Evidence has suggested that emotional dysregulation is a transdiagnostic feature in schizophrenia and major affective disorders. However, the relationship between emotional dysregulation and appetite hormone disturbance remains unknown in nonobese adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder.

In total, 22 adolescents with schizophrenia; 31 with bipolar disorder; 33 with major depressive disorder; and 41 healthy age-, sex-, and body mass index (BMI)/BMI percentile-matched controls were enrolled for assessing levels of appetite hormones, namely leptin, ghrelin, insulin, and adiponectin. Emotional regulation symptoms were measured using the parent-reported Child Behavior Checklist―Dysregulation Profile.

Adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder exhibited greater emotional dysregulation symptoms than the control group (P = .037). Adolescents with bipolar disorder demonstrated higher log-transformed levels of insulin (P = .029) and lower log-transformed levels of leptin (P = .018) compared with the control group. BMI (P < .05) and log-transformed ghrelin levels (P = .028) were positively correlated with emotional dysregulation symptoms.

Emotional dysregulation and appetite hormone disturbance may occur in the early stage of severe mental disorders. Further studies are required to clarify the unidirectional or bidirectional association of emotional dysregulation with BMI/BMI percentile and appetite hormones among patients with severe mental disorder.

The genetic load for major depressive disorder (MDD) may be higher in people who develop MDD earlier in life. This study aimed to investigate whether the parents of adolescents with MDD were more likely to have MDD, bipolar disorder (BD), schizophrenic disorder (SZ), alcohol use disorder, or substance use disorder than the parents of adolescents without MDD. We also examined whether the response to antidepressant treatment predicted the likelihood of parental psychiatric disorders.

In all, 1,758 adolescents aged 12–19 years with antidepressant-resistant depression, 7,032 (1:4) age-/sex-matched adolescents with antidepressant-responsive depression and 7,032 (1:4) age-/sex-matched controls were included. Parental psychiatric disorders of individuals enrolled were assessed.

The parents of the adolescents with MDD were more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than the parents of the control group. The parents of adolescents who were antidepressant resistant and the mothers of adolescents who were either treatment resistant or treatment responsive were more likely to be diagnosed with a psychiatric disorder.

Our study demonstrated that parents of adolescents with MDD may be more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than parents of adolescents without MDD, suggesting the within-disorder transmission and cross-disorder transmission of these psychiatric disorders. Furthermore, the parent’s sex and the response to antidepressant treatment may affect the within-disorder transmission of MDD.

Previous studies have confirmed that miR-146a-5p overexpression suppresses neurogenesis, thereby enhancing depression-like behaviors. However, it remains unclear how miR-146a-5p dysregulation produces in vivo brain structural abnormalities in patients with major depressive disorder (MDD).

In this case–control study, we combined cortical morphology analysis of magnetic resonance imaging (MRI) and miR-146a-5p quantification to investigate the neuropathological effect of miR-146a-5p on cortical thickness in MDD patients. Serum-derived exosomes that were considered to readily cross the blood-brain barrier and contain miR-146a-5p were isolated for miRNA quantification. Moreover, follow-up MRI scans were performed in the MDD patients after 6 weeks of antidepressant treatment to further validate the clinical relevance of the relationship between miR-146a-5p and brain structural abnormalities.

In total, 113 medication-free MDD patients and 107 matched healthy controls were included. Vertex-vise general linear model revealed miR-146a-5p-dependent cortical thinning in MDD patients compared with healthy individuals, i.e., overexpression of miR-146a-5p was associated with reduced cortical thickness in the left orbitofrontal cortex (OFC), anterior cingulate cortex, bilateral lateral occipital cortices (LOCs), etc. Moreover, this relationship between baseline miR-146a-5p and cortical thinning was nonsignificant for all regions in the patients who had received antidepressant treatment, and higher baseline miR-146a-5p expression was found to be related to greater longitudinal cortical thickening in the left OFC and right LOC.

The findings of this study reveal a relationship between miR-146a-5p overexpression and cortical atrophy and thus may help specify the in vivo mediating effect of miR-146a-5p dysregulation on brain structural abnormalities in patients with MDD.

Emotional dysregulation (ED) is a common characteristic of both attention deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD), especially in adolescents. However, whether ADHD and MDD may share the specific ED-related neural networks remains unknown.

In total, 43 adolescents with clinical ED (22 adolescents with ADHD and 21 with MDD) were recruited; in addition, 29 sex- and age-matched healthy controls (HCs) were included. Resting-state functional connectivity (RSFC) analysis, voxel-based morphometry, and diffusion tensor imaging analysis were performed for each patient. In addition, we determined the significant regions of interest in patients with ED due to ADHD and MDD as compared with HCs and tested their correlations with clinical rating scale scores.

Compared with HCs, patients with ED had greater RSFC in the cerebellum and supramarginal gyrus (SMG), especially between vermis VI and the SMG in the attention networks, and lower RSFC between the right supplementary motor area and right lateral parietal area. Lower gray matter (GM) volume in the SMG was also found. RSFC was significantly correlated with clinical rating scale scores for all patients with ED due to ADHD or MDD. GM change was correlated with ED and MDD rating scale scores.

The cerebellum and attention networks might play major roles in ED pathophysiology in adolescents with ADHD and MDD. Increased connectivity of the vermis to the SMG serves as a possible underlying neural network.

Evidence has demonstrated associations of bipolar disorder (BD) with cognitive impairment, dysregulated proinflammatory cytokines, and appetite hormones.

To compare executive dysfunction, proinflammatory cytokines, and appetite hormones between patients with first-episode and multiple-episode BDs.

This cross-sectional study included young adults aged 18 to 39 years who were diagnosed as having type 1 BD in the first or recurrent episode and a group of age-/sex-matched healthy controls. Data regarding patient characteristics, clinical symptoms, cytokines (C-reactive protein [CRP], interleukin-6, and tumor necrosis factor [TNF]-α), appetite hormones (leptin, adiponectin, ghrelin, and insulin), and executive function evaluated using the Wisconsin Card Sorting Test (WCST) were collected.

A total of 112 participants (38 patients in the multiple-episode BD group, 31 patients in the first-episode BD group, and 43 in the control group) were included. Multivariate analysis revealed that patients in the multiple-episode BD group performed significantly worse in the WCST (P < .05) and had higher levels of ghrelin (P = .002), and lower levels of CRP (P = .040) than those in the first-episode BD group. Patients with BD had significantly higher TNF-α and ghrelin levels compared with the healthy controls. No significant associations of CRP, TNF-α, and ghrelin levels with executive function were observed.

Profiles in proinflammatory cytokines and appetite hormones as well as executive function significantly differed between patients with first-episode and multiple-episode BDs and controls, which may suggest their potential roles in the clinical stages and pathophysiology of type 1 BD.

Few studies have explored the complex relationship of pro- and anti-inflammatory cytokines with cognitive function in adolescents with first-episode schizophrenia, bipolar disorder, or major depressive disorder.

In total, 26, 35, and 29 adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder, respectively, and 22 age- and sex-matched controls were included in the current study. Cytokines, namely interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP), were assessed. The Wisconsin Card Sorting Test (WCST) and the working memory task were administered to assess cognitive function.

Using generalized linear models with adjustment for demographic data and clinical symptoms, patients with bipolar disorder were found to exhibit the highest levels of CRP (P = .023), IL-6 (P = .022), and TNF-α (P = .011), and had the lowest IL-2 levels (P = .034) among the four groups. According to the results of the WCST and working memory task, adolescents with schizophrenia exhibited the lowest performance in cognitive function. In addition, among the assessed cytokines, only CRP levels (P = .027) were negatively associated with WCST scores.

Dysregulated pro- and anti-inflammatory cytokines and impaired cognitive functioning were observed in first-episode adolescent-onset schizophrenia, bipolar disorder, and major depressive disorder. The altered cytokine profiles may play important roles in the pathophysiology of schizophrenia, bipolar disorder, and major depressive disorder.

Providing good end-of-life (EOL) care for noncancer patients has been made a national priority in Singapore. A combined medical and nursing ward-based intervention known as the EOL care plan was piloted in a general medicine ward at our institution, aiming to guide key aspects of EOL care. The aim of this study is to assess the EOL care plan's effect on EOL care for general medicine patients.

We conducted a retrospective cohort study on inpatients who died in a general ward under the discipline “General Medicine” from May to October 2019. We collected data around symptom management, rationalization of care and communication with families. The primary analysis compared care received by patients who died in the pilot ward with that of a control group of patients who died in other wards.

In total, 112 records were included in the analysis. Pain assessment was more common in the pilot ward compared with the control group (35.3% vs. 6.3%, p < 0.001), as were anti-psychotic prescriptions for delirium (64.7% vs. 24.4%, p = 0.001). Fewer patients received blood glucose monitoring in the last 48 h of life in the pilot ward (69.5% vs. 35.3%, p = 0.007). There were also less frequent parameters monitoring in the pilot ward (p < 0.004).

The implementation of the EOL care plan was associated with process-level indicators of better EOL care, suggesting that it could have a significant positive impact when implemented on a wider scale.

Dysregulated proinflammatory cytokines have been shown to be associated with suicidal behavior. Cognitive deficits in working memory and inhibitory control have been demonstrated in depressed patients and people with suicidal ideation (SI). However, the association between proinflammatory cytokines, SI, and cognitive deficits in patients with major depressive disorder (MDD) remains unclear.

A total of 77 patients with MDD and age-/sex-matched 60 healthy individuals were recruited. MDD patients were divided into two groups: with SI (n = 36) and no SI (n = 41). SI was defined by a score of ≥2 in item 3 of the 17-item Hamilton Rating Scale for Depression. Levels of proinflammatory cytokines, including soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1, and C-reactive protein (CRP), were measured, and cognitive function was assessed using 2-back task and Go/No-Go task.

Patients with SI had higher levels of CRP than those without SI and controls (P = .007). CRP was positively associated with SI (β = 0.21, P = .037), independent of cognitive function and depressive symptoms. Furthermore, SI was associated with cognitive deficits in working memory and inhibitory control after adjusting for confounding factors (P < .05).

Our findings suggest that higher levels of serum CRP and deficits in working memory and inhibitory control may be associated with higher SI among patients with MDD.

The current study evaluated the associations between different forms and sources of Fe and breast cancer risk in Southern Chinese women.

Case–control study. We collected data on the consumption of Fe from different forms and food sources by using a validated FFQ. Multivariable logistic regression and restricted cubic spline (RCS) analysis was used to reveal potential associations between Fe intake and breast cancer risk.

A case-control study of women at three major hospitals in Guangzhou, China.

From June 2007 to March 2019, 1591 breast cancer cases and 1622 age-matched controls were recruited.

In quartile analyses, Fe from plants and Fe from white meat intake were inversely associated with breast cancer risk, with OR of 0·65 (95 % CI 0·47, 0·89, Ptrend = 0·006) and 0·76 (95 % CI 0·61, 0·96, Ptrend = 0·014), respectively, comparing the highest with the lowest quartile. No associations were observed between total dietary Fe, heme or non-heme Fe, Fe from meat or red meat and breast cancer risk. RCS analysis demonstrated J-shaped associations between total dietary Fe, non-heme Fe and breast cancer, and reverse L-shaped associations between heme Fe, Fe from meat and Fe from red meat and breast cancer.

Fe from plants and white meat were inversely associated with breast cancer risk. Significant non-linear J-shaped associations were found between total dietary Fe, non-heme Fe and breast cancer risk, and reverse L-shaped associations were found between heme Fe, Fe from meat or red meat and breast cancer risk.

Altered immunity and metabolic profiles have been compared between bipolar depression (BD) and major depressive disorder (MDD). This study aimed at developing a composite predictor of appetite hormones and proinflammatory cytokines to differentiate BD from MDD.

This cross-sectional study enrolled patients with BD and those with MDD aged 20 to 59 years and displaying depressive episodes. Clinical characteristics (age, sex, body mass index, and depression severity), cytokines (C-reactive protein, interleukin [IL]-2, IL-6, tumor necrosis factor [TNF]-α, P-selectin, and monocyte chemoattractant protein), and appetite hormones (leptin, adiponectin, ghrelin, and insulin) were assessed as potential predictors using a classification and regression tree (CRT) model for differentiating BD from MDD.

The predicted probability of a composite predictor of ghrelin and TNF-α was significantly greater (for BD: area under curve = 0.877; for MDD: area under curve = 0.914) than that of any one marker (all P > .05) to distinguish BD from MDD. The most powerful predictors for diagnosing BD were high ghrelin and TNF-α levels, whereas those for MDD were low ghrelin and TNF-α levels.

A composite predictor of ghrelin and TNF-α driven by CRT could assist in the differential diagnosis of BD from MDD with high specificity. Further clinical studies are warranted to validate our results and to explore underlying mechanisms.

Recent imaging studies of large datasets suggested that psychiatric disorders have common biological substrates. This study aimed to identify all the common neural substrates with connectomic abnormalities across four major psychiatric disorders by using the data-driven connectome-wide association method of multivariate distance matrix regression (MDMR).

This study analyzed a resting functional magnetic resonance imaging dataset of 100 patients with schizophrenia, 100 patients with bipolar I disorder, 100 patients with bipolar II disorder, 100 patients with major depressive disorder, and 100 healthy controls (HCs). We calculated a voxel-wise 4,330 × 4,330 matrix of whole-brain functional connectivity (FC) with 8-mm isotropic resolution for each participant and then performed MDMR to identify structures where the overall multivariate pattern of FC was significantly different between each patient group and the HC group. A conjunction analysis was performed to identify common neural regions with FC abnormalities across these four psychiatric disorders.

The conjunction of the MDMR maps revealed that the four groups of patients shared connectomic abnormalities in distributed cortical and subcortical structures, which included bilateral thalamus, cerebellum, frontal pole, supramarginal gyrus, postcentral gyrus, lingual gyrus, lateral occipital cortex, and parahippocampus. The follow-up analysis based on pair-wise FC of these regions demonstrated that these psychiatric disorders also shared similar patterns of FC abnormalities characterized by sensory/subcortical hyperconnectivity, association/subcortical hypoconnectivity, and sensory/association hyperconnectivity.

These findings suggest that major psychiatric disorders share common connectomic abnormalities in distributed cortical and subcortical regions and provide crucial support for the common network hypothesis of major psychiatric disorders.

Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive.

This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID).

FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50–19.67), ADHD 3.94 (CI 3.72–4.17), schizophrenia 3.05 (CI 2.74–3.40), BD 2.22 (CI 1.98–2.48) and MDD 1.88 (CI 1.76–2.00). Higher RRs of schizophrenia (4.47, CI 3.95–5.06) and ASD (18.54, CI 16.18–21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only.

The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.