Network Analysis Reveals Which Negative Symptom Domains Are Most Central in Schizophrenia vs Bipolar Disorder.
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ABSTRACT:
SUBMITTER: Strauss GP
PROVIDER: S-EPMC6811832 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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Project description:Elevated peripheral proline is associated with psychiatric disorders, and there is evidence that proline is a neuromodulator. The proline dehydrogenase (PRODH) gene, which encodes the enzyme that catalyzes proline catabolism, maps to human chromosome 22q11.2, a region conferring risk of schizophrenia. In the Prodh-null mouse, an interaction between elevated peripheral proline and another 22q11.2 gene, catechol-O-methyltransferase (COMT), on neurotransmission and behavior has been reported. We explored the relationship between fasting plasma proline levels and COMT Val(158)Met genotype on symptoms (positive, negative and total) in schizophrenia patients. In an exploratory study we also examined symptom change in patients with bipolar disorder. There was a significant interaction between peripheral proline and COMT on negative symptoms in schizophrenia (P<0.0001, n=95). In COMT Val/Val patients, high proline was associated with low Scale for the Assessment of Negative Symptom (SANS) scores. In contrast, high proline was associated with high SANS scores in patients carrying a Met allele. The relationship between proline and COMT also appears to modify negative symptoms across psychiatric illness. In bipolar disorder, a significant interaction was also observed on negative-symptom change (P=0.007, n=43). Negative symptoms are intractable and largely unaddressed by current medications. These data indicate a significant interaction between peripheral proline and COMT genotype, influencing negative symptoms in schizophrenia and bipolar disorder. That high proline has converse effects on symptoms by COMT genotype, may have implications for therapeutic decisions.
| S-EPMC5048199 | biostudies-literature
Project description:BackgroundAcross clinical settings, black individuals are disproportionately less likely to be diagnosed with bipolar disorder compared to schizophrenia, a traditionally more severe and chronic disorder with lower expectations for remission. The causes of this disparity are likely multifactorial, ranging from the effects of implicit bias, to developmental and lifelong effects of structural racism, to differing cultural manifestations of psychiatric symptoms and distress. While prior studies examining differences have found a greater preponderance of specific psychotic symptoms (such as persecutory delusions and hallucinations) and a more dysphoric/mixed mania presentation in Black individuals, these studies have been limited by a lack of systematic phenotypic assessment and small sample sizes. In the current report, we have combined data from two large multi-ethnic studies of bipolar disorder with comparable semi-structured interviews to investigate differences in symptoms presentation across the major clinical symptom domains of bipolar disorder.ResultsIn the combined meta-analysis, there were 4423 patients diagnosed with bipolar disorder type I, including 775 of self-reported as Black race. When symptom presentations were compared in Black versus White individuals, differences were found across all the major clinical symptom domains of bipolar disorder. Psychotic symptoms, particularly persecutory hallucinations and both persecutory and mood-incongruent delusions, were more prevalent in Black individuals with bipolar disorder type I (ORs = 1.26 to 2.45). In contrast, Black individuals endorsed fewer prototypical manic symptoms, with a notably decreased likelihood of endorsing abnormally elevated mood (OR = 0.44). Within depression associated symptoms, we found similar rates of mood or cognitive related mood symptoms but higher rates of decreased appetite (OR = 1.32) and weight loss (OR = 1.40), as well as increased endorsement of initial, middle, and early-morning insomnia (ORs = 1.73 to 1.82). Concurrently, we found that black individuals with BP-1 were much less likely to be treated with mood stabilizers, such as lithium (OR = 0.45), carbamazepine (OR = 0.37) and lamotrigine (OR = 0.34), and moderately more likely to be on antipsychotic medications (OR = 1.25).ConclusionsIn two large studies spanning over a decade, we found highly consistent and enduring differences in symptoms across the major clinical symptom domains of bipolar disorder. These differences were marked by a greater burden of mood-incongruent psychotic symptoms, insomnia and irritability, and fewer prototypical symptoms of mania. While such symptoms warrant better recognition to reduce diagnostic disparities, they may also represent potential targets of treatment that can be addressed to mitigate persistent disparities in outcome.
| S-EPMC10175527 | biostudies-literature
Project description:Background: Cognitive dysfunction is considered a core feature among schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Despite abundant literature comparing cognitive dysfunction among these disorders, the relationship between cognitive dysfunction and symptom dimensions remains unclear. The study aims are a) to identify the factor structure of the BPRS-18 and b) to examine the relationship between symptom domains and cognitive function across SZ, BD, and MDD. Methods: A total of 716 participants [262 with SZ, 104 with BD, 101 with MDD, and 249 healthy controls (HC)] were included in the study. One hundred eighty participants (59 with SZ, 23 with BD, 24 with MDD, and 74 HC) completed the MATRICS Consensus Cognitive Battery (MCCB), and 507 participants (85 with SZ, 89 with BD, 90 with MDD, and 243 HC) completed the Wisconsin Card Sorting Test (WCST). All patients completed the Brief Psychiatric Rating Scale (BPRS). Results: We identified five BPRS exploratory factor analysis (EFA) factors ("affective symptoms," "psychosis," "negative/disorganized symptoms," "activation," and "noncooperation") and found cognitive dysfunction in all of the participant groups with psychiatric disorders. Negative/disorganized symptoms were the most strongly associated with cognitive dysfunctions across SZ, BD, and MDD. Conclusions: Our findings suggest that cognitive dysfunction severity relates to the negative/disorganized symptom domain across SZ, BD, and MDD, and negative/disorganized symptoms may be an important target for effective cognitive remediation in SZ, BD, and MDD.
| S-EPMC6498739 | biostudies-literature
Project description:This study introduces a novel way to use the lifetime ratings of symptoms of psychosis, mania and depression in genetic linkage analysis of schizophrenia (SZ) and bipolar disorder (BP). It suggests using a latent class model developed for family data to define more homogeneous symptom subtypes that are influenced by a smaller number of genes that will thus be more easily detectable. In a two-step approach, we proposed: (i) to form homogeneous clusters of subjects based on the symptom dimensions and (ii) to use the information from these homogeneous clusters in linkage analysis. This framework was applied to a unique SZ and BP sample composed of 1278 subjects from 48 large kindreds from the Eastern Quebec population. The results suggest that our strategy has the power to increase linkage signals previously obtained using the diagnosis as phenotype and allows for a better characterization of the linkage signals. This is the case for a linkage signal, which we formerly obtained in chromosome 13q and enhanced using the dimension mania. The analysis also suggests that the methods may detect new linkage signals not previously uncovered by using diagnosis alone, as in chromosomes 2q (delusion), 15q (bizarre behavior), 7p (anhedonia) and 9q (delusion). In the case of the 15q and 2q region, the results coincide with linkage signals detected in other studies. Our results support the view that dissecting phenotypic heterogeneity by modeling symptom dimensions may provide new insights into the genetics of SZ and BP.
| S-EPMC3476706 | biostudies-literature
Project description:The brain's default mode network (DMN) is highly heritable and is compromised in a variety of psychiatric disorders. However, genetic control over the DMN in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is largely unknown. Study subjects (n = 1,305) underwent a resting-state functional MRI scan and were analyzed by a two-stage approach. The initial analysis used independent component analysis (ICA) in 324 healthy controls, 296 SZ probands, 300 PBP probands, 179 unaffected first-degree relatives of SZ probands (SZREL), and 206 unaffected first-degree relatives of PBP probands to identify DMNs and to test their biomarker and/or endophenotype status. A subset of controls and probands (n = 549) then was subjected to a parallel ICA (para-ICA) to identify imaging-genetic relationships. ICA identified three DMNs. Hypo-connectivity was observed in both patient groups in all DMNs. Similar patterns observed in SZREL were restricted to only one network. DMN connectivity also correlated with several symptom measures. Para-ICA identified five sub-DMNs that were significantly associated with five different genetic networks. Several top-ranking SNPs across these networks belonged to previously identified, well-known psychosis/mood disorder genes. Global enrichment analyses revealed processes including NMDA-related long-term potentiation, PKA, immune response signaling, axon guidance, and synaptogenesis that significantly influenced DMN modulation in psychoses. In summary, we observed both unique and shared impairments in functional connectivity across the SZ and PBP cohorts; these impairments were selectively familial only for SZREL. Genes regulating specific neurodevelopment/transmission processes primarily mediated DMN disconnectivity. The study thus identifies biological pathways related to a widely researched quantitative trait that might suggest novel, targeted drug treatments for these diseases.
| S-EPMC4024891 | biostudies-literature
Project description:BackgroundThe network approach to psychopathology has become increasingly popular. Little research has examined the dynamic network structure of mental disorders, and, to date, no study has investigated the network dynamics of positive affect, negative affect, and physical activity in bipolar disorder. This represents the first study to estimate the dynamic network structure of affect and physical activity in individuals with and without bipolar I disorder.MethodsAn intensive longitudinal design was used to assess positive affect, negative affect, and actigraphy-based estimates of physical activity. The overall sample consisted of 32 adults with bipolar I disorder and 36 healthy control participants. Eligible participants underwent an 8-week assessment period, in which once-per-day ratings of affect and actigraphy estimates were obtained. Participants were re-assessed on baseline measures afterwards. Dynamic network analysis was used to examine the network structure of affect and physical activity over time. Multilevel models were used to examine the relationship between autocorrelation and changes in depression symptoms among participants with bipolar disorder.LimitationsThe network analyses assume stationarity. Future research should consider time-varying multilevel network models to better account for time trends.ResultsThe results of the temporal networks indicated that the directed edges between positive and negative affect were mostly positive among individuals with bipolar I disorder. Among healthy control participants, the directed edges between positive and negative affect were mostly negative in direction. Physical activity, as assessed by daily actigraphy indices, was more densely connected in the healthy control network than the bipolar disorder network. Furthermore, the results indicated that critical slowing down predicted worsening of mood symptoms in the bipolar I disorder group.ConclusionsThis study suggests that certain dynamic patterns of affect may be an underlying process that contributes to the maintenance of bipolar disorder. These results have both theoretical and practical implications.
| S-EPMC7438157 | biostudies-literature
Project description:Purpose of study is revealing significant differences in serum proteomes in schizophrenia, bipolar disorder (BD), and matched healthy controls. The sample preparation included affinity removing of six major proteins, separation by 1D electrophoresis, in-gel tryptic hydrolysis, and LC-MS/MS peptide analysis using LTQ Orbitrap Velos mass spectrometer. When comparing proteome profiles, different unique protein sets were revealed (absent in other groups): 22 proteins typical for schizophrenia, and 20 – for BD. Protein set in schizophrenia was mostly associated with nucleic acid and protein metabolism, immune response, cell communication, and cell growth and maintenance. Protein set in BD was mostly associated with cell growth and maintenance, nucleic acid metabolism regulation, immune response, protein metabolism, transport and cell communication. Concentrations of ankyrin repeat domain-containing protein 12 (ANKRD12), coagulation factor XIII, and cadherin 5 in serum samples were determined by ELISA. Significant difference between three groups was revealed in ANKRD12 concentration (p=0.02), with maximum elevation of ANKRD12 concentration (median level) in schizophrenia followed by BD. Cadherin 5 concentration differed significantly (p=0.035) between schizophrenic patients with prevailing positive symptoms (4.78 [2.71;7.12] ng/ml) and those with prevailing negative symptoms (1.86 [0.001;4.11] ng/ml). Our results are presumably useful for discovering the new pathways involved in endogenous psychotic disorders.
2019-11-12 | PXD009219 | Pride
Project description:IntroductionSchizophrenia is a severe psychiatric disorder with a large symptomatic heterogeneity. Moreover, many patients with schizophrenia present with comorbid psychiatric symptoms or disorders. The relation between depressive symptoms and negative symptoms, such as blunted affect, alogia, anhedonia, asociality and avolition, is particularly intriguing. The negative symptoms can be primary or secondary of depression or overlapping with depressive symptoms. The aim of the present network analysis was to better understand the interactions between depressive symptoms and the different symptoms of schizophrenia and to investigate whether negative symptoms and depressive symptoms can be better delineated.MethodsA network analysis on the baseline item scores of the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) from the cariprazine-risperidone study in patients with predominant negative symptoms (PNS) was performed. The connections between all these symptoms (PANSS and CDSS) were investiged: node strength and network centrality were estimated and the Mohr 5-factor model of the PANSS was applied to test the validity of its different symptoms clusters.ResultsAcross 460 patients with schizophrenia and PNS, the most central symptom (largest node strength) was depression (PANSS) followed by depression (CDSS), anxiety, lack of judgment and insight and tension. The PANSS negative symptom cluster together and was only poorly connected with CDSS depresson symptoms. The Mohr 5 factor model was clearly recognized in the overall clustering of symptoms.ConclusionThis network analysis suggests that depression and anxiety symptoms are the most central in this PNS patient population, despite the baseline low depression scores, and that negative symptoms are a clearly independent symptom cluster that can be delineated from depressive symptoms.
| S-EPMC9081724 | biostudies-literature
Project description:While there are many studies on pareidolia in healthy individuals and patients with schizophrenia, to our knowledge, there are no prior studies on pareidolia in patients with bipolar disorder. Accordingly, in this study, we, for the first time, measured pareidolia in patients with bipolar disorder (N = 50), and compared that to patients with schizophrenia (N = 50) and healthy controls (N = 50). We have used (a) the scene test, which consists of 10 blurred images of natural scenes that was previously found to produce illusory face responses and (b) the noise test which had 32 black and white images consisting of visual noise and 8 images depicting human faces; participants indicated whether a face was present on these images and to point to the location where they saw the face. Illusory responses were defined as answers when observers falsely identified objects that were not on the images in the scene task (maximum illusory score: 10), and the number of noise images in which they reported the presence of a face (maximum illusory score: 32). Further, we also calculated the total pareidolia score for each task (the sum number of images with illusory responses in the scene and noise tests). The responses were scored by two independent raters with an excellent congruence (kappa > 0.9). Our results show that schizophrenia patients scored higher on pareidolia measures than both healthy controls and patients with bipolar disorder. Our findings are agreement with prior findings on more impaired cognitive processes in schizophrenia than in bipolar patients.
| S-EPMC8702957 | biostudies-literature
Project description:Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders associated with cognitive impairment, which is considered a major determinant of functional outcome. Despite this, the etiology of the cognitive impairment is poorly understood, and no satisfactory cognitive treatments exist. Increasing evidence indicates that genetic risk for SCZ may contribute to cognitive impairment, whereas the genetic relationship between BD and cognitive function remains unclear. Here, we combined large genome-wide association study data on SCZ (n = 82,315), BD (n = 51,710), and general intelligence (n = 269,867) to investigate overlap in common genetic variants using conditional false discovery rate (condFDR) analysis. We observed substantial genetic enrichment in both SCZ and BD conditional on associations with intelligence indicating polygenic overlap. Using condFDR analysis, we leveraged this enrichment to increase statistical power and identified 75 distinct genomic loci associated with both SCZ and intelligence, and 12 loci associated with both BD and intelligence at conjunctional FDR < 0.01. Among these loci, 20 are novel for SCZ, and four are novel for BD. Most SCZ risk alleles (61 of 75, 81%) were associated with poorer cognitive performance, whereas most BD risk alleles (9 of 12, 75%) were associated with better cognitive performance. A gene set analysis of the loci shared between SCZ and intelligence implicated biological processes related to neurodevelopment, synaptic integrity, and neurotransmission; the same analysis for BD was underpowered. Altogether, the study demonstrates that both SCZ and BD share genetic influences with intelligence, albeit in a different manner, providing new insights into their genetic architectures.
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