learning model to cluster a sample of 127 FEP patients and 117 healthy controls (HC), based on the peripheral blood expression levels of 12 psychosis-related immune gene transcripts. To validate the model, we applied a resampling strategy based on the half-splitting of the total sample with random allocation of the cases. Further, we performed a post-hoc univariate analysis to verify the clinical, cognitive, and structural brain correlates of the subgroups identified. The model identified and validated two distinct clusters: 1) a FEP cluster characterized by the high expression of inflammatory and immune-activating genes (IL1B, CCR7, IL12A and CXCR3); 2) a cluster consisting of an equal number of FEP and HC subjects, which did not show a relative over or under expression of any immune marker (balanced subgroup). None of the subgroups was related to specific symptoms dimensions or longitudinal diagnosis of affective vs non-affective psychosis. FEP patients included in the balanced immune subgroup showed a thinning of the left supramarginal and superiorfrontal cortex (FDR-adjusted p-values < 0.05). Our results demonstrated the existence of a FEP patients' subgroup identified by a multivariate pattern of immunomarkers involved in inflammatory activation. This evidence may pave the way to sample stratification in clinical studies aiming to develop diagnostic tools and therapies targeting specific immunopathogenic pathways of psychosis.

Prevalence of suicide attempts and correlates among first-episode and untreated major depressive disorder patients with comorbid dyslipidemia of different ages of onset in a Chinese Han population: a large cross-sectional study

BackgroundPatients with dyslipidemia are at increased risk for suicide, especially those with major depressive disorder (MDD). Few studies have investigated the independent effects of suicide attempts on comorbid dyslipidemia in patients with MDD. Moreover, there are no comparisons of differences in factors associated with suicide attempts among patients with MDD with dyslipidemia at different ages of onset. The aim of this study was to investigate the prevalence of suicide attempts and associated variables in first episode and untreated patients with MDD with comorbid dyslipidemia at different ages of onset.MethodsWe recruited 1718 patients with first-episode untreated MDD in this study. Demographical and clinical data were collected, and lipid profiles, thyroid function, and blood glucose levels were measured. The Hamilton Depression Scale 17 (HAMD-17), Hamilton Anxiety Scale (HAMA), Clinical Global Impression Severity Scale (CGI), and Positive and Negative Syndrome Scale (PANSS) positive subscale were assessed for depression, anxiety and illness severity, as well as psychotic symptoms, respectively.ResultsThe percentage of patients with MDD with comorbid dyslipidemia was 61% (1048/1718). Among patients with MDD with comorbid dyslipidemia, the incidence of suicide attempts was 22.2% (170/765) for early adulthood onset and 26.5% (75/283) for mid-adulthood onset. Independent factors associated with suicide attempts in early adulthood onset patients with MDD with dyslipidemia were as follows: HAMA score (B = 0.328, P < 0.0001, OR = 1.388), Suspicion /persecution (B = -0.554, P = 0.006, OR = 0.575), CGI (B = 0.878, P < 0.0001, OR = 2.406), systolic blood pressure (B = 0.048, P = 0.004, OR = 1.049), hallucinatory behavior (B = 0.334, P = 0.025, OR = 1.397), and TPOAb (B = 0.003, p < 0.0001, OR = 1.003). Independent factors associated with suicide attempts in mid-adulthood onset patients with MDD with comorbid dyslipidemia were as follows: HAMA score (B = 0.182, P < 0.0001, OR = 1.200), CGI (B = 1.022, P < 0.0001, OR = 2.778), and TPOAb (B = 0.002, P = 0.009, OR = 1.002).ConclusionOur findings suggest an elevated risk of suicide attempts in patients with MDD with comorbid dyslipidemia. The incidence of suicide attempts was similar in the early- and mid-adulthood onset subgroups among patients with MDD with dyslipidemia, but the factors associated with suicide attempts were different in these two subgroups.

1066-P: Association of T2D Subgroups with MCI/Dementia

Objectives: To assess whether T2D subgroups are associated with MCI/dementia, and whether the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) differs in prevention of MCI/dementia by T2D subgroup. Methods: Included 3760 participants (73% of original cohort after death and attrition) with T2D and overweight/obesity randomized to years of ILI or diabetes support and education. We characterized T2D subgroups at randomization using k-means clustering methods and data on age of T2D diagnosis, BMI, waist circumference, and HbA1c. We estimated marginal probabilities for prevalent MCI/dementia 10-13 years post-randomization by T2D subgroup with adjustment for cohort attrition and covariates (Table) and assessed for differential effects of ILI on MCI/dementia by T2D subgroup. Results: T2D subgroups were characterized by (1) older and (2) younger age at T2D onset, (3) high HbA1c, and (4) severe obesity (Table) . Prevalence of MCI/dementia was 8.4% and differed by T2D subgroup. After adjustment, rate of MCI/dementia was highest for the severe obesity and lowest for the younger onset subgroups. There were no differences in MCI/dementia rates between intervention arms for any T2D subgroup (interaction p-value=0.84) . Conclusions: T2D subgroups differ in rate of MCI/dementia, with the highest rate for a subgroup of participants with severe obesity. Lifestyle intervention did not modify rate of MCI/dementia in any T2D subgroup. Disclosure M.Bancks: None. J.Lovato: None. A.Balasubramanyam: None. M.Coday: None. K.C.Johnson: None. M.Munshi: Consultant; Sanofi. C.J.Rebello: None. L.E.Wagenknecht: None. M.Espeland: None.

Factors That Influence Susceptibility Vessel Sign in Patients With Acute Stroke Referred for Mechanical Thrombectomy.

Background and PurposeThe presence of a Susceptibility Vessel Sign (SVS) in the acute phase of proximal occlusion ischemic stroke indicates the presence of deoxyhemoglobin in the thrombus. Thrombi composition changes over time. The aim of this study was to investigate whether the absence of SVS is associated with a shorter symptom onset to imaging time.MethodsWe retrospectively analyzed all patients referred for mechanical thrombectomy at Besançon University Hospital between 1 January 2015 and 31 December 2020 for whom readable T2*-weighted imaging was available. We compared patient characteristics according to the presence or absence of an SVS. We also studied the subgroup for whom the exact symptom onset time was known. We performed a univariate statistical analysis, then a multivariate analysis on the variables that were statistically significant in the univariate analysis.ResultsOf the 389 patients included, 309 (79.4%) were SVS+. We found no significant relationship between SVS– and the time between symptom onset and imaging in the whole cohort. In the multivariate analysis, SVS– was associated with anticoagulant treatment (p < 0.01), and SVS+ with age (p = 0.023) and carotid terminus occlusion (p = 0.042). In the known symptom onset subgroup, SVS– was significantly associated with a shorter symptom onset -imaging time (p < 0.001), and this was confirmed in the multivariate analysis (p = 0.011; OR 0.911; 95% CI [0.844; 0.972]).ConclusionIn the acute phase of proximal occlusion ischemic stroke, absence of SVS was associated with a shorter symptom onset–imaging time for patients with a known symptom onset time.

Earlier age of onset is associated with a pro-inflammatory state in major depressive disorder

Major depressive disorder (MDD) is a common condition that affects the general population over a wide range of ages, regardless of gender and social background. Early-onset of MDD in adulthood, between ages of 18 and 30 years, is associated with worse outcomes and increased years of disability. Stress load and physical health have been associated with age of onset in MDD. We aim to investigate whether early onset MDD might be associated with changes in systemic inflammatory markers. We examined levels of following cytokines: IL-1β, IL-6, IL-10 and TNFα in 234 patients with MDD. Higher serum levels of TNFα and IL-1β are associated with the early onset of the disorder in patients with MDD. IL-6 levels were also higher in the early onset group and IL-10 levels were higher in the late onset group, but with no significant difference. Changes in the anti-inflammatory/pro-inflammatory balance have been described in mood disorders and may be implicated in its severity and pattern of progression. Our findings reinforce that higher serum levels of IL-1β and TNFα may be associated with the earlier onset subgroup of MDD patients. Future research that target inflammatory markers of immune modulation may be, key in the search for novel preventative therapeutics.

Antiplatelet regimens after ischemic stroke or transient ischemic attack: a systematic review and updated network meta-analysis.

BackgroundIt is still uncertain which antiplatelet regimen had the greatest net clinical benefit in patients who have suffered a transient ischemic attack or non-cardioembolic ischemic stroke, and it is necessary to choose the optimal regimen according to the clinical situation.MethodsWe utilized 3 databases of Medline, Embase, and the Cochrane Central Register of Controlled Trials to find randomized controlled trials that met our criteria, and performed network meta-analyses in recurrent stroke, composite outcomes, major bleeding events, recurrent ischemic stroke, and all bleeding events. Three-dimensional clustered rank plots were used to obtain the net clinical benefit. Subgroup analyses were performed according to the symptom-onset-to-treatment time (<72 and >72 h), stroke subtypes (large artery atherosclerosis and small vessel occlusion), and dual antiplatelet agent treatment duration.ResultsA total of 69 trials were enrolled. Cilostazol was associated with a lower risk of recurrent stroke, major bleeding events, composite outcomes, recurrent ischemic stroke, and all bleeding events compared to low to medium dose aspirin. The three-dimensional rank plot showed that cilostazol had the highest net clinical benefit. The combination of aspirin plus clopidogrel had greater efficacy in the <72 h after stroke onset and large artery atherosclerosis subgroups, and when it was restricted to1 month of use major bleeding risk was not higher than aspirin. The combination of aspirin plus dipyridamole had greater efficacy and safety comparable to aspirin in terms of small vessel occlusion.ConclusionsThe efficacy and safety profiles among antiplatelet regimens may differ according to clinical situation, although cilostazol, aspirin plus clopidogrel, and aspirin plus dipyridamole may be considered as preferable options.