Genes, biomarkers, and clinical features associated with the course of bipolar disorder

Smedler, Erik; Bergen, Sarah E.; Song, Jie; Landén, Mikael

doi:10.1016/j.euroneuro.2019.07.132

Cited by 12 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In another study, pathway analysis of SCZ risk SNPs suggested an association of CACNA2D3 with the response to lurasidone, an antipsychotic drug used to treat SCZ [62]. Furthermore, regional enrichment analysis associated the genomic region 3p21.1_1, which also contains CACNA2D3, with SCZ and BPD [63], a link which also is supported by other studies [63,67,70,101,134]. While the abovementioned SNPs are all located in exons, one intronic SNP (rs75407252) has been linked to MDD [33].…”

Section: Cacna2d3supporting

confidence: 52%

Neuronal α2δ proteins and brain disorders

Ablinger

Geisler

Stanika

et al. 2020

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

α 2 δ proteins are membrane-anchored extracellular glycoproteins which are abundantly expressed in the brain and the peripheral nervous system. They serve as regulatory subunits of voltage-gated calcium channels and, particularly in nerve cells, regulate presynaptic and postsynaptic functions independently from their role as channel subunits. α 2 δ proteins are the targets of the widely prescribed anti-epileptic and anti-allodynic drugs gabapentin and pregabalin, particularly for the treatment of neuropathic pain conditions. Recently, the human genes (CACNA2D1-4) encoding for the four known α 2 δ proteins (isoforms α 2 δ-1 to α 2 δ-4) have been linked to a large variety of neurological and neuropsychiatric disorders including epilepsy, autism spectrum disorders, bipolar disorders, schizophrenia, and depressive disorders. Here, we provide an overview of the hitherto identified disease associations of all known α 2 δ genes, hypothesize on the pathophysiological mechanisms considering their known physiological roles, and discuss the most immanent future research questions. Elucidating their specific physiological and pathophysiological mechanisms may open the way for developing entirely novel therapeutic paradigms for treating brain disorders.

show abstract

Section: Cacna2d3supporting

confidence: 52%

Neuronal α2δ proteins and brain disorders

Ablinger

Geisler

Stanika

et al. 2020

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

show abstract

“…The genome-wide significant association between CACNA2D 3 and suicide attempts in the Hispanic-American cohort also represents a promising avenue for future investigation. CACNA2D 3 has been associated with bipolar disorder, 53 depression, 54 schizophrenia, 55 autism spectrum disorder, 56 nicotine dependence, 57 and pain sensitivity. 37 …”

Section: Discussionmentioning

confidence: 99%

A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci

et al. 2022

View full text Add to dashboard Cite

To identify pan-ancestry and ancestry-specific loci associated with attempting suicide among veterans, we conducted a genome-wide association study (GWAS) of suicide attempts within a large, multi-ancestry cohort of U.S. veterans enrolled in the Million Veterans Program (MVP). Cases were defined as veterans with a documented history of suicide attempts in the electronic health record (EHR; N =14,089) and controls were defined as veterans with no documented history of suicidal thoughts or behaviors in the EHR ( N =395,064). GWAS was performed separately in each ancestry group, controlling for sex, age and genetic substructure. Pan-ancestry risk loci were identified through meta-analysis and included two genome-wide significant loci on chromosomes 20 ( p =3.64×10 −9 ) and 1 ( p =3.69×10 −8 ). A strong pan-ancestry signal at the Dopamine Receptor D2 locus ( p =1.77×10 −7 ) was also identified and subsequently replicated in a large, independent international civilian cohort ( p =7.97×10 −4 ). Additionally, ancestry-specific genome-wide significant loci were also detected in African-Americans, European-Americans, Asian-Americans, and Hispanic-Americans. Pathway analyses suggested overrepresentation of many biological pathways with high clinical significance, including oxytocin signaling, glutamatergic synapse, cortisol synthesis and secretion, dopaminergic synapse, and circadian rhythm. These findings confirm that the genetic architecture underlying suicide attempt risk is complex and includes both pan-ancestry and ancestry-specific risk loci. Moreover, pathway analyses suggested many commonly impacted biological pathways that could inform development of improved therapeutics for suicide prevention.

show abstract

“…Finally, subjects had on average been experiencing symptoms of the disease for almost 20 years. According to the kindling theory of bipolar disorder, affective episodes gradually increase in frequency with time and become less and less dependent on external factors (34‐36), which means that results might be different in a cohort of new‐onset patients.…”

Section: Discussionmentioning

confidence: 99%

Reporting trigger factors for (hypo)manic episodes in bipolar disorder: association with personality and prognosis

Smedler

Sparding

Hattab

et al. 2020

Acta Psychiatr Scand

Self Cite

View full text Add to dashboard Cite

Smedler E, Sparding T, Hattab A, Sellgren CM, Land en M. Reporting trigger factors for (hypo)manic episodes in bipolar disorder: association with personality and prognosis.Objective: To investigate external factors that trigger manic and hypomanic relapses and how this is associated with personality and clinical outcome measured as number of affective episodes over a 7-year period. Method: This is a prospective cohort study of 204 meticulously characterized Swedish bipolar disorder patients. Personality was evaluated at baseline using the Swedish universities Scales of Personality in 170 patients, and 90 patients were followed up after approximately 7 years in order to evaluate clinical outcomes. Results: We found that 44% of the patients reported trigger factors, including sleep disturbance, work-or family-related issues, medication, and illicit drug use. There were no significant differences in any of the personality traits when comparing the 74 patients that reported triggers with the 90 patients that did not. At 7-year follow-up, there was no difference between the groups in number of affective episodes (depressive, hypomanic, manic, or mixed), involuntary commitments, suicide attempts, or self-harm incidents since baseline. Conclusions: Around 40% of the patients reported external triggers for manic and hypomanic episodes. However, this was neither associated with personality traits nor number of affective episodes at 7-year followup.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Significant outcomes• Around 40% of all bipolar disorder patients reported trigger factors for manic or hypomanic episodes.• Reporting trigger factors was not associated with personality • Reporting trigger factors was not associated with outcomes over a 7-year period. Limitations• Patients had on average long duration of illness and may be less sensitive to external stressors than persons with recent onset.• Trigger factors were identified retrospectively and may thus be prone to recall bias. • The number of affective episodes might be a too crude outcome measure as most subjects had not suffered any affective episodes at follow-up.

show abstract

Genes, biomarkers, and clinical features associated with the course of bipolar disorder

Cited by 12 publications

References 36 publications

Neuronal α2δ proteins and brain disorders

Neuronal α2δ proteins and brain disorders

A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci

Reporting trigger factors for (hypo)manic episodes in bipolar disorder: association with personality and prognosis

Contact Info

Product

Resources

About