Contribution of ceramides metabolism in psychiatric disorders

Bernal-Vega, Sofía; García-Juárez, Martín; Camacho‐Morales, Alberto

doi:10.1111/jnc.15759

Cited by 17 publications

(11 citation statements)

References 183 publications

(241 reference statements)

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“…Lower levels of sphingomyelins were also consistently observed across groups of men who had abnormal scores for the BSI subscales but were particularly notable for phobic anxiety, which showed the most associations with this pathway. Sphingolipid metabolism has been implicated in several mental disorders [ 43 , 44 , 45 , 46 ], and the inverse associations observed in this study may suggest a disruption in the balance between sphingomyelins and pro-apoptotic ceramides in men who reported abnormal scores. However, metabolism of some lipid pathways tended to be divided across the BSI subscales, which may reveal important pathways that are unique to one or two of the subscales but not representative of the overlap across all three.…”

Section: Discussionmentioning

confidence: 67%

Metabolomics and Self-Reported Depression, Anxiety, and Phobic Symptoms in the VA Normative Aging Study

et al. 2023

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Traditional approaches to understanding metabolomics in mental illness have focused on investigating a single disorder or comparisons between diagnoses, but a growing body of evidence suggests substantial mechanistic overlap in mental disorders that could be reflected by the metabolome. In this study, we investigated associations between global plasma metabolites and abnormal scores on the depression, anxiety, and phobic anxiety subscales of the Brief Symptom Inventory (BSI) among 405 older males who participated in the Normative Aging Study (NAS). Our analysis revealed overlapping and distinct metabolites associated with each mental health dimension subscale and four metabolites belonging to xenobiotic, carbohydrate, and amino acid classes that were consistently associated across all three symptom dimension subscales. Furthermore, three of these four metabolites demonstrated a higher degree of alteration in men who reported poor scores in all three dimensions compared to men with poor scores in only one, suggesting the potential for shared underlying biology but a differing degree of perturbation when depression and anxiety symptoms co-occur. Our findings implicate pathways of interest relevant to the overlap of mental health conditions in aging veterans and could represent clinically translatable targets underlying poor mental health in this high-risk population.

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Section: Discussionmentioning

confidence: 67%

Metabolomics and Self-Reported Depression, Anxiety, and Phobic Symptoms in the VA Normative Aging Study

et al. 2023

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“…The results also point to the involvement of sphingolipids, specifically ceramides, in the distinct pathomechanisms of mood disorders. This may signify intrinsic immunometabolic or signaling differences between BD and MDD 15 or the body’s adaptive responses to these conditions.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Biomarker Signatures for Bipolar and Unipolar Depression

Tomasik,

Harrison,

Rustogi

et al. 2024

JAMA Psychiatry

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ImportanceBipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) because of overlapping symptoms and the lack of objective diagnostic tools.ObjectiveTo identify a reproducible metabolomic biomarker signature in patient dried blood spots (DBSs) that differentiates BD from MDD during depressive episodes and assess its added value when combined with self-reported patient information.Design, Setting, and ParticipantsThis diagnostic analysis used samples and data from the Delta study, conducted in the UK between April 27, 2018, and February 6, 2020. The primary objective was to identify BD in patients with a recent (within the past 5 years) diagnosis of MDD and current depressive symptoms (Patient Health Questionnaire–9 score of 5 or more). Participants were recruited online through voluntary response sampling. The analysis was carried out between February 2022 and July 2023.Main Outcomes and MeasuresPatient data were collected using a purpose-built online questionnaire (n = 635 questions). DBS metabolites (n = 630) were analyzed using a targeted mass spectrometry–based platform. Mood disorder diagnoses were established using the Composite International Diagnostic Interview.ResultsOf 241 patients in the discovery cohort, 170 (70.5%) were female; 67 (27.8%) were subsequently diagnosed with BD and 174 (72.2%) were confirmed as having MDD; and the mean (SD) age was 28.1 (7.1) years. Of 30 participants in the validation cohort, 16 (53%) were female; 9 (30%) were diagnosed with BD and 21 (70%) with MDD; and the mean (SD) age was 25.4 (6.3) years. DBS metabolite levels were assessed in 241 patients with depressive symptoms with a recent diagnosis of MDD, of whom 67 were subsequently diagnosed with BD by the Composite International Diagnostic Interview and 174 were confirmed as having MDD. The identified 17-biomarker panel provided a mean (SD) cross-validated area under the receiver operating characteristic curve (AUROC) of 0.71 (SD, 0.12; P &lt; .001), with ceramide d18:0/24:1 emerging as the strongest biomarker. Combining biomarker data with patient-reported information significantly enhanced diagnostic performance of models based on extensive demographic data, PHQ-9 scores, and the outcomes from the Mood Disorder Questionnaire. The identified biomarkers were correlated primarily with lifetime manic symptoms and were validated in a separate group of patients who received a new clinical diagnosis of MDD (n = 21) or BD (n = 9) during the study’s 1-year follow-up period, with a mean (SD) AUROC of 0.73 (0.06; P &lt; .001).Conclusions and RelevanceThis study provides a proof of concept for developing an accessible biomarker test to facilitate the differential diagnosis of BD and MDD and highlights the potential involvement of ceramides in the pathophysiological mechanisms of mood disorders.

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“…In another study by the same group, the hippocampal concentrations of N-acetyl-aspartate (NAA) and N-acetyl-aspartyl-glutamate (NAG), markers of neuronal integrity related to microglial activation (53,69), were increased in BD compared to HC (69). Moving to another direction, one recent work points to the involvement of ceramides in BD neuroinflammatory processes (253). BD patients displayed high levels of ultralong-chain ceramides and galactosylsphingosine in the cortex, substantia nigra, and nucleus accumbens, as well as elevated serum levels of ceramides, including glucosylceramides and lactosylceramides (253).…”

Section: Inflammatory Correlates Of Behavioural and Neurobiological M...mentioning

confidence: 98%

“…Moving to another direction, one recent work points to the involvement of ceramides in BD neuroinflammatory processes (253). BD patients displayed high levels of ultralong-chain ceramides and galactosylsphingosine in the cortex, substantia nigra, and nucleus accumbens, as well as elevated serum levels of ceramides, including glucosylceramides and lactosylceramides (253). One tentative hypothesis posits that ceramide enhances the FC between the nucleus accumbens core and PFC, favouring defective myelination and enhancing neuroinflammation.…”

Section: Inflammatory Correlates Of Behavioural and Neurobiological M...mentioning

confidence: 99%

Inflammation and emotional regulation: a narrative review of evidence and mechanisms in emotional dysregulation disorders

Petruso¹,

Giff²,

Milano³

et al. 2023

Preprint

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Emotion dysregulation (ED) describes a difficulty with the modulation of which emotions are felt, as well as when and how these emotions are experienced or expressed. It is a focal overarching symptom in many severe and prevalent neuropsychiatric diseases, including bipolar disorders (BD), attention deficit and hyperactivity disorder (ADHD), and borderline personality disorder (BPD). In all these disorders, ED can manifest through symptoms of depression, anxiety, or affective lability. Considering the many similarities in symptoms between BD, ADHD, and BPD, a transdiagnostic approach is a promising lens of investigation. Mounting evidence supports the role of peripheral inflammatory markers and stress in the multifactorial aetiology and physiopathology of BD, ADHD, and BPD. Of note, neural circuits that regulate emotions appear particularly vulnerable to inflammatory insults and peripheral inflammation, which can impact the neuroimmune milieu of the central nervous system. Thus far, few studies have examined the link between ED and inflammation in BD, ADHD, and BPD. To our knowledge, no specific work has provided a critical comparison of the results from these disorders. To fill this gap in the literature, we review the known associations and mechanisms linking ED and inflammation in general, and clinically, in BD, ADHD, and BD. Our narrative review begins with an examination of the routes linking ED and inflammation, followed by a discussion of disorder-specific results accounting for methodological limitations and relevant confounding factors. Finally, we critically discuss both correspondences and discrepancies in the results and comment on potential vulnerability markers and promising therapeutic interventions.

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Contribution of ceramides metabolism in psychiatric disorders

Cited by 17 publications

References 183 publications

Metabolomics and Self-Reported Depression, Anxiety, and Phobic Symptoms in the VA Normative Aging Study

Metabolomics and Self-Reported Depression, Anxiety, and Phobic Symptoms in the VA Normative Aging Study

Metabolomic Biomarker Signatures for Bipolar and Unipolar Depression

Inflammation and emotional regulation: a narrative review of evidence and mechanisms in emotional dysregulation disorders

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