A genome-wide association study of seasonal pattern mania identifies NF1A as a possible susceptibility gene for bipolar disorder

Lee, Heon Jeong; Woo, Hyun Goo; Greenwood, Tiffany A.; Kripke, Daniel F.; Kelsoe, John R.

doi:10.1016/j.jad.2012.07.032

Cited by 42 publications

(33 citation statements)

References 54 publications

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“…As was described above, rs41350144 which lies within the intron of NF1A on 1p31 may be a susceptibility gene for seasonality in BD (Lee et al, 2013). Other genes linked to psychiatric conditions have been recreated and inserted into mice, such as the disrupted in schizophrenia 1 (DISC1)/boymaw transfusion gene (Ji et al, 2014) that has been related to schizophrenia and BD.…”

Section: Future Directionsmentioning

confidence: 96%

“…Heritability studies of BD estimate a 60 – 80% heritability supporting this genetic basis for sufferers. Numerous GWAS studies have been conducted in BD (Baum et al, 2008; Greenwood et al, 2012; Greenwood et al, 2006b; Lee et al, 2013; Sklar et al, 2008; Smith et al, 2009), but few observed statistical significant findings required for such studies. Such lack of effect may come from the heterogeneity of BD groups where studying subsets of patients may provide greater information.…”

Section: Key Studies Investigating Cycling/switching Into Other Stmentioning

confidence: 99%

“…Such lack of effect may come from the heterogeneity of BD groups where studying subsets of patients may provide greater information. A GWAS study on patients self-identifying as having seasonal patterns of mania vs. non-seasonal sufferers discovered an association for rs41350144 which lies within the intron of NF1A on 1p31 (Lee et al, 2013). Importantly, genes contributing to the control of circadian rhythm are also implicated in BD.…”

Section: Key Studies Investigating Cycling/switching Into Other Stmentioning

confidence: 99%

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Investigating the mechanism(s) underlying switching between states in bipolar disorder

Young

Dulcis

2015

European Journal of Pharmacology

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Bipolar Disorder (BD) is a unique disorder that transcends domains of function since the same patient can exhibit depression or mania, states with polar opposite mood symptoms. During depression, people feel helplessness, reduced energy, and risk aversion, while with mania behaviors include grandiosity, increased energy, less sleep, and risk preference. The neural mechanism(s) underlying each state are gaining clarity, with catecholaminergic disruption seen during mania, and cholinergic dysfunction during depression. The fact that the same patient cycles/switches between these states is the defining characteristic of BD however. Of greater importance therefore, is the mechanism(s) underlying cycling from one state - and its associated neural changes - to another, considered the ‘holy grail’ of BD research. Herein, we review studies investigating triggers that induce switching to these states. By identifying such triggers, researchers can study neural mechanisms underlying each state and importantly how such mechanistic changes can occur in the same subject. Current animal models of this switch are also discussed, from submissive- and dominant-behaviors to kindling effects. Focus however, is placed on how seasonal changes can induce manic and depressive states in BD sufferers. Importantly, changing photoperiod lengths can induce local switches in neurotransmitter expression in normal animals, from increased catecholaminergic expression during periods of high activity, to increased somatostatin and corticotrophin releasing factor during periods of low activity. Identifying susceptibilities to this switch would enable the development of targeted animal models. From animal models, targeted treatments could be developed and tested that would minimize the likelihood of switching.

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Section: Future Directionsmentioning

confidence: 96%

Section: Key Studies Investigating Cycling/switching Into Other Stmentioning

confidence: 99%

Section: Key Studies Investigating Cycling/switching Into Other Stmentioning

confidence: 99%

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Investigating the mechanism(s) underlying switching between states in bipolar disorder

Young

Dulcis

2015

European Journal of Pharmacology

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“…In addition, the AUTS2 locus has been shown to be implicated or altered in individuals with schizoaffective disorder [45], bipolar disorder [46,47], epilepsy [48], ADHD [49], differential processing speed [50], suicidal tendencies under the influence of alcohol [51], and dyslexia [23], either through CNV or genome-wide association studies. A 2012 article sequenced balanced chromosomal abnormalities in patients with neurodevelopmental disorders, and found the AUTS2 locus to be perturbed in individuals with microcephaly, macrocephaly, ataxia, visual impairment, language disability, seizure disorder, dysmorphic features, behavioral problems, motor delay, or Rubinstein–Taybi syndrome [24].…”

Section: Auts2 and Other Neurological Conditionsmentioning

confidence: 99%

The role of AUTS2 in neurodevelopment and human evolution

2013

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The autism susceptibility candidate 2 (AUTS2) gene is associated with multiple neurological diseases, including autism, and has been implicated as an important gene in human-specific evolution. Recent functional analysis of this gene has revealed a potential role in neuronal development. Here, we review the literature regarding AUTS2, including its discovery, expression, association with autism and other neurological and non-neurological traits, implication in human evolution, function, regulation, and genetic pathways. Through progress in clinical genomic analysis, the medical importance of this gene is becoming more apparent, as highlighted in this review, but more work needs to be done to discover the precise function and the genetic pathways associated with AUTS2.

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“…Findings from various studies have revealed that patients with BD demonstrate seasonal patterns of behavior, with more manic episodes observed during the spring and summer months 52,53. This highlights a potential circadian component of the pathophysiology of BD, which is possibly influenced by alterations in the photoperiod, i.e., seasonal changes in day length.…”

Section: What Happens To the Circadian System In Bipolar Disorder?mentioning

confidence: 99%

Circadian Rhythm Hypotheses of Mixed Features, Antidepressant Treatment Resistance, and Manic Switching in Bipolar Disorder

Lee

Son

Geum

2013

Psychiatry Investig

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Numerous hypotheses have been put forth over the years to explain the development of bipolar disorder. Of these, circadian rhythm hypotheses have gained much importance of late. While the hypothalamus-pituitary-adrenal (HPA) axis hyperactivation hypothesis and the monoamine hypothesis somewhat explain the pathogenic mechanism of depression, they do not provide an explanation for the development of mania/hypomania. Interestingly, all patients with bipolar disorder display significant disruption of circadian rhythms and sleep/wake cycles throughout their mood cycles. Indeed, mice carrying the Clock gene mutation exhibit an overall behavioral profile that is similar to human mania, including hyperactivity, decreased sleep, lowered depression-like behavior, and lower anxiety. It was recently reported that monoamine signaling is in fact regulated by the circadian system. Thus, circadian rhythm instability, imposed on the dysregulation of HPA axis and monoamine system, may in turn increase individual susceptibility for switching from depression to mania/hypomania. In addition to addressing the pathophysiologic mechanism underlying the manic switch, circadian rhythm hypotheses can explain other bipolar disorder-related phenomena such as treatment resistant depression and mixed features.

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A genome-wide association study of seasonal pattern mania identifies NF1A as a possible susceptibility gene for bipolar disorder

Cited by 42 publications

References 54 publications

Investigating the mechanism(s) underlying switching between states in bipolar disorder

Investigating the mechanism(s) underlying switching between states in bipolar disorder

The role of AUTS2 in neurodevelopment and human evolution

Circadian Rhythm Hypotheses of Mixed Features, Antidepressant Treatment Resistance, and Manic Switching in Bipolar Disorder

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