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Introduction: Chronic low-grade inflammation is suggested to play a pathophysiological role in bipolar disorder (BD) and its related cognitive dysfunctions. Although kynurenine (KYN) pathway metabolites are key inflammatory mediators, studies investigating the association between KYN metabolism and cognition in BD are scarce. We aimed to explore the relationship between KYN metabolism and cognitive functioning across different mood states in BD. Methods: Sixty-seven patients with BD (35 depressed and 32 [hypo] manic) and 29 healthy controls were included. Cognitive functioning was assessed at 3 time intervals (baseline, 4, and 8 months) assessing processing speed, sustained attention, verbal memory, working memory, and response inhibition. Plasma samples for quantification of 3-hydroxykynurenine, quinolinic acid, and kynurenic acid (KYNA) were concurrently provided. Linear mixed models were used for statistical analysis. Results: The manic group showed deficits in all assessed cognitive domains with the exception of verbal memory at all test moments. The bipolar depression group showed deficits in the processing speed at all test moments. Throughout the whole follow-up period, KYNA was significantly lower in both patient groups than in controls. Only in the bipolar depression group, low KYNA was associated with worse global cognitive functioning (B = 0.114, p = 0.02) and slower processing speed in particular (B = 0.139, p = 0.03). Conclusion: Only in the bipolar depression group, lower KYNA was associated with worse cognitive functioning. Future large-scale longitudinal studies are warranted to confirm the role of KYN metabolites in cognitive impairment in patients with BD and the possible therapeutic implications of this relationship. [ABSTRACT FROM AUTHOR]

Background: The "cognitive dysmetria hypothesis" of schizophrenia proposes a disrupted communication between the cerebellum and cerebral cortex, resulting in sensorimotor and cognitive symptoms. Sensorimotor adaptation relies strongly on the function of the cerebellum. Objectives: This study investigated whether sensorimotor adaptation is reduced in schizophrenia compared with age-matched and elderly healthy controls. Methods: Twenty-nine stably treated patients with schizophrenia, 30 age-matched, and 30 elderly controls were tested in three motor adaptation tasks in which visual movement feedback was unexpectedly altered. In the "rotation adaptation task" the perturbation consisted of a rotation (30° clockwise), in the "gain adaptation task" the extent of the movement feedback was reduced (by a factor of 0.7) and in the "vertical reversal task," up- and downward pen movements were reversed by 180°. Results: Patients with schizophrenia adapted to the perturbations, but their movement times and errors were substantially larger than controls. Unexpectedly, the magnitude of adaptation was significantly smaller in schizophrenia than elderly participants. The impairment already occurred during the first adaptation trials, pointing to a decline in explicit strategy use. Additionally, post-adaptation aftereffects provided strong evidence for impaired implicit adaptation learning. Both negative and positive schizophrenia symptom severities were correlated with indices of the amount of adaptation and its aftereffects. Conclusions: Both explicit and implicit components of sensorimotor adaptation learning were reduced in patients with schizophrenia, adding to the evidence for a role of the cerebellum in the pathophysiology of schizophrenia. Elderly individuals outperformed schizophrenia patients in the adaptation learning tasks. [ABSTRACT FROM AUTHOR]

Background: Although differences in symptom profiles and outcome between depressive patients with an underlying major depressive disorder (MDD) and bipolar depression (BD) have been reported, studies with sequential short-interval assessments in a real-life inpatient setting are scarce. Objectives: To examine potential differences in symptom profile and course of depressive symptomatology in depressive inpatients with underlying MDD and BD. Methods: A cohort of 276 consecutive inpatients with MDD (n = 224) or BD (n = 52) was followed during their hospitalization using routine outcome monitoring (ROM), which included a structured diagnostic interview at baseline (Mini-International Neuropsychiatric Interview Plus [MINI-Plus]) and repeated 17-item Hamilton Depression Rating Scale every 2 weeks. MDD and BD were compared regarding their symptom profiles and time to response and remission. Furthermore, the concordance between the MINI-Plus and clinical diagnosis was analyzed. Results: Patients were on average 52 and 47 years old in the MDD and BD group, respectively, and 66 versus 64% were female. Compared to patients with BD, patients with MDD scored higher on weight loss (p = 0.02), whereas the BD group showed a higher long-term likelihood of response (hazard ratio = 1.93, 95% confidence interval 1.16–3.20, p for interaction with time = 0.04). Although the same association was seen for remission, the interaction with time was not significant (p = 0.48). Efficiency between the MINI-Plus and clinical diagnosis of BD was high (0.90), suggesting that the MINI-Plus is an adequate ROM diagnostic tool. Conclusions: In routine clinical inpatient care, minor differences in the symptom profile and the course of depressive symptomatology may be helpful in distinguishing MDD and BD, particularly when using sequential ROM assessments. [ABSTRACT FROM AUTHOR]

Background: Retardation and agitation are symptoms of major depressive disorder (MDD), and their presence could play a role in determining clinically meaningful depressive subtypes such as nonmelancholic depression (NMD) and melancholic depression (MD). In this project, we explored whether three depression subgroups (NMD, MD with psychotic symptoms, and MD without psychotic symptoms) could be distinguished based on objective measures of psychomotor functioning. Methods: Sixty-nine patients with MDD underwent extensive clinical and psychomotor testing prior to treatment with electroconvulsive therapy. Psychomotor functioning was assessed subjectively using the Core Assessment of Psychomotor Change (CORE) and objectively by means of both 24-h actigraphy and performance on a fine motor drawing task. Results: The daytime activity levels measured by actigraphy were significantly lower (F = 7.1, p = 0.0004) in MD patients both with and without psychotic symptoms than in those with NMD. No objective psychomotor variable was able to distinguish between melancholic patients with and those without psychotic symptoms. Conclusions: The depression subtypes NMD, MD with psychotic symptoms, and MD without psychotic symptoms are not marked by increasing psychomotor retardation, possibly because psychomotor disturbance in MD with psychotic symptoms often consists of agitation rather than retardation, or a mixture of the two. However, psychomotor functioning as measured by actigraphy can be used to distinguish between NMD patients and MD patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Major depressive disorder (MDD) is highly recurrent. This may be due to increased stress sensitivity after remission. Both inflammatory and psychosocial stressors are implicated in the pathogenesis of MDD, but the additive or differential effect is unclear. Methods: We conducted a single-blind placebo-controlled study to investigate the effects of inflammatory stress (i.e., typhoid vaccination), psychosocial stress (i.e., Trier Social Stress Test [TSST]), or a combination of both in women (25-45 years old) with (partially) remitted recurrent MDD (n = 21) and healthy female controls (n = 18). We evaluated the effect on mood measured by the Profile of Mood States, markers of the hypothalamic-pituitary- adrenal (HPA) axis activity, and inflammatory system activation. The study was performed during 2 testing days, separated by a washout of 7-14 days. In a crossover design, subjects received one of the interventions on one day and placebo on the other. Results: A lowering of mood was seen in patients (β [95% CI] = -4.79 [-6.82 to -2.75], p < 0.001) only after vaccination, but not after the TSST or the combination; this effect was not observed in controls. Controls experienced a significantly different response on adrenocorticotropic hormone (ACTH) after vaccination, with a general rise in ACTH not observed in patients. In both groups, the TSST activated the HPA axis and suppressed the inflammatory parameters. Conclusions: There is a differential effect of inflammatory and psychosocial stress on mood and HPA axis activation in patients with remitted recurrent MDD. This may be an interesting treatment target in MDD. [ABSTRACT FROM AUTHOR]