b'A. Nestsiarovich et al.4Background information in the article advised that mood disorders are one of thethreeleadingcausesofdisability worldwide. In the United States, more than 17 million people have been diag-nosedwithmajordepressivedisorder (MDD) and seven million with bipolar disorder (BD).Rates of serious mental illness appear tobeespeciallyhighamongservice-membersandveterans,atleastpartly because trauma exposure leads to vari-ouspsychiatricdisorders,including depression,anxiety,bipolardisorders, personality disorders and psychotic dis-orders. That is especially the case with post-traumatic stress disorder, according to a 2018 review. 2The issue is not limited to more-recent veterans,however. AttheVA,bipolar Fig.2 ThehazardratioofdiagnosticMDDtoBDconversionasafunctionofriskscoreintheCCAEdatabase.Thegray shadow indicatesdisorderaffectslargenumbersofvet- con denceintervalforthehazardratio(y-axis).Ariskscoreof0wasusedasareference.MDDmajordepressivedisorder.therespective95% Fig. 2 The hazard ratio of diagnostic MDD to BD conversion as a function of risk score in erans across their entire life spans, withCCAEIBM MarketScan Commercial Claims and Encounters database.BD - bipolar disorder. the CCAE database. The gray shadow indicates the respective 95% confidence interval for the useofhealthcareresourcesincreasinghazard ratio (y-axis). A risk score of 0 was used as a reference. MDDmajor depressive disorder.BD - bipolar disorder. CCAEIBM MarketScan Commercial Claims and Encounters database.overtime.OlderpatientswithbipolarSource: Predictors of diagnostic transition from major depressive disorder to bipolar disorder: a retrospective observational disorder have unique treatment require- network study; Translational Psychiatry; www.nature.com/articles/s41398-021-01760-6ments and clinical presentations, accord-ing to the report in Psychiatric Services. 3 subsequently had their MDD diagnosis changed to BD, The retrospective analysis of a large VA databasewith a mean time to change being 1.89-2.98 years. 4was conducted by Case Western Reserve UniversityThat matters because patients with BD have less SchoolofMedicineresearchersinCleveland.Itfavorable illness course, and outcomes require com-noted that, at the beginning of this century, the VAspletely different treatments. For example, antide-registry listed 65,556 patients as having bipolar dis- pressants might trigger a manic mood switch among order, with nearly one-fourth of them 60 or older andthose with BD, according to the authors of the recent 10% 70 or older. study. It is suggested that the use of antidepressants by patients with unrecognized BD can contribute to Is It an Earlier Stage? their drug resistance, making them difficult to treat.Both MDD and BD are chronic debilitating psychi- On the other hand, a number of new drugs have recently Fig. 3 KaplanMeier curves of diagnostic conversion in the CCAE dataset based on risk score range. Each colored line represents aatric conditions, with overlapping neurobiology andgainedFoodandDrugAdministrationapproval,brightpink:anyscore.differentscorerange(fromtoptothebottom):orange:-8to 1;yellow:09;green:1019;teal:2029;darkblue:3044,symptoms (recurrent depressive episodes), however,Claims and Encounters database. MDDmajor depressive disorder.for treat- disorder.CCAE IBM MarketScan Commercial including lumateperone, marketed as Caplyta, BDbipolarBDisdiagnosedifatleast onemanic/hypomanicment of adults with depressive episodes associated withto BD withinDISCUSSION were predictive of MDD diagnostic transitionIn our nal regression model, younger patient age, higher one year.episode was present during the patient lifetime, thebipolar I and II disorder, as monotherapy or adjunctivea younger age canseverity of the initial depressive episode, the presence of The association of diagnostic transition withTranslationalPsychiatryresearcherspointedout.therapy wi nd anxiety m or va the following explanation: BD typically manifests at apsychotic features during the index depression, a th lithiu have lproate and a combination It is debatable whether MDD represents an earlierof olanzapine and samidorphan, marketed as Lybalvi, Translational Psychiatry \x1f\x1f\x1f\x1f\x1f\x1f\x1f\x1f\x1f(2021)\x1f11:642\x1fstage of BD or is part of the same illness, given highwhichisapprovedforthetreatmentofadultswith MDD to BD prospective conversion rates (20-yearschizophrenia and for adults with bipolar I disorder, as rate of 25% and annual rate of 0.8-3.9%. a maintenance monotherapy or to treat acute manic or They cited a retrospective study following up sub- mixed episodes, as either monotherapy or an adjunct to jects with MDD for eight years; 7.612.1% of themlithium or valproate.10'