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Objectives: The kynurenine (KYN) pathway has been attracting attention as a relevant pathway in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We conducted a systematic review and meta-analysis of studies examining KYN pathway metabolites from cerebrospinal fluid (CSF) samples in SZ, BD, and MDD. Methods: The PubMed and Scopus databases were systematically searched to identify peer-reviewed case-control studies published until April 2022 that assessed KYN metabolites, namely, tryptophan (TRP), KYN, kynurenic acid (KA), quinolinic acid (QA), and 3-hydroxykynurenine (3-HK), in subjects with SZ, BD, or MDD compared with healthy controls (HC). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The random effects model method was selected for comparison of standardized mean differences (SMD) between two groups. Results: Twenty-three articles met the inclusion criteria (k = 8, k = 8, k = 11, for SZ, BD, and MDD, respectively). In SZ, KA levels were increased (SMD = 2.64, confidence interval [CI] = 1.16 to 4.13, p = 0.0005, I2 = 96%, k = 6, n=384). TRP (k = 5) and KYN (k = 4) did not differ significantly. In BD, TRP levels (k = 7) did not differ significantly. The level of KA was increased in MDD (k = 2), but the small number of studies precluded evaluation of statistical significance. Finally, in MDD, although some studies tended to show an increased level of KYN in those with remission vs. decreased levels in those with current depression, no significant difference was found in any KYN metabolite levels. Similarly, an increased level of QA was found, but the number of studies (k = 2) was small. Conclusion: KA, which has possibly neuroprotective effects, is increased in SZ. QA, which has neurotoxic effects, may be increased in MDD. There were no alterations in BD. Alterations in the KYN pathway may occur based on population characteristics and mood states. Future studies should explore the utility of these metabolites as biomarkers.

Objectives:Staging models for medical diseases are widely used to guide treatment and prognosis. Bipolar disorder (BD) is a chronic condition and it is among the most disabling disorders in medicine. The staging model proposed by Kapczinski in 2009 presents four progressive clinical stages of BD. Our aim was to evaluate pharmacological maintenance treatment across these stages in patients with BD.Methods:One hundred and twenty-nine subjects who met DSM-IV criteria for BD were recruited from the Bipolar Disorders Program at Hospital de Clínicas de Porto Alegre, Brazil. All patients were in remission. The subjects were classified according to the staging model: 31 subjects were classified as stage I, 44 as stage II, 31 as stage III, and 23 as stage IV.Results:Patterns of pharmacological treatment differed among the four stages (p = 0.001). Monotherapy was more frequent in stage I, and two-drug combinations in stage II. Patients at stages III and IV needed three or more medications or clozapine. Impairment in functional status (Functioning Assessment Short Test [FAST] scale scores) correlated positively with the number of medications prescribed.Conclusions:This study demonstrated differences in pharmacological treatment in patients with stable BD depending on disease stage. Treatment response can change with progression of BD. Clinical guidelines could consider the staging model to guide treatment effectiveness.

This article reviews the most common non-psychiatric comorbidities associated with affective disorders, examining the implications of their possible bidirectional link. A narrative review was conducted on the association among the three most common non-psychiatric diseases in major depressive disorder and bipolar disorder (obesity, metabolic syndrome, and cardiovascular diseases) in articles published from January 1994 to April 2020. The evidence suggests that obesity, metabolic syndrome, and cardiovascular diseases are highly prevalent in patients diagnosed with affective disorders. The presence of non-psychiatric comorbidities significantly worsens the therapeutic management and prognosis of affective disorders and vice versa. In many cases, these comorbidities may precede the onset of affective disorders, although in most cases they appear after it. The presence of these concurrent non-psychiatric diseases in an individual diagnosed with an affective disorder is associated with a more complex disease presentation and management. For professionals, the evidence unequivocally supports routine surveillance of comorbidities from a multidisciplinary approach.