Dataset Information

Coding and noncoding gene expression biomarkers in mood disorders and schizophrenia.

ABSTRACT: Mood disorders and schizophrenia are common and complex disorders with consistent evidence of genetic and environmental influences on predisposition. It is generally believed that the consequences of disease, gene expression, and allelic heterogeneity may be partly the explanation for the variability observed in treatment response. Correspondingly, while effective treatments are available for some patients, approximately half of the patients fail to respond to current neuropsychiatric treatments. A number of peripheral gene expression studies have been conducted to understand these brain-based disorders and mechanisms of treatment response with the aim of identifying suitable biomarkers and perhaps subgroups of patients based upon molecular fingerprint. In this review, we summarize the results from blood-derived gene expression studies implemented with the aim of discovering biomarkers for treatment response and classification of disorders. We include data from a biomarker study conducted in first-episode subjects with schizophrenia, where the results provide insight into possible individual biological differences that predict antipsychotic response. It is concluded that, while peripheral studies of expression are generating valuable results in pathways involving immune regulation and response, larger studies are required which hopefully will lead to robust biomarkers for treatment response and perhaps underlying variations relevant to these complex disorders.

SUBMITTER: Mamdani F

PROVIDER: S-EPMC3774957 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Coding and noncoding gene expression biomarkers in mood disorders and schizophrenia.

Mamdani Firoza F Martin Maureen V MV Lencz Todd T Rollins Brandi B Robinson Delbert G DG Moon Emily A EA Malhotra Anil K AK Vawter Marquis P MP

Disease markers 20130721 1

Mood disorders and schizophrenia are common and complex disorders with consistent evidence of genetic and environmental influences on predisposition. It is generally believed that the consequences of disease, gene expression, and allelic heterogeneity may be partly the explanation for the variability observed in treatment response. Correspondingly, while effective treatments are available for some patients, approximately half of the patients fail to respond to current neuropsychiatric treatments ...[more]

PMID: 24167345

Similar Datasets

Project description:ImportanceChildren with strabismus have poorer functional vision and decreased quality of life than those without strabismus.ObjectiveTo evaluate the association between strabismus and mental illness among children.Design, setting, and participantsThis cross-sectional study analyzed claims data from the OptumLabs Data Warehouse, a longitudinal deidentified commercial insurance claims database, from 12 005 189 patients enrolled in the health plan between January 1, 2007, and December 31, 2017. Eligibility criteria included age younger than 19 years at the time of strabismus diagnosis, enrollment in the health plan between 2007 and 2018, and having at least 1 strabismus claim based on International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification codes. Controls were children in the same database with no eye disease codes other than refractive error reported. Demographic characteristics and mental illness claims were compared. Statistical analysis was conducted from December 1, 2018, to July 31, 2021.Main outcomes and measuresPresence of mental illness claims.ResultsAmong the 12 005 189 patients (6 095 523 boys [50.8%]; mean [SD] age, 8.0 [5.9] years) in the study, adjusted odds ratios for the association of mental illnesses with strabismus were 2.01 (95% CI, 1.99-2.04) for anxiety disorder, 1.83 (95% CI, 1.76-1.90) for schizophrenia, 1.64 (95% CI, 1.59-1.70) for bipolar disorder, 1.61 (95% CI, 1.59-1.63) for depressive disorder, and 0.99 (95% CI, 0.97-1.02) for substance use disorder. There was a moderate association between each strabismus type (esotropia, exotropia, and hypertropia) and anxiety disorder, schizophrenia, bipolar disorder, and depressive disorder; odds ratios ranged from 1.23 (95% CI, 1.17-1.29) for the association between esotropia and bipolar disorder to 2.70 (95% CI, 2.66-2.74) for the association between exotropia and anxiety disorder.Conclusions and relevanceThis cross-sectional study suggests that there was a moderate association between strabismus and anxiety disorder, schizophrenia, bipolar disorder, and depressive disorder but not substance use disorder. Recognizing that these associations exist should encourage mental illness screening and treatment for patients with strabismus.

Project description:Autism spectrum disorder often co-occurs with other psychiatric disorders. Although a high prevalence of autistic-like traits/symptoms has been identified in the pediatric psychiatric population of normal intelligence, there are no reports from adult psychiatric population. This study examined whether there is a greater prevalence of autistic-like traits/symptoms in patients with adult-onset psychiatric disorders such as major depressive disorder (MDD), bipolar disorder, or schizophrenia, and whether such an association is independent of symptom severity. The subjects were 290 adults of normal intelligence between 25 and 59 years of age (MDD, n=125; bipolar disorder, n=56; schizophrenia, n=44; healthy controls, n=65). Autistic-like traits/symptoms were measured using the Social Responsiveness Scale for Adults. Symptom severity was measured using the Positive and Negative Symptoms Scale, the Hamilton Depression Rating Scale, and/or the Young Mania Rating Scale. Almost half of the clinical subjects, except those with remitted MDD, exhibited autistic-like traits/symptoms at levels typical for sub-threshold or threshold autism spectrum disorder. Furthermore, the proportion of psychiatric patients that demonstrated high autistic-like traits/symptoms was significantly greater than that of healthy controls, and not different between that of remitted or unremitted subjects with bipolar disorder or schizophrenia. On the other hand, remitted subjects with MDD did not differ from healthy controls with regard to the prevalence or degree of high autistic-like traits/symptoms. A substantial proportion of adults with bipolar disorder and schizophrenia showed high autistic-like traits/symptoms independent of symptom severity, suggesting a shared pathophysiology among autism spectrum disorder and these psychiatric disorders. Conversely, autistic-like traits among subjects with MDD were associated with the depressive symptom severity. These findings suggest the importance of evaluating autistic-like traits/symptoms underlying adult-onset psychiatric disorders for the best-suited treatment. Further studies with a prospective design and larger samples are needed.

Project description:Obesity is accompanied by hyperphagia in several classical genetic obesity-related syndromes that are rare, including Prader-Willi syndrome (PWS) and Alström syndrome (ALMS). We compared coding and noncoding gene expression in adult males with PWS, ALMS, and nonsyndromic obesity relative to nonobese males using readily available lymphoblastoid cells to identify disease-specific molecular patterns and disturbed mechanisms in obesity. We found 231 genes upregulated in ALMS compared with nonobese males, but no genes were found to be upregulated in obese or PWS males and 124 genes were downregulated in ALMS. The metallothionein gene (MT1X) was significantly downregulated in ALMS, in common with obese males. Only the complex SNRPN locus was disturbed (downregulated) in PWS along with several downregulated small nucleolar RNAs (snoRNAs) in the 15q11-q13 region (SNORD116, SNORD109B, SNORD109A, SNORD107). Eleven upregulated and ten downregulated snoRNAs targeting multiple genes impacting rRNA processing, developmental pathways, and associated diseases were found in ALMS. Fifty-two miRNAs associated with multiple, overlapping gene expression disturbances were upregulated in ALMS, and four were shared with obese males but not PWS males. For example, seven passenger strand microRNAs (miRNAs) (miR-93*, miR-373*, miR-29b-2*, miR-30c-1*, miR27a*, miR27b*, and miR-149*) were disturbed in association with six separate downregulated target genes (CD68, FAM102A, MXI1, MYO1D, TP53INP1, and ZRANB1). Cell cycle (eg, PPP3CA), transcription (eg, POLE2), and development may be impacted by upregulated genes in ALMS, while downregulated genes were found to be involved with metabolic processes (eg, FABP3), immune responses (eg, IL32), and cell signaling (eg, IL1B). The high number of gene and noncoding RNA disturbances in ALMS contrast with observations in PWS and males with nonsyndromic obesity and may reflect the progressing multiorgan pathology of the ALMS disease process.

Project description:BackgroundBrain-derived neurotrophic factor (BDNF), tyrosine kinase receptor (trkB-TK+) and glutamic acid decarboxylase (GAD67) mRNA levels have previously been found to be reduced in the prefrontal cortex of patients with schizophrenia. To determine whether this reduction extends to other brain regions, we measured the expression levels of BDNF, trkB-TK+ and GAD67 mRNA in regions of the hippocampus, including the dentate gyrus (DG), cornu ammonis subfields (CA1-4), subiculum and entorhinal cortex (EC) of individuals with schizophrenia, bipolar disorder, major depression and unaffected controls.MethodsIn situ hybridization was performed on postmortem brain tissue obtained from the Stanley Foundation Consortium and analyzed using film-based quantification.ResultsAnalyses of covariance comparing the expression of mRNA among all groups revealed a significant decrease in BDNF mRNA in CA4 in the bipolar disorder group compared with controls (33%). We found trkB-TK+ mRNA levels to be significantly reduced in CA4 in the schizophrenia group (36%) and in layer II of the EC in the bipolar disorder and major depression groups (28%, 21%, respectively) compared with controls. In addition, GAD67 mRNA levels were reduced in patients with schizophrenia in both the DG (23%) and CA4 (60%) compared with controls. Individuals with major depression also expressed significantly less GAD67 mRNA (44%) compared with controls in CA4 of the hippocampus.LimitationsIt is necessary to account for factors that influence the molecular preservation in postmortem brain tissue, including pH, postmortem interval and tissue storage time. Moreover, there are limitations to the sensitivity of the film-based method of quantification.ConclusionOur findings show abnormal BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders, indicating that fundamental properties of hippocampal signalling transmission, plasticity and circuitry may be affected in individuals with these major mental illnesses.

Dataset Information

Coding and noncoding gene expression biomarkers in mood disorders and schizophrenia.

Publications

Coding and noncoding gene expression biomarkers in mood disorders and schizophrenia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets