Objective: There are several models of staging in bipolar disorder (BD), but none has been validated. The aims of this study were to empirically investigate clinical variables that may be useful to classify patients in clusters according to stage and study the association with biomarkers as biological validators. Method: This was a historical cohort study. Patients (n = 115) diagnosed with BD and not in an acute episode and first-degree relatives of patients diagnosed with BD (n = 25) were recruited. Sociodemographic, clinical, and functional data were collected. Serum cytokines, brain-derived neurotrophic factor, and biomarkers of lipid and protein oxidation were assessed. Cluster analysis was carried out to build a model of staging, and logistic regression was conducted to study associations between the model and biomarkers. Results: Cluster analysis divided the sample into two equitable groups, denominated early and late stage, with empirical cutoffs for the Functioning Assessment Short Test score, number of episodes, age at onset of the disorder, and time elapsed since first episode. In the logistic regression, IL-6 was associated with late stage (P = 0.029). Conclusion: This study supports that clinical, functional, and biochemical variables may help to define a classification of staging in BD. Significant outcomes• A model of staging based on early and late stages according to functioning, number of episodes, age at onset of the disorder, and time elapsed since the first episode can be feasible and useful in bipolar disorder.• IL-6 is a valid biological biomarker for this proposal of staging in bipolar disorder. Limitations• Patients with subsyndromal symptoms were not excluded from the sample. • Biomarker assessment was carried out peripherally. • Lack of a prospective assessment hampers to test the validity of a model of staging.

ipolar disorder (BD) is a mood disorder that has an early onset at a median age of 20 years. It is a long-term and recurrent disorder characterized by cyclic episodes of depression and either mania (BD type 1) or hypomania (BD type 2). Although the etiology of BD has not been established, it is a multifactorial disorder with genetic and environmental factors playing an important role. 1 Despite the pathophysiology of BD being uncertain, there is a putative role of the dopaminergic system, as levodopa has been shown to induce hypomania or mania in patients with BD, 2 and antipsychotic medications that block dopamine receptors can improve manic symptoms. 3 There is also evidence that the switch from a depressive to a manic state occurs concurrently with an upregulation of dopamine receptors. 4 The standard treatment for BD that includes lithium, antipsychotic medications, and antiepileptic medications may be associated with drug-induced parkinsonism, which is not clinically distinguishable from Parkinson disease (PD), both being characterized by bradykinesia, resting tremor, rigidity, and postural instability. [5][6][7] Since drug-induced parkinsonism is more common among patients with BD, physicians may be more inclined to misdiagnose PD as drug-induced parkinsonism. On the other hand, PD is typically seen in older patients. Small studies have previously shown that BD may be more common in patients with PD compared with the general population. 6 Therefore, we conducted a systematic review to assess the possible association of BD with a later diagnosis of idiopathic PD. IMPORTANCE Parkinson disease (PD) manifests by motor and nonmotor symptoms, which may be preceded by mood disorders by more than a decade. Bipolar disorder (BD) is characterized by cyclic episodes of depression and mania. It is also suggested that dopamine might be relevant in the pathophysiology of BD.OBJECTIVE To assess the association of BD with a later diagnosis of idiopathic PD.DATA SOURCES An electronic literature search was performed of Cochrane Controlled Register of Trials, MEDLINE, Embase, and PsycINFO from database inception to May 2019 using the terms Parkinson disease, bipolar disorder, and mania, with no constraints applied.STUDY SELECTION Studies that reported data on the likelihood of developing PD in BD vs non-BD populations were included. Two review authors independently conducted the study selection. DATA EXTRACTION AND SYNTHESISTwo review authors independently extracted study data. Data were pooled using a random-effects model, results were abstracted as odds ratios and 95% CIs, and heterogeneity was reported as I 2 . MAIN OUTCOME AND MEASURES Odds ratios of PD.RESULTS Seven studies were eligible for inclusion and included 4 374 211 participants overall. A previous diagnosis of BD increased the likelihood of a subsequent diagnosis of idiopathic PD (odds ratio, 3.35; 95% CI, 2.00-5.60; I 2 = 92%). A sensitivity analysis was performed by removing the studies that had a high risk of bias and also showed an increased risk of PD in pe...

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Brain-derived neurotrophic factor (BDNF) plays a critical role in neurodevelopment and neuroplasticity. Altered BDNF signaling is thought to contribute to the pathogenesis of schizophrenia (SZ) especially in relation to cognitive deficits. Clozapine (CLZ) has been shown a beneficial effect on cognition in SZ in some studies and a detrimental effect in others. To examine serum BDNF, two groups of chronically medicated DSM-IV SZ patients (n=44), on treatment with clozapine (n=31) and typical antipsychotics (n=13) had 5ml blood samples collected by venipuncture. Serum BDNF levels were significantly correlated with CLZ daily dose (r=0.394, p=0.028), but not with typical antipsychotic daily dose (r=0.208, p=0.496). This study suggests that serum BDNF levels are correlated with CLZ daily dose, and this may lead to the cognitive enhancement as seen in patients with SZ under CLZ. Despite the strong evidence that chronic administration of CLZ is effective for patients with SZ, it is still unknown whether atypical antipsychotic drugs regulate BDNF expression. Serum BDNF levels concentration in SZ merits further investigations with regard to the role of neurotrophins in the cognitive response to treatment with CLZ and other atypical antipsychotics.