Life cycle patterns of professional performance from Go world champions

Abstract

While in her early 40s and working full time, she developed hypomania: she worked energetically, juggling many tasks, and found the work enjoyable. She showed euphoria, inflated self-esteem, overtalkativeness, and racing thoughts. However, in her mid-40s, she began to suffer from chronic pain, fatigue, and insomnia. She reported an uncomfortable sensation in her legs at night and was diagnosed with restless legs syndrome. Over time, her depressive symptoms recurred and worsened. She also reported racing thoughts and was restless. She was involuntarily hospitalized, but her condition subsequently deteriorated into a substupor. Substupor improved with benzodiazepine therapy, but she still showed hypomanic symptoms. She was diagnosed with bipolar II disorder, and her hypomanic symptoms finally improved following treatment with valproate and quetiapine.Six months later after discharge from the hospital, she experienced depressive mood, fatigue, insomnia, and psychomotor agitation. She showed increased activity despite fatigue, and was hospitalized again. After admission, her symptoms progressively worsened, mood-congruent delusions emerged, and she fell into a substupor again. Although treatment with benzodiazepine improved her condition, her delusions persisted despite an increased dose of quetiapine. Her antipsychotic medication was changed to olanzapine, and finally the symptoms resolved. Laboratory tests revealed latent hypothyroidism. Brain magnetic resonance imaging showed no abnormal findings.We conducted copy number variation analysis with array comparative genomic hybridization (Agilent SurePrint G3 Human CGH 400k) and identified a deletion at the 5 0 -untranslated region (UTR) of MBD5 (Fig. 1a). The inheritance pattern of this deletion was unknown. This deletion was validated with the TaqMan Copy Number Assay. The 5 0 -UTR of MBD5 is a hotspot for pathogenic deletion, and deletions in this region cause a reduction in MBD5 mRNA expression. 1,2 Of note, the deletion we identified was very similar to a previously reported deletion in an early-onset BD patient 4 in that both affect the same exon of MBD5. We determined the breakpoint of the deletion with Sanger sequencing: chr2:148292937-148405024 (hg38, 112088 bps). The breakpoint had a 5-bp microhomology (CTGGA) at both ends (Fig. 1b), implicating the microhomology-mediated end joining pathway in the formation of this deletion. 6 MBD5 belongs to the MBD family of proteins, which are involved in regulating gene expression through an epigenetic mechanism. MBD family members bind preferentially to methylated DNA and recruit protein complexes containing transcriptional repressors to the regions, causing gene silencing. Epigenetic dysregulations including DNA methylation alterations were observed in brain tissues of BD patients, and mood stabilizers such as valproate also affect DNA methylation. 7 Considering that the present patient responded to valproate, epigenetic dysregulation caused by MBD5 deletion may have been mitigated by the epigenetic effect of valpr...