Bipolar disorders

McIntyre, Roger S.; Berk, Michael; Brietzke, Elisa; Goldstein, Benjamin I.; López‐Jaramillo, Carlos; Kessing, Lars Vedel; Malhi, Gin S; Nierenberg, Andrew A.; Rosenblat, Joshua D.; Majeed, Amna; Vieta, Eduard; Vinberg, Maj; Young, Allan H.; Mansur, Rodrigo B.

doi:10.1016/s0140-6736(20)31544-0

Cited by 607 publications

(481 citation statements)

References 188 publications

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“…Bipolar disorder (BD) is a devastating mental illness which affects 2–4% of the world population 3 . As its name implies, it entails two distinct oscillating and opposing states, a state of energy and hyperactivity (the manic phase), and a state of low energy (depression) 4 . Lithium (Li) administration is the first-line treatment of bipolar illness 3 , 5 – 7 .…”

Section: Introductionmentioning

confidence: 99%

Entangled radicals may explain lithium effects on hyperactivity

Zadeh-Haghighi

Simon

2021

Sci Rep

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It is known that bipolar disorder and its lithium treatment involve the modulation of oxidative stress. Moreover, it has been observed that lithium’s effects are isotope-dependent. Based on these findings, here we propose that lithium exerts its effects by influencing the recombination dynamics of a naturally occurring radical pair involving oxygen. We develop a simple model inspired by the radical-pair mechanism in cryptochrome in the context of avian magnetoreception and xenon-induced anesthesia. Our model reproduces the observed isotopic dependence in the lithium treatment of hyperactivity in rats. It predicts a magnetic-field dependence of the effectiveness of lithium, which provides one potential experimental test of our hypothesis. Our findings show that Nature might harness quantum entanglement for the brain’s cognitive processes.

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Section: Introductionmentioning

confidence: 99%

Entangled radicals may explain lithium effects on hyperactivity

Zadeh-Haghighi

Simon

2021

Sci Rep

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“…Bipolar disorder is a severe mental disorder which affects more than 1% of the population and constitutes one of the main causes of disability worldwide (McIntyre et al ., 2020 ). People with bipolar disorder have markedly elevated risk of premature mortality (Hayes et al ., 2015 ), with approximately 8–15-years shorter lifespan relative to the general population (Chang et al ., 2011 ; Laursen, 2011 ; Kodesh et al ., 2012 ; Ajetunmobi et al ., 2013 ; Crump et al ., 2013 ; Kessing et al ., 2015 ; Pan et al ., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Excess mortality and life-years lost in people with bipolar disorder: an 11-year population-based cohort study

Chan

Wong

Yung

et al. 2021

Epidemiol Psychiatr Sci

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Aims Bipolar disorder is associated with premature mortality, but evidence is mostly derived from Western countries. There has been no research evaluating shortened lifespan in bipolar disorder using life-years lost (LYLs), which is a recently developed mortality metric taking into account illness onset for life expectancy estimation. The current study aimed to examine the extent of premature mortality in bipolar disorder patients relative to the general population in Hong Kong (HK) in terms of standardised mortality ratio (SMR) and excess LYLs, and changes of mortality rate over time. Methods This population-based cohort study investigated excess mortality in 12 556 bipolar disorder patients between 2008 and 2018, by estimating all-cause and cause-specific SMRs, and LYLs. Trends in annual SMRs over the 11-year study period were assessed. Study data were retrieved from a territory-wide medical-record database of HK public healthcare services. Results Patients had higher all-cause [SMR: 2.60 (95% CI: 2.45–2.76)], natural-cause [SMR: 1.90 (95% CI: 1.76–2.05)] and unnatural-cause [SMR: 8.63 (95% CI: 7.34–10.03)] mortality rates than the general population. Respiratory diseases, cardiovascular diseases and cancers accounted for the majority of deaths. Men and women with bipolar disorder had 6.78 (95% CI: 6.00–7.84) years and 7.35 (95% CI: 6.75–8.06) years of excess LYLs, respectively. The overall mortality gap remained similar over time, albeit slightly improved in men with bipolar disorder. Conclusions Bipolar disorder is associated with increased premature mortality and substantially reduced lifespan in a predominantly Chinese population, with excess deaths mainly attributed to natural causes. Persistent mortality gap underscores an urgent need for targeted interventions to improve physical health of patients with bipolar disorder.

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“…Peripheral levels of miR-499-5p were significantly increased in BD patients compared to healthy controls, after correction for age and antidepressant treatment (Figure 1B). Traumatic experiences, especially during childhood, are one of the most important environmental risk factors associated with the development of BD (11,39). Therefore, for a more comprehensive understanding of the pathogenesis of the disorder, we next asked whether childhood maltreatment influenced the expression of peripheral miR-499-5p.…”

Section: Mir-499-5p Expression Is Increased In Human Bd Patients and The Rat Social Isolation Model Of Early Life Adversitymentioning

confidence: 99%

Bipolar-associated miR-499-5p controls neuroplasticity by downregulating the Ca_v1.2 L-type voltage gated calcium channel subunit CACNB2

Gilardi

et al. 2021

Preprint

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Bipolar disorder (BD) is a chronic mood disorder characterized by alternating manic and depressive episodes, often in conjunction with cognitive deficits. Dysregulation of neuroplasticity and calcium homeostasis as a result of complex genetic environment interactions are frequently observed in BD patients, but the underlying molecular mechanisms are largely unknown. Here, we show that a BD-associated microRNA, miR-499-5p, regulates neuronal dendrite development and cognitive function by downregulating the BD risk gene CACNB2. miR-499-5p expression is increased in peripheral blood of BD patients and healthy subjects at risk of developing the disorder due to a history of childhood maltreatment. This up-regulation is paralleled in the hippocampus of rats which underwent juvenile social isolation. Elevating miR-499-5p levels in rat hippocampal pyramidal neurons impairs dendritogenesis and reduces surface expression and activity of the voltage-gated L-type calcium channel Cav1.2. We further identified CACNB2, which encodes a regulatory β-subunit of Cav1.2, as a direct target of miR-499-5p in neurons. CACNB2 downregulation is required for the miR-499-5p dependent impairment of dendritogenesis, suggesting that CACNB2 is an important downstream target of miR-499-5p in the regulation of neuroplasticity. Finally, elevating miR-499-5p in the hippocampus in vivo is sufficient to induce short-term memory impairments in rats haploinsufficient for the Cav1.2 pore forming subunit Cacna1c. Taken together, we propose that stress-induced upregulation of miR-499-5p contributes to dendritic impairments and deregulated calcium homeostasis in BD, with specific implications for the neurocognitive dysfunction frequently observed in BD patients.

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Bipolar disorders

Cited by 607 publications

References 188 publications

Entangled radicals may explain lithium effects on hyperactivity

Entangled radicals may explain lithium effects on hyperactivity

Excess mortality and life-years lost in people with bipolar disorder: an 11-year population-based cohort study

Bipolar-associated miR-499-5p controls neuroplasticity by downregulating the Ca_v1.2 L-type voltage gated calcium channel subunit CACNB2

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Bipolar disorders

Cited by 607 publications

References 188 publications

Entangled radicals may explain lithium effects on hyperactivity

Entangled radicals may explain lithium effects on hyperactivity

Excess mortality and life-years lost in people with bipolar disorder: an 11-year population-based cohort study

Bipolar-associated miR-499-5p controls neuroplasticity by downregulating the Cav1.2 L-type voltage gated calcium channel subunit CACNB2

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Bipolar-associated miR-499-5p controls neuroplasticity by downregulating the Ca_v1.2 L-type voltage gated calcium channel subunit CACNB2