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1.
Artigo em Inglês | MEDLINE | ID: mdl-31463563

RESUMO

Aim of the study was to examine the course of schizophrenia patients within 2 years after discharge. Within a multicenter study of the German Competence Network on Schizophrenia, patients suffering from a schizophrenia spectrum disorder were examined regarding their psychopathological improvement, tolerability, and the treatment regime applied during hospitalization and a 2-year follow-up period. Response, remission, the level of everyday functioning, and relapse were furthermore evaluated during the follow-up period using established definitions for these outcome domains. The psychopharmacological treatment was specifically evaluated in terms of a potential association with relapse. 149 patients were available for analysis, with 65% of the patients being in response, 52% in symptomatic remission, and 64% having a satisfiable everyday functioning 2 years after their discharge from hospital. Despite these favorable outcome rates, 63% of the patients suffered from a relapse within the 2-year follow-up period with 86% of these patients being rehospitalized. Discharge non-responder and non-remitter were twice as likely to relapse during follow-up. A significant decrease of side-effects was observed with negligible rates of extrapyramidal side-effects, sedation, and weight gain during follow-up. Patients receiving treatment with atypical antipsychotics were found to have the lowest risk to relapse (p < 0.0001). The results highlight the natural and unsteady course of schizophrenia in most patients underlining the need to develop more specific treatment strategies ensuring ongoing stability and preventing relapse.

2.
Hum Mutat ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464095

RESUMO

Rare coding variants in the triggering receptor expressed on myeloid cells-2 (TREM2) gene have been associated with Alzheimer disease (AD) and homozygous TREM2 loss-of-function variants have been reported in families with monogenic frontotemporal-like dementia with/without bone abnormalities. In a whole-exome sequencing study of a family with probable AD-type dementia without pathogenic variants in known autosomal dominant dementia disease genes and negative for the apolipoprotein E (APOE) ε4 allele, we identified an extremely rare TREM2 coding variant, i.e. a glycine-to-tryptophan substitution at amino acid position 145 (NM_018965.3:c.433G>T/p.(Gly145Trp)). This alteration is found in only 1 of 251,150 control alleles in gnomAD. It was present in both severely affected as well as in another putatively affected and one 61 years old as yet unaffected family member suggesting incomplete penetrance and/or a variable age of onset. Gly145 maps to an intrinsically disordered region (IDR) of TREM2 between the immunoglobulin-like and transmembrane domain. Subsequent cellular studies showed that the variant led to IDR shortening and structural changes of the mutant protein resulting in an impairment of cellular responses upon receptor activation. Our results, suggest that a p.(Gly145Trp)-induced structural disturbance and functional impairment of TREM2 may contribute to the pathogenesis of an AD-like form of dementia. This article is protected by copyright. All rights reserved.

3.
Aging Clin Exp Res ; 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31422564

RESUMO

BACKGROUND: Hospitalization is a key driver of health care costs. Thus far, there are only a few longitudinal studies investigating whether changes in explanatory variables lead to hospitalization. Moreover, these longitudinal studies did not focus on individuals in highest age. AIM: The purpose of the current study was to examine the correlates of hospitalization among the oldest old in Germany longitudinally. METHODS: A multicenter prospective cohort study ["Study on Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)", AgeQualiDe]. Primary care patients ≥ 85 years took part [n = 861 at follow-up (FU) 7, average age of 89.0 years; 85-100 years]. Two waves were used. Hospitalization in the last 6 months was used as outcome measure. Well-established scales were used to quantify the independent variables such as Instrumental Activities of Daily Living Scale, Global Deterioration Scale or Geriatric Depression Scale. RESULTS: Logistic random effects regressions showed that the probability of hospitalization in the preceding 6 months significantly increased with increases in the social network, more depressive symptoms, functional decline, and increase in chronic conditions, whereas it was not significantly associated with age, sex, marital status, education, and cognitive impairment. Social networks moderate the relationship between functional decline and hospitalization. DISCUSSION: The results of the present longitudinal study emphasize the association of depressive symptoms, functional decline, more social networks, and chronic conditions with hospitalization among the oldest old. CONCLUSIONS: Treatments with the aim to reduce or postpone these factors might also help to reduce hospitalization.

4.
PLoS One ; 14(7): e0218111, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31283791

RESUMO

Late onset Alzheimer's disease is the most common form of dementia for which about 30 susceptibility loci have been reported. The aim of the current study is to identify novel genes associated with Alzheimer's disease using the largest up-to-date reference single nucleotide polymorphism (SNP) panel, the most accurate imputation software and a novel gene-based analysis approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 million genotypes from 17,008 Alzheimer's cases and 37,154 controls. In addition to earlier reported genes, we detected three novel gene-wide significant loci PPARGC1A (p = 2.2 × 10-6), RORA (p = 7.4 × 10-7) and ZNF423 (p = 2.1 × 10-6). PPARGC1A and RORA are involved in circadian rhythm; circadian disturbances are one of the earliest symptoms of Alzheimer's disease. PPARGC1A is additionally linked to energy metabolism and the generation of amyloid beta plaques. RORA is involved in a variety of functions apart from circadian rhythm, such as cholesterol metabolism and inflammation. The ZNF423 gene resides in an Alzheimer's disease-specific protein network and is likely involved with centrosomes and DNA damage repair.

5.
J Affect Disord ; 256: 650-657, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301630

RESUMO

BACKGROUND: Old age is accompanied by a higher risk of losing a spouse. This study aims to longitudinally investigate the effect of widowhood on depression severity with a special focus on sex differences. We examine depression before and after widowhood in men and women separately to investigate which sex is at greater risk after losing a spouse. METHODS: Data came from the AgeDifferent.de platform, which includes three pooled old age cohort studies. In order to examine factors associated with depression over time, we applied a linear hybrid mixed-effects regression model for the overall sample and analysed additional separate models for men and women. RESULTS: Of 2470 respondents (mean age at baseline 79.2 (SD 3.64) years), 1256 were men. In total, 209 men and 332 women experienced spousal bereavement after baseline. In general, both sexes showed higher depression severity after widowhood. However, there were significant sex differences. Widowed men were more prone to subsequent depression than widowed women. In terms of depression severity, widowed men differed significantly compared to non-widowed men; however, this was not the case for women. LIMITATION: We harmonized three cohort studies which used different measurement scales for depression and different recruitment procedures. CONCLUSION: Our study showed that although both genders suffer from losing a spouse, men are more prone to subsequently develop depressive symptoms. Raising the awareness among practitioners for sex-specific differences as well as developing tailored interventions for both widowed men and women should be considered.

6.
PLoS Genet ; 15(7): e1008099, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31339880

RESUMO

The length of cilia is controlled by a poorly understood mechanism that involves members of the conserved RCK kinase group, and among them, the LF4/MOK kinases. The multiciliated protist model, Tetrahymena, carries two types of cilia (oral and locomotory) and the length of the locomotory cilia is dependent on their position with the cell. In Tetrahymena, loss of an LF4/MOK ortholog, LF4A, lengthened the locomotory cilia, but also reduced their number. Without LF4A, cilia assembled faster and showed signs of increased intraflagellar transport (IFT). Consistently, overproduced LF4A shortened cilia and downregulated IFT. GFP-tagged LF4A, expressed in the native locus and imaged by total internal reflection microscopy, was enriched at the basal bodies and distributed along the shafts of cilia. Within cilia, most LF4A-GFP particles were immobile and a few either diffused or moved by IFT. We suggest that the distribution of LF4/MOK along the cilium delivers a uniform dose of inhibition to IFT trains that travel from the base to the tip. In a longer cilium, the IFT machinery may experience a higher cumulative dose of inhibition by LF4/MOK. Thus, LF4/MOK activity could be a readout of cilium length that helps to balance the rate of IFT-driven assembly with the rate of disassembly at steady state. We used a forward genetic screen to identify a CDK-related kinase, CDKR1, whose loss-of-function suppressed the shortening of cilia caused by overexpression of LF4A, by reducing its kinase activity. Loss of CDKR1 alone lengthened both the locomotory and oral cilia. CDKR1 resembles other known ciliary CDK-related kinases: LF2 of Chlamydomonas, mammalian CCRK and DYF-18 of C. elegans, in lacking the cyclin-binding motif and acting upstream of RCKs. The new genetic tools we developed here for Tetrahymena have potential for further dissection of the principles of cilia length regulation in multiciliated cells.

7.
J Clin Psychiatry ; 80(4)2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31318184

RESUMO

BACKGROUND: Suicidal ideation is a frequent and difficult-to-treat clinical challenge among patients with major depressive disorder (MDD). However, little is known regarding the differential development during antidepressant treatment and whether some patients may suffer from persistent suicidal ideation. METHODS: Among 811 patients with Schedules for Clinical Assessment in Neuropsychiatry (SCAN)-verified MDD from 2004-2007 assessed weekly for 12 weeks of escitalopram or nortriptyline antidepressant treatment, we applied item response theory to integrate a suicidality score based on 3 rating scales. We performed latent growth mixture modeling analysis to empirically identify trajectories. Multinomial logistic regression analyses estimated associations with potential predictors. RESULTS: We identified 5 distinct classes of suicidal ideation. The Persistent-low class (53.7%) showed no suicidal ideation whereas the Persistent-high class (9.8%) had high suicidal ideation throughout 12 weeks. Two classes showed a fluctuating course: the Fluctuating class (5.2%) ended at a low level of suicidal ideation, whereas the Slow-response-relapse class (4.8%) initially responded slowly but then experienced a large increase to a high level of suicidal ideation after 12 weeks. The Fast-response class (26.5%) had a high baseline severity similar to the Persistent-high class but responded quickly within a few weeks and remained at a low level. Previous suicide attempts and higher mood symptom severity were associated with worse suicidal ideation trajectories, whereas living with a partner showed a trend toward better response. CONCLUSION: Approximately 1 of 5 patients with MDD showed high or fluctuating suicidal ideation despite antidepressant treatment. Studies should investigate whether suicidal ideation may persist for longer periods and more targeted treatment possibilities. TRIAL REGISTRATION: ISRCTN​​ identifier: ISRCTN03693000​​​​.

8.
Geriatr Gerontol Int ; 19(8): 705-710, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31237101

RESUMO

AIM: The purpose of this study was to investigate whether transpersonal trust (TPT) moderates the relationship between chronic conditions and general practitioner (GP) visits among the oldest old in Germany. METHODS: The multicenter prospective cohort Study on Needs, health service use, costs and health-related quality of life in a large sample of oldest old primary care patients (85+) (AgeQualiDe) was carried out. Individuals were recruited through GP offices at six study centers in Germany (follow-up wave 7). Primary care patients were aged ≥85 years (n = 861, mean age 89.0 years; range 85-100 years). The self-reported number of outpatient visits to the GP was used as the outcome measure. To explore religious and spiritual beliefs, the short form of the Transpersonal Trust scale was used. The presence or absence of 36 chronic conditions was recorded by the GP. RESULTS: Multiple Poisson regressions showed that GP visits were positively associated with the number of chronic conditions (incidence rate ratio 1.03, P < 0.05). TPT moderated the relationship between chronic conditions and GP visits (incidence rate ratio 1.01, P < 0.05). The association between chronic conditions and GP visits was significantly more pronounced when TPT was high. CONCLUSION: Our findings highlight the importance of TPT in the relationship between chronic conditions and GP visits. Future longitudinal studies are required to clarify this subject further. Geriatr Gerontol Int 2019; 19: 705-710.

9.
J Alzheimers Dis ; 69(3): 857-869, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31127762

RESUMO

BACKGROUND: Sex differences in verbal episodic memory function have been widely reported. However, sex-specific effects on rates of episodic memory decline remain controversial, and evidence is particularly scarce in the oldest-old population. OBJECTIVE: We aimed to investigate sex differences in trajectories of episodic memory performance in oldest-old individuals. METHODS: Based on 13-year longitudinal data with 9 follow-up assessments of a large sample of cognitively unimpaired old (75+) primary care patients (n = 3,254) participating in the German AgeCoDe/AgeQualiDe study, we used linear mixed effects analyses to model sex-specific trajectories of change in verbal episodic memory while accounting for covarying factors. RESULTS: We found that even in the highest age group women outperformed men in immediate (b = -1.71, p < 0.001) and delayed (b = -0.85, p < 0.001) free recall conditions. Associated late-life trajectories, however, did not differ significantly between the sexes. We further demonstrated that younger age, higher education, and an absence of depressive symptoms predicted better performance in both sexes. In contrast, past occurrences of stroke and APOE ɛ4 carrier status showed a negative relation to test scores. CONCLUSION: Our findings confirm previous research suggesting that women perform better in verbal episodic memory tests. We add that this advantage is still present in the oldest-old age groups. Our results indicate that sociodemographic and health related factors are as important as genetically based APOE ɛ4 carrier status in the prediction of normal cognitive development in advanced old age.

10.
Psychoneuroendocrinology ; 106: 284-292, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31039525

RESUMO

Altered reproductive hormone levels have been associated with the pathophysiology of depressive disorders and this risk may be imparted by their modulatory effect upon hippocampal structure and function. Currently it is unclear whether altered levels of reproductive hormones are causally associated with hippocampal volume reductions and the risk of depressive disorders. Here, we utilize genome-wide association study (GWAS) summary statistics from a GWAS focusing on reproductive hormones, consisting of 2913 individuals. Using this data, we generated polygenic risk scores (PRS) for estradiol, progesterone, prolactin and testosterone in the European RADIANT cohort consisting of 176 postpartum depression (PPD) cases (100% female, mean age: 41.6 years old), 2772 major depressive disorder (MDD) cases (68.6% female, mean age: 46.9 years old) and 1588 control participants (62.5% female, mean age: 42.4 years old), for which there was also a neuroimaging subset of 111 individuals (60.4% female, mean age: 50.0 years old). Only the best-fit PRS for estradiol showed a significant negative association with hippocampal volume, as well as many of its individual subfields; including the molecular layer and granule cell layer of the dentate gyrus, subiculum, CA1, CA2/3 and CA4 regions. Interestingly, several of these subfields are implicated in adult hippocampal neurogenesis. When we tested the same estradiol PRS for association with case-control status for PPD or MDD there was no significant relationship observed. Here, we provide evidence that genetic risk for higher plasma estradiol is negatively associated with hippocampal volume, but this does not translate into an increased risk of MDD or PPD. This work suggests that the relationship between reproductive hormones, the hippocampus, and depression is complex, and that there may not be a clear-cut pathway for etiology or risk moderation.

11.
Schizophr Res ; 209: 185-192, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31138482

RESUMO

BACKGROUND: Despite being recommended for use in clinical trials, the consensus remission criteria were found to leave patients with persisting symptoms, relevant areas of functional impairment and a decreased sense of wellbeing. Therefore, to evaluate the appropriateness of the schizophrenia consensus criteria, a definition of remission based on the Clinical Global Impression Scale (CGI) was developed and remitter subgroups were compared. METHODS: 239 patients with a schizophrenia spectrum disorder were evaluated regarding their remission status after inpatient treatment. Remission in schizophrenia was defined according to the symptom-severity component of the consensus criteria by Andreasen et al. and a CGI based definition was calculated using sensitivity and specificity using receiver operating curves (asymptomatic remitter). Both remitter groups (schizophrenia consensus versus asymptomatic remitters) were compared regarding different clinical variables at discharge as well as the likelihood to relapse within a 1-year follow-up period. Both schizophrenia remitter subgroups were compared to remitters in major depression as a reference value. RESULTS: Following the consensus criteria, 63% of the schizophrenia patients were in remission compared to only 18% following the asymptomatic criterion. The schizophrenia consensus remitters were less likely to be concurrent treatment responders (p < 0.0001), had a significantly greater illness severity (p < 0.0001) and less functioning (p = 0.0358) as well as a significantly greater risk to relapse (p = 0.0174) compared to the schizophrenia asymptomatic remitters as well as the depressed remitters. CONCLUSION: It should be critically re-evaluated if the currently proposed consensus criteria are adequate to measure what is traditionally understood to be remission.

12.
Arch Gerontol Geriatr ; 82: 245-250, 2019 May - Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30877986

RESUMO

AIM: To present data on the prevalence of driving habits and to identify the determinants of driving habits among the oldest old in Germany. METHODS: Cross-sectional data were used from the "Study on Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)" (AgeQualiDe), including primary care patients aged 85 years and above (n = 549 at FU 9, mean age was 90.3 years; 86-101 years). Driving habits were measured (driving a car; frequency of driving a car and driving duration). Correlates were quantified using widely established scales (e.g., Geriatric Depression Scale, Instrumental Activities of Daily Living Scale). Multiple regression models were used to identify the determinants of driving habits. RESULTS: Sixteen percent (87 out of 549) drove a car. Among the car-drivers, about 80% drove at least several times a week and about two-thirds drove longer distances (>15 min). Multiple logistic regressions showed that among the oldest old being a male was more likely to be a current driver compared to being a female. Other significant factors were subjective memory impairment, severe visual impairment, functional and cognitive impairment. Correlates of frequency of driving a car and driving duration were further identified. CONCLUSION: About one in six very old Germans is still a regular car driver. Several determinants of driving habits among the oldest old were identified. Future longitudinal studies are required to clarify the factors leading to changes in driving habits.

13.
J Alzheimers Dis ; 68(4): 1469-1478, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30909220

RESUMO

BACKGROUND/OBJECTIVE: Subjective cognitive decline (SCD) has often been associated with an increased risk for subsequent dementia. However, sex-specific associations are understudied until now. METHODS: Cross-sectional and longitudinal associations over a follow-up period of up to 13 years were investigated in a sample of participants without objective cognitive impairment at baseline (n = 2,422, mean age = 79.63 years). Logistic regression and Cox proportional hazards models were conducted. RESULTS: Women less frequently reported SCD without worries (p < 0.001), but tended to report more often SCD with worries (p = 0.082) at baseline compared to men. In models adjusted for age, education, cognitive status, and depressive symptoms, SCD at baseline increased the risk for subsequent dementia (p < 0.001), and this effect was less pronounced in males (interaction sex×SCD: p = 0.022). Stratified analyses showed that SCD increased the risk for subsequent dementia in women (HR = 1.77, p < 0.001), but not in men (HR = 1.07, p = 0.682). Similar results were found in analyses with SCD without and with worries, except that SCD with worries also predicted subsequent Alzheimer's disease (AD) in men (p = 0.037). CONCLUSION: At baseline, men reported more SCD without worries and women tended to report more SCD with worries. SCD in women was more strongly associated with subsequent dementia. SCD without and with worries was related to incident dementia and AD in women, whereas in men only SCD with worries increased the risk for AD, but not for all-cause dementia.

14.
Int J Geriatr Psychiatry ; 34(5): 765-776, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30821399

RESUMO

OBJECTIVE: To analyze the association of anxiety symptoms with health care use and costs in people aged 85 and older. METHODS: Baseline data from AgeQualiDe (N = 856), a multicenter prospective cohort study of primary care patients aged 85 and older, were analyzed. Anxiety symptoms (Geriatric Anxiety Inventory-Short Form) and health care use were assessed via questionnaires. Health care use was monetarily valued using German unit costs to obtain sectoral (inpatient, outpatient, nursing care, medical supplies, and medication) and total costs. Health care use and costs were analyzed in regression models as a function of anxiety symptoms, as well as relevant covariates (predisposing, enabling, and other need characteristics based on the Behavioral Model of Health Care Use). RESULTS: On a descriptive level, people with increased anxiety symptoms (12% of the sample) incurred on average € 10 909 (SD: 16 023) in the last 6 months, 31% more than those without increased anxiety (€ 8303, SD: 11 175; P = 0.12). Adjusting for predisposing, enabling, and other need characteristics, anxiety symptoms were not significantly associated with health care use or costs. Specifically, need characteristics (morbidity, cognitive decline, and functional impairment) were associated with total or sectoral costs, depending on the cost category analyzed. CONCLUSION: In a sample of people of the oldest-old age group, the severity of anxiety symptoms was not associated with health care use or costs, when adjusting for relevant covariates. A longitudinal analysis could assess whether a change in anxiety symptom severity is associated with health care use or costs in old age.

17.
Artigo em Inglês | MEDLINE | ID: mdl-30784233

RESUMO

AIM: Meta-analyses indicate positive effects of both antipsychotic and cognitive-behavioural interventions in subjects clinically at high risk (CHR) for psychosis in terms of a delay or prevention of psychotic disorders. However, these effects have been limited regarding social functioning and the relative efficacy of both types of interventions remains unclear. Furthermore, neuroprotective substances seem to be a promising alternative agent in psychosis-prevention as they are associated with few and weak side-effects. METHODS: In this multi-centre randomized controlled trial (RCT), we investigate the effects of two interventions on transition to psychosis and social functioning: (a) an integrated preventive psychological intervention (IPPI) including stress-/symptom-management and social-cognitive remediation; (b) N-acetyl-l-cysteine (NAC) as a pharmacological intervention with glutamatergic, neuroprotective and anti-inflammatory capabilities. RESULTS: This is a double-blind, placebo-controlled RCT with regard to NAC and a single-blind RCT with regard to IPPI using a 2 × 2-factorial design to investigate the individual and combined preventive effects of both interventions. To this aim, a total of 200 CHR subjects will be randomized stratified by site to one of four conditions: (a) IPPI and NAC; (b) IPPI and Placebo; (c) NAC and psychological stress management; (d) Placebo and psychological stress management. Interventions are delivered over 26 weeks with a follow-up period of 12 months. CONCLUSION: This paper reports on the rationale and protocol of an indicated prevention trial to detect the most effective and tolerable interventions with regard to transition to psychosis as well as improvements in social functioning, and to evaluate the synergistic effects of these interventions.

18.
Transl Psychiatry ; 9(1): 55, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30705288

RESUMO

Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer's disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Doença de Alzheimer/etnologia , Doença de Alzheimer/genética , Glicoproteínas de Membrana/genética , Fosfolipase C gama/genética , Receptores Imunológicos/genética , Grupo com Ancestrais do Continente Africano/genética , Idoso , Idoso de 80 Anos ou mais , Argentina/etnologia , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Índios Norte-Americanos/genética , Masculino , Pessoa de Meia-Idade
19.
Artigo em Inglês | MEDLINE | ID: mdl-30635714

RESUMO

Saccadic eye movements are well-described markers of cerebral function and have been widely studied in schizophrenia spectrum populations. However, less is known about saccades in individuals clinically at risk for schizophrenia. Therefore, we studied individuals in an at-risk mental state (ARMS) (N = 160), patients in their first episode of schizophrenia (N = 32) and healthy controls (N = 75). N = 88 ARMS participants showed an early at-risk mental state (E-ARMS), defined by cognitive-perceptive basic symptoms (COPER) or a combination of risk and loss of function, whereas N = 72 were in a late at-risk mental state (L-ARMS), defined by attenuated psychotic symptoms or brief limited intermittent psychotic symptoms. We examined prosaccades, reflecting overt attentional shifts, and antisaccades, measuring inhibitory control, as well as their relationship as an indicator of the interplay of bottom-up and top-down influences. L-ARMS but not E-ARMS participants had increased antisaccade latencies compared to controls. First-episode patients had higher antisaccade error rates compared to E-ARMS participants and controls, and increased latencies compared to all other groups. Prosaccade latencies did not differ between groups. We observed the expected negative correlation between prosaccade latency and antisaccade error rate, indicating that individuals with shorter prosaccade latencies made more antisaccade errors. The magnitude of the association did not differ between groups. No saccadic measure predicted conversion to psychosis within 2 years. These findings confirm the existence of antisaccade impairments in patients with schizophrenia and provide evidence that volitional response generation in the antisaccade task may be affected even before onset of clinically overt psychosis.

20.
Br J Psychiatry ; 215(2): 494-501, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30698114

RESUMO

BACKGROUND: For patients with major depressive disorder (MDD) experiencing side-effects or non-response to their first antidepressant, little is known regarding the effect of switching between a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI).AimsTo compare the switch between the TCA nortriptyline and the SSRI escitalopram. METHOD: Among 811 adults with MDD treated with nortriptyline or escitalopram for up to 12 weeks, 108 individuals switched from nortriptyline to escitalopram or vice versa because of side-effects or non-response (trial registration: EudraCT No.2004-001723-38 (https://eudract.ema.europa.eu/) and ISRCTN No.03693000 (http://www.controlled-trials.com)). Patients were followed for up to 26 weeks after switching and response was measured with the Montgomery-Åsberg Depression Rating scale (MADRS). We performed adjusted mixed-effects linear regression models with full information maximum likelihood estimation reporting ß-coefficients with 95% CIs. RESULTS: Switching antidepressants resulted in a significant decrease in MADRS scores. This was present for switchers from escitalopram to nortriptyline (n = 36, ß = -0.38, 95% CI -0.51 to -0.25, P<0.001) and from nortriptyline to escitalopram (n = 72, ß = -0.34, 95% CI -0.41 to -0.26, P<0.001). Both switching options resulted in significant improvement among individuals who switched because of non-response or side-effects. The results were supported by analyses on other rating scales and symptom dimensions. CONCLUSIONS: These results suggest that switching from a TCA to an SSRI or vice versa after non-response or side-effects to the first antidepressant may be a viable approach to achieve response among patients with MDD.Declarations of interestK.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. K.J.A. has been a member of various advisory boards, received consultancy fees and honoraria, and has received research grants from various companies including Johnson and Johnson Pharmaceuticals Research and Development and Bristol-Myers Squibb Pharmaceuticals Limited. D.S. has served on advisory boards for, and received unrestricted grants from, Lundbeck and AstraZeneca. A.F. and P.M. have received honoraria for participating in expert panels for Lundbeck and GlaxoSmithKline.

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