Tryptophan Metabolism in Bipolar Disorder in a Longitudinal Setting.
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ABSTRACT:
SUBMITTER: Fellendorf FT
PROVIDER: S-EPMC8615217 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTryptophan catabolites (TRYCATs) are implicated in the pathophysiology of mood disorders by mediating immune-inflammation and neurodegenerative processes. We performed a meta-analysis of TRYCAT levels in bipolar disorder (BD) patients compared to healthy controls.MethodsA systematic literature search in seven electronic databases (PubMed, Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier) was conducted on TRYCAT levels in cerebrospinal fluid or peripheral blood according to the PRISMA statement. A minimum of three studies per TRYCAT was required for inclusion. Standardized mean differences (SMD) were computed using random effect models. Subgroup analyses were performed for BD patients in a different mood state (depressed, manic). The methodological quality of the studies was rated using the modified Newcastle-Ottawa Quality assessment Scale.ResultsTwenty-one eligible studies were identified. Peripheral levels of tryptophan (SMD = -0.44; p < 0.001), kynurenine (SMD = - 0.3; p = 0.001) and kynurenic acid (SMD = -.45; p = < 0.001) were lower in BD patients versus healthy controls. In the only three eligible studies investigating TRP in cerebrospinal fluid, tryptophan was not significantly different between BD and healthy controls. The methodological quality of the studies was moderate. Subgroup analyses revealed no significant difference in TRP and KYN values between manic and depressed BD patients, but these results were based on a limited number of studies.ConclusionThe TRYCAT pathway appears to be downregulated in BD patients. There is a need for more and high-quality studies of peripheral and central TRYCAT levels, preferably using longitudinal designs.
| S-EPMC8170319 | biostudies-literature
Project description:OBJECTIVE:The authors sought to identify diagnostic risk factors of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder ("high-risk offspring"). METHOD:High-risk offspring 6-18 years old (N=391) and demographically matched offspring (N=248) of community parents without bipolar disorder were assessed longitudinally with standardized diagnostic instruments by staff blind to parental diagnoses. Follow-up assessments were completed in 91% of the offspring (mean follow-up interval, 2.5 years; mean follow-up duration, 6.8 years). RESULTS:Compared with community offspring, high-risk offspring had significantly higher rates of subthreshold mania or hypomania (13.3% compared with 1.2%), manic, mixed, or hypomanic episodes (9.2% compared with 0.8%), and major depressive episodes (32.0% compared with 14.9%). They also had higher rates of attention deficit hyperactivity disorder (30.7% compared with 18.1%), disruptive behavior disorders (27.4% compared with 15.3%), anxiety disorders (39.9% compared with 21.8%), and substance use disorders (19.9% compared with 10.1%), but not unipolar major depressive disorder (major depression with no bipolarity; 18.9% compared with 13.7%). Multivariate Cox regressions showed that in the high-risk offspring, subthreshold manic or hypomanic episodes (hazard ratio=2.29), major depressive episodes (hazard ratio=1.99), and disruptive behavior disorders (hazard ratio=2.12) were associated with subsequent manic, mixed, or hypomanic episodes. Only subthreshold manic or hypomanic episodes (hazard ratio=7.57) were associated when analyses were restricted to prospective data. CONCLUSIONS:Subthreshold manic or hypomanic episodes were a diagnostic risk factor for the development of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder and should be a target for clinical assessment and treatment research. Major depressive episodes and disruptive behavior disorders are also indications for close clinical monitoring of emergent bipolarity in high-risk offspring.
| S-EPMC4489996 | biostudies-literature
Project description:OBJECTIVE:To provide the first longitudinal characterization of mood and psychosocial functioning in youth with comorbid bipolar (BD) and autism spectrum (ASD) disorders. METHOD:The Course and Outcome of Bipolar Youth study followed 368 youth (aged 7-17 years) with DSM-IV bipolar I (BP-I), BP-II, or Not Otherwise Specified (NOS) for, on average, 9 years using the Longitudinal Interval Follow-up Evaluation. This subgroup analysis compared youth with and without ASD on clinical presentation, percentage of time with mood symptomatology, and psychosocial functioning. RESULTS:Thirty youth (?8%) met DSM-IV criteria for Asperger's disorder or pervasive developmental disorder-NOS (referred to here as ASD). Lifetime worst episode severity was similar in both groups, but youth with both BD and ASD (BD+ASD) had elevated rates of comorbid attention-deficit/hyperactivity and obsessive-compulsive disorders, were younger at intake, and had an earlier onset of mood symptoms. Over time, in both groups, the proportion of predominantly euthymic youth increased, and episode recurrence decreased. Compared to youth with BD, the clinical presentation of youth with BD+ASD more frequently involved distractibility, racing thoughts, depressed mood, social withdrawal, and low reactivity of negative mood states. ASD-related symptomatic differences were generally strongest early and decreased over time. Youth with BD+ASD had significantly greater impairment in friendships throughout follow-up. CONCLUSION:Youth with BD+ASD exhibit typical BD mood symptoms but with earlier onset, mixed symptom presentation, and additive functional impairments. Significant amelioration of clinical symptoms occurred over time, suggesting that early recognition and treatment of mood disorders in youth with ASD may improve clinical outcomes.
| S-EPMC5123749 | biostudies-literature
Project description:The Diagnostic and Statistical Manual of Mental Disorder (DSM) classification of bipolar disorder defines categories to reflect common understanding of mood symptoms rather than scientific evidence. This work aimed to determine whether bipolar I can be objectively classified from longitudinal mood data and whether resulting classes have clinical associations. Bayesian nonparametric hierarchical models with latent classes and patient-specific models of mood are fit to data from Longitudinal Interval Follow-up Evaluations (LIFE) of bipolar I patients (N=209). Classes are tested for clinical associations. No classes are justified using the time course of DSM-IV mood states. Three classes are justified using the course of subsyndromal mood symptoms. Classes differed in attempted suicides (P=0.017), disability status (P=0.012) and chronicity of affective symptoms (P=0.009). Thus, bipolar I disorder can be objectively classified from mood course, and individuals in the resulting classes share clinical features. Data-driven classification from mood course could be used to enrich sample populations for pharmacological and etiological studies.
| S-EPMC5315544 | biostudies-other
Project description:BackgroundTraditionally, assessment of psychiatric symptoms has been relying on their retrospective report to a trained interviewer. The emergence of smartphones facilitates passive sensor-based monitoring and active real-time monitoring through time-stamped prompts; however there are few validated self-report measures designed for this purpose.MethodsWe introduce a novel, compact questionnaire, Mood Zoom (MZ), embedded in a customised smart-phone application. MZ asks participants to rate anxiety, elation, sadness, anger, irritability and energy on a 7-point Likert scale. For comparison, we used four standard clinical questionnaires administered to participants weekly to quantify mania (ASRM), depression (QIDS), anxiety (GAD-7), and quality of life (EQ-5D). We monitored 48 Bipolar Disorder (BD), 31 Borderline Personality Disorders (BPD) and 51 Healthy control (HC) participants to study longitudinal (median±iqr: 313±194 days) variation and differences of mood traits by exploring the data using diverse time-series tools.ResultsMZ correlated well (|R|>0.5,p<0.0001) with QIDS, GAD-7, and EQ-5D. We found statistically strong (|R|>0.3,p<0.0001) differences in variability in all questionnaires for the three cohorts. Compared to HC, BD and BPD participants exhibit different trends and variability, and on average had higher self-reported scores in mania, depression, and anxiety, and lower quality of life. In particular, analysis of MZ variability can differentiate BD and BPD which was not hitherto possible using the weekly questionnaires.LimitationsAll reported scores rely on self-assessment; there is a lack of ongoing clinical assessment by experts to validate the findings.ConclusionsMZ could be used for efficient, long-term, effective daily monitoring of mood instability in clinical psychiatric practice.
| S-EPMC5296237 | biostudies-literature
Project description:Bipolar disorder (BD) is a severe affective disorder, mainly characterized by alternative depressive and manic or hypomanic episodes, yet the pathogenesis of BD has not been fully elucidated. Recent researches have implicated the altered kynurenine (KYN) metabolism involved in the neurobiology of BD. Excessive activation of the immune system also occurs in patients with BD, which further accelerates the KYN pathway for tryptophan metabolism. Changes of the KYN metabolites have effects on neuronal receptors and are involved in neuroendocrine transmissions. Interactions between KYN metabolism and the immune system may contribute to the neuropathogenesis of BD. Various studies have shown that alterations of the KYN metabolites were associated with mood, psychotic symptoms, and cognitive functions in patients with BD. In this review, we briefly introduce the KYN pathway and describe the immune dysregulation in BD as well as their interactions. We then focus on the research advances on the KYN metabolism in BD, which hold promise for identifying novel treatment targets in patients stricken with this disorder.
| S-EPMC8349985 | biostudies-literature
Project description:OBJECTIVES:The objective of this work was to study characteristics and clinical treatment patterns of bipolar disorder (BD) patients admitted to hospital and treated with quetiapine (immediate-release [IR] or extended-release [XR] formulations). METHODS:BD patients admitted to hospital and prescribed quetiapine IR were followed by linking two Swedish nationwide registries; the hospitalization and drug dispense registries [ClinicalTrials.gov identifier: NCT01455961]. The study period was from 1 January 2008, to end of 31 December 2011. Data was primarily analysed using descriptive methods. RESULTS:Quetiapine IR was used in 1761 patients of whom 1303 subsequently switched to XR (switch XR) and 458 remained on IR (continuous IR). At baseline, Switch XR patients were younger (-3.3 years), more frequently employed (+7.1%), had higher prevalence of single depressive episodes (+6.7%) and anxiety disorders (+5.8%), lower mean daily IR dose (-19.3%) and fewer medications for somatic disorders (-7.5%) than continuous IR patients. During follow up, the number of concomitant psychiatric medications was lower in switch XR patients (-6%) and higher in continuous IR patients (+6%). Mean daily quetiapine dose was 21% higher in switch XR versus continuous IR patients. Prescriptions of lower quetiapine dosages calculated below 50 mg per day in the XR switch and IR continuous groups were seen in 8% versus 10% of the patients, respectively. CONCLUSIONS:Differential use of quetiapine XR and IR in bipolar disorder patients with different and important characteristics was demonstrated. Patients who were switched to quetiapine XR had a higher psychiatric disease burden, were younger and had a higher degree of employment. These differences demonstrate the heterogeneity among bipolar disorder patients and indicate the need in clinical practice for individualized treatment to reduce the risk for both patient and society related losses.
| S-EPMC4315674 | biostudies-literature
Project description:Background: A mild pro-inflammatory status accompanies bipolar disorder (BD). Inflammation can cause a shift in monoamine metabolism, thereby activating more cytotoxic pathways. The extent to which low-grade inflammation in BD interacts with monoamine metabolism and how this accords to aging and clinical course is unknown. Objectives: We evaluated the presence of alterations in inflammation and monoamine metabolism in BD throughout different mood states and the role of aging therein. Methods: Sixty-seven patients with BD were included during an acute mood episode, either depressive (n = 29), (hypo)manic (n = 29), or mixed (n = 9). Plasma levels of inflammatory markers [tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-y), interleukin-6 (IL-6), and C-reactive protein (CRP)] and markers of monoamine metabolism (neopterin, tryptophan, kynurenine, phenylalanine, and tyrosine) were measured repeatedly during a follow-up of 8 months. Levels in patients were compared to controls (n = 35) and correlated to HDRS-17 and YMRS scores. Spearman correlations and linear mixed model analysis were used for statistical analysis. Results: Forty-nine patients and 30 controls (age range: 22-62 years) completed the study. No significant differences in inflammatory markers were found between patients and controls overall. Tryptophan, tyrosine, and phenylalanine levels were lower in patients. In both patients and controls, markers of inflammation correlated only weakly with markers of monoamine metabolism, but correlations representative for activity of cytotoxic pathways in monoamine metabolism were more pronounced in patients. In patients, but not in controls, older age was associated with increases in inflammatory markers (IL-6, CRP, neopterin) and the kynurenine/tryptophan ratio. None of the biological markers correlated significantly with mood symptom severity. Conclusion: Our data suggest an increased susceptibility of patients with BD to develop a pro-inflammatory state and to shift monoamine metabolism toward more cytotoxic pathways. These findings are in support of the theory of neuroprogression and accelerated aging in BD. Since associations between biological markers and clinical characteristics are limited, it remains to be determined if alterations in biological markers are due to a disease effect or rather are a consequence of confounding factors.
| S-EPMC6010913 | biostudies-literature
Project description:OBJECTIVE:Migraine is a common comorbidity of bipolar disorder and is more prevalent in women than men. We hypothesized comorbid migraine would be associated with features of illness and psychosocial risk factors that would differ by gender and impact outcome. METHOD:A retrospective analysis was conducted to assess association between self-reported, physician-diagnosed migraine, clinical variables of interest, and mood outcome in subjects with DSM-IV bipolar disorder (N = 412) and healthy controls (N = 157) from the Prechter Longitudinal Study of Bipolar Disorder, 2005-2010. Informed consent was obtained from all participants. RESULTS:Migraine was more common in subjects with bipolar disorder (31%) than in healthy controls (6%) and had elevated risk in bipolar disorder women compared to men (OR = 3.5; 95% CI, 2.1-5.8). In men, migraine was associated with bipolar II disorder (OR = 9.9; 95% CI, 2.3-41.9) and mixed symptoms (OR = 3.5; 95% CI, 1.0-11.9). In comparison to absence of migraine, presence of migraine was associated with an earlier age at onset of bipolar disorder by 2 years, more severe depression (? = .13, P = .03), and more frequent depression longitudinally (? = .13, P = .03). Migraine was correlated with childhood emotional abuse (P = .01), sexual abuse (P = 4 × 10?³), emotional neglect (P = .01), and high neuroticism (P = 2 × 10?³). Protective factors included high extraversion (P = .02) and high family adaptability at the trend level (P = .08). CONCLUSIONS:Migraine is a common comorbidity with bipolar disorder and may impact long-term outcome of bipolar disorder, particularly depression. Clinicians should be alert for migraine comorbidity in women and in men with bipolar II disorder. Effective treatment of migraine may impact mood outcome in bipolar disorder as well as headache outcome. Joint pathophysiologic mechanisms between migraine and bipolar disorder may be important pathways for future study of treatments for both disorders.
| S-EPMC4211932 | biostudies-literature
Project description:BACKGROUND:Individuals with bipolar disorder (BD) show aberrant brain activation patterns during reward and loss anticipation. We examined for the first time longitudinal changes in brain activation during win and loss anticipation to identify trait markers of aberrant anticipatory processing in BD. METHODS:Thirty-four euthymic and depressed individuals with BD-I and 17 healthy controls (HC) were scanned using functional magnetic resonance imaging twice 6 months apart during a reward task. RESULTS:HC, but not individuals with BD, showed longitudinal reductions in the right lateral occipital cortex (RLOC) activation during processing of cues predicting possible money loss (p-corrected <0.05). This result was not affected by psychotropic medication, mood state or the changes in depression/mania severity between the two scans in BD. Elevated symptoms of subthreshold hypo/mania at baseline predicted more aberrant longitudinal patterns of RLOC activation explaining 12.5% of variance in individuals with BD. CONCLUSIONS:Increased activation in occipital cortex during negative outcome anticipation may be related to elevated negative emotional arousal during anticipatory cue processing. One interpretation is that, unlike HC, individuals with BD were not able to learn at baseline that monetary losses were smaller than monetary gains and were not able to reduce emotional arousal for negative cues 6 months later. Future research in BD should examine how modulating occipital cortical activation affects learning from experience in individuals with BD.
| S-EPMC6663653 | biostudies-literature