scholarly journals Fatty Acid Desaturase Gene Polymorphisms and Metabolic Measures in Schizophrenia and Bipolar Patients Taking Antipsychotics

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Kyle J. Burghardt ◽  
Kristen N. Gardner ◽  
Joshua W. Johnson ◽  
Vicki L. Ellingrod
Keyword(s):  
Insulin Resistance ◽  
Bipolar Disorder ◽  
Fatty Acid ◽  
Side Effects ◽  
High Risk ◽  
Atypical Antipsychotics ◽  
Fatty Acid Desaturase ◽  
Metabolic Side Effects ◽  
Increased Risk ◽  
Bipolar Patients

Atypical antipsychotics have become a common therapeutic option in both schizophrenia and bipolar disorder. However, these medications come with a high risk of metabolic side effects, particularly dyslipidemia and insulin resistance. Therefore, identification of patients who are at increased risk for metabolic side effects is of great importance. The genetics of fatty acid metabolism is one area of research that may help identify such patients. Therefore, in this present study, we aimed to determine the effect of one commonly studied genetic polymorphism from both fatty acid desaturase 1 (FADS1) and FADS2 gene on a surrogate measure of insulin resistance and lipid levels in a metabolically high-risk population of patients largely exposed to atypical antipsychotics. This study used a cross-sectional design, fasting blood draws, and genetic analysis to investigate associations between polymorphisms, haplotypes, and metabolic measures. A total of 320 subjects with schizophrenia (n=226) or bipolar disorder (n=94) were included in this study. The mean age of the population was 42.5 years and 45% were male. A significant association between FADS1 and FADS2 haplotypes was found with insulin resistance while controlling for confounders. Further investigation is required to replicate this finding.

Risk and coaggregation of major psychiatric disorders among first-degree relatives of patients with bipolar disorder: a nationwide population-based study

2018 ◽  
Vol 49 (14) ◽  
pp. 2397-2404 ◽  
Author(s):  
Mu-Hong Chen ◽  
Ju-Wei Hsu ◽  
Kei-Lin Huang ◽  
Tung-Ping Su ◽  
Cheng-Ta Li ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Population Based ◽  
Autism Spectrum ◽  
The Public ◽  
First Degree Relatives ◽  
Relative Risks ◽  
Dependent Relationship ◽  
Increased Risk ◽  
Bipolar Patients

AbstractBackgroundBipolar disorder is a highly heritable mental illness that transmits intergeneratively. Previous studies supported that first-degree relatives (FDRs), such as parents, offspring, and siblings, of patients with bipolar disorder, had a higher risk of bipolar disorder. However, whether FDRs of bipolar patients have an increased risk of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) remains unclear.MethodsAmong the entire population in Taiwan, 87 639 patients with bipolar disorder and 188 290 FDRs of patients with bipolar disorder were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with bipolar disorder.ResultsFDRs of patients with bipolar disorder were more likely to have a higher risk of major psychiatric disorders, including bipolar disorder (RR 6.12, 95% confidence interval (CI) 5.95–6.30), MDD (RR 2.89, 95% CI 2.82–2.96), schizophrenia (RR 2.64, 95% CI 2.55–2.73), ADHD (RR 2.21, 95% CI 2.13–2.30), and ASD (RR 2.10, 95% CI 1.92–2.29), than the total population did. These increased risks for major psychiatric disorders were consistent across different familial kinships, such as parents, offspring, siblings, and twins. A dose-dependent relationship was also found between risk of each major psychiatric disorder and numbers of bipolar patients.ConclusionsOur study was the first study to support the familial coaggregation of bipolar disorder with other major psychiatric disorders, including schizophrenia, MDD, ADHD, and ASD, in a Taiwanese (non-Caucasian) population. Given the elevated risks of major psychiatric disorders, the public health government should pay more attention to the mental health of FDRs of patients with bipolar disorder.

The Neurobiology and Treatment of Bipolar Disorder

2017 ◽  
Author(s):  
Katherine E. Burdick ◽  
Luz H. Ospina ◽  
Stephen J. Haggarty ◽  
Roy H. Perlis
Keyword(s):  
Bipolar Disorder ◽  
High Risk ◽  
Genetic Risk ◽  
Biological Models ◽  
Increased Risk ◽  
Psychotic Features ◽  
Prodromal Syndrome ◽  
Abnormal Sleep ◽  
Epigenetic Processes ◽  
High Risk Children

Bipolar disorder (BPD) is a severe mood disorder that often has psychotic features. Its most severe forms are more common and significantly more likely to cause disability than originally thought. Studies of high-risk children have found them to be at increased risk for a variety of symptoms and neurobiological abnormalities. In contrast to schizophrenia, there is no formal prodromal syndrome that has been identified, and cognitive abnormalities do not precede the onset of the disorder. Abnormal sleep and circadian rhythms are prominent and have led to intriguing biological models. Neurobiological experiments have primarily focused on candidate pathways and include circadian abnormalities, epigenetic processes including histone modification, WNT/GSK3 signaling, other modulators of neuroplasticity, and mitochondrial dysfunction. Recent data suggest that BPD is a highly polygenic disease and that integration of prior modeling and data with the wide variety of new genetic risk loci will be productive in the future.

scholarly journals 62 Predictors of Tardive Dyskinesia in Psychiatric Patients Taking Concomitant Antipsychotics

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 207-208 ◽  
Author(s):  
Oscar Patterson-Lomba ◽  
Rajeev Ayyagari ◽  
Benjamin Carroll
Keyword(s):  
Quality Of Life ◽  
New York ◽  
Bipolar Disorder ◽  
Depressive Disorder ◽  
Prediction Model ◽  
Psychiatric Disorders ◽  
Index Date ◽  
Atypical Antipsychotics ◽  
Increased Risk

AbstractBackgroundTardive dyskinesia (TD) is typically caused by exposure to antipsychotics, is often irreversible, and can be debilitating. TD symptoms can increase the social stigma of patients with comorbid psychiatric disorders, negatively impact quality of life, and potentially increase medical morbidity and mortality. An increased risk of developing TD has been associated with factors such as older age, female sex, underlying mental illness, and long-term use and higher doses of antipsychotics. The association of TD with the use of typical versus atypical antipsychotics has also been evaluated, with mixed results. To date, predictive models assessing the joint effect of clinical characteristics on TD risk have not been developed and validated in the US population.Study ObjectiveTo develop a prediction model to identify patient and treatment characteristics associated with the occurrence of TD among patients with psychiatric disorders taking antipsychotic medications, using a retrospective database analysis.MethodsAdult patients with schizophrenia, major depressive disorder, or bipolar disorder who were taking oral antipsychotics, and who had 6months of data prior to the index date were identified from Medicaid claims from six US states. The index date was defined as the date of the first claim for an antipsychotic drug after a claim for the underlying disorder but before TD diagnosis. A multivariate Cox prediction model was developed using a cross-validated version of the least absolute shrinkage and selection operator (LASSO) regression method to improve prediction accuracy and interpretability of the model. The predictive performance was assessed in a separate validation set via model discrimination (concordance) and calibration.ResultsA total of 189,415 patients were identified: 66,723 with bipolar disorder, 68,573 with depressive disorder, and 54,119 with schizophrenia. The selected prediction model had a clinically meaningful concordance of 70% and was well calibrated (P=0.46 for Hosmer–Leme show goodness-of-fit test). Patient’s age at index date (hazard ratio [HR]: 1.03), diagnosis of schizophrenia (HR: 1.73), dosage of antipsychotic at index date (up to 100mg/day chlorpromazine equivalent; HR: 1.40), and presence of bipolar and related disorders (HR: 1.16) were significantly associated with an increased risk of TD diagnosis. Use of atypical antipsychotics at index date was associated with a modest reduction in the risk of TD (HR=0.94).ConclusionsThis study identified a group of factors associated with the development of TD among patients with psychiatric disorders treated with antipsychotics. This may allow physicians to better monitor their patients receiving antipsychotics, allowing for the prompt identification and treatment of TD to help maintain quality of life.Presented at: American Psychiatric Association Annual Meeting; May 5–9, 2018, New York, New York, USAFunding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.

scholarly journals The developmental trajectory of bipolar disorder

2014 ◽  
Vol 204 (2) ◽  
pp. 122-128 ◽  
Author(s):  
Anne Duffy ◽  
Julie Horrocks ◽  
Sarah Doucette ◽  
Charles Keown-Stoneman ◽  
Shannon McCloskey ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
High Risk ◽  
Psychotic Disorders ◽  
Familial Risk ◽  
Childhood Anxiety ◽  
Developmental Trajectory ◽  
Developmental Approach ◽  
Increased Risk ◽  
Clinical Stages

BackgroundBipolar disorder is highly heritable and therefore longitudinal observation of children of affected parents is important to mapping the early natural history.AimsTo model the developmental trajectory of bipolar disorder based on the latest findings from an ongoing prospective study of the offspring of parents with well-characterised bipolar disorder.MethodA total of 229 offspring from families in which 1 parent had confirmed bipolar disorder and 86 control offspring were prospectively studied for up to 16 years. High-risk offspring were divided into subgroups based on the parental long-term response to lithium. Offspring were clinically assessed and DSM-IV diagnoses determined on masked consensus review using best estimate procedure. Adjusted survival analysis and generalised estimating equations were used to calculate differences in lifetime psychopathology. Multistate models were used to examine the progression through proposed clinical stages.ResultsHigh-risk offspring had an increased lifetime risk of a broad spectrum of disorders including bipolar disorder (hazard ratio (HR) = 20.89; P = 0.04), major depressive disorder (HR = 17.16; P = 0.004), anxiety (HR = 2.20; P = 0.03), sleep (HR = 28.21; P = 0.02) and substance use disorders (HR = 2.60; P = 0.05) compared with controls. However, only offspring from lithium non-responsive parents developed psychotic disorders. Childhood anxiety disorder predicted an increased risk of major mood disorder and evidence supported a progressive transition through clinical stages, from non-specific psychopathology to depressive and then manic or psychotic episodes.ConclusionsFindings underscore the importance of a developmental approach in conjunction with an appreciation of familial risk to facilitate earlier accurate diagnosis in symptomatic youth.

scholarly journals A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246211
Author(s):  
Heidi N. Boyda ◽  
Ric M. Procyshyn ◽  
Lurdes Tse ◽  
Jessica W. Y. Yuen ◽  
William G. Honer ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Side Effects ◽  
Glucose Tolerance ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
Fasting Glucose ◽  
Metabolic Effects ◽  
Metabolic Side Effects ◽  
Second Generation Antipsychotic ◽  
Dose Dependent

Background The second generation antipsychotic drugs represent the most common form of pharmacotherapy for schizophrenia disorders. It is now well established that most of the second generation drugs cause metabolic side-effects. Risperidone and its active metabolite paliperidone (9-hydroxyrisperidone) are two commonly used antipsychotic drugs with moderate metabolic liability. However, there is a dearth of preclinical data that directly compares the metabolic effects of these two drugs, using sophisticated experimental procedures. The goal of the present study was to compare metabolic effects for each drug versus control animals. Methods Adult female rats were acutely treated with either risperidone (0.1, 0.5, 1, 2, 6 mg/kg), paliperidone (0.1, 0.5, 1, 2, 6 mg/kg) or vehicle and subjected to the glucose tolerance test; plasma was collected to measure insulin levels to measure insulin resistance with HOMA-IR. Separate groups of rats were treated with either risperidone (1, 6 mg/kg), paliperidone (1, 6 mg/kg) or vehicle, and subjected to the hyperinsulinemic euglycemic clamp. Results Fasting glucose levels were increased by all but the lowest dose of risperidone, but only with the highest dose of paliperidone. HOMA-IR increased for both drugs with all but the lowest dose, while the three highest doses decreased glucose tolerance for both drugs. Risperidone and paliperidone both exhibited dose-dependent decreases in the glucose infusion rate in the clamp, reflecting pronounced insulin resistance. Conclusions In preclinical models, both risperidone and paliperidone exhibited notable metabolic side-effects that were dose-dependent. Differences between the two were modest, and most notable as effects on fasting glucose.

First-line atypical antipsychotics for schizophrenia are appropriate – with psychosocial interventions

2001 ◽  
Vol 25 (8) ◽  
pp. 287-288 ◽  
Author(s):  
A. M. Mortimer
Keyword(s):  
Side Effects ◽  
Negative Symptoms ◽  
Atypical Antipsychotics ◽  
Treatment Resistance ◽  
Psychosocial Interventions ◽  
First Line ◽  
Conventional Antipsychotics ◽  
Increased Risk ◽  
Loss Of Libido ◽  
The Individual

Conventional antipsychotics, historically the mainstay of schizophrenia treatment, were ineffective in many patients, at least 30% fitting treatment-resistance criteria (Kane & Lieberman, 1987). All had the same mechanism of action: none was any more effective in the individual than any other. Therapeutic nihilism accepted poorly controlled positive symptoms and disabling negative symptoms: nearly all patients suffered side-effects (Barnes & Edwards, 1993), particularly extrapyramidal side-effects (EPS) and hyperprolactinaemia. Conventional antipsychotics raise prolactin to a range associated with sexual dysfunction or even macroprolactinoma: effects in men include erectile dysfunction and hypospermatogenesis; in women, galactorrhoea, oligo- or amenorrhoea, hirsutism and increased risk of osteoporosis. In both men and women there is loss of libido, and a link between hyperprolactinaemia and weight gain.

scholarly journals The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Rafaela Torres Portugal Leite ◽  
Sarah de Oliveira Nogueira ◽  
João Paulo Rodrigues do Nascimento ◽  
Laisa Soares de Lima ◽  
Taís Bastos da Nóbrega ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Early Onset ◽  
Suicide Attempts ◽  
Age At Onset ◽  
Prognostic Significance ◽  
Manic Episode ◽  
Cannabis Use ◽  
Pubmed Database ◽  
Increased Risk ◽  
Bipolar Patients

Introduction. Bipolar disorder (BD) implies risk of suicide. The age at onset (AAO) of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts.Materials and Methods. PubMed database was searched for articles using key words “bipolar disorder,” “suicide attempts,” “cannabis,” “marijuana,” “early age at onset,” and “early onset.”Results. The following percentages in bipolar patients were found: suicide attempts 3.6–42%; suicide attempts and substance use 5–60%; suicide attempts and cannabis use 15–42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD) was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide.Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear.

Can Metformin or Rosiglitazone Reduce Metabolic Side Effects Associated with Atypical Antipsychotics?

2009 ◽  
Vol 30 (12) ◽  
pp. 803-805 ◽  
Author(s):  
Audrey K. Housel ◽  
Nancee Waterbury ◽  
Tami R. Argo ◽  
Marian Roman
Keyword(s):  
Side Effects ◽  
Atypical Antipsychotics ◽  
Metabolic Side Effects

scholarly journals Serum fatty acid profiling within distinct lipid fractions provides a more robust indicator of insulin resistance in humans than total triglyceride and fatty acid profiles

2014 ◽  
Vol 39 (10) ◽  
pp. 1182-1182
Author(s):  
Michael A. Zulyniak
Keyword(s):  
Insulin Resistance ◽  
At Risk ◽  
Fatty Acid ◽  
International Diabetes Federation ◽  
Total Serum ◽  
Total Blood ◽  
Serum Fatty Acid ◽  
Cross Sectional ◽  
Increased Risk ◽  
Lipid Fractions

The need to better predict the development of insulin resistance (IR) and type 2 diabetes (T2D) is necessary as the prevalence of T2D is projected to increase in Canada and cost Canadians ∼$18 billion by 2030. The International Diabetes Federation currently advises the use of total blood triglycerides (TGs) as a predictor for identifying individuals at risk of developing IR and T2D. However, it has been demonstrated that total TG levels do not reliably reflect IR across multiple ethnicities. This suggests that a more accurate marker of IR is required. Interestingly, recent evidence suggests that distinct fatty acids (FAs) in blood TGs can reflect an individual’s IR status more accurately than total TGs. It is therefore reasonable to postulate that an analysis of the FAs within TGs and other blood lipids could lead to the discovery of a more accurate marker of IR. Over the course of 3 studies, the following thesis aimed to demonstrate that distinct FAs within serum lipids are associated with markers of IR more robustly than total TGs or total FAs. First, a large cross-sectional cohort that comprised young adults was used to demonstrate the associations between individual serum FAs and markers of IR (e.g., fasting glucose). Second, a population of Caucasian men that varied in IR-risk was examined to demonstrate that specific serum FAs within TGs associate with markers of IR more strongly than total TG levels. Finally, a cohort of individuals was investigated to demonstrate the improved ability of phospholipid and TG FA profiles (compared with total FAs) to distinguish individuals varying in metabolic health. This thesis demonstrated that circulating FAs associate with markers of IR and that these associations vary between individuals of different sex and ethnicity. Furthermore, the findings of this thesis indicate that compared with total serum TGs, specific FAs within lipid fractions may provide a more accurate means to identify individuals at increased risk of developing IR and T2D. Collectively, this thesis encourages future investigations of FAs within serum lipid fractions to uncover an improved method for identifying individuals at risk of IR and T2D.

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