Analysis of genome-wide significant bipolar disorder genes in borderline personality disorder

Witt, Stephanie H.; Kleindienst, Nikolaus; Frank, Josef; Treutlein, Jens; Mühleisen, Thomas W.; Degenhardt, Franziska; Jungkunz, Martin; Krumm, Bertram; Cichon, Sven; Tadić, André; Dahmen, Norbert; Schwarze, Cornelia E.; Schott, Björn H.; Dietl, Lydia; Nöthen, Markus M.; Mobascher, Arian; Lieb, Klaus; Röepke, Stefan; Rujescu, Dan; Rietschel, Marcella; Schmahl, Christian; Bohus, Martin

doi:10.1097/ypg.0000000000000060

Cited by 27 publications

(11 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The minor allele of the CACNA1C polymorphism rs1006737 increased the risk of psychiatric disease only in females (Dao et al 2010;Witt et al 2014), while others found that the same polymorphism leads to traits associated with negative effects in men (Strohmaier et al 2013). The latter finding appears incongruent with the present results.…”

Section: Discussioncontrasting

confidence: 98%

See 1 more Smart Citation

A Common CACNA1C Gene Risk Variant has Sex-Dependent Effects on Behavioral Traits and Brain Functional Activity

et al. 2018

View full text Add to dashboard Cite

Genome-wide association studies have suggested that allelic variations in the CACNA1C gene confer susceptibility to schizophrenia and bipolar disorder only in women. Here we investigated the sex-specific effects of the CACNA1C variant rs1024582 on psychiatry-related traits, brain activity during tasks and rest, and brain volume in 1207 normal male and female subjects. After correcting for multiple comparisons, there were significant interaction effects between sex and the minor allele of this polymorphism on the hostile behavior subscale scores of the Coronary-Prone Type Scale mediated by higher scores in female carriers of the minor allele. Imaging analyses revealed significant interaction effects between sex and the minor allele on fractional amplitude of low-frequency fluctuations in the right dorsolateral prefrontal cortex and on brain activity during the 2-back task in areas of the right posterior cingulate cortex, right thalamus, and right hippocampus, which were all mediated by reduced activity in female carriers of the minor allele. Our results demonstrated that the rs1024582 risk variant of CACNA1C is associated with reduced activity in the frontolimbic regions at rest and during a working memory task as well as with greater hostility in females in the healthy population.

show abstract

Section: Discussioncontrasting

confidence: 98%

“…Multiple studies have found effects of rs1006737 on psychiatric diseases only in women (Dao et al 2010;Witt et al 2014). Moreover, another minor variant of CACNA1C was associated with impaired recovery from schizophrenia-spectrum disorder in women but not in men (Heilbronner et al 2015).…”

Section: Introductionmentioning

confidence: 99%

A Common CACNA1C Gene Risk Variant has Sex-Dependent Effects on Behavioral Traits and Brain Functional Activity

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Moreover, embryonic deletion of this gene in the mouse forebrain results in increased anxiety-like behavior and increased susceptibility to chronic stress (Dedic et al, 2018). Some clinical and animal studies have also found a significant interaction between sex and Cacna1c genotype (Dao et al, 2010;Takeuchi et al, 2018;Witt et al, 2014); for instance, female, but not male, Cacna1c heterozygous mice have been shown to display decreased risk-taking behavior and increased anxiety in multiple tests (Dao et al, 2010). Our study has revealed that this gene is very sensitive to developmental stress and that, depending of the number of hits, the effects of stress can be sex-specific.…”

Section: Discussionmentioning

confidence: 99%

Sex and Estrous Cycle Effects on Anxiety- and Depression-related Phenotypes in Two-hit Developmental Stress Model

Jarić

Rocks

Cham

et al. 2019

Preprint

View full text Add to dashboard Cite

Stress during sensitive developmental periods can adversely affect physical and psychological development and contribute to later-life mental disorders. In particular, adverse experiences during childhood dramatically increase the risk for the development of depression and anxiety disorders. Although women of reproductive age are twice as likely to develop anxiety and depression than men of the corresponding age, little is known about sex-specific factors that promote or protect against the development of psychopathology. To examine potential developmental mechanisms driving sex disparity in risk for anxiety and depression, we established a two-hit developmental stress model including maternal separation in early life followed by social isolation in adolescence. Our study shows complex interactions between early-life and adolescent stress, between stress and sex, and between stress and female estrogen status in shaping behavioral phenotypes of adult animals. In general, increased locomotor activity and body weight reduction were the only two phenotypes where two stressors showed synergistic activity. In terms of anxiety- and depression-related phenotypes, single exposure to early-life stress had the most significant impact and was female-specific. We show that early-life stress disrupts the protective role of estrogen in females, and promotes female vulnerability to anxiety- and depression-related phenotypes associated with the low-estrogenic state. We found plausible transcriptional and epigenetic alterations in psychiatric risk genes, Nr3c1 and Cacna1c, that likely contributed to the stress-induced behavioral effects. In addition, two general transcriptional regulators, Egr1 and Dnmt1, were found to be dysregulated in maternally-separated females and in animals exposed to both stressors, respectively, providing insights into possible transcriptional mechanisms that underlie behavioral phenotypes. Our findings provide a novel insight into developmental risk factors and biological mechanisms driving sex differences in depression and anxiety disorders, facilitating the search for more effective, sex-specific treatments for these disorders.

show abstract

“…Behavioral studies in humans suggest that rs1006737 is linked to facial emotion recognition in both healthy individuals and patients with BD [164,165]. Some studies suggest that rs1006737 is also associated with borderline personality disorder in females, but not males [166,167]. rs1006737 has significant association with reduced baseline affective startle modulation in healthy males.…”

Section: Genetic Associations Between Cav Genes and Psychiatric Disormentioning

confidence: 99%

Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders

Andrade

Brennecke

Mallat

et al. 2019

Preprint

View full text Add to dashboard Cite

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (CaVs). Calcium entering through CaVs is key for multiple neuronal processes. In this review, we will summarize recent findings that link CaVs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of CaVs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in CaV genes when available. We will review pharmacological evidence of the use of CaV modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of CaVs.

show abstract

Analysis of genome-wide significant bipolar disorder genes in borderline personality disorder

Abstract: Supplemental Digital Content is available in the text.

Cited by 27 publications

References 21 publications

A Common CACNA1C Gene Risk Variant has Sex-Dependent Effects on Behavioral Traits and Brain Functional Activity

A Common CACNA1C Gene Risk Variant has Sex-Dependent Effects on Behavioral Traits and Brain Functional Activity

Sex and Estrous Cycle Effects on Anxiety- and Depression-related Phenotypes in Two-hit Developmental Stress Model

Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders

Contact Info

Product

Resources

About