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The nature and degree of cognitive impairments in schizoaffective disorder is not well established. The aim of this meta-analysis was to characterise cognitive functioning in schizoaffective disorder and compare it with cognition in schizophrenia and bipolar disorder. Schizoaffective disorder was considered both as a single category and as its two diagnostic subtypes, bipolar and depressive disorder.
Following a thorough literature search (468 records identified), we included 31 studies with a total of 1685 participants with schizoaffective disorder, 3357 with schizophrenia and 1095 with bipolar disorder. Meta-analyses were conducted for seven cognitive variables comparing performance between participants with schizoaffective disorder and schizophrenia, and between schizoaffective disorder and bipolar disorder.
Participants with schizoaffective disorder performed worse than those with bipolar disorder (g = −0.30) and better than those with schizophrenia (g = 0.17). Meta-analyses of the subtypes of schizoaffective disorder showed cognitive impairments in participants with the depressive subtype are closer in severity to those seen in participants with schizophrenia (g = 0.08), whereas those with the bipolar subtype were more impaired than those with bipolar disorder (g = −0.23) and less impaired than those with schizophrenia (g = 0.29). Participants with the depressive subtype had worse performance than those with the bipolar subtype but this was not significant (g = 0.25, p = 0.05).
Cognitive impairments increase in severity from bipolar disorder to schizoaffective disorder to schizophrenia. Differences between the subtypes of schizoaffective disorder suggest combining the subtypes of schizoaffective disorder may obscure a study's results and hamper efforts to understand the relationship between this disorder and schizophrenia or bipolar disorder.
Measurements of a variety of physical properties of muscle tissue have been proposed as objective tests for meat tenderness. We have attempted to single out a specific physical factor, namely tensile stress, and to determine its effect on the ultrastructure of raw and cooked muscle tissue. Extension of this approach to the other physical factors involved in mastication will hopefully establish the structural factors important to meat tenderness.
The bovine semitendenosus muscle (eye round) was obtained either commercially or excised from a carcass aged under controlled conditions for 10 days. Small strips (¼” x ¼” x 1-½”), raw and cooked at 90°C, were subjected to tensile stress and then fixed in glutaraldehyde. A motorized minitensile stage (Fig. 1), designed to be small enough to operate within the SEM, stressed the muscle samples while viewed by a stereomicroscope and simultaneously monitored with a closed circuit TV system. Identical areas of samples subjected to tensile stress could be observed in both the light and scanning electron microscopes (Fig. 2).
It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
Mood disorders, i.e. major depressive disorder (MDD) and bipolar disorders, are leading sources of disability worldwide. Currently available treatments do not yield remission in approximately a third of patients with a mood disorder. This is in part because these treatments do not target a specific core pathology underlying these heterogeneous disorders. In recent years, abnormal inflammatory processes have been identified as putative pathophysiological mechanisms and treatment targets in mood disorders, particularly among individuals with treatment-resistant conditions.
In this selective review, we aimed to summarise recent advances in the field of immunopsychiatry, including emerging pathophysiological models and findings from treatment ttrials of immunomodulatory agents for both MDD and bipolar disorders.
We performed a literature review by searching Medline for clinical trials of immunomodulating agents as monotherapy or adjunctive treatments in MDD and bipolar disorders. Included studies are randomised controlled trials (RCTs), cluster RCTs or cross-over trials of immunomodulating agents that had an active comparator or a placebo-arm.
Current evidence shows an association between inflammation and mood symptoms. However, there is conflicting evidence on whether this link is causal.
Future studies should focus on identifying specific neurobiological underpinnings for the putative causal association between an activated inflammatory response and mood disorders. Results of these studies are needed before further treatment trials of immunomodulatory agents can be justified.
Emerging research suggests that maternal immune activation (MIA) may be associated with an increased risk of adverse neurodevelopmental and mental health outcomes in offspring. Using data from the Raine Study, we investigated whether MIA during pregnancy was associated with increased behavioral and emotional problems in offspring longitudinally across development.
Mothers (Generation 1; N = 1905) were classified into the following categories: AAAE (Asthma/Allergy/Atopy/Eczema; N = 1267); infection (during pregnancy; N = 1082); no AAAE or infection (N = 301). The Child Behavior Checklist (CBCL) was administered for offspring at ages 5, 8, 10, 14, and 17. Generalized estimating equations were used to investigate the effect of maternal immune status on CBCL scores.
AAAE conditions were associated with significant increases in CBCL Total (β 2.49; CI 1.98–3.00), Externalizing (β 1.54; CI 1.05–2.03), and Internalizing (β 2.28; CI 1.80–2.76) scores. Infection conditions were also associated with increased Total (β 1.27; CI 0.77–1.78), Externalizing (β 1.18; CI 0.70–1.66), and Internalizing (β 0.76; CI 0.28–1.24) scores. Exposure to more than one AAAE and/or infection condition was associated with a greater elevation in CBCL scores than single exposures in males and females. Females showed greater increases on the Internalizing scale from MIA, while males showed similar increases on both Internalizing and Externalizing scales.
MIA was associated with increased behavioral and emotional problems in offspring throughout childhood and adolescence. This highlights the need to understand the relationship between MIA, fetal development, and long-term outcomes, with the potential to advance early identification and intervention strategies.
For patients with methicillin-resistant Staphylococcus aureus (MRSA) colonization, a traditional fist-bump greeting did not significantly reduce MRSA transfer in comparison to a handshake. However, transfer was reduced with a modified fist bump that minimized the surface area of contact and when hand hygiene was performed before the handshake.
We examine the critical viscous mode of the Taylor–Couette strato-rotational instability, concentrating on cases where the buoyancy frequency
and the inner cylinder rotation rate
are comparable, giving a detailed account for
. The ratio of the outer to the inner cylinder rotation rates
and the ratio of the inner to the outer cylinder radius
. We find considerable variation in the structure of the mode, and the critical Reynolds number
at which the flow becomes unstable. For
, we classify different regions of the
-plane by the critical viscous mode of each region. We find that there is a triple point in the
-plane where three different viscous modes all onset at the same Reynolds number. We also find a discontinuous change in
along a curve in the
-plane, on one side of which exist closed unstable domains where the flow can restabilise when the Reynolds number is increased. A new form of viscous instability occurring for wide gaps has been detected. We show for the first time that there is a region of the parameter space for which the critical viscous mode at the onset of instability corresponds to the inviscid radiative instability of Le Dizès & Riedinger (J. Fluid Mech., vol. 660, 2010, pp. 147–161). Focusing on small-to-moderate wavenumbers, we demonstrate that the viscous and inviscid systems are not always correlated. We explore which viscous modes relate to inviscid modes and which do not. For asymptotically large vertical wavenumbers, we have extended the inviscid analysis of Park & Billant (J. Fluid Mech., vol. 725, 2013, pp. 262–280) to cover the cases where
Introduction: Medical record review (MRR) studies are commonly used in Emergency Medicine (EM) research. It is not always clear how sample size calculations are reported, or the methods by which they were derived. This scoping review sought to examine reporting and justification of MRR sample sizes from the EM literature. Methods: Using Web of Science, we identified the top ten journals, based on impact factor rating in 2018, within the field of Emergency Medicine. Journals were excluded if they were not in English or did not include sufficient articles for analysis. Within each of these ten selected journals, we searched for chart reviews and related terms: "medical record", "outpatient record", "inpatient record", "clinical record", and "nursing note". From this search subset, five articles were randomly selected from each journal. Data about sample size and sample size selection were extracted and analyzed by two reviewers independently for each article. Results: Of the 50 articles randomly selected, 48 articles were retrospective MRRs and two articles were prospective MRRs. 78% (39 articles) chose sample size based on availability, 14% (seven articles) chose sample size based on power calculations, 4% (two articles) chose sample size based on a previous study's methodology, and 4% (two articles) did not give details on sample size selection. Conclusion: While some emergency medicine MRRs based sample size selection on power or previous studies, the vast majority are based on availability with study-specific exclusion/inclusion criteria. This may indicate they are using a smaller sample size than necessary to be sufficiently powered to assess their end goal. More work is required to determine the effect of this on outcomes and interpretability of results, as well as which method is most accurate and efficient.
One major challenge in the study of late-Quaternary extinctions (LQEs) is providing better estimates of past megafauna abundance. To show how megaherbivore population size varied before and after the last extinctions in interior Alaska, we use both a database of radiocarbon-dated bone remains (spanning 25–0 ka) and spores of the obligate dung fungus, Sporormiella, recovered from radiocarbon-dated lake-sediment cores (spanning 17–0 ka). Bone fossils show that the last stage of LQEs in the region occurred at about 13 ka ago, but the number of megaherbivore bones remains high into the Holocene. Sporormiella abundance also remains high into the Holocene and does not decrease with major vegetation changes recorded by arboreal pollen percentages. At two sites, the interpretation of Sporormiella was enhanced by additional dung fungal spore types (e.g., Sordaria). In contrast to many sites where the last stage of LQEs is marked by a sharp decline in Sporormiella abundance, in interior Alaska our results indicate the continuance of megaherbivore abundance, albeit with a major taxonomic turnover (including Mammuthus and Equus extinction) from predominantly grazing to browsing dietary guilds. This new and robust evidence implies that regional LQEs were not systematically associated with crashes of overall megaherbivore abundance.
The neurodevelopmental model of schizophrenia includes the etiological impact of fetal brain stressors possibly connected with birth seasonality. Specification of social class of origin (SES) as a related risk factor remains unexamined as does type of schizophrenia as an outcome variable. The objective of this study was to test for an interconnection between SES, type of schizophrenia and seasonality of birth.
Patients (N = 436) from a United States psychiatric hospital were separated into deficit/nondeficit presentation and bifurcated into poor/nonpoor SES. Birth seasonality was assessed by months hypothetically connected with winter-related trimesters of gestation.
Results showed that there is a significant difference (p = 0.0411) in the monthly birth patterns of poor vs. nonpoor patients and that the difference connects with the likelihood of deficit vs. nondeficit schizophrenia. Specifically, an elevated proportion of patients with deficit schizophrenia were born to impoverished women who likely conceived in January. Findings were confirmed by multiple levels of statistical assessment including log linear analysis.
The resultant model suggests the environmental location (lower SES) and timing (winter conception) of adult schizophrenia with poor outcome (deficit).
To compare CATIE, a randomized double blind study, and SOHO, a 3-year prospective non-randomized observational European study of outpatients with schizophrenia, on the Number Needed to Treat (NNT) for all-cause medication discontinuation. NNTs place data into a clinically meaningful context - the number of patients needed to be treated with one antipsychotic instead of another to prevent one negative outcome, defined here as one additional medication discontinuation for any cause.
Rate of medication discontinuation for any cause during the 18 months post initiation was calculated for patients newly initiated on olanzapine (N=4247), risperidone (N=1549), quetiapine (N=583), amisulpride (N=256), clozapine (N=274), oral typicals (N=471) or depot typicals (N=348). Cox models were employed to adjust for treatment group differences at baseline. NNTs with their 95% confidence intervals were calculated and compared with published NNTs for CATIE (Phase 1).
The NNTs for all-cause discontinuation of olanzapine vs. each studied atypical antipsychotic during the 18 month following medication initiation in SOHO were comparable to CATIE: 4.3(95% CI: 3.6–5.3) for olanzapine vs. quetiapine (5.5 in CATIE); 16.1(11.0–28.1) for olanzapine vs. risperidone (10.1 in CATIE); 6.9(5.2–10.1) for olanzapine vs. oral typicals (9.0 in CATIE for olanzapine vs. perphenazine).
The NNTs for all-cause medication discontinuation based on CATIE appeared comparable to NNTs based on SOHO. The NNTs for olanzapine therapy were consistently better when compared to each studied atypical antipsychotic (except clozapine) and when compared to typical antipsychotics. Results should be interpreted conservatively, due to the observational design of SOHO.
Follow-up studies of schizophrenia have reported divergent rates of outcomes. In addition to definition and measurement challenges, one reason for divergence may be due to sampling biases. Our aim was to report clinical and social outcomes of schizophrenia in the longitudinal, unselected, population-based Northern Finland 1966 Birth Cohort, and describe associated factors.
Subjects with DSM-III-R schizophrenia (N=109) were followed prospectively from mid-pregnancy up to age 35 years. Used outcome measures were positive and negative symptoms, global clinical impression, use of antipsychotics, psychiatric hospitalisations, social and occupational functioning. Several definitions of good and poor outcomes were explored, and predictors of outcomes were analysed.
In a subsample of 59 cases with complete information of outcomes, good clinical outcome varied from 10% to 59%, and good social outcome 15-46%, depending on definition of outcomes. Poor clinical outcome varied 41-77% and poor social 37-54%. Two subjects recovered fully using the most stringent definition of outcome. Lack of friends in childhood, father's high social class, lower school performance and earlier age of illness onset predicted poor outcomes. When the whole sample was considered, early infant development around the age of 1 year was associated with worse course of illness.
Outcomes were heterogeneous and relatively poor in this sample of relatively young schizophrenia subjects. The results were influenced by the definitions and measurements of outcomes. Persons having a sub-optimal developmental trajectory with poor social contacts, poor school performance, and early age of illness onset seem to have the worst outcome.
To describe symptom expression and functional outcome in psychotic disorders in relation with temperament traits assessed with the Temperament and Character Inventory (TCI) in a population-based sample.
As part of the 31-year follow-up survey of the Northern Finland 1966 Birth Cohort, TCI temperament items were filled in by 4349 members of the cohort. In individuals with psychotic disorders, also positive and negative symptoms and outcome variables were assessed in a 35-year follow-up. Information of TCI and outcomes were available for altogether 41 individuals with psychosis.
Reward dependence (RD) (rho = −0.45) and Persistence (P) (rho = −0.52) were significantly correlated with Positive and Negative Syndrome Scale (PANSS) negative symptoms. Higher P scores predicted higher social and occupational functioning (as measured by Social and Occupational Functioning Assessment Scale [SOFAS]), and higher Harm avoidance (HA) predicted a higher likelihood of being on a disability pension.
Results indicate that understanding of personality dimensions support better understanding of outcome and symptom expressions in psychotic disorders.
There are lacking prospective studies in general population of adolescents about symptoms predicting the onset of first episode psychosis.
Members (N= 9,215) of the Northern Finland 1986 Birth Cohort, an unselected general population cohort, were invited to participate in a field survey during 2001, at ages of 15-16 years. The study included a 21-item PROD-screen questionnaire screening prodromal symptoms for psychosis for last six months (Heinimaa et al. 2003). PROD-screen included nine questions for positive and five questions for negative features. The Finnish Hospital Discharge Register was used to find out new cases of hospital treated mental disorders during 2002-2005.
Of the subjects 17 (0.3%) were treated due to first episode psychosis and 95 (1.5%) due to non-psychotic disorder during the follow-up period. Positive symptoms did not associate with the onset of psychosis, but negative symptoms did. 94% of subjects who got psychosis reported negative symptoms. Respective figure for those who were treated for non-psychotic disorder was 48%, and for those ‘healthy’ without psychiatric hospital treatment 46% (Fisher's exact test: psychosis vs. healthy p<0.001, psychosis vs. non-psychosis p<0.001, and non-psychosis vs. healthy p=0.61).
This study may be the only one exploring prospectively in general population features predicting onset of first episode psychosis. The findings emphasize the importance of negative symptoms in the development of neuropsychiatric disorder of first episode psychosis (Weinberger 1995).
The Academy of Finland, the Signe and Ane Gyllenberg Foundation, the Sigrid Juselius Foundation and the Thule Institute, Finland.
Schizophrenia is one of the most devastating neuropsychiatric disorders. One of the most consistent findings in schizophrenia is a decrease in cell number and volume of the medial dorsal nucleus (MD) of the thalamus which has reciprocal connections to the prefrontal cortex, another region affected in schizophrenia. During development, the MD aides in the differentiation and maturation of pyramidal cells in the prefrontal cortex. To better understand the role of the MD in schizophrenia we lesioned the MD of postnatal day 4 rats and examined their prefrontal cortex as adults. In rats, the MD projects to dorsolateral anterior (human area 9), medial prelimbic (human area 32) and Cg-1 (human area 24). We hypothesized that a lesion of the MD would lead to morphological changes in all three regions similar to that observed in humans. Using a Golgi stain we counted the number of primary and secondary dendrites and determined spine density in the three regions. Analysis of layers III and V pyramidal cells showed a significant reduction in primary dendrites III/V (Cg-1 25%/23%, prelimbic 25%/25% and dorsolateral 24%/15%) and secondary dendrites (Cg-1 40%/34%, prelimbic 40%/32% and dorsolateral 41%/30%). Using two different counting methods we observed that spines on primary and secondary dendrites were significantly reduced for both laminas for all three regions. These current data suggest that a lesion of the MD early in development affects dendritic morphology in the prefrontal cortex similar to that observed in schizophrenia making this model a good candidate for better understanding of schizophrenia.