-
Scientific Reports Dec 2023Patients with bipolar disorder (BD) show higher immuno-inflammatory setpoints, with in vivo alterations in white matter (WM) microstructure and post-mortem infiltration...
Patients with bipolar disorder (BD) show higher immuno-inflammatory setpoints, with in vivo alterations in white matter (WM) microstructure and post-mortem infiltration of T cells in the brain. Cytotoxic CD8 T cells can enter and damage the brain in inflammatory disorders, but little is known in BD. Our study aimed to investigate the relationship between cytotoxic T cells and WM alterations in BD. In a sample of 83 inpatients with BD in an active phase of illness (68 depressive, 15 manic), we performed flow cytometry immunophenotyping to investigate frequencies, activation status, and expression of cytotoxic markers in CD8 and tested for their association with diffusion tensor imaging (DTI) measures of WM microstructure. Frequencies of naïve and activated CD8 cell populations expressing Perforin, or both Perforin and Granzyme, negatively associated with WM microstructure. CD8 Naïve cells negative for Granzyme and Perforin positively associates with indexes of WM integrity, while the frequency of CD8 memory cells negatively associates with index of WM microstructure, irrespective of toxins expression. The resulting associations involve measures representative of orientational coherence and myelination of the fibers (FA and RD), suggesting disrupted oligodendrocyte-mediated myelination. These findings seems to support the hypothesis that immunosenescence (less naïve, more memory T cells) can detrimentally influence WM microstructure in BD and that peripheral CD8 T cells may participate in inducing an immune-related WM damage in BD mediated by killer proteins.
Topics: Humans; Bipolar Disorder; White Matter; Diffusion Tensor Imaging; CD8-Positive T-Lymphocytes; Granzymes; Perforin; Anisotropy
PubMed: 38097657
DOI: 10.1038/s41598-023-49146-6 -
EClinicalMedicine Dec 2023There is an urgent need to better understand and prevent relapse in major depressive disorder (MDD). We explored the differential impact of various MDD relapse...
Differential impact of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment on affect fluctuations and individual affect networks and impact on relapse: a secondary analysis of a randomised controlled trial.
BACKGROUND
There is an urgent need to better understand and prevent relapse in major depressive disorder (MDD). We explored the differential impact of various MDD relapse prevention strategies (pharmacological and/or psychological) on affect fluctuations and individual affect networks in a randomised setting, and their predictive value for relapse.
METHODS
We did a secondary analysis using experience sampling methodology (ESM) data from individuals with remitted recurrent depression that was collected alongside a randomised controlled trial that ran in the Netherlands, comparing: (I) tapering antidepressants while receiving preventive cognitive therapy (PCT), (II) combining antidepressants with PCT, or (III) continuing antidepressants without PCT, for the prevention of depressive relapse, as well as ESM data from 11 healthy controls. Participants had multiple past depressive episodes, but were remitted for at least 8 weeks and on antidepressants for at least six months. Exclusion criteria were: current (hypo)mania, current alcohol or drug abuse, anxiety disorder that required treatment, psychological treatment more than twice per month, a diagnosis of organic brain damage, or a history of bipolar disorder or psychosis. Fluctuations (within-person variance, root mean square of successive differences, autocorrelation) in negative and positive affect were calculated. Changes in individual affect networks during treatment were modelled using time-varying vector autoregression, both with and without applying regularisation. We explored whether affect fluctuations or changes in affect networks over time differed between treatment conditions or relapse outcomes, and predicted relapse during 2-year follow-up. This ESM study was registered at ISRCTN registry, ISRCTN15472145.
FINDINGS
Between Jan 1, 2014, and Jan 31, 2015, 72 study participants were recruited, 42 of whom were included in the analyses. We found no indication that affect fluctuations differed between treatment groups, nor that they predicted relapse. We observed large individual differences in affect network structure across participants (irrespective of treatment or relapse status) and in healthy controls. We found no indication of group-level differences in how much networks changed over time, nor that changes in networks over time predicted time to relapse (regularised models: hazard ratios [HR] 1063, 95% CI <0.0001->10 000, p = 0.65; non-regularised models: HR 2.54, 95% CI 0.23-28.7, p = 0.45) or occurrence of relapse (regularised models: odds ratios [OR] 22.84, 95% CI <0.0001->10 000, p = 0.90; non-regularised models: OR 7.57, 95% CI 0.07-3709.54, p = 0.44) during complete follow-up.
INTERPRETATION
Our findings should be interpreted with caution, given the exploratory nature of this study and wide confidence intervals. While group-level differences in affect dynamics cannot be ruled out due to low statistical power, visual inspection of individual affect networks also revealed no meaningful patterns in relation to MDD relapse. More studies are needed to assess whether affect dynamics as informed by ESM may predict relapse or guide personalisation of MDD relapse prevention in daily practice.
FUNDING
The Netherlands Organisation for Health Research and Development, Dutch Research Council, University of Amsterdam.
PubMed: 38078193
DOI: 10.1016/j.eclinm.2023.102329 -
Research Square Dec 2023Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide...
BACKGROUND
Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.
RESULTS
We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.
CONCLUSIONS
Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
PubMed: 38077040
DOI: 10.21203/rs.3.rs-3677630/v1 -
Translational Psychiatry Dec 2023Suicidality in mood disorder patients is common, especially in emergency department (ED), but the patterns and associated factors of suicidality are not clear. This...
Suicidality in mood disorder patients is common, especially in emergency department (ED), but the patterns and associated factors of suicidality are not clear. This study compared biomarkers and mental health symptoms (i.e., depression, anxiety, and psychiatric symptoms) between mood disorder patients with and without the whole range of suicidality comprising suicidal ideation (SI), suicide plan (SP), and suicide attempt (SA). This cross-sectional, comparative, convenient-sampling study was conducted between January 2021 and March 2022, in emergency department of Beijing Anding Hospital, China. Patients with mood disorders at a psychiatric emergency department were assessed, with measurements of suicidality, biomarkers, depressive, anxiety, and psychiatric symptoms were assessed using the 24 items-Hamilton Depression Rating Scale (HAMD-24), Hamilton Anxiety Rating Scale (HAMA), Young Manic Rating Scale (YMRS) and Brief Psychiatric Rating Scale (BPRS), respectively. The propensity score matching (PSM) method was used to identify patients in mood disorder with and without SI, SP, and SA. A generalized linear model (GLM) was used to assess the differences in biomarkers, depressive, anxiety, and psychiatric symptoms between patients in mood disorder with and without SI, SP, and SA. In total, 898 participated in this survey and completed the assessment. Illness duration was significantly negatively associated with SA (OR = 0.969, 95%CI = 0.939-0.999, P = 0.046). HAMD-24 total score was significantly positively associated with the SI (OR = 1.167, 95%CI = 1.134-1.201, p < 0.001), SP (OR = 1.159, 95%CI = 1.126-1.192, p < 0.001) and SA (OR = 1.189, 95%CI = 1.144-1.235, p < 0.001) of the matched samptched sample. However, YMRS total score was significantly negatively associated with the SI (OR = 0.928, 95%CI = 0.905-0.951, p < 0.001), SP (OR = 0.920, 95%CI = 0.897-0.944, p < 0.001) and SA (OR = 0.914, 95%CI = 0.890-0.938, p < 0.001) of the matched sample after adjusting for age, gender, marital status, and occupation. The duration of illness, severity of depressive symptoms and severity of manic symptoms appeared to be more likely to influence suicidality. Considering the significant risk of suicide in mood disorders on psychiatric emergency care, timely treatment and effective management of suicidality in this population group need to be developed.
Topics: Humans; Suicidal Ideation; Cross-Sectional Studies; Propensity Score; Suicide; Mood Disorders; Biomarkers
PubMed: 38040690
DOI: 10.1038/s41398-023-02675-0 -
The Journal of Clinical Endocrinology... May 2024Synthetic glucocorticoids are widely used to treat patients with a broad range of diseases. While efficacious, glucocorticoids can be accompanied by neuropsychiatric... (Meta-Analysis)
Meta-Analysis
CONTEXT
Synthetic glucocorticoids are widely used to treat patients with a broad range of diseases. While efficacious, glucocorticoids can be accompanied by neuropsychiatric adverse effects.
OBJECTIVE
This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids.
METHODS
Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort studies, and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and nonusers were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model.
RESULTS
We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95% CI, 14%-33%), 11% for mania (2%-46%), 8% for anxiety (2%-25%), 16% for delirium (6%-36%), and 52% for behavioral changes (42%-61%). Questionnaire scores for depression (SMD of 0.80 [95% CI 0.35-1.26]), and mania (0.78 [0.14-1.42]) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use.
CONCLUSION
The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed.
Topics: Humans; Glucocorticoids; Mental Disorders
PubMed: 38038629
DOI: 10.1210/clinem/dgad701 -
Case Reports in Psychiatry 2023Delirious mania is an acute neurobehavioral syndrome which can have the features of mania, delirium, psychosis and catatonia. There are no diagnostic and treatment...
Delirious mania is an acute neurobehavioral syndrome which can have the features of mania, delirium, psychosis and catatonia. There are no diagnostic and treatment guidelines of delirious mania which can lead to delayed treatment, increasing morbidity and mortality. The primary goal of this report is to raise awareness among healthcare professionals and improve patient outcomes for this potentially life-threatening condition. In this case report, we present an octogenarian female, a case of bipolar disorder, current episode manic, who had impaired orientation, delusion of persecution, and altered sleep-wake cycle. She was treated with a combination of mood stabilizer and antipsychotic and discharged after 24 days of admission.
PubMed: 38028755
DOI: 10.1155/2023/8984062 -
Cureus Oct 2023Mental disorders affect a person's thinking, mood, and/or behaviour and can range in severity from minor to severe. Nearly one in five persons have a mental disease as... (Review)
Review
Mental disorders affect a person's thinking, mood, and/or behaviour and can range in severity from minor to severe. Nearly one in five persons have a mental disease as stated by the National Institute of Mental Health. A serious mental illness called bipolar disorder causes extreme mood swings that can range from manic to depressive states. Schizophrenia is a brain condition that leads individuals to perceive reality differently. They cannot distinguish between what they are actually experiencing and what they are just imagining. Both illnesses have a variety of negative effects on the patient as well as the primary caregiver, who may be the patient's family or other relatives. In the case of a patient with mental illness, the family's role is crucial. Family members' long-term caregiving obligations may result in a caregiving burden that negatively impacts the caregivers' quality of life, career and personal relationships. Depression generally undermines carers' ability to fulfil their crucial supportive role towards their relative with a mental illness while contributing to their distress and handicap. Given the high prevalence of caregiver depression, it is critical to address this issue not just by creating therapies to treat caregiver depression once it has started, but also by preventing caregiver depression.
PubMed: 38022267
DOI: 10.7759/cureus.47497 -
Cureus Oct 2023Dengue fever is primarily known as a mosquito-borne viral infection that causes a range of physical symptoms, ranging from myalgia to bleeding tendencies. However,...
Dengue fever is primarily known as a mosquito-borne viral infection that causes a range of physical symptoms, ranging from myalgia to bleeding tendencies. However, there is growing recognition of its potential to trigger psychiatric manifestations, although such cases remain relatively rare. We report a case of acute dengue fever in a 25-year-old male who developed mania and psychotic symptoms after one week of infection. A comprehensive diagnostic workup, including laboratory tests, including cerebrospinal fluid analysis, and neuroimaging, confirmed the absence of organic causes for his psychiatric symptoms, except for his prior exposure to the dengue virus. The patient was initiated on mood stabilizers and antipsychotic medications, leading to a gradual improvement in his mental health.
PubMed: 38022096
DOI: 10.7759/cureus.47425 -
BioRxiv : the Preprint Server For... Nov 2023Infradian mood and sleep-wake rhythms with periods of 48 hr and beyond have been observed in bipolar disorder (BD) subjects that even persist in time isolation,...
Infradian mood and sleep-wake rhythms with periods of 48 hr and beyond have been observed in bipolar disorder (BD) subjects that even persist in time isolation, indicating an endogenous origin. Here we show that mice exposed to methamphetamine (Meth) in drinking water develop infradian locomotor rhythms with periods of 48 hr and beyond which extend to sleep length and mania-like behaviors in support of a model for cycling in BD. This cycling capacity is abrogated upon genetic disruption of DA production in DA neurons of the ventral tegmental area (VTA) or ablation of nucleus accumbens (NAc) projecting, dopamine (DA) neurons. Chemogenetic activation of NAc-projecting DA neurons leads to locomotor period lengthening in clock deficient mice, while cytosolic calcium in DA processes of the NAc was found fluctuating synchronously with locomotor behavior. Together, our findings argue that BD cycling relies on infradian rhythm generation that depends on NAc-projecting DA neurons.
PubMed: 38014299
DOI: 10.1101/2023.11.14.566955 -
Psychiatry Investigation Nov 2023Neurotrophin-like brain-derived neurotrophic factor (BDNF) and pro-inflammatory cytokines may modulate the pathophysiology of mood disorders. Although several studies...
OBJECTIVE
Neurotrophin-like brain-derived neurotrophic factor (BDNF) and pro-inflammatory cytokines may modulate the pathophysiology of mood disorders. Although several studies show alterations in these biomarkers during the depressive, manic, and euthymic states of mood disorders, evidence is lacking for those in a mixed state. Therefore, this study aimed to investigate the relationship between the depressive mixed state (DMX) and peripheral neurobiological factors.
METHODS
We enrolled 136 patients with major depressive episodes. Depressive symptoms were assessed using the Quick Inventory of Depressive Symptomatology Self-Report Japanese version (QIDS-SR-J). The severity of DMX was assessed using the self-administered 12-item questionnaire (DMX-12). Categorical screening as DMX-positive (n=54) was determined by a cutoff score of 13 or more in the specific eight symptoms from the DMX-12; the remaining were DMX-negative (n=82). Serum BDNF, tumor necrosis factor-α, highsensitivity C-reactive protein, and interleukin-6 levels were measured.
RESULTS
When comparing biomarkers between the DMX-positive and DMX-negative groups, higher serum BDNF concentration in the DMX-positive group than in the DMX-negative group was the only significant finding (p=0.009). A positive correlation existed between the total score of the eight specific symptoms of DMX-12 and the BDNF concentration (r=0.190, p=0.027). After adjustment for confounders, logistic regression analysis revealed that BDNF (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.00-1.14, p=0.045), bipolar diagnosis (OR=3.43, 95% CI=1.36-8.66, p=0.009), and total QIDS-SR-J score (OR=1.29, 95% CI=1.15-1.43, p<0.001) were significantly associated with DMX positivity.
CONCLUSION
BDNF was positively associated with DMX severity, suggesting that higher BDNF concentrations may be involved in the pathophysiology of DMX.
PubMed: 37997330
DOI: 10.30773/pi.2023.0104