Bipolar Disorder Group Research Articles

Can retinal nerve fiber layer (RNFL) thickness be a marker for distinguishing bipolar depression from unipolar depression?

Objective We aimed to compare retinal nerve fiber layer (RNFL) thickness and ganglion cell complex (GCC) thickness in bipolar disorder (BD) and major depressive disorder (MDD). Method The study included thirty MDD, thirty-two BD participants in depressive episode, and thirty-seven controls matched according to age, gender, body mass index (BMI), and smoking status. Optic coherence tomography (OCT) measurements were performed for both participants and controls. The RNFL and GCC thickness were measured and recorded automatically by a spectral OCT device. Participants were also subjected to Hamilton Depression Rating Scale (HAM-D). Results RNFL superior thickness was significantly lower in BD participants, compared to the MDD participants and controls (p = 0.001). GCC inferior (p = 0.022) and inferonasal (p = 0.005) thickness were detected lower in BD group, compared to the control groups. In the BD group, HAM-D scores were negatively correlated with RNFL-temporal (p = 0.049, r= −0.357), GCC inferotemporal (p = 0.02, r= −0.416) and superotemporal thickness (p = 0.002, r= −0.546). Conclusions RNFL thickness were lower in BD participants compared to the MDD and controls and, GCC thickness were lower in BD participants compared to the controls. Our findings support the hypothesis that neurodegeneration is part of the pathogenesis of BD. Future research are needed to confirm the lack of RNFL thickness in MDD, which could have immediate therapeutic consequences as well as implications for distinguishing BD from MDD.

Study on the Treatment of Bipolar Disorders Group Based on Neuroregulatory Techniques

Study on the Treatment of Bipolar Disorders Group Based on Neuroregulatory Techniques

Optical coherence tomography angiography in patients with bipolar disorder and major depressive disorder

BackgroundCerebral microvascular dysfunction is a promising area for research into the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). Despite the scientific and clinical potential of studying microvascular dysfunction, progress in this area has long been hampered by the lack of methods to study microvessels intravitally. AimsThe aim of the present study was to search for potential optical coherence tomography (OCT) and OCT-angiography (OCTA) biomarkers of BD and MDD. MethodsOne hundred and five consecutive patients with a current depressive episode were enrolled in the study (39 – BD and 66 – MDD). In addition, forty-one generally healthy subjects were enrolled as a control group. Only the right eye was examined in all subjects. Structural OCT and OCTA scans with signal strength ≥7 were included. ResultsStructural OCT measurements showed no significant differences between the groups. OCTA measurements of foveal avascular zone (FAZ), area and skeleton density showed a decrease in the retinal capillary bed in BD patients, whereas OCTA values in MDD patients did not differ from the control group. Several significant differences were found between the BD and control groups. In the BD group, the FAZ of the deep capillary plexus was increased, reflecting a reduction in capillary perfusion in the central subfield of this plexus. ConclusionsOCTA measurements of FAZ, area and skeleton density showed a decrease in the retinal capillary bed in BD patients, whereas OCTA values in MDD patients did not differ from the control group.

Pilot study of circulating cell-free mitochondrial DNA in relation to brain structure in youth bipolar disorder

BackgroundMitochondrial dysfunction is implicated in the neuropathology of bipolar disorder (BD). Higher circulating cell-free mitochondrial DNA (ccf-mtDNA), generally reflecting poorer mitochondrial health, has been associated with greater symptoms severity in BD. The current study examines the association of serum ccf-mtDNA and brain structure in relation to youth BD. We hypothesized that higher ccf-mtDNA will be associated with measures of lower brain structure, particularly in the BD group.MethodsParticipants included 40 youth (BD, n = 19; Control group [CG], n = 21; aged 13–20 years). Serum ccf-mtDNA levels were assayed. T1-weighted brain images were acquired using 3T-MRI. Region of interest (ROI) analyses examined prefrontal cortex (PFC) and whole brain gray matter, alongside exploratory vertex-wise analyses. Analyses examined ccf-mtDNA main-effects and ccf-mtDNA-by-diagnosis interaction effects controlling for age, sex, and intracranial volume.ResultsThere was no significant difference in ccf-mtDNA levels between BD and CG. In ROI analyses, higher ccf-mtDNA was associated with higher PFC surface area (SA) (β = 0.32 p < 0.001) and PFC volume (β = 0.32 p = 0.002) in the overall sample. In stratified analyses, higher ccf-mtDNA was associated with higher PFC SA within both subgroups (BD: β = 0.39 p = 0.02; CG: β = 0.24 p = 0.045). Higher ccf-mtDNA was associated with higher PFC volume within the BD group (β = 0.39 p = 0.046). In vertex-wise analyses, higher ccf-mtDNA was associated with higher SA and volume in frontal clusters within the overall sample and within the BD group. There were significant ccf-mtDNA-by-diagnosis interactions in three frontal and parietal clusters, whereby higher ccf-mtDNA was associated with higher neurostructural metrics in the BD group but lower neurostructural metrics in CG.ConclusionsContrasting our hypothesis, higher ccf-mtDNA was consistently associated with higher, rather than lower, regional neuralstructural metrics among youth with BD. While this finding may reflect a compensatory mechanism, future repeated-measures prospective studies evaluating the inter-relationship among ccf-mtDNA, mood, and brain structure across developmental epochs and illness stages are warranted.

Deficits in prefrontal metabotropic glutamate receptor 5 are associated with functional alterations during emotional processing in bipolar disorder

BackgroundElucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the metabotropic glutamate receptor 5 (mGlu5) in the pathology of BD, here, we therefore test the hypothesis that recently identified deficits in mGlu5 are associated with functional brain differences during emotion processing in BD. MethodsPositron emission tomography (PET) with [18F]FPEB was used to measure mGlu5 receptor availability and functional imaging (fMRI) was performed while participants completed an emotion processing task. Data were analyzed from 62 individuals (33 ± 12 years, 45 % female) who completed both PET and fMRI, including individuals with BD (n = 18), major depressive disorder (MDD: n = 20), and psychiatrically healthy comparisons (HC: n = 25). ResultsConsistent with some prior reports, the BD group displayed greater activation during fear processing relative to MDD and HC, notably in right lateralized frontal and parietal brain regions. In BD, (but not MDD or HC) lower prefrontal mGlu5 availability was associated with greater activation in bilateral pre/postcentral gyri and cuneus during fear processing. Furthermore, greater prefrontal mGlu5-related brain activity in BD was associated with difficulties in psychomotor function (r≥0.904, p≤0.005) and attention (r≥0.809, p≤0.028). LimitationsThe modest sample size is the primary limitation. ConclusionsDeficits in prefrontal mGlu5 in BD were linked to increased cortical activation during fear processing, which in turn was associated with impulsivity and attentional difficulties. These data further implicate an mGlu5-related mechanism unique to BD. More generally these data suggest integrating PET and fMRI can provide novel mechanistic insights.

Disrupted default mode network connectivity in bipolar disorder: a resting-state fMRI study

BackgroundTheoretical 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.MethodsA 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.ResultsCompared 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.ConclusionsOur 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.

Posterior cingulate and medial prefrontal excitation-inhibition balance in euthymic bipolar disorder.

Persistent cognitive deficits and functional impairments are associated with bipolar disorder (BD), even during the euthymic phase. The dysfunction of default mode network (DMN) is critical for self-referential and emotional mental processes and is implicated in BD. The current study aims to explore the balance of excitatory and inhibitory neurotransmitters, i.e. glutamate and γ-aminobutyric acid (GABA), in hubs of the DMN during the euthymic patients with BD (euBD). Thirty-four euBD and 55 healthy controls (HC) were recruited to the study. Using proton magnetic resonance spectroscopy (1H-MRS), glutamate (with PRESS sequence) and GABA levels (with MEGAPRESS sequence) were measured in the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and the posterior cingulate gyrus (PCC). Measured concentrations of excitatory glutamate/glutamine (Glx) and inhibitory GABA were used to calculate the excitatory/inhibitory (E/I) ratio. Executive and attentional functions were respectively assessed using the Wisconsin card-sorting test and continuous performance test. euBD performed worse on attentional function than controls (p = 0.001). Compared to controls, euBD had higher E/I ratios in the PCC (p = 0.023), mainly driven by a higher Glx level in the PCC of euBD (p = 0.002). Only in the BD group, a marginally significant negative association between the mPFC E/I ratio (Glx/GABA) and executive function was observed (p = 0.068). Disturbed E/I balance, particularly elevated Glx/GABA ratio in PCC is observed in euBD. The E/I balance in hubs of DMN may serve as potential biomarkers for euBD, which may also contribute to their poorer executive function.

A two-year longitudinal evaluation of the impact of the COVID-19 pandemic on pre-existing mental health service attenders.

To examine if the COVID-19 pandemic was associated with a differential effect longitudinally in relation to its psychological and functional impact on patients with bipolar disorder and Emotionally Unstable Personality Disorder (EUPD). Semi-structured interviews were conducted with 29 individuals attending the Galway-Roscommon Mental Health Services with an ICD-10 diagnosis of either bipolar disorder (n = 18) or EUPD (n = 11). The impact of the COVID-19 pandemic was assessed in relation to anxiety and mood symptoms, social and occupational functioning, and quality of life utilising psychometric instruments and Likert scale data, with qualitative data assessing participants' subjective experiences. Individuals with EUPD exhibited significant anxiety and depressive symptoms and increased hopelessness compared to individuals with bipolar disorder. Repeated measures data demonstrated no significant change in symptomatology for either the EUPD or bipolar disorder group over time, but demonstrated an improvement in social (t = 4.40, p < 0.001) and occupational functioning (t = 3.65, p = 0.03), and in quality of life (t = 4.03, p < 0.001) for both participant groups. Themes attained from qualitative data included the positive impact of the discontinuation of COVID-19 mandated restrictions (n = 19), and difficulties experienced secondary to reductions in the provision of mental health services during the COVID-19 pandemic (n = 17). Individuals with EUPD demonstrated increased symptomatology over a two-year period compared to those with bipolar disorder. The importance of face-to-face mental health supports for this cohort are indicated, particularly if future pandemics impact the delivery of mental health services.

The Relationship Between Sexual Dysfunctions With Disease Prolactin and Genetic Polymorphisms in Schizophrenia and Bipolar Disorder Patients Receiving Pharmacotherapy.

The aim of this study is to investigate sexual dysfunctions (SDs) and related factors in patients with schizophrenia and bipolar disorder receiving pharmacotherapy. This study included 111 patients. The Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Calgary Depression Scale for Schizophrenia (CDSS) were applied to the schizophrenia, and the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D) to the bipolar patient group. The sociodemographic data form and the Arizona Sexual Experiences Scale (ASEX) were applied to both of the patient groups. Blood was drawn from all patients to evaluate the indicated gene polymorphisms and evaluate prolactin levels. SD was detected in 45.9% (N = 34) of the schizophrenia group, and 59.5% (N = 22) in the bipolar disorder group. SD was significantly higher in elderly patients and patients with a high smoking amount and low education levels. The eNOS -786T>C T allele frequency was found to be significantly higher in patients with SD. The logistic regression analysis determined that eNOS -786T>C CT and TT genotypes increased the risk of SD. In this study, the high rates of SD in patients with schizophrenia and bipolar disorder, and the presence of modifiable factors that influence the presence of SD, suggest that SD should be given more attention in these patient groups. On the other hand, the high rate of SD in patients with the eNOS -786T>C T allele indicates the importance of carrying out new studies investigating the factors affecting the enzyme activity in this genotype.There is a need for more studies on eNOS genotypes and enzyme activites in this area.

Association of lipids and inflammatory markers with left ventricular wall thickness in patients with bipolar disorder

BackgroundIndividuals with bipolar disorder (BD) face a high risk of heart failure and left ventricular (LV) dysfunction. Despite strong evidence that high LV relative wall thickness (RWT) is a risk marker for heart failure, few studies have evaluated LV RWT and aggravating factors in individuals with BD. MethodsWe recruited 104 participants (52 patients with BD and 52 age- and sex-matched mentally healthy controls) to undergo echocardiographic imaging and biochemistry, high-sensitivity C-reactive protein (hs-CRP), and blood cell count measurements. LV RWT was estimated using the following equation: (2 × LV posterior wall end-diastolic thickness)/LV end-diastolic diameter. Clinical data were obtained through interviews and chart reviews. ResultsThe BD group exhibited a significantly greater LV RWT (Cohen's d = 0.53, p = 0.003) and a less favorable mitral valve E/A ratio (Cohen's d = 0.54, p = 0.023) and LV global longitudinal strain (Cohen's d = 0.57, p = 0.047) than did the control group. Multiple linear regression revealed that in the BD group, serum triglyceride levels (β = 0.466, p = 0.001), platelet-to-lymphocyte ratios (β = 0.324, p = 0.022), and hs-CRP levels (β = 0.289, p = 0.043) were all significantly and positively associated with LV RWT. LimitationsThis study applied a cross-sectional design, meaning that the direction of causation could not be inferred. ConclusionsPatients with BD are at a risk of heart failure, as indicated by their relatively high LV RWT. Lipid levels and systemic inflammation may explain this unfavorable association.

High Risk Factors and Preventive Measures of Bipolar Disorder After Ischemic Stroke.

Bipolar disorder (BD) is a recurrent chronic disease. There are few Chinese studies to explore the BD after ischemic stroke. This study aimed to analyze the high risk factors of BD after ischemic stroke and investigate prevention strategies. 197 patients with ischemic stroke in our hospital from March 2020 to March 2022 were selected as research subjects. The demographic information, clinical data, and scores of Mood Disorder Questionnaire (MDQ) and Activity of Daily Living Scale (ADL) in patients were retrospectively analyzed to count the incidence of BD in patients. Binary logistic regression analysis was used to analyze the influencing factors for BD after ischemic stroke, and preventive measures were discussed based on study results. The incidence of BD in patients with ischemic stroke was 45.18% (89/197), and the median and quartile in the first part of MDQ score was 6.00 (5.00,10.00) points. The subjects were divided into BD group (n = 89) and non-BD group (n = 108) based on the presence of BD in patients with ischemic stroke. Education background (OR = 0.485), lesions involving the frontal or temporal lobes (OR = 2.724), sleep disorders (OR = 2.246), and daily living ability (OR = 3.108) were influencing factors for BD after ischemic stroke (P < .05). The risk of BD after ischemic stroke is high. Based on the above research results, clinical attention should be paid to knowledge popularization, lesion examination, and the improvement of sleep quality and daily living ability, to prevent the occurrence of BD and improve the prognosis.

Metabolic Differentiation in Manic Episode of Bipolar Disorder Compared to Substance-Induced Psychosis and Substance Use Disorder Based on Serum Valproate Level

Aim: Valproic acid (VPA) is primarily used in the treatment of epilepsy but also has uses in the treatment of manic episodes in bipolar disorder and substance use disorders. Manic episodes and psychosis may also affect hepatic clearance and drug distribution volume. The aim of this study was to assess the effect of mania and psychosis compared to substance use on VPA pharmacokinetics, specifically changes in total and unbound clearance. Material and Methods: Fifty patients with a manic episode of bipolar disorder, and 51 patients with substance use disorder, 38 of whom were considered as substance-induced psychosis, were included in this retrospective study. All patients received a constant dose of 1000 mg VPA daily for at least five days, and serum VPA concentrations were measured. Results: The mean serum levels of VPA were 59.2±17.4 μg/ml in the substance use disorder group, 60.9±13.5 μg/ml in the substance-induced psychosis group, and 61.8±13.7 μg/ml in the manic episode of bipolar disorder group. No significant difference was found between the groups (p=0.840). When considering substance use disorder and substance-induced psychosis as one group, the mean VPA level of 60.5±14.4 μg/ml in this group showed no significant difference compared to 61.8±13.7 μg/ml in the manic episode of bipolar disorder (p=0.630). Conclusion: After reaching steady-state plasma levels, no significant difference in serum VPA levels was observed between the three groups. This suggests that manic episodes do not lead to a significant increase in VPA metabolism compared to substance use disorder or substance-induced psychosis.

Reduced myelin content in bipolar disorder: A study of inhomogeneous magnetization transfer

BackgroundPrevious neuroimaging and pathological studies have found myelin-related abnormalities in bipolar disorder (BD), which prompted the use of magnetic resonance (MR) imaging technology sensitive to neuropathological changes to explore its neuropathological basis. We holistically investigated alterations in myelin within BD patients by inhomogeneous magnetization transfer (ihMT), which is sensitive and specific to myelin content. MethodsThirty-one BD and 42 healthy controls (HC) were involved. Four MR metrics, i.e., ihMT ratio (ihMTR), pseudo-quantitative ihMT (qihMT), magnetization transfer ratio and pseudo-quantitative magnetization transfer (qMT), were compared between groups using analysis methods based on whole-brain voxel-level and white matter regions of interest (ROI), respectively. ResultsThe voxel-wise analysis showed significantly inter-group differences of ihMTR and qihMT in the corpus callosum. The ROI-wise analysis showed that ihMTR, qihMT, and qMT values in BD group were significantly lower than that in HC group in the genu and body of corpus callosum, left anterior limb of the internal capsule, left anterior corona radiate, and bilateral cingulum (p < 0.001). And the qihMT in genu of corpus callosum and right cingulum were negatively correlated with depressive symptoms in BD group. LimitationsThis study is based on cross-sectional data and the sample size is limited. ConclusionThese findings suggest the reduced myelin content of anterior midline structure in the bipolar patients, which might be a critical pathophysiological feature of BD.

Evaluation of Neurocognitive Functions of Children and Adolescents Diagnosed with Pediatric Bipolar Disorder and Disruptive Mood Dysregulation and at High Risk for Bipolar Disorder

IntroductionPediatric Bipolar Disorder (BPD) is a chronic psychiatric disorder that alters normal and psychological development processes among patients. Although cognitive deficits in BPD have identified in recent studies, little is known about the developmental trajectory of these deficits. DMDD is a newly defined diagnosis included in the DSM-V. Since it added a new dimension to the clinical spectrum but few studies conducted on DMDD, there are some conflicting discussions in the literature about how to distinguish this disorder from other childhood psychiatric disorders and how to treat it.ObjectivesThe aim of this study was to determine the phenomenological and neuropsychological differences between children and adolescents with a diagnosis of BPD (Pediatric Bipolar Disorder), DMDD (Disruptive Mood Dysregulation Disorder), and children and adolescents who are genetically at high risk for Bipolar Disorder (BD), and healthy controls (HCs) who do not have any psychiatric diagnosis, to investigate endophenotypes that may be predictive for BD.MethodsOur study sample consists of four groups, the BPD group (n=30), the Risk group (n=25), the DMDD group (n=36), and the Healthy Control group (n=29). All participants were evaluated by the “Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children—Now and Lifetime Pattern (K-SADS-PL)”. “Young Mania Rating Scale/Parent Form (YMRS-ABF), Conner’s Parent Rating Scale (CPRS-48), Child and Adolescent Behavior Rating Scale (CBCL)” scales were filled by parents, and “Child Depression Inventory (CDI), Youth Self-Report Form for 11-18 Years Olds (YSR)” scales were filled by children and adolescents. Neurocognitive test battery was applied to each participant: Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), Stroop Color and Word Test (SCWT), Trait Making Test A and B sections (TMT-A/B), California Verbal Learning Test-Child version (CVLT-C).ResultsWhile it was determined that the cases in the BPD and DMDD groups performed significantly worse in CPT, SCWT, CVLT-C, TMT A/B tests compared to healthy controls, it was found that the subjects in the Risk group performed worse at the CPT test than healthy controls. In addition, the cases in the BPD, Risk and DMDD groups reported more clinical and behavioral problems than the healthy controls.ConclusionsThere is a significant deterioration in the areas of continuous attention, processing speed, cognitive flexibility, response prevention, verbal memory and working memory in the BPD and DMDD groups, and in the continuous attention area in the Risk group compared to healthy controls. Prospective follow-up and imaging studies using larger samples and a larger neurocognitive test battery in the future will better reveal the neuropsychological characteristics of the BPD, Risk and DMDD groups.Disclosure of InterestNone Declared

Study on exosomes for identifying bipolar disorder in early stage: A cross-sectional and validation study protocol.

The difficulty is remained to accurately distinguish bipolar disorder (BD) from major depressive disorder (MDD) in early stage, with a delayed diagnosis for 5-10 years. BD patients are often treated with antidepressants systematically due to being diagnosed with MDD, affecting the disease course and clinical outcomes. The current study aims to explore the role of plasma exosomes as biomarker to distinguish BD from MDD in early stage. Two stages are included. The first stage is a cross-sectional study, comparing the concentrations of plasma exosome microRNA and related proteins among BD group, MDD group, and healthy controls (HC) group (n=40 respectively), to identify target biomarkers preliminarily. The "Latent Class Analysis" and "Receiver Operating Characteristic" analysis will be performed to determine the optimal concentration range for each biomarker. The second stage is to validate target markers in subjects, coming from an ongoing study focusing on patients with a first depressive episode. All target biomarkers will be test in plasma samples reserved at the initial stage to detect whether the diagnosis indicated by biomarker level is consistent with the diagnosis by DSM-5. Furthermore, the correlation between specific biomarkers and the manic episode, suicidal ideation, and adverse reactions will also be observed. Exosome-derived microRNA and related proteins have potential in serving as a good medium for exploring mental disorders because it can pass through the blood-brain barrier bidirectionally and convey a large amount of information stably. Improving the early diagnosis of BD would help implement appropriate intervention strategy as early as possible and significantly reduce the burden of disease.

The violence profile of male mentally disordered offenders in a high secure unit in Turkiye

Our knowledge of the severity and reoffending is limited for mentally disordered offenders, and studies generally evaluate without separation between different diagnostic groups. It was aimed to determine the general profile of mentally disordered offenders who are inpatients in a high secure psychiatry unit from Turkiye and to evaluate the factors associated with violence profiles among different diagnostic groups. According to the results the schizophrenia patients committed the most severe crimes, and intellectual disability patients had some different features from schizophrenia and bipolar disorder patients. History of substance misuse in the intellectual disability group (p = 0,045) and comorbid antisocial personality disorder in the bipolar disorder group (p = 0,015) were associated with increased crime severity. Substance misuse history, history of substance use during the crime, and the existence of comorbid antisocial personality disorder were associated with increased offenses in each of the three diagnosis groups. Living alone (p = 0,004) and having a suicide history (p= 0,052) were associated with the high number of offenses in the schizophrenia group. This study is the first study that compares three diagnostic groups to involve a large patient group. We believe that clinicians must evaluate these parameters for the violence risk assessment of patients.

COVID-19-associated mortality in individuals with serious mental disorders in Sweden during the first two years of the pandemic– a population-based register study

BackgroundReports at the beginning of the COVID-19 pandemic suggested differences in COVID-19-associated mortality between individuals with serious mental disorders (SMD) and the population at large.AimTo compare the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden over the two main pandemic years.MethodsWe compared the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden during 2020 and 2021. For SMD, we included psychotic disorder, bipolar disorder, and severe depression. The analysis was based on summary data from the Swedish Board of Health and Welfare covering the entire adult Swedish population.ResultsThe overall relative risk (RR) for experiencing a COVID-19-associated death was 1.66 (CI 1.50–1.83; p < 0.001) for individuals with SMD versus individuals without SMD. The corresponding RRs were 3.25 (CI 2.84–3.71; p < 0.001) for individuals with psychotic disorder, 1.06 (CI 0.88–1.26; p = 0.54) for individuals with bipolar disorder, and 1.03 (CI 0.80–1.32; p = 0.80) for individuals with severe depression. Compared to their respective counterparts in the non-SMD group, in the psychotic disorder and severe depression group, the RR were higher in women than in men. In the bipolar disorder group, the RR was higher in men than in women. The RR of COVID-19-associated death was generally higher in younger individuals with SMD. Individuals with psychosis between 18 and 59 years had the highest RR of COVID-19-associated death with 7.25 (CI 4.54–11.59; p<0.001).ConclusionsIndividuals with SMD, and particularly those with psychotic disorders, had a higher risk of COVID-19-associated death than the general population. As this is a pattern also seen with other infections, people with SMD may be similarly vulnerable in future pandemics.

The relationship of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate cortex of bipolar disorder subjects: A post-mortem study

Increased levels of inflammation markers have been found in the peripheral tissue of individuals with bipolar disorder (BD), especially during mood episodes. Previous studies found distinctive inflammatory profiles across different brain regions, but potential associations with clinical symptoms are still lacking. This study aims to evaluate the association of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate of individuals with BD. Levels of IL-1β, IL-6, IL-17A, cortisol, and C-reactive protein (CRP) were measured in the hippocampus and anterior cingulate of 14 BD individuals and their non-psychiatric controls. Neuropsychiatric symptoms present in the three months before death were assessed using the Neuropsychiatric Inventory (NPI). In the BD group, greater NPI scores were associated with higher IL-6 in the hippocampus (p = 0.011) and cingulate (p = 0.038) and higher IL-1β (p = 0.039) in the hippocampus. After adjusting for age, sex and CDR, IL-1β and IL-6 were still associated with higher NPI in the hippocampus. In correlation analysis considering both BD and their controls, moderate positive associations were found between NPI and IL-6 and cortisol in the hippocampus (p < 0.001 and p = 0.006) and cingulate (p = 0.024 and p = 0.016), IL-1β (p < 0.001) and IL-17A in the hippocampus (p = 0.002). No difference in inflammatory markers was found according to type of psychotropic medication used. Hence, in individuals with BD, neuropsychiatric symptoms were differently associated with specific inflammatory cytokines and CRP in the hippocampus and cingulate. These results suggest that the neuroinflammatory changes occurring in BD may be more complex than previously expected and could be associated with clinical manifestations.

Cerebral Blood Flow and Mood in Adolescents With Bipolar Disorder

ObjectiveMultiple prior studies have examined cerebral blood flow (CBF) in relation to mood states in adults with bipolar disorder (BD). This study examined CBF related to mood states in adolescents early in the course of BD, about which little is known. MethodThe study recruited 155 adolescents (mean [SD] age = 17.23 [1.62] years), including 81 with BD (32 hypomanic/mixed, 25 depressed, 24 euthymic) and 74 healthy controls. CBF was ascertained using pseudocontinuous arterial spin labeling magnetic resonance imaging. Region-of-interest analysis (amygdala, anterior cingulate cortex, middle frontal gyrus) controlling for age, sex, and race was complemented by whole-brain voxel-wise analyses. Within-BD regression analysis using age and sex as covariates examined the association of mania and depression severity with CBF. ResultsIn region-of-interest analyses, there were no group differences in CBF. Within the overall BD group, higher depression scores were associated with lower anterior cingulate cortex CBF (β = −.27, p = .01). In corrected voxel-wise analyses, CBF in the euthymic BD group was significantly higher compared with healthy controls in temporal and precentral regions. ConclusionThe finding of elevated regional CBF in adolescents with euthymic BD diverges from prior findings of reduced regional CBF in adults with BD. Higher CBF in adolescents with euthymic BD may reflect a developmentally specific compensatory perfusion mechanism required to maintain euthymia. However, longitudinal studies are needed to understand the temporal association of CBF and mood state in adolescents with BD, ideally followed into adulthood. Diversity & Inclusion StatementWe worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Circadian rhythms of melatonin and its relationship with anhedonia in patients with mood disorders: a cross-sectional study

BackgroundMood disorders are strongly associated with melatonin disturbances. However, it is unclear whether there is a difference in melatonin concentrations and melatonin circadian rhythm profiles between depression and bipolar disorder. In addition, the relationship between anhedonia, a common symptom of affective disorders, and its melatonin circadian rhythm remains under-investigated.MethodsThirty-four patients with depression disorder, 20 patients diagnosed with bipolar disorder and 21 healthy controls participated in this study. The Revised Physical Anhedonia Scale (RPAS) was performed to assess anhedonia. Saliva samples were collected from all subjects at fixed time points (a total of 14 points) in two consecutive days for measuring the melatonin concentrations to fit circadian rhythms of subjects. Melatonin circadian rhythms were compared between the three groups using ANOVA. Partial correlation analysis and linear regression analysis were used to explore the correlation between melatonin rhythm variables and anhedonia.ResultsWe found that the peak phase of melatonin in the depression group was significantly advanced compared to the control group (P < 0.001) and the bipolar disorder group (P = 0.004). The peak phase of melatonin and RPAS showed a negative correlation (P = 0.003) in depression patients, which was also demonstrated in the multiple linear regression model (B=-2.47, P = 0.006).ConclusionsThese results suggest that circadian rhythms of melatonin are differentiated in depression and bipolar disorder and correlate with anhedonia in depression. Future research needs to explore the neurobiological mechanisms linking anhedonia and melatonin circadian rhythms in depressed patients.