Background:
The six-item version of the Positive and Negative Syndrome Scale (PANSS-6) has shown promise as a brief measure of the severity of core symptoms of schizophrenia. However, since all prior ...analyses of the PANSS-6 were based on data extracted from studies using the full 30-item PANSS (PANSS-30), it remains unknown whether it is possible to obtain valid information for the PANSS-6 ratings via a brief interview, such as the Simplified Negative and Positive Symptoms Interview (SNAPSI).
Aims:
We aimed to validate the PANSS-6 ratings obtained via the SNAPSI using the PANSS-6 scores extracted from the PANSS-30 ratings obtained via the comprehensive Structured Clinical Interview for PANSS (SCI-PANSS) as the gold-standard reference.
Methods:
The PANSS-6 ratings based on the SNAPSI and the PANSS-30 ratings based on the SCI-PANSS were conducted by independent raters with established inter-rater reliability.
Results:
Seventy-seven inpatients with schizophrenia (Mage = 35.1 ± 11.7 years; males = 57%; paranoid schizophrenia = 75%) participated in the study. The intraclass correlation coefficient (ICC) of the PANSS-6 total scores obtained using the SNAPSI and the PANSS-30-derived PANSS-6 total scores via the SCI-PANSS was 0.77 (p < 0.001). The ICC for the PANSS-6 total score and the PANSS-30-derived PANSS-8 (Andreasen’s remission criteria) was 0.75 (p < 0.001). Spearman’s rank correlation coefficient for changes in PANSS-6 total scores via the SNAPSI and changes in PANSS-30-derived PANSS-6 total scores was 0.70 (p < 0.001).
Conclusions:
Using the SNAPSI to rate the PANSS-6 enables a focused and brief assessment of the severity of core symptoms of schizophrenia, which facilitates measurement-based care and clinical decision making in the treatment of schizophrenia.
Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the
gene, suggesting its ...implication in the association between depression and obesity.
To confirm these findings by investigating the
polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.
The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.
In the replication cohorts, we observed a significant interaction between
, BMI and depression with fixed effects meta-analysis (β = 0.12,
= 2.7 × 10
) and with the Han/Eskin random effects method (
= 1.4 × 10
) but not with traditional random effects (β = 0.1,
= 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12,
= 0.027) being highly significant based on the Han/Eskin model (
= 6.9 × 10
). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of
This meta-analysis provides additional support for a significant interaction between
, depression and BMI, indicating that depression increases the effect of
on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
Schizophrenia is often associated with distinctive or odd social behaviours. Previous work suggests this could be due to a general reduction in conformity; however, this work only assessed the ...tendency to publicly agree with others, which may involve a number of different mechanisms. In this study, we specifically investigated whether patients display a reduced tendency to adopt other people's opinions (socially learned attitude change). We administered a computerized conformity task, assumed to rely on reinforcement learning circuits, to 32 patients with schizophrenia or schizo-affective disorder and 39 matched controls. Each participant rated 153 faces for trustworthiness. After each rating, they were immediately shown the opinion of a group. After approximately 1 hour, participants were unexpectedly asked to rate all the faces again. We compared the degree of attitude change towards group opinion in patients and controls. Patients presented equal or more social influence on attitudes than controls. This effect may have been medication induced, as increased conformity was seen with higher antipsychotic dose. The results suggest that there is not a general decline in conformity in medicated patients with schizophrenia and that previous findings of reduced conformity are likely related to mechanisms other than reinforcement based social influence on attitudes.
Background:
The six-item Positive and Negative Syndrome Scale (PANSS-6) is a measure of the severity of core symptoms of schizophrenia, which can be administered via the brief Simplified Negative and ...Positive Symptoms Interview (SNAPSI). A recent study has confirmed the validity of PANSS-6 ratings as derived by SNAPSI (PANSS-6SNAPSI) among inpatients with schizophrenia.
Aims:
We aimed to test the validity of PANSS-6SNAPSI among outpatients with schizophrenia using PANSS-6 ratings extracted from the 30-item PANSS-30 as derived by the Structured Clinical Interview for the Positive and Negative Syndrome Scale (PANSS-6SCI-PANSS) as a gold standard reference.
Methods:
PANSS-6SNAPSI and PANSS-6SCI-PANSS ratings were obtained at two time points by independent raters with established inter-rater reliability. Agreement between PANSS-6SNAPSI and PANSS-6SCI-PANSS ratings was estimated via intra-class coefficients (ICCs) and responsiveness over time was quantified using Spearman’s rank correlation coefficients. Post hoc “leave-one-out” analyses were carried out, in which each rater in turn was excluded from the ICC calculations.
Results:
Seventy-three outpatients with schizophrenia participated in the study (mean age: 38.3 years; 56% males). The ICC for PANSS-6SNAPSI versus PANSS-6SCI-PANSS was 0.67 95%CI = 0.56–0.76 and the Spearman’s rank correlation coefficient for responsiveness was 0.40 (p = 0.004). When data from a specific outlying rater were excluded, the ICC for PANSS-6SNAPSI versus PANSS-6SCI-PANSS was 0.75 95% CI = 0.63–0.83 and the Spearman’s rank correlation coefficient for responsiveness was 0.55 (p = 0.018).
Conclusions:
We found PANSS-6SNAPSI ratings to have acceptable clinical validity, suggesting that PANSS-6SNAPSI can be used for both inpatients and outpatients with schizophrenia.
Gastrointestinal infections can be life threatening, but not much is known about the host’s genetic contribution to susceptibility to gastrointestinal infections or the latter’s association with ...psychiatric disorders. We utilized iPSYCH, a genotyped population-based sample of individuals born between 1981 and 2005 comprising 65,534 unrelated Danish individuals (45,889 diagnosed with mental disorders and 19,645 controls from a random population sample) in which all individuals were linked utilizing nationwide population-based registers to estimate the genetic contribution to susceptibility to gastrointestinal infections, identify genetic variants associated with gastrointestinal infections, and examine the link between gastrointestinal infections and psychiatric and neurodevelopmental disorders. The SNP heritability of susceptibility to gastrointestinal infections ranged from 3.7% to 6.4% on the liability scale. Significant correlations were found between gastrointestinal infections and the combined group of mental disorders (OR = 2.09; 95% CI: 1.82–2.4,
P
= 1.87 × 10
–25
). Correlations with autism spectrum disorder, attention deficit hyperactivity disorder, and depression were also significant. We identified a genome-wide significant locus associated with susceptibility to gastrointestinal infections (OR = 1.13; 95% CI: 1.08–1.18,
P
= 2.9 × 10
–8
), where the top SNP was an eQTL for the
ABO
gene. The risk allele was associated with reduced
ABO
expression, providing, for the first time, genetic evidence to support previous studies linking the O blood group to gastrointestinal infections. This study also highlights the importance of integrative work in genetics, psychiatry, infection, and epidemiology on the road to translational medicine.
Background:
Antipsychotics are key for the treatment of psychotic and several non-psychotic disorders. Unfortunately, antipsychotic medications are associated with side effects, which may reduce ...quality of life and treatment adherence. Therefore, regular screening of antipsychotic side effects is essential. The Glasgow Antipsychotic Side-effect Scale is a patient self-report scale developed for this purpose. However, the Glasgow Antipsychotic Side-effect Scale has only been validated against another self-report side effect measure, which is suboptimal.
Objective:
We aimed to validate the Glasgow Antipsychotic Side-effect Scale using the clinician-rated Udvalg for Kliniske Undersøgelser side-effect rating scale as the gold standard reference.
Results:
81 antipsychotic-treated outpatients with schizophrenia-spectrum disorders (age = 42±13 years; males = 43%, schizophrenia = 77%, illness duration: median = 11 years) completed the Glasgow Antipsychotic Side-effect Scale and were subsequently scored on the Udvalg for Kliniske Undersøgelser by trained raters. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for paired Glasgow Antipsychotic Side-effect Scale and Udvalg for Kliniske Undersøgelser items. Sensitivity of Glasgow Antipsychotic Side-effect Scale items ranged from 33–96%, with 19 (86%) having >75% sensitivity. Lowest sensitivity emerged for “nocturnal enuresis” (33%), “galactorrhea” (50%) and “hyperkinesia” 14–99%, with 14 items (64%) having >75% specificity, being lowest for “asthenia” (14%), “polyuria/polydipsia” (35%), “sedation” (41%), “akathisia” (53%), “dystonia” (65%), “hyperkinesia” (68%), “hypokinesia” (70%) and “accommodation” (70%). Positive predictive value ranged from 7–85%, with six items (27%) having a positive predictive value >75%. Negative predictive value ranged from 40–98%, with 21 items (95%) having a negative predictive value >75%. The mean time to complete the Glasgow Antipsychotic Side-effect Scale was 4±2 minutes.
Conclusion:
The Glasgow Antipsychotic Side-effect Scale demonstrated satisfactory validity as a self-rated tool for antipsychotic side effects and may aid measurement-based care and decision-making.
Little is known whether cholesterol levels affect depression treatment outcomes. We aimed to study the association between baseline and changes in blood cholesterol levels with drug-specific ...antidepressant response and long-term prognosis in patients with major depressive disorder (MDD).
From the Danish site of the GENDEP trial, we included patients with MDD randomized to escitalopram or nortriptyline treatment. Total and free cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and depression severity using the Montgomery-Åsberg Depression rating scale (MADRS) were measured at baseline and after 26 weeks of treatment initiation. By linkage with nationwide registers, we analyzed psychiatric and cardiometabolic hospital contacts during the five years after the trial. We assessed the association of cholesterol levels with a) depression severity using linear and mixed effects regression analyses; and b) the register-based outcomes using Cox regression analyses.
Among 78 patients (mean age 38 years, 74% women, mean MADRS score 28 SD=4.5), baseline cholesterol levels were not correlated with antidepressant response. Among 58 patients with measurements at week 0 and 26, cholesterol levels significantly increased in both treatment groups. Only in patients using escitalopram did the increase in total and free cholesterol and LDL correlate with improved antidepressant response. Baseline or changes in cholesterol were not associated with 5-year outcomes.
Secondary analyses on a rather small sample.
This study provides clinical insight into potential drug-specific associations between increases in cholesterol levels and antidepressant response to escitalopram but not nortriptyline.
•Cholesterol levels increased during 26 weeks of antidepressant treatment.•Among those treated with escitalopram, the increase correlated with improved response.•We found no correlation between change in cholesterol and response in the nortriptyline group.•Baseline or change in cholesterol levels were not associated with differential 5-year prognosis.
Abstract Background Brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor A (VEGF) have been suggested to play a role in the pathophysiology of depression. The neurotrophic ...model of depression hypothesises that the serum level of e.g. BDNF is decreased during depression and increased in response to treatment. The aim of the present study was to investigate BDNF and VEGF as potential predictors of response to antidepressant treatment. Methods We investigated the longitudinal associations between depression scores and serum levels of these neurotrophic factors during antidepressant treatment in 90 individuals with depression of at least moderate severity. Serum levels were measured at baseline and after 8 and 12 weeks of treatment with nortriptyline or escitalopram. Results No baseline or longitudinal correlations between depression scores and serum levels of BDNF and VEGF were found, and the baseline serum levels did not predict the MADRS depression score after 12 weeks of treatment or the improvement in depression scores. Interestingly, we observed a significant baseline and longitudinal correlation between serum levels of BDNF and VEGF. The two classes of antidepressant treatment did not affect the results differently. Limitations Information on potential factors influencing the serum levels is missing. Conclusion Our results do not support the neurotrophic model of depression, since a significant decrease in serum BDNF and VEGF levels after 12 weeks of antidepressant treatment was observed. Our study encourages future studies with large sample sizes, more observations and a longer follow-up period.
It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test ...the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.
The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10(-8)). No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10(-8)) were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.
No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the Editors' Summary.
The main objective of the study was to find genetic variants that in combination are significantly associated with bipolar disorder. In previous studies of bipolar disorder, combinations of three and ...four single nucleotide polymorphisms (SNP) genotypes taken from 803 SNPs were analyzed, and five clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of ten SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder. Combinations from the new cluster and from the five previous clusters were identified in the genomes of 266 or 44% of the 607 patients in the study whereas none of the 1355 control participants had any of these combinations in their genome.The SNP genotypes in the smaller combinations were the normal homozygote, heterozygote or variant homozygote. In the combinations containing 10 SNP genotypes almost all the genotypes were the normal homozygote. Such a finding may indicate that accumulation in the genome of combinations containing few SNP genotypes may be a risk factor for bipolar disorder when those combinations contain relatively many rare SNP genotypes, whereas combinations need to contain many SNP genotypes to be a risk factor when most of the SNP genotypes are the normal homozygote.
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