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Translational Psychiatry Jun 2024Major depressive disorder (MDD) and bipolar disorder (BD) are highly disabling illnesses defined by different psychopathological, neuroimaging, and cognitive profiles.... (Review)
Review
Major depressive disorder (MDD) and bipolar disorder (BD) are highly disabling illnesses defined by different psychopathological, neuroimaging, and cognitive profiles. In the last decades, immune dysregulation has received increasing attention as a central factor in the pathophysiology of these disorders. Several aspects of immune dysregulations have been investigated, including, low-grade inflammation cytokines, chemokines, cell populations, gene expression, and markers of both peripheral and central immune activation. Understanding the distinct immune profiles characterizing the two disorders is indeed of crucial importance for differential diagnosis and the implementation of personalized treatment strategies. In this paper, we reviewed the current literature on the dysregulation of the immune response system focusing our attention on studies using inflammatory markers to discriminate between MDD and BD. High heterogeneity characterized the available literature, reflecting the heterogeneity of the disorders. Common alterations in the immune response system include high pro-inflammatory cytokines such as IL-6 and TNF-α. On the contrary, a greater involvement of chemokines and markers associated with innate immunity has been reported in BD together with dynamic changes in T cells with differentiation defects during childhood which normalize in adulthood, whereas classic mediators of immune responses such as IL-4 and IL-10 are present in MDD together with signs of immune-senescence.
Topics: Humans; Bipolar Disorder; Depressive Disorder, Major; Cytokines; Inflammation Mediators; Biomarkers; Inflammation; Interleukin-6
PubMed: 38851764
DOI: 10.1038/s41398-024-02921-z -
Journal of Affective Disorders Jun 2024Childhood maltreatment (CM) is prevalent among patients with mood disorders and considered an important risk factor for suicide in the general population. Despite mood...
BACKGROUND
Childhood maltreatment (CM) is prevalent among patients with mood disorders and considered an important risk factor for suicide in the general population. Despite mood disorders being implicated in up to 60 % of completed suicides, the predictive role of CM on suicide attempt (SA) among early mood disorder patients remains poorly understood.
METHODS
We enrolled 480 participants diagnosed with early-onset major depressive disorder (MDD), bipolar I disorder (BD I), and bipolar II disorder (BD II). Over an average of 60 weeks, participants underwent follow-up assessments at 12-week intervals. Using multivariate logistic regression, we examined the association between CM and SA history at baseline. Further, the Cox proportional hazard model assessed the predictive role of childhood maltreatment in SA during follow-up.
RESULTS
At baseline, 38 % of the total participants reported SA history, with a follow-up prevalence of 10 %. Childhood maltreatment was significantly associated with past SAs and was a robust predictor of future SA, adjusting for relevant clinical risk factors. Emotional abuse and sexual abuse related to SA history, and physical abuse increased future SA risk.
LIMITATIONS
Potential biases in reporting SA and childhood maltreatment, along with unexplored factors such as additional environmental and familial risks, may affect the study's findings.
CONCLUSIONS
Childhood maltreatment emerged as a robust predictor of SA among early-onset mood disorder patients. Systematic evaluation of CM early in the clinical process may be crucial for effective risk management. Additionally, our findings highlight the importance of implementing proactive interventions for CM to prevent the onset of adverse psychological trajectories.
PubMed: 38851432
DOI: 10.1016/j.jad.2024.06.012 -
Journal of the American Academy of... Jun 2024Adolescent offspring of parents with bipolar disorder (BD) are at high risk to develop BD and other psychopathology, yet how this risk continues into middle adulthood...
OBJECTIVE
Adolescent offspring of parents with bipolar disorder (BD) are at high risk to develop BD and other psychopathology, yet how this risk continues into middle adulthood remains unknown. This study aimed to determine the window of risk for BD and other psychopathology in offspring of parents with BD followed from adolescence into adulthood.
METHOD
This study reported on the 22-year follow-up assessment of the Dutch Bipolar Offspring Study, a fixed cohort study of 140 participants established in 1997. Offspring (n = 100; mean [SD] age = 38.28 [2.74] years) of parents with bipolar I disorder or bipolar II disorder were assessed at baseline and 1-, 5-, 12-, and 22-year follow-up.
RESULTS
No new BD onsets occurred since the 12-year follow-up (lifetime prevalence = 11%-13%; bipolar I disorder = 4%; bipolar II disorder = 7%). Lifetime prevalence of any mood disorder was 65%; for major depressive disorder, prevalence was 36%; and for recurrent mood episodes, prevalence was 37%. Prevalence of major depressive disorder more than doubled in the past decade. Point prevalence of any psychopathology peaked between 20 and 25 years (38%-46%), subsiding to 29% to 35% per year after age 30. Overall, 71% of offspring contacted mental health services since the last assessment.
CONCLUSION
The risk for homotypic transmission of BD in offspring of parents with BD is highest during adolescence. The heterotypic risk for mood disorder onset and recurrences continues over the life course. Severe mood disorders are often preceded by milder psychopathology, emphasizing the need for early identification and interventions. This study allows for better understanding of the onset and course of mood disorders and specific windows of risk in a familial high-risk population.
PubMed: 38851383
DOI: 10.1016/j.jaac.2024.05.024 -
BMC Psychiatry Jun 2024Theoretical and empirical evidence indicates the critical role of the default mode network (DMN) in the pathophysiology of the bipolar disorder (BD). This study aims to...
BACKGROUND
Theoretical and empirical evidence indicates the critical role of the default mode network (DMN) in the pathophysiology of the bipolar disorder (BD). This study aims to identify the specific brain regions of the DMN that is impaired in patients with BD.
METHODS
A total of 56 patients with BD and 71 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Three commonly used functional indices, i.e., fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC), were utilized to identify the brain region showing abnormal spontaneous brain activity in patients with BD. Then, this region served as the seed region for resting-state functional connectivity (rsFC) analysis.
RESULTS
Compared to the HC group, the BD group showed reduced fALFF, ReHo, and DC values in the left precuneus. Moreover, patients exhibited decreased rsFCs within the left precuneus and between the left precuneus and the medial prefrontal cortex. Additionally, there was diminished negative connectivity between the left precuneus and the left putamen, extending to the left insula (putamen/insula). The abnormalities in DMN functional connectivity were confirmed through various analysis strategies.
CONCLUSIONS
Our findings provide convergent evidence for the abnormalities in the DMN, particularly located in the left precuneus. Decreased functional connectivity within the DMN and the reduced anticorrelation between the DMN and the salience network are found in patients with BD. These findings suggest that the DMN is a key aspect for understanding the neural basis of BD, and the altered functional patterns of DMN may be a potential candidate biomarker for diagnosis of BD.
Topics: Humans; Bipolar Disorder; Magnetic Resonance Imaging; Female; Male; Adult; Default Mode Network; Nerve Net; Parietal Lobe; Connectome; Prefrontal Cortex; Case-Control Studies; Young Adult; Middle Aged; Brain; Brain Mapping
PubMed: 38849793
DOI: 10.1186/s12888-024-05869-y -
Scientific Reports Jun 2024Epigenetic mechanisms contribute to the maintenance of both type 2 diabetes mellitus (T2DM) and psychiatric disorders. Emerging evidence suggests that molecular pathways...
Epigenetic mechanisms contribute to the maintenance of both type 2 diabetes mellitus (T2DM) and psychiatric disorders. Emerging evidence suggests that molecular pathways and neurocognitive performance regulate epigenetic dynamics in these disorders. The current combined and transdiagnostic study investigated whether inflammatory, oxidative stress, adhesion molecule, neurocognitive and functional performance are significant predictors of telomere dynamics in a sample stratified by global DNA methylation levels. Peripheral blood inflammation, oxidative stress and adhesion molecule biomarkers and neurocognitive function were assessed twice over a 1-year period in 80 individuals, including 16 with schizophrenia (SZ), 16 with bipolar disorder (BD), 16 with major depressive disorder (MDD), 15 with T2DM, and 17 healthy controls (HCs). Leukocyte telomere length (LTL) was measured by qRT-PCR using deoxyribonucleic acid (DNA) extracted from peripheral blood samples. A posteriori, individuals were classified based on their global methylation score (GMS) at baseline into two groups: the below-average methylation (BM) and above-average methylation (AM) groups. Hierarchical and k-means clustering methods, mixed one-way analysis of variance and linear regression analyses were performed. Overall, the BM group showed a significantly higher leukocyte telomere length (LTL) than the AM group at both time points (p = 0.02; ηp = 0.06). Moreover, the BM group had significantly lower levels of tumor necrosis factor alpha (TNF-α) (p = 0.03; ηp = 0.06) and C-reactive protein (CRP) (p = 0.03; ηp = 0.06) than the AM group at the 1-year follow-up. Across all participants, the regression models showed that oxidative stress (reactive oxygen species [ROS]) (p = 0.04) and global cognitive score [GCS] (p = 0.02) were significantly negatively associated with LTL, whereas inflammatory (TNF-α) (p = 0.04), adhesion molecule biomarkers (inter cellular adhesion molecule [ICAM]) (p = 0.009), and intelligence quotient [IQ] (p = 0.03) were significantly positively associated with LTL. Moreover, the model predictive power was increased when tested in both groups separately, explaining 15.8% and 28.1% of the LTL variance at the 1-year follow-up for the AM and BM groups, respectively. Heterogeneous DNA methylation in individuals with T2DM and severe mental disorders seems to support the hypothesis that epigenetic dysregulation occurs in a transdiagnostic manner. Our results may help to elucidate the interplay between epigenetics, molecular processes and neurocognitive function in these disorders. DNA methylation and LTL are potential therapeutic targets for transdiagnostic interventions to decrease the risk of comorbidities.
Topics: Humans; DNA Methylation; Male; Female; Oxidative Stress; Inflammation; Adult; Middle Aged; Telomere; Schizophrenia; Diabetes Mellitus, Type 2; Biomarkers; Bipolar Disorder; Depressive Disorder, Major; Leukocytes; Epigenesis, Genetic; Telomere Homeostasis; Cognition; Case-Control Studies
PubMed: 38849401
DOI: 10.1038/s41598-024-62980-6 -
NeuroImage Aug 2024The perspective of personalized medicine for brain disorders requires efficient learning models for anatomical neuroimaging-based prediction of clinical conditions....
The perspective of personalized medicine for brain disorders requires efficient learning models for anatomical neuroimaging-based prediction of clinical conditions. There is now a consensus on the benefit of deep learning (DL) in addressing many medical imaging tasks, such as image segmentation. However, for single-subject prediction problems, recent studies yielded contradictory results when comparing DL with Standard Machine Learning (SML) on top of classical feature extraction. Most existing comparative studies were limited in predicting phenotypes of little clinical interest, such as sex and age, and using a single dataset. Moreover, they conducted a limited analysis of the employed image pre-processing and feature selection strategies. This paper extensively compares DL and SML prediction capacity on five multi-site problems, including three increasingly complex clinical applications in psychiatry namely schizophrenia, bipolar disorder, and Autism Spectrum Disorder (ASD) diagnosis. To compensate for the relative scarcity of neuroimaging data on these clinical datasets, we also evaluate three pre-training strategies for transfer learning from brain imaging of the general healthy population: self-supervised learning, generative modeling and supervised learning with age. Overall, we find similar performance between randomly initialized DL and SML for the three clinical tasks and a similar scaling trend for sex prediction. This was replicated on an external dataset. We also show highly correlated discriminative brain regions between DL and linear ML models in all problems. Nonetheless, we demonstrate that self-supervised pre-training on large-scale healthy population imaging datasets (N≈10k), along with Deep Ensemble, allows DL to learn robust and transferable representations to smaller-scale clinical datasets (N≤1k). It largely outperforms SML on 2 out of 3 clinical tasks both in internal and external test sets. These findings suggest that the improvement of DL over SML in anatomical neuroimaging mainly comes from its capacity to learn meaningful and useful abstract representations of the brain anatomy, and it sheds light on the potential of transfer learning for personalized medicine in psychiatry.
Topics: Humans; Neuroimaging; Female; Schizophrenia; Male; Deep Learning; Adult; Brain; Machine Learning; Autism Spectrum Disorder; Bipolar Disorder; Middle Aged; Young Adult; Psychiatry
PubMed: 38848981
DOI: 10.1016/j.neuroimage.2024.120665 -
JAMA Network Open Jun 2024Alcohol use disorder (AUD) is present in nearly half of individuals with bipolar disorder (BD) and is associated with markedly worsening outcomes. Yet, the concurrent...
IMPORTANCE
Alcohol use disorder (AUD) is present in nearly half of individuals with bipolar disorder (BD) and is associated with markedly worsening outcomes. Yet, the concurrent treatment of BD and AUD remains neglected in both research and clinical care; characterizing their dynamic interplay is crucial in improving outcomes.
OBJECTIVE
To characterize the longitudinal alcohol use patterns in BD and examine the temporal associations among alcohol use, mood, anxiety, and functioning over time.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study selected participants and analyzed data from the Prechter Longitudinal Study of Bipolar Disorder (PLS-BD), an ongoing cohort study that recruits through psychiatric clinics, mental health centers, and community outreach events across Michigan and collects repeated phenotypic data. Participants selected for the present study were those with a diagnosis of BD type I (BDI) or type II (BDII) who had been in the study for at least 5 years. Data used were extracted from February 2006 to April 2022, and follow-up ranged from 5 to 16 years.
MAIN OUTCOMES AND MEASURES
Alcohol use was measured using the Alcohol Use Disorders Identification Test. Depression, mania or hypomania, anxiety, and functioning were measured using the 9-Item Patient Health Questionnaire, the Altman Self-Rating Mania Scale, the 7-item Generalized Anxiety Disorder assessment scale, and the Life Functioning Questionnaire, respectively.
RESULTS
A total of 584 individuals (386 females (66.1%); mean [SD] age, 40 [13.6] years) were included. These participants had a BDI (445 [76.2%]) or BDII (139 [23.8%]) diagnosis, with or without a lifetime diagnosis of AUD, and a median (IQR) follow-up of 9 (0-16) years. More problematic alcohol use was associated with worse depressive (β = 0.04; 95% credibility interval [CrI], 0.01-0.07) and manic or hypomanic symptoms (β = 0.04; 95% CrI, 0.01-0.07) as well as lower workplace functioning (β = 0.03; 95% CrI, 0.00-0.06) over the next 6 months, but increased depressive and manic or hypomanic symptoms were not associated with greater subsequent alcohol use. These latter 2 associations were more pronounced in BDII than BDI (mania or hypomania: β = 0.16 [95% CrI, 0.02-0.30]; workplace functioning: β = 0.26 [95% CrI, 0.06-0.45]). Alcohol use was not associated with anxiety over time.
CONCLUSIONS AND RELEVANCE
This study found that alcohol use, regardless of diagnostic status, was associated with mood instability and poorer work functioning in BD, but increased mood symptoms were not associated with subsequent alcohol use. Given its prevalence and repercussions, dimensional and longitudinal assessment and management of alcohol use are necessary and should be integrated into research and standard treatment of BD.
Topics: Humans; Bipolar Disorder; Female; Male; Adult; Longitudinal Studies; Middle Aged; Alcohol Drinking; Alcoholism; Affect; Michigan; Anxiety
PubMed: 38848066
DOI: 10.1001/jamanetworkopen.2024.15295 -
Frontiers in Psychiatry 2024A high homocysteine (Hcy) level is a risk factor for schizophrenia, depression, and bipolar disorder. However, the role of hyperhomocysteinemia as either an independent...
A high homocysteine (Hcy) level is a risk factor for schizophrenia, depression, and bipolar disorder. However, the role of hyperhomocysteinemia as either an independent factor or an auxiliary contributor to specific psychiatric symptoms or disorders remains unclear. This study aimed to examine Hcy levels in first-episode inpatients with psychotic symptoms and various psychiatric diseases to elucidate the association between Hcy levels and psychiatric disorders. This study enrolled 191 patients (aged 18-40 years) with psychiatric disorders. Seventy-five patients were diagnosed with schizophrenia, 48 with acute and transient psychotic disorders, 36 with manic episodes with psychosis, 32 with major depressive episodes with psychosis, and 56 healthy controls. Serum Hcy levels were measured using the enzyme cycle method. A Hcy concentration level of > 15 μmol/L was defined as hyperhomocysteinemia. Hcy levels were significantly higher in first-episode patients with psychiatric disorders compared to healthy controls (5.99 ± 3.60 vs. 19.78 ± 16.61 vs. 15.50 ± 9.08 vs. 20.00 ± 11.33 vs. 16.22 ± 12.06, = 12.778, < 0.001). Hcy levels were significantly higher in males with schizophrenia, acute and transient psychotic disorder, and major depressive disorder but not in mania [schizophrenia, ( = -4.727, < 0.001); acute and transient psychotic disorders, ( = -3.389, = 0.001); major depressive episode with psychosis, ( = -3.796, < 0.001); manic episodes with psychosis, ( = -1.684, = 0.101)]. However, serum Hcy levels were not significantly different among the psychiatric disorder groups ( = 0.139, = 0.968). Multivariate linear regression showed that males had an increased risk for homocysteinemia. (95% CI = 8.192-15.370, < 0.001). These results suggest that first-episode patients with psychiatric disorders have higher Hcy levels than in the general population, and men are at greater risk for psychiatric disorders. In conclusion, elevated Hcy levels may contribute to the pathogenesis of first-episode patients with psychotic symptoms.
PubMed: 38846917
DOI: 10.3389/fpsyt.2024.1380900 -
Sleep Science (Sao Paulo, Brazil) Jun 2024Insomnia is highly prevalent among individuals with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the biological mechanisms shared between both...
Insomnia is highly prevalent among individuals with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the biological mechanisms shared between both conditions is still elusive. We aimed to investigate whether insomnia's genomic component is able to predict ADHD in childhood and adolescence. A Brazilian sample of 259 ADHD probands and their biological parents were included in the study. Their genomic DNA genotypes were used to construct the polygenic risk score for insomnia (Insomnia PRS), using the largest GWAS summary statistics as a discovery sample. The association was tested using logistic regression, under a case-pseudocontrol design. Insomnia PRS was nominally associated with ADHD (OR = 1.228, = 0.022), showing that the alleles that increase the risk for insomnia also increase the risk for ADHD. Our results suggest that genetic factors associated with insomnia may play a role in the ADHD genetic etiology, with both phenotypes likely to have a shared genetic mechanism.
PubMed: 38846582
DOI: 10.1055/s-0043-1777787 -
Frontiers in Neurology 2024The prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has...
PURPOSE
The prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has used bibliometric methods to analyze the research progress and knowledge structure in this field. Our research is dedicated to systematically exploring the global trends and focal points in scientific research on pain comorbidity with bipolar disorder from 2003 to 2023, with the goal of contributing to the field.
METHODS
Relevant publications in this field were retrieved from the Web of Science core collection database (WOSSCC). And we used VOSviewer, CiteSpace, and the R package "Bibliometrix" for bibliometric analysis.
RESULTS
A total of 485 publications (including 360 articles and 125 reviews) from 66 countries, 1019 institutions, were included in this study. Univ Toront and Kings Coll London are the leading research institutions in this field. J Affect Disorders contributed the largest number of articles, and is the most co-cited journal. Of the 2,537 scholars who participated in the study, Stubbs B, Vancampfort D, and Abdin E had the largest number of articles. Stubbs B is the most co-cited author. "chronic pain," "neuropathic pain," "psychological pain" are the keywords in the research.
CONCLUSION
This is the first bibliometric analysis of pain-related bipolar disorder. There is growing interest in the area of pain and comorbid bipolar disorder. Focusing on different types of pain in bipolar disorder and emphasizing pain management in bipolar disorder are research hotspots and future trends. The study of pain related bipolar disorder still has significant potential for development, and we look forward to more high-quality research in the future.
PubMed: 38846044
DOI: 10.3389/fneur.2024.1393022