Table 1 Disruption of clock genes in mood disorders.
Human diseases or animal models | Involved genes | Main findings | References |
|---|---|---|---|
MDD:592, Control:776 | ARNTL, CLOCK, NPAS2, PER3 | Mood disorders associates with a CLOCK variant in males and a PER3 variant in females. | Shi et al. [242] |
MDD:775, Control:440 | CRY1 NPAS2 | Significant association CRY1 (rs2287161), NPAS2 (rs11123857) and VIPR2 (rs885861) genes in mood disorders samples. | Soria et al. [243] |
MDD:34, Control:55 | BMAL1, PER1,2,3, NR1D1, DBP, BHLHE40, BHLHE41 | Time-of-death analysis to gene expression data of post-mortem brain of mood disorders patients showed association of canonical clock genes BMAL1(ARNTL), PER1-2-3, NR1D1(REV-ERBa), DBP, BHLHE40 (DEC1), and BHLHE41(DEC2). | Li et al. [180] |
MDD:12, Control:12 | PER1, PER2, PER3, CRY1, BMAL1, NPAS2, GSK-3β | mood disorders patients showed disruptions in diurnal rhythms of PERIOD1, PERIOD2, CRY1, BMAL1, NPAS2, GSK-3b and disruptions in diurnal rhythms of melatonin, VIP, cortisol, ACTH, IGF-1release. | Li et al. [185] |
MDD: 105, Control: 485 | CRY1, CRY2, TEF | CRY1 rs2287161 and TEF rs738499 are associated with the susceptibility of mood disorders. Carriers of CRY1 rs2287161 were 1.91 times and TEF rs738499 were 2.66 times more likely to suffer from mood disorders | Hua et al. [190] |
MDD:383, Control: 4154 | CRY2, PRKCDBP | Association of CRY2 (p<0.05) and novel associations of PRKCDBP rs1488864 with depressive disorders (p=0.02) and with major depressive disorder in specific (p=0.007). | Kovanen et al. [183] |
BD: 215, Control: 773 | CSNK1E | Association of SNP rs2075984 and bipolar disorder in both allelic (p= 0.003) and genotypic (p=0.006). | Lee at al. [244] |
MDD: 359, Control: 341 | CLOCK | Abnormal processing of pre-miR-182 in patients with T allele of rs76481776 polymorphism leads to dysregulated circadian rhythm in MDD patients with insomnia | Saus et al. [186] |
BD:260, Control: 350 | CLOCK | CLOCK 3111T/C showed significant allelic (p = 0.012) and genotypic (p = 0.033) associations with bipolar disorder. | Lee et al. [245] |
BD: 121, Control: 121 | PERIOD | PER2 rs2304672 G allele frequency increased in risk for BD. | Yegin et al. [246] |
Mouse model of depression and anxiety | Bmal1 | Disruption of circadian rhythms by knocking down Bmal1 expression in the SCN caused depression and anxiety-like behaviors in mice. | Landgraf et al. [207] |
Mouse model of depression | Cry1 | The Cry1 knockout mice showed depressive-like behaviors. | Schnell et al. [208] |
Rat model of depression | Clock | Sleep deprivation alters circadian oscillations of clock genes and causes depressive-like behavior in rats. | Xing et al. [209] |
Rat model of depression | Per1, Per2, and Bmal1 | Per1, Per2, and Bmal1 is associated with the induction of a depression-like state in the chronic mild stress model in rats. | Christiansen et al. [210] |
Mouse model of mania | Clock | Clock mutant mice show overall profile similar to human mania | Roybal et al. [200] |
Mouse model of mania | Clock | Mice with a deletion of exon 19 in the Clock gene (ClockΔ19 mice) exhibit abnormal behaviors similar to BD mania. | van Enkhuizen et al. [247] |
Mouse model of mania | Clock | Knockdown of Clock in ventral tegmental area of mice leads to mixed state of mania and depression like behavior | Mukherjee et al. [202] |
