Sociodemographic and clinical predictors of depression in children and adolescents: results of a two-year follow-up study

Depressive disorders are a main cause of disability-adjusted life years already in children and adolescents, in whom the clinical picture somewhat differs from adult-onset depression. Thus, we studied sociodemographic and clinical predictors of depression/dysthymia in a sample of minors. Our baseline sample (N=676) included patients at clinical high-risk for psychosis (CHR-P, n=183), inpatients admitted for non-psychotic, non-affective disorders (n=277), and community participants (n=216) of age 7.0 to 17.9 years (43.8% male). They were assessed by clinical psychologists for mental disorders and symptoms with various clinical interviews including the Mini International Neuropsychiatric Interview for Children and Adolescents, which was also used to assess depression/dysthymia in the CHR-P group at 1- and 2-year-follow up (n=117 and 73, respectively). Analyses followed a stepwise procedure at baseline with stepwise logistic regression analyses to identify the final baseline model that was tested in the follow-up samples. The final cross-sectional model included nationality and 13 clinical variables Mild depressive symptoms in particular played a decisive role here. Variables contributing significantly to the prediction varied over time, indicating that CAD depression/dysthymia may require different predictors depending on the follow-up time. Furthermore, the prospective accuracy of ruling out depression/dysthymia was superior to the accuracy of ruling it in. This lower positive likelihood ratio might be overcome in future by stepwise approaches that further stratify risk in those initially identified as at increased risk of depression/dysthymia

Neurocognitive profiles in help-seeking individuals: comparison of risk for psychosis and bipolar disorder criteria

Background. Neurocognitive deficits are important aspects of the schizophrenic disorders because they have a strong impact on social and vocational outcomes. We expanded on previous research by focusing on the neurocognitive profiles of persons at high risk (HR) or ultra-high risk (UHR) for schizophrenic and affective psychoses. Our main aim was to determine whether neurocognitive measures are sufficiently sensitive to predict a group affiliation based on deficits in functional domains. Method. This study included 207 help-seeking individuals identified as HR (n=75), UHR (n=102) or at high risk for bipolar disorder (HRBip; n=30), who were compared with persons comprising a matched, healthy control group (CG; n=50). Neuropsychological variables were sorted according to their load in a factor analysis and were compared among groups. In addition, the likelihood of group membership was estimated using logistic regression analyses. Results. The performance of HR and HRBip participants was comparable, and intermediate between the controls and UHR. The domain of processing speed was most sensitive in discriminating HR and UHR [odds ratio (OR) 0.48, 95% confidence interval (CI) 0.28-0.78, p=0.004] whereas learning and memory deficits predicted a conversion to schizophrenic psychosis (OR 0.47, 95% CI 0.25-0.87, p=0.01). Conclusions. Performances on neurocognitive tests differed among our three at-risk groups and may therefore be useful in predicting psychosis. Overall, cognition had a profound effect on the extent of general functioning and satisfaction with life for subjects at risk of psychosis. Thus, this factor should become a treatment target in itsel

Acapsular Staphylococcus aureus with a non-functional agr regains capsule expression after passage through the bloodstream in a bacteremia mouse model

Selection pressures exerted on Staphylococcus aureus by host factors during infection may lead to the emergence of regulatory phenotypes better adapted to the infection site. Traits convenient for persistence may be fixed by mutation thus turning these mutants into microevolution endpoints. The feasibility that stable, non-encapsulated S. aureus mutants can regain expression of key virulence factors for survival in the bloodstream was investigated. S. aureus agr mutant HU-14 (IS256 insertion in agrC) from a patient with chronic osteomyelitis was passed through the bloodstream using a bacteriemia mouse model and derivative P3.1 was obtained. Although IS256 remained inserted in agrC, P3.1 regained production of capsular polysaccharide type 5 (CP5) and staphyloxanthin. Furthermore, P3.1 expressed higher levels of asp23/SigB when compared with parental strain HU-14. Strain P3.1 displayed decreased osteoclastogenesis capacity, thus indicating decreased adaptability to bone compared with strain HU-14 and exhibited a trend to be more virulent than parental strain HU-14. Strain P3.1 exhibited the loss of one IS256 copy, which was originally located in the HU-14 noncoding region between dnaG (DNA primase) and rpoD (sigA). This loss may be associated with the observed phenotype change but the mechanism remains unknown. In conclusion, S. aureus organisms that escape the infected bone may recover the expression of key virulence factors through a rapid microevolution pathway involving SigB regulation of key virulence factors.Fil: Suligoy Lozano, Carlos Mauricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Díaz, Rocío E.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Gehrke, Ana-katharina Elsa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Ring, Natalie. University of Edinburgh; Reino UnidoFil: Yebra, Gonzalo. University of Edinburgh; Reino UnidoFil: Alves, Joana. University of Edinburgh; Reino UnidoFil: Gómez, Marisa Ileana. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Wendler, Sindy. Universitätsklinikum Jena Und Medizinische Fakultät; AlemaniaFil: Fitzgerald, J. Ross. University of Edinburgh; Reino UnidoFil: Tuchscherr, Lorena. Jena University Hospital; AlemaniaFil: Löffler, Bettina. Jena University Hospital; AlemaniaFil: Sordelli, Daniel Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Noto Llana, Mariangeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Buzzola, Fernanda Roxana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Changes in neurocognitive functioning during transition to manifest disease: comparison of individuals at risk for schizophrenic and bipolar affective psychoses

BACKGROUND Neurocognitive deficits are important aspects of schizophrenic disorder because they have a strong impact on social and vocational outcomes. Previously it was assumed that cognitive abilities progressively deteriorate with illness onset. However, recent research results have contradicted this with observations of continuous or even improved performance in individuals at risk for psychosis or manifest schizophrenia. The objective of our longitudinal study was to examine neurocognitive functioning in help-seeking individuals meeting basic symptoms or ultra-high-risk criteria for schizophrenic psychosis (HRSchiz) or risk criteria for affective psychosis (HRBip). The progression of cognitive functioning in individuals converting to psychosis was compared with that of at-risk individuals who did not convert during the follow-up period. METHOD Data were available from 86 study participants who completed neurocognitive and clinical assessments at baseline and, on average, 12.8 (s.d. = 1.5) months later. Neurocognitive measures were grouped according to their load in factor analysis to five cognitive domains: speed, attention, fluency, learning and memory, and working memory. RESULTS Neurocognitive functioning in HRSchiz and HRBip individuals generally improved over time. Subjects converting to manifest psychosis displayed a stable neurocognitive profile from baseline to follow-up. Compared with non-converters, they had already demonstrated a significantly lower level of performance during their baseline examinations. CONCLUSIONS Our data provide no evidence for a progressive cognitive decline in individuals at risk of psychosis. In line with the neurodevelopmental model, our findings suggest that cognitive deficits are already present very early, before or during the prodromal stage of the illness

Neurocognitive profiles in help-seeking individuals: comparison of risk for psychosis and bipolar disorder criteria

BACKGROUND: Neurocognitive deficits are important aspects of the schizophrenic disorders because they have a strong impact on social and vocational outcomes. We expanded on previous research by focusing on the neurocognitive profiles of persons at high risk (HR) or ultra-high risk (UHR) for schizophrenic and affective psychoses. Our main aim was to determine whether neurocognitive measures are sufficiently sensitive to predict a group affiliation based on deficits in functional domains. METHOD: This study included 207 help-seeking individuals identified as HR (n = 75), UHR (n = 102) or at high risk for bipolar disorder (HRBip; n = 30), who were compared with persons comprising a matched, healthy control group (CG; n = 50). Neuropsychological variables were sorted according to their load in a factor analysis and were compared among groups. In addition, the likelihood of group membership was estimated using logistic regression analyses. RESULTS: The performance of HR and HRBip participants was comparable, and intermediate between the controls and UHR. The domain of processing speed was most sensitive in discriminating HR and UHR [odds ratio (OR) 0.48, 95% confidence interval (CI) 0.28-0.78, p = 0.004] whereas learning and memory deficits predicted a conversion to schizophrenic psychosis (OR 0.47, 95% CI 0.25-0.87, p = 0.01). CONCLUSIONS: Performances on neurocognitive tests differed among our three at-risk groups and may therefore be useful in predicting psychosis. Overall, cognition had a profound effect on the extent of general functioning and satisfaction with life for subjects at risk of psychosis. Thus, this factor should become a treatment target in itself

Changes in neurocognitive functioning during transition to manifest disease: comparison of individuals at risk for schizophrenic and bipolar affective psychoses

Background Neurocognitive deficits are important aspects of schizophrenic disorder because they have a strong impact on social and vocational outcomes. Previously it was assumed that cognitive abilities progressively deteriorate with illness onset. However, recent research results have contradicted this with observations of continuous or even improved performance in individuals at risk for psychosis or manifest schizophrenia. The objective of our longitudinal study was to examine neurocognitive functioning in help-seeking individuals meeting basic symptoms or ultra-high-risk criteria for schizophrenic psychosis (HRSchiz) or risk criteria for affective psychosis (HRBip). The progression of cognitive functioning in individuals converting to psychosis was compared with that of at-risk individuals who did not convert during the follow-up period. Method Data were available from 86 study participants who completed neurocognitive and clinical assessments at baseline and, on average, 12.8 (s.d.=1.5) months later. Neurocognitive measures were grouped according to their load in factor analysis to five cognitive domains: speed, attention, fluency, learning and memory, and working memory. Results Neurocognitive functioning in HRSchiz and HRBip individuals generally improved over time. Subjects converting to manifest psychosis displayed a stable neurocognitive profile from baseline to follow-up. Compared with non-converters, they had already demonstrated a significantly lower level of performance during their baseline examinations. Conclusions Our data provide no evidence for a progressive cognitive decline in individuals at risk of psychosis. In line with the neurodevelopmental model, our findings suggest that cognitive deficits are already present very early, before or during the prodromal stage of the illnes

Prediction of the functional outcome in Children and Adolescents with and without clinical high risk- a Machine Learning Approach

Aims: Studies on the early detection of psychosis have shown that numerous patients at clinical high risk (CHR) do not develop a manifest psychosis but, nevertheless, do present poor clinical outcomes. Therefore, psychosocial functioning has become a valuable parameter to quantify disease state in CHR patients. Methods: Within a Swiss-German naturalistic longitudinal study, we examined psychosocial functioning in 8- to 17-year-olds using the Social and Occupational Functioning Scale (sofas) within 2 years. The sample included 69 clinical high-risk patients, 147 inpatients not suspected to develop psychosis and 110 community subjects. Participants were examined with the Schizophrenia Proneness Instrument-Child & Youth version (SPI-CY), the Structured Interview for Psychosis-Risk Syndromes (SIPS), the Structured Clinical Interview for DSM-IV and a neurocognitive test battery. We focussed on participants with poor psychosocial functioning (sofas < 70) at T0 and differentiated between 'remaining impaired' versus 'recovered' at either T1 or T2. An external validation was performed with a 13- to 17-year-old CHR sample of an independent prospective naturalistic Swiss study (N=41, 19 recovered). Results: One hundred and ninety participants presented a recovered psychosocial functioning in the model developing sample. Twenty-three significant predictors were identified. Using these predictors only, BAC increased to 75.9% (sensitivity: 67.9%, specificity: 83.8%). External validation revealed a sufficient generalizability of BAC = 64.7% (sensitivity: 61.5%, specificity: 67.9%). Conclusions: The higher number of predictors, compared to similar analyses in adults, indicate that predictions in children and adolescents might be more complex than in adults, due to ongoing developmental processes

Prediction of Psychosis in Children and Adolescents: a Machine Learning Approach

Aims: Because community and clinical studies indicated an impact of development on the early detection of psychosis, we studied the development of psychosis over two years in 8- to 17-year-olds. Methods: Within a Swiss-German naturalistic longitudinal study, we examined clinical predictors of conversion to psychosis within 2 years in 69 clinical high-risk patients (35% male), 147 inpatients not suspected to develop psychosis (47% male) and 110 community subjects (46% male) using a multistep machine-learning approach. Participants were examined with the Schizophrenia Proneness Instrument-Child & Youth version (SPI-CY), the Structured Interview for Psychosis-Risk Syndromes (SIPS), the Structured Clinical Interview for DSM-IV and a neurocognitive battery. Additionally, an external validation was performed with a 13- to 17-year-old CHR sample of an independent prospective naturalistic Swiss study (N=80, 14 converters) that used the same diagnostic instruments. Results: Thirteen participants converted to psychosis in the model developing sample, 12 of them had met CHR criteria at baseline. Fifty-one significant predictors were identified, predominately SPI-CY and SIPS items. Using these predictors only, BAC increased to 88.5% (sensitivity: 84.6%, specificity: 92.3%). External validation in terms of an out of sample cross validation revealed a sufficient generalizability of BAC = 63.1% determined by a high sensitivity (92.9%) and a low specificity (33.3%). Conclusions: The high number of predictors, compared to similar analyses in adult samples, and low specificity in the older validation sample indicate that prediction of psychosis in children and adolescents might be more complex than in adults, likely for the ongoing development

Adolescents and adults at clinical high-risk for psychosis: age-related differences in attenuated positive symptoms syndrome prevalence and entanglement with basic symptoms

BACKGROUND: The attenuated positive symptoms syndrome (APSS) is considered an at-risk indicator for psychosis. However, the characteristics and developmental aspects of the combined or enriched risk criteria of APSS and basic symptom (BS) criteria, including self-experienced cognitive disturbances (COGDIS) remain under-researched. METHOD: Based on the Structured Interview of Prodromal Syndromes (SIPS), the prevalence of APSS in 13- to 35-year-old individuals seeking help in an early recognition program for schizophrenia and bipolar-spectrum disorders was examined. BS criteria and COGDIS were rated using the Schizophrenia Proneness Instrument for Adults/Children and Youth. Participants meeting APSS criteria were compared with participants meeting only BS criteria across multiple characteristics. Co-occurrence (APSS+/BS+, APSS+/COGDIS+) was compared across 13-17, 18-22 and 23-35 years age groups. RESULTS: Of 175 individuals (age = 20.6 ± 5.8, female = 38.3%), 94 (53.7%) met APSS criteria. Compared to BS, APSS status was associated with suicidality, higher illness severity, lower functioning, higher SIPS positive, negative, disorganized and general symptoms scores, depression scores and younger age (18.3 ± 5.0 v. 23.2 ± 5.6 years, p < 0.0001) with age-related differences in the prevalence of APSS (ranging from 80.3% in 13- to 17-year-olds to 33.3% in 23- to 35-year-olds (odds ratio 0.21, 95% confidence interval 0.11-0.37). Within APSS+ individuals, fewer adolescents fulfilled combined risk criteria of APSS+/BS+ or APSS+/COGDIS+ compared to the older age groups. CONCLUSIONS: APSS status was associated with greater suicidality and illness/psychophathology severity in this help-seeking cohort, emphasizing the need for clinical care. The age-related differences in the prevalence of APSS and the increasing proportion of APSS+/COGDIS+ may point to a higher proportion of non-specific/transient, rather than risk-specific attenuated positive symptoms in adolescents