{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:05:20Z","timestamp":1791378320684,"version":"4.3.2"},"reference-count":85,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Psychiatry Clin Neurosci"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Bipolar disorder (BD) is characterized by circadian dysregulation, altered sleep\u2013wake behaviors, and heterogeneous antidepressant response. Chronotherapeutic interventions such as total sleep deprivation combined with light therapy (TSD\u2009+\u2009LT) produce rapid antidepressant effects, but predictors of outcome are lacking. We investigated whether fractal dynamics of motor activity, indexed by the short\u2010term scaling exponent \u03b1\u2081, are associated with antidepressant response, sleep\u2013wake regulation, and structural brain measures and may serve as a biomarker of treatment responsiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty\u2010eight BD inpatients underwent three cycles of TSD\u2009+\u2009LT. Depressive symptoms were assessed with the Hamilton Depression Rating Scale (HDRS), and treatment response was defined as a post\u2010treatment HDRS score &lt;8. \u03b1\u2081 was derived from actigraphy using detrended fluctuation analysis, with values close to 1 indicating optimal fractal regulation. \u03b1\u2081 was computed before and after TSD\u2009+\u2009LT, and \u0394\u03b1\u2081 represented treatment\u2010related change. Sleep\u2013wake and circadian parameters were examined. A subsample underwent multimodal magnetic resonance imaging (MRI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TSD\u2009+\u2009LT induced clinical improvement in 65.3% of patients. Responders showed a significant reduction in \u03b1\u2081 toward values close to 1, whereas nonresponders did not. \u0394\u03b1\u2081 correlated with symptom improvement (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.035) and was independently associated with treatment response (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.039). Baseline \u03b1\u2081 was associated with sleep\u2013wake parameters, cerebellar gray matter volume, and white\u2010matter microstructure, including cerebellar peduncles and thalamo\u2010cortical tracts. Circadian rhythmicity increased in responders and decreased in nonresponders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Fractal motor activity tracks clinical changes during chronotherapeutic treatment in BD and may represent a candidate marker of treatment\u2010related behavioral regulation. Its association with cerebellar and white\u2010matter measures suggests multimodal relevance, warranting validation in larger longitudinal studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pcn.70107","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T01:34:07Z","timestamp":1785116047000},"page":"845-855","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fractal dynamics in spontaneous motor activity associate with effective antidepressant chronotherapeutic response, cerebellar volumes, and white matter microstructure in bipolar disorder"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0559-0164","authenticated-orcid":false,"given":"Chiara","family":"Verga","sequence":"first","affiliation":[{"name":"Division of Neuroscience, Psychiatry and Clinical Psychobiology Unit IRCCS San Raffaele Hospital  Milan 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