Meta-analysis of Positive and Negative Symptoms Reveals Schizophrenia Modifier Genes

BACKGROUND: Evidence suggests that genetic factors may influence both schizophrenia (Scz) and its clinical presentation. In recent years, genome-wide association studies (GWAS) have demonstrated considerable success in identifying risk loci. Detection of "modifier loci" has the potential to further elucidate underlying disease processes.

METHODS: We performed GWAS of empirically derived positive and negative symptom scales in Irish cases from multiply affected pedigrees and a larger, independent case-control sample, subsequently combining these into a large Irish meta-analysis. In addition to single-SNP associations, we considered gene-based and pathway analyses to better capture convergent genetic effects, and to facilitate biological interpretation of these findings. Replication and testing of aggregate genetic effects was conducted using an independent European-American sample.

RESULTS: Though no single marker met the genome-wide significance threshold, genes and ontologies/pathways were significantly associated with negative and positive symptoms; notably, NKAIN2 and NRG1, respectively. We observed limited overlap in ontologies/pathways associated with different symptom profiles, with immune-related categories over-represented for negative symptoms, and addiction-related categories for positive symptoms. Replication analyses suggested that genes associated with clinical presentation are generalizable to non-Irish samples.

CONCLUSIONS: These findings strongly support the hypothesis that modifier loci contribute to the etiology of distinct Scz symptom profiles. The finding that previously implicated "risk loci" actually influence particular symptom dimensions has the potential to better delineate the roles of these genes in Scz etiology. Furthermore, the over-representation of distinct gene ontologies/pathways across symptom profiles suggests that the clinical heterogeneity of Scz is due in part to complex and diverse genetic factors.

White matter pathway organization of the reward system is related to positive and negative symptoms in schizophrenia

The reward systemin schizophrenia has been linked to the emergence of delusions on the one hand and to negative symptoms such as affective flattening on the other hand. Previous Diffusion Tensor Imaging (DTI) studies reported white matter microstructure alterations of regions related to the reward system. The present study aimed at extending these findings by specifically investigating connection pathways of the reward system in schizophrenia. Therefore, 24 patients with schizophrenia and 22 healthy controls matched for age and gender underwent DTI-scans. Using a probabilistic fiber tracking approachwe bilaterally extracted pathways connecting the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), themedial and lateral orbitofrontal cortices (mOFC, lOFC), the dorsolateral prefrontal cortex (dlPFC) and the amygdala; as well as pathways connecting NAcc with mOFC, lOFC, dlPFC and amygdala resulting in a total of 18 connections. Probability indices forming part of a bundle of interest (PIBI) were compared between groups using independent t-tests. In 6 connection pathways PIBI-valueswere increased in schizophrenia. In 3 of these pathways the spatial extension of connection pathways was decreased. In schizophrenia patients, there was a negative correlation of PIBI-values and PANSS negative scores in the left VTA–amygdala and in the left NAcc–mOFC connection. A sum score of delusions and hallucinations correlated positively with PIBI-values of the left amygdala–NAcc connection. Structural organization of specific segments ofwhite matter pathways of the reward systemin schizophrenia may contribute to the emergence of delusions and negative symptoms in schizophrenia.

A neuropsychological study of prefrontal lobe function in the positive and negative subtypes of schizophrenia.

The symptoms of schizophrenia are frequently divided into positive and negative subtypes. It has been suggested that the negative symptoms are similar to those seen with prefrontal lobe cortical dysfunction. Several neuropsychological investigations of that hypothesis have been carried out, but none have directly compared a negative symptom group with a positive symptom group on the same test battery. In the present study, the Positive and Negative Syndrome Scale (PANSS; Kay, Fiszbein, & Opler, 1987) was used to distinguish two groups of 20 patients with schizophrenia with predominant positive or negative symptoms. A battery of 7 neuropsychological tests considered capable of isolating prefrontal lobe dysfunction was administered. A significant group difference was noted on 6 of the tests; the negative symptom group performed much worse than the positive symptom group. The results of this study support the hypothesis that a relationship exists between the negative symptoms of schizophrenia and prefrontal lobe dysfunction.

Dimensional approaches to schizophrenia: A comparison of the Bern Psychopathology scale and the five-factor model of the Positive and Negative Syndrome Scale

The aim was to examine to what extent the dimensions of the BPS map the five factors derived from the PANSS in order to explore the level of agreement of these alternative dimensional approaches in patients with schizophrenia. 149 inpatients with schizophrenia spectrum disorders were recruited. Psychopathological symptoms were assessed with the Bern Psychopathology Scale (BPS) and the Positive and Negative Syndrome Scale (PANSS). Linear regression analyses were conducted to explore the association between the factors and the items of the BPS. The robustness of patterns was evaluated. An understandable overlap of both approaches was found for positive and negative symptoms and excitement. The PANSS positive factor was associated with symptoms of the affect domain in terms of both inhibition and disinhibition, the PANSS negative factor with symptoms of all three domains of the BPS as an inhibition and the PANSS excitement factor with an inhibition of the affect domain and a disinhibition of the language and motor domains. The results show that here is only a partial overlap between the system-specific approach of the BPS and the five-factor PANSS model. A longitudinal assessment of psychopathological symptoms would therefore be of interest.

The relationship between significant others' positive and negative statements, self-talk and self-esteem

This study investigated the effect of self-talk in mediating between positive and negative statements made by significant others and self-esteem with children in grades 3 to 7. Students completed questionnaires on the frequency of positive and negative statements from parents, teachers, and peers. Findings suggest that self-talk does mediate between significant others' statements and children's self-esteem.

Children's self-talk and significant others' positive and negative statements

A sample of 675 elementary school children in Grades 3-7 were administered the Self-talk Inventory and the Significant Others' Statements Inventory. The psychometric properties of both scales were investigated and the relationships between positive and negative self-talk and significant others' (parents, teachers, siblings and peers) positive and negative statements were explored using correlational and multiple regression analyses. Sex and age differences were also examined. The significant relationships and differences are described.

Mining positive and negative patterns for relevance feature discovery

It is a big challenge to guarantee the quality of discovered relevance features in text documents for describing user preferences because of the large number of terms, patterns, and noise. Most existing popular text mining and classification methods have adopted term-based approaches. However, they have all suffered from the problems of polysemy and synonymy. Over the years, people have often held the hypothesis that pattern-based methods should perform better than term-based ones in describing user preferences, but many experiments do not support this hypothesis. The innovative technique presented in paper makes a breakthrough for this difficulty. This technique discovers both positive and negative patterns in text documents as higher level features in order to accurately weight low-level features (terms) based on their specificity and their distributions in the higher level features. Substantial experiments using this technique on Reuters Corpus Volume 1 and TREC topics show that the proposed approach significantly outperforms both the state-of-the-art term-based methods underpinned by Okapi BM25, Rocchio or Support Vector Machine and pattern based methods on precision, recall and F measures.

Feedback information and consumer motivation : the moderation role of positive and negative reference values in self-regulation

Marketers spend considerable resources to motivate people to consume their products and services as a means of goal attainment (Bagozzi and Dholakia, 1999). Why people increase, decrease, or stop consuming some products is based largely on how well they perceive they are doing in pursuit of their goals (Carver and Scheier, 1992). Yet despite the importance for marketers in understanding how current performance influences a consumer’s future efforts, this topic has received little attention in marketing research. Goal researchers generally agree that feedback about how well or how poorly people are doing in achieving their goals affects their motivation (Bandura and Cervone, 1986; Locke and Latham, 1990). Yet there is less agreement about whether positive and negative performance feedback increases or decreases future effort (Locke and Latham, 1990). For instance, while a customer of a gym might cancel his membership after receiving negative feedback about his fitness, the same negative feedback might cause another customer to visit the gym more often to achieve better results. A similar logic can apply to many products and services from the use of cosmetics to investing in mutual funds. The present research offers managers key insights into how to engage customers and keep them motivated. Given that connecting customers with the company is a top research priority for managers (Marketing Science Institute, 2006), this article provides suggestions for performance metrics including four questions that managers can use to apply the findings.

Comparison of the binding stoichiometries of positively charged DNA-binding drugs using positive and negative ion electrospray ionization mass spectrometry

Positive and negative ion electrospray ionization (ESI) mass spectra of complexes of positively charged small molecules (distamycin, Hoechst 33258, [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2) have been compared. [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2 bind to DNA by intercalation. Negative ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA showed ions from DNA-ligand complexes consistent with solution studies. In contrast, only ions from freeDNAwere present in positive ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA, highlighting the need for obtaining ESI mass spectra of non-covalent complexes under a range of experimental conditions. Negative ion spectra of mixtures of the minor groove binder Hoechst 33258 with DNA containing a known minor groove binding sequence were dominated by ions from a 1:1 complex. In contrast, in positive ion spectra there were also ions present from a 2:1 (Hoechst 33258: DNA) complex, suggesting an alternative binding mode was possible either in solution or in the gas phase. When Hoechst 33258 was mixed with a DNA sequence lacking a high affinity minor groove binding site, the negative ion ESI mass spectra showed that 1:1 and 2:1 complexes were formed, consistent with existence of binding modes other than minor groove binding. The data presented suggest that comparison of positive and negative ion ESI-MS spectra might provide an insight into various binding modes in both solution and the gas phase.

International assessments of science learning : their positive and negative contributions to science education

The establishment and continuity of two international comparative assessments of science learning—the IEA’s TIMSS project and the OECD’s PISA project—have meant that there are now high-status reference points for other national and more local approaches to assessing the efficacy of science teaching and learning. Both projects, albeit with very different senses of what the outcome of science learning should be, have contributed positively and negatively to the current state of assessment of school science. The TIMSS project looks back at the science that is commonly included in the curricula of the participating countries. It is thus not about established school science nor about innovations in it. PISA is highly innovative looking, prospectively forward to see how students can use their science learning in everyday life situations. In this chapter some of these positives and negatives are discussed.

Predicting positive and negative impacts of cancer among long-term endometrial cancer survivors

OBJECTIVE Although the survival outcomes among women diagnosed with endometrial cancer are very favorable, little is known about the long-term impact of their cancer experience. This study identifies the extent of positive and negative impacts of cancer and factors associated with this, amongst long-term survivors of endometrial cancer. METHODS Australian women diagnosed with endometrial cancer (N=632) were sent questionnaires at the time of diagnosis and 3-5 years later. Hierarchical multiple regression models were used to examine whether a range of variables at diagnosis/treatment predicted subsequent scores on the Impact of Cancer Scale, which examines positive (e.g. health awareness) and negative (e.g. appearance concerns) impacts amongst cancer survivors. RESULTS Overall, women had a higher mean score for the positive than negative impact scales (M=3.5 versus M=2.5, respectively). An intermediate grade of endometrial cancer, a prior diagnosis of cancer and lower levels of education were significant, but weak, predictors of higher scores on the positive impact scale. Higher scores on the negative impact scale were predicted by a higher grade of cancer, poor physical and mental health, a younger age, being single or having lower levels of education. CONCLUSIONS The study demonstrates that factors that predict positive impact in cancer survivors differ to those that predict negative impact, suggesting that interventions to optimize cancer survivors' quality of life will need to be multi-dimensional, and this supports the need for tailored intervention.