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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
We aimed to evaluate the prevalence, clinical determinants, and consequences (falls and hospitalization) of frailty in older adults with mental illness.
Retrospective clinical cohort study.
We collected the data in a specialized psychogeriatric ward, in Boston, USA, between July 2018 and June 2019.
Two hundred and fourty-four inpatients aged 65 years old and over.
Psychiatric diagnosis was based on a multi-professional consensus meeting according to DSM-5 criteria. Frailty was assessed according to two common instruments, that is, the FRAIL questionnaire and the deficit accumulation model (aka Frailty Index [FI]). Multiple linear regression analyses were conducted to evaluate the association between frailty and sample demographics (age, female sex, and non-Caucasian ethnicity) and clinical characteristics (dementia, number of clinical diseases, current infection, number of psychotropic, and non-psychotropic medications in use). Multiple regression between frailty assessments and either falls or number of hospital admissions in the last 6 and 12 months, respectively, were analyzed and adjusted for covariates.
Prevalence of frailty was high, that is, 83.6% according to the FI and 55.3% according to the FRAIL questionnaire. Age, the number of clinical (somatic) diseases, and the number of non-psychotropic medications were independently associated with frailty identified by the FRAIL. Dementia, current infection, the number of clinical (somatic) diseases, and the number of non-psychotropic medications were independently associated with frailty according to the FI. Falls were significantly associated with both frailty instruments. However, we found only a significant association for the number of hospital admissions with the FI.
Frailty is highly prevalent among geriatric psychiatry inpatients. The FRAIL questionnaire and the FI may capture different forms of frailty dimensions, being the former probably more associated with the phenotype model and the latter more associated with multimorbidity.
To compare and validate neurocognitive tests in the Harmonized Cognitive Assessment Protocol (HCAP) for the China Health and Retirement Longitudinal Study (CHARLS), and to identify appropriate tests to be administered in future waves of CHARLS.
We recruited 825 individuals from the CHARLS sample and 766 subjects from hospitals in six provinces and cities in China. All participants were administered the HCAP-neurocognitive tests, and their informants were interviewed regarding the respondents’ functional status. Trained clinicians administered the Clinical Dementia Rating scale (CDR) to assess the respondents’ cognitive status independently.
The testing protocol took an average of 58 minutes to complete. Refusal rates for tests of general cognition, episodic memory, and language were less than 10%. All neurocognitive test scores significantly correlated with the CDR global score (correlation coefficients ranged from 0.139 to 0.641). The Mini-Mental State Examination (MMSE), the Health and Retirement Study (HRS) - telephone interview for cognitive status (TICS), community screening instrument for dementia (CSI-D) for respondent, episodic memory and language tests each accounted for more than 20% of the variance in global CDR score (p < 0.001) in bivariate tests. In the CHARLS subsample, age and education were associated with neuropsychological performance across most cognitive domains, and with functional status.
A brief set of the CHARLS-HCAP neurocognitive tests are feasible and valid to be used in the CHARLS sample and hospital samples. It could be applied in the future waves of the CHARLS study, and it allows estimating the prevalence of dementia in China through the population-based CHARLS.
We present ALMA [CII] line and far-infrared (FIR) continuum observations of seven z > 6 low-luminosity quasars (M1450 > −25 mag) discovered by our on-going Subaru Hyper Suprime-Cam survey. The [CII] line was detected in all targets with luminosities of ∼(2−10) × 108 L⊙, about one order of magnitude smaller than optically luminous quasars. Also found was a wide scatter of FIR continuum luminosity, ranging from LFIR < 1011L⊙ to ∼2 × 1012L⊙. With the [CII]-based dynamical mass, we suggest that a significant fraction of low-luminosity quasars are located on or even below the local Magorrian relation, particularly at the massive end of the galaxy mass distribution. This is a clear contrast to the previous finding that luminous quasars tend to have overmassive black holes relative to the relation. Our result is expected to show a less-biased nature of the early co-evolution of black holes and their host galaxies.
The Conclusion reviews the theoretical approaches that run through the volume, and reviews the essays through an historian’s eyes, looking for ways in which we might think about the global and deep time dimensions of the state simultaneously. We propose that the premodern state was “enchanted,” composite/tributary, and patrimonial. It was imbued with sacred authority, it grew by a federated system of encapsulating tribute polities, and it was almost always patrimonial in form. While the classical, western European transition to modernity involved a reversal of all of these qualities toward disenchantment, unified sovereignty, and bureaucratic governance, this transition was complicated by the power dynamics of empire-building in the sixteenth to nineteenth centuries. In particular, the United States – formed in direct tension with the tribute empire model, constructed a modern state form with a very complex multi-tiered sovereignty.
The Introduction presents the volume’s global and historical problematics, and reviews key approaches in state theory, focusing on the development of and tensions between Weberian/institutionalist approaches and the variety of “cultural” approaches that descend through various pathways from the work of Antonio Gramsci on hegemony. Focusing on the engagement with these two broad traditions among historians of medieval, early modern, and modern state formations, we discuss the recent engagement of archaeologists with both of these approaches. We explore the possibility of hybrid Weberian-culturalist models, and close the Introduction with discussion of the theoretical approaches of the twenty-one substantive essays in the volume.