Risk of traumatic brain injury among patients with ADHD and their unaffected siblings.

BACKGROUND: As the relationship between attention deficit hyperactivity disorder (ADHD) and traumatic brain injury (TBI) is gaining increasing attention, the TBI risk in patients with ADHD, unaffected siblings of ADHD probands, and non-ADHD controls remains unclear. METHODS: Overall, 18,645 patients with ADHD, 18,880 unaffected siblings of ADHD probands, and 188,800 age-/sex-matched controls were followed up from enrollment to the end of 2011. The cases of TBI and TBI requiring hospitalization were identified during follow-up. RESULTS: Patients with ADHD (hazard ratio [HR]: 1.57) and unaffected siblings (HR: 1.20) had an increased risk of any TBI compared with non-ADHD controls. Surprisingly, the likelihood of developing TBI requiring hospitalization during follow-up was higher in the unaffected siblings group (HR: 1.21) than in the control group, whereas it was lower in the ADHD probands group (HR: 0.86). CONCLUSIONS: Patients with ADHD and unaffected siblings of ADHD probands were more likely to develop any TBI during follow-up than controls. Unaffected siblings of patients with ADHD exhibited the highest risk of subsequent TBI requiring hospitalization compared with patients with ADHD and healthy controls. Therefore, TBI risk in patients with ADHD and their unaffected siblings would require further investigation. IMPACT: ADHD diagnosis and ADHD trait are associated with risk of traumatic brain injury (TBI). Both patients with ADHD and their unaffected siblings were more likely to develop TBI during the follow-up compared with the control group. TBI requiring hospitalization occurred more in the sibling group than in the proband group. TBI risk should be closely monitored among unaffected siblings of patients with ADHD.

Proinflammatory cytokine levels, cognitive function, and suicidal symptoms of adolescents and young adults with major depressive disorder.

Whether proinflammatory cytokine dysregulation and cognitive dysfunction are associated with suicidal symptoms in adolescents and young adults with major depressive disorder (MDD) remains uncertain. We assessed the cognitive function and proinflammatory cytokine levels of 43 and 51 patients aged 15-29 years with MDD and severe and mild suicidal symptoms, respectively, as well as those of 85 age- and sex-matched healthy controls. Specifically, we measured serum levels of C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-2, and interleukin-6 and assessed cognitive function by using working memory and go/no-go tasks. The severity of the patients' suicidal symptoms was based on Item 10 of the Montgomery-Åsberg Depression Rating Scale; scores of ≤ 2 and ≥ 4 indicated mild and severe symptoms, respectively. The patients with MDD and severe suicidal symptoms had higher levels of C-reactive protein (p = .019) and TNF-α (p = .002) than did the patients with mild symptoms or the healthy controls. The number of errors committed on the go/no-go by patients with MDD and severe suicidal symptoms (p = .001) was significantly higher than those by patients with MDD and mild symptoms or by controls. After adjusting for nonsuicidal depressive symptoms, we observed suicidal symptoms to be positively associated with TNF-α levels (p = .050) and errors on the go/no-go task (p = .021). Compared with mild suicidal symptoms, severe symptoms are associated with greater serum levels of proinflammatory cytokines and inferior cognitive function in adolescents and young adults with MDD.

Dysfunction of circulating endothelial progenitor cells in major depressive disorder.

OBJECTIVES: Despite mounting evidence demonstrates circulating endothelial progenitor cells (cEPCs) quantitative changes in depression, no study has investigated cEPC functions in major depressive disorder (MDD). We investigated the role of cEPC adhesive and apoptotic functions in MDD. METHODS: We recruited 68 patients with MDD and 56 healthy controls (HCs). The depression symptoms, anxiety, psychosomatic symptoms, subjective cognitive dysfunction, quality of life, and functional disability were evaluated using the Hamilton Depression Rating Scale and Montgomery-Åsberg Depression Rating Scale, Hamilton Anxiety Rating Scale, Depression and Somatic Symptoms Scale (DSSS), Perceived Deficits Questionnaire-Depression, 12-Item Short Form Health Survey (SF-12), and Sheehan Disability Scale (SDS), respectively. Working memory and executive function were assessed using a 2-back task and Wisconsin Card Sorting Test (WCST). Inflammatory marker (soluble interleukin-6 receptor, C-reactive protein, and tumor necrosis factor-α receptor-1), cEPC adhesive, and apoptotic levels were measured using in vitro assays. RESULTS: The MDD patients showed significantly lower cEPC adhesive levels than the HCs, and this difference in adhesive function remained statistically significant even after adjusting for inflammatory marker levels. The cEPC adhesion levels were in inverse correlations with commission and omission errors in 2-back task, the percent perseverative response and percent perseverative errors in WCST, and the DSSS and SDS scores, but in positive correlations with SF-12 physical and mental component scores. cEPC apoptotic levels did not differ significantly between the groups. CONCLUSION: The findings indicate that cEPC adhesive function is diminished in MDD and impacts various aspects of cognitive and psychosocial functions associated with the disorder.

Appetite hormone dysregulation and executive dysfunction among adolescents with bipolar disorder and disruptive mood dysregulation disorder.

Appetite hormone dysregulation may play a role in the pathomechanisms of bipolar disorder and chronic irritability. However, its association with executive dysfunction in adolescents with bipolar disorder and those with disruptive mood dysregulation disorder (DMDD) remains unclear. We included 20 adolescents with bipolar disorder, 20 adolescents with DMDD, and 47 healthy controls. Fasting serum levels of appetite hormones, including leptin, ghrelin, insulin, and adiponectin were examined. All participants completed the Wisconsin Card Sorting Test. Generalized linear models with adjustments for age, sex, body mass index, and clinical symptoms revealed that patients with DMDD had elevated fasting log-transformed insulin levels (p = .023) compared to the control group. Adolescents with DMDD performed worse in terms of the number of tries required to complete tasks associated with the first category (p = .035), and adolescents with bipolar disorder performed worse in terms of the number of categories completed (p = .035). A positive correlation was observed between log-transformed insulin levels and the number of tries required for the first category (ß = 1.847, p = .032). Adolescents with DMDD, but not those with bipolar disorder, were more likely to exhibit appetite hormone dysregulation compared to healthy controls. Increased insulin levels were also related to executive dysfunction in these patients. Prospective studies should elucidate the temporal association between appetite hormone dysregulation, executive dysfunction, and emotional dysregulation.

Congenital cleft lip and palate and elevated risks of major psychiatric disorders: A nationwide longitudinal study.

BACKGROUND: Congenital cleft lip and palate (CCLP) may be associated with major psychiatric disorders, including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia, bipolar disorder, and major depressive disorder. METHODS: From the Taiwan National Health Insurance Research Database, 1,158 children and adolescents with CCLP and 11,580 age/sex-matched controls without CCLP were included in this study between 2001 and 2010; they were followed up until the end of 2011 to identify the aforementioned major psychiatric disorders. RESULTS: After adjustment for age, sex, income, residence, and family history, the Cox regression model revealed a positive relationship of CCLP with subsequent schizophrenia (hazard ratio [HR]: 7.60, 95% confidence interval [CI]: 2.03-28.54), ASD (HR: 6.03, 95% CI: 1.76-20.61), and ADHD (HR: 7.33, 95% CI: 5.01-10.73). DISCUSSION: These findings suggest that clinicians should be attentive to the presence or emergence of mental health conditions in patients with CCLP. Further studies are necessary to investigate the pathogenesis between CCLP and major psychiatric disorders.

The Utilization of Optically Induced Dielectrophoresis (ODEP)-Based Cell Manipulation in a Microfluidic System for the Purification and Sorting of Circulating Tumor Cells (CTCs) with Different Sizes.

The analysis of circulating tumor cells (CTCs) at the molecular level holds great promise for several clinical applications. For this goal, the harvest of high-purity, size-sorted CTCs with different subtypes from a blood sample are important. For this purpose, a two-step CTC isolation protocol was proposed, by which the immunomagnetic beads-based cell separation was first utilized to remove the majority of blood cells. After that, an optically induced dielectrophoresis (ODEP) microfluidic system was developed to (1) purify the CTCs from the remaining magnetic microbeads-bound blood cells and to (2) sort and separate the CTCs with different sizes. In this study, the ODEP microfluidic system was designed and fabricated. Moreover, its optimum operation conditions and performance were explored. The results exhibited that the presented technique was able to purify and sort the cancer cells with two different sizes from a tested cell suspension in a high-purity (93.5% and 90.1% for the OECM 1 and HA22T cancer cells, respectively) manner. Overall, this study presented a technique for the purification and sorting of cancer cells with different sizes. Apart from this application, the technique is also useful for other applications in which the high-purity and label-free purification and sorting of cells with different sizes is required.

Development of an Optically Induced Dielectrophoresis (ODEP) Microfluidic System for High-Performance Isolation and Purification of Bacteria.

For the rapid detection of bacteria in a blood sample, nucleic acid amplification-based assays are believed to be promising. Nevertheless, the nucleic acids released from the dead blood cells or bacteria could affect the assay performance. This highlights the importance of the isolation of live bacteria from blood samples. To address this issue, this study proposes a two-step process. First, a blood sample was treated with the immuno-magnetic microbeads-based separation to remove the majority of blood cells. Second, an optically induced dielectrophoresis (ODEP) microfluidic system with an integrated dynamic circular light image array was utilized to further isolate and purify the live bacteria from the remaining blood cells based on their size difference. In this work, the ODEP microfluidic system was developed. Its performance for the isolation and purification of bacteria was evaluated. The results revealed that the method was able to harvest the live bacteria in a high purity (90.5~99.2%) manner. Overall, the proposed method was proven to be capable of isolating and purifying high-purity live bacteria without causing damage to the co-existing cells. This technical feature was found to be valuable for the subsequent nucleic-acid-based bacteria detection, in which the interferences caused by the nontarget nucleic acids could be eliminated.

Risk of periodontitis in adolescents with bipolar disorder: a cohort study of 21,255 subjects.

Although a growing number of studies have investigated the relationship between psychosocial factors and periodontitis, studies investigating the association between bipolar disorder (BD) and periodontitis are lacking. Using the Taiwan National Health Insurance Research Database, 4251 adolescents with BD and 17,004 age- and sex-matched controls were included. They were followed up from enrollment to the end of 2011 or death. Periodontitis was diagnosed during the follow-up. Cox regression analysis indicated that adolescents with BD had a higher risk of periodontitis (hazard ratio [HR]: 2.96, 95% confidence interval [CI] 2.77-3.17) than did controls. Subanalyses stratified by sex revealed a higher risk of periodontitis in male (HR: 2.83, 95% CI 2.56-3.14) and female (HR: 3.01, 95% CI 2.74-3.30) adolescents with BD than their respective controls. The long-term use of mood stabilizers was associated with a higher risk of periodontitis (HR: 1.19, 95% CI 1.06-1.35) in the BD cohort. Our study highlighted an increased risk of periodontitis in adolescents with BD compared with controls during the follow-up. We recommend that more attention should be paid to the prevention of periodontitis in adolescents with BD, especially those who are female or receiving mood stabilizers.

Risks and familial coaggregation of death by suicide, accidental death and major psychiatric disorders in first-degree relatives of individuals who died by suicide.

BACKGROUND: Evidence suggests a familial coaggregation of major psychiatric disorders, including schizophrenia, bipolar disorder, major depression (MDD), autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Those disorders are further related to suicide and accidental death. However, whether death by suicide may coaggregate with accidental death and major psychiatric disorders within families remains unclear. AIMS: To clarify the familial coaggregation of deaths by suicide with accidental death and five major psychiatric disorders. METHOD: Using a database linked to the entire Taiwanese population, 68 214 first-degree relatives of individuals who died by suicide between 2003 and 2017 and 272 856 age- and gender-matched controls were assessed for the risks of death by suicide, accidental death and major psychiatric disorders. RESULTS: A Poisson regression model showed that the first-degree relatives of individuals who died by suicide were more likely to die by suicide (relative risk RR = 4.61, 95% CI 4.02-5.29) or accident (RR = 1.62, 95% CI 1.43-1.84) or to be diagnosed with schizophrenia (RR = 1.53, 95% CI 1.40-1.66), bipolar disorder (RR = 1.99, 95% CI 1.83-2.16), MDD (RR = 1.98, 95% CI 1.89-2.08) or ADHD (RR = 1.34, 95% CI 1.24-1.44). CONCLUSIONS: Our findings identified a familial coaggregation of death by suicide with accidental death, schizophrenia, major affective disorders and ADHD. Further studies would be required to elucidate the pathological mechanisms underlying this coaggregation.

All-cause mortality and suicide mortality in autistic individuals: An entire population longitudinal study in Taiwan.

LAY ABSTRACT: Our study was the first population-based study in an Asian country to investigate the mortality rates among autistic individuals. Among the entire Taiwanese population (N = 29,253,529), between 2003 and 2017, 45,398 autistic individuals were identified and 1:4 age-/sex-matched to 181,592 non-autistic individuals. We found that autistic individuals had increased risks of all-cause mortality, natural-cause mortality, and suicide mortality compared with non-autistic individuals. Furthermore, autistic males were more likely to die by suicide, and autistic females were more likely to die of accident compared with the non-autistic individuals.

Disease progression to bipolar disorder among adolescents and young adults with antidepressant-resistant and antidepressant-responsive depression: Does antidepressant class matter?

Studies have demonstrated a positive relationship between antidepressant resistance and the progression of bipolar disorder. However, the influence of antidepressant classes such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) in this context has yet to be investigated. A total of 5,285 adolescents and young adults with antidepressant-resistant depression and 21,140 with antidepressant-responsive depression were recruited in the present study. The antidepressant-resistant depression group was divided into two subgroups: only resistant to SSRIs (n = 2,242, 42.4%) and additionally resistant to non-SSRIs (n = 3,043, 57.6%) groups. The status of bipolar disorder progression was monitored from the date of depression diagnosis to the end of 2011. Patients with antidepressant-resistant depression were more likely to develop bipolar disorder during the follow-up (hazard ratio [HR]: 2.88, 95% confidence interval [CI]: 2.67-3.09) than those with antidepressant-responsive depression. Furthermore, the group that was additionally resistant to non-SSRIs were at the highest risk of bipolar disorder (HR: 3.02, 95% CI: 2.76-3.29), followed by the group that was only resistant to SSRIs (2.70, 2.44-2.98). Adolescents and young adults with antidepressant-resistant depression, especially those who responded poorly to both SSRIs and SNRIs, were at increased risk of subsequent bipolar disorder compared with those with antidepressant-responsive depression. Further studies are warranted to elucidate the molecular pathomechanisms underlying the resistance to SSRIs and SNRIs and subsequent bipolar disorder.

Autism spectrum disorder and periodontitis risk: A cohort study of 38,203 adolescents.

BACKGROUND: People with autism spectrum disorder (ASD) may have poor oral health status because they often experience challenges with daily oral hygiene and have inadequate access to oral health care services. This study explored periodontitis risk in adolescents with ASD compared with those who did not have a diagnosis of ASD. METHODS: Data from 2001 through December 31, 2011 from the Taiwan National Health Insurance Research Database on 3,473 adolescents with ASD and 34,730 age- and sex-matched people who did not have a diagnosis of ASD were obtained, and subsequent periodontitis was identified from enrollment through December 31, 2011. RESULTS: Adolescents with ASD (hazard ratio, 2.01; 95% CI, 1.84 to 2.20) were more likely to develop periodontitis at follow-up than those who did not have a diagnosis of ASD. Findings remained consistent in subanalyses stratified by sex and intellectual disability. People with ASD had periodontitis onset at an earlier mean (SD) age than those who did not have a diagnosis of ASD (17.97 [3.12] vs 21.86 [2.28] years; P < .001). CONCLUSIONS: ASD is an independent risk factor for subsequent periodontitis development. PRACTICAL IMPLICATIONS: Oral health should be closely monitored in adolescents with ASD. Future investigation of the common pathogenesis between periodontitis and ASD is warranted.

Risk of suicide after a diagnosis of sleep apnea: A nationwide longitudinal study.

Previous studies have presented evidence on the association between sleep apnea and suicidal ideation and planning, but the relationship between a clinical diagnosis of sleep apnea and suicide attempts remains unknown. We investigated the risk of suicide after a diagnosis with sleep apnea using data from a nationwide community-based population database, i.e., the Taiwan National Health Insurance Research Database. We recruited 7,095 adults with sleep apnea and 28,380 age-, sex-, and comorbidity-matched controls between 1998 and 2010 and followed them up until the end of 2011. Individuals who exhibited any (once or repeated) suicide attempts were identified during the follow-up period. The E value was calculated for unmeasured bias. Sensitivity analysis was conducted. Patients with sleep apnea were more likely to carry out any suicide attempt (hazard ratio: 4.53; 95% confidence interval: 3.48-5.88) during the follow-up period than the controls after adjusting for demographic data, mental disorders, and physical comorbidities. The hazard ratio remained significant after excluding individuals with mental disorders (4.23; 3.03-5.92). The hazard ratio was 4.82 (3.55-6.56) for male patients and 3.86 (2.33-6.38) for female patients. Consistent findings of increased risk of repeated suicide attempt were found among patients with sleep apnea. No association was found between continuous positive airway pressure treatment and suicide risk. The calculated E values support suicide risk after the diagnosis of sleep apnea. The risk of suicide was 4.53-fold higher in patients diagnosed with sleep apnea than in their counterparts without sleep apnea.

Risk of Prescription Opioid Exposure in Children and Adolescents With Attention Deficit Hyperactivity Disorder: A Nationwide Longitudinal Study.

BACKGROUND: US studies suggest a positive association between attention deficit-hyperactivity disorder (ADHD) and the risk of exposure to prescription opioids. However, whether this association holds in Asian countries remains unclear. METHODS: In total, 91,518 children and adolescents with ADHD and 91,518 age- and sex-matched controls were enrolled for the period of 2001 to 2009; they were followed up until the end of 2011 to determine whether they had used prescription opioids. RESULTS: Children (hazard ratio [HR]: 5.83) and adolescents (HR: 3.44) with ADHD had a higher likelihood of receiving opioid prescriptions than did their matched controls. Furthermore, patients with ADHD had greater likelihoods of cumulative exposure to opioids of >14 (HR: 5.93) and >30 days (HR: 6.07). DISCUSSION: Owing to the evidence of a significant link between opioid prescription use and eventual abuse, close monitoring for prescription opioid use is necessary for at-risk children and adolescents with ADHD.

Longitudinal follow-up of subsequent psychiatric comorbidities among children and adolescents with autism spectrum disorder.

BACKGROUND: The mental health of children and adolescents with autism spectrum disorder (ASD) is a concern of recent years. However, a large-scale longitudinal study investigating the risk and the time course of subsequent psychiatric comorbidities is still lacking. METHODS: Using the Taiwan National Health Insurance Research Database, 13,382 children and adolescents with ASD, and 53,528 age- and sex-matched non-ASD controls were enrolled between 2001 and 2009, and followed to the end of 2011. The adjusted hazard ratio (HR) with a corresponding 95 % confidence interval for psychiatric comorbidities among children and adolescents with ASD vs matched controls was estimated. The subjects who developed schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and obsessive-compulsive disorder (OCD) were identified during the follow-up. RESULTS: Children and adolescents with ASD compared with controls were more likely to be diagnosed with schizophrenia (19.21; 13.74, 26.88), bipolar disorder (17.59; 12.66, 24.44), depressive disorder (5.56; 4.72, 6.56), anxiety disorder (5.01; 4.49, 5.59), and OCD (16.12; 11.66, 22.30) later in life. The time course of subsequent psychiatric comorbidity showed that anxiety disorder occurred first, usually in late childhood, with psychotic and affective disorders proceeding in adolescence. Those with ASD and anxiety disorder had an additionally increased likelihood of developing subsequent psychiatric comorbidity compared with those with ASD only. LIMITATION: In claims data analysis, clinical parameters or possible confounders may not be fully captured. CONCLUSION: Patients with ASD are predisposed to the development of anxiety disorder in late childhood, as well as schizophrenia, bipolar disorder, depressive disorder, and OCD in adolescence.

Appetite hormone dysregulation, body mass index, and emotional dysregulation in nonobese adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder: a cross-sectional association study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Risk of type 2 diabetes mellitus between adolescents with antidepressant-resistant and antidepressant-responsive depression: A cohort study of 15,651 adolescents.

BACKGROUND: Whether response to antidepressants is related to the risk of developing type 2 diabetes mellitus (T2DM) in adolescents with depression remains unknown. METHODS: This study used the Taiwan National Health Insurance Research Database to enroll 1739 adolescents with antidepressant-resistant depression, 6956 with antidepressant-responsive depression, and 6956 controls between 2001 and 2010, with an end-of-2011 follow-up. Physician-diagnosed T2DM was identified at follow-up. T2DM-related risk factors, namely hypertension, dyslipidemia, and obesity, were assessed and controlled for as confounding factors. RESULTS: Adolescents with antidepressant-resistant depression (hazard ratio [HR], 95 % confidence interval [CI]: 4.62, 2.75-7.75) and those with antidepressant-responsive depression (HR, 95 % CI: 3.06, 1.98-4.72) had a higher risk of developing T2DM at follow-up than did the control group. Those with antidepressant-resistant depression were more likely to receive a diagnosis of T2DM (HR, 95 % CI: 1.51, 1.04-2.19) later in life than were those with antidepressant-responsive depression. DISCUSSION: Clinicians should closely monitor factors related to T2DM, such as fasting blood sugar, in high-risk populations, especially in adolescents with antidepressant-resistant depression.

Risk of parental psychiatric disorders among adolescents with major depressive disorder according to response to antidepressant treatment: does the type of antidepressant matter?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Procollagen type 1 N-terminal propeptide, neurofilament light chain, proinflammatory cytokines, and cognitive function in bipolar and major depressive disorders: An exploratory study of brain- bone axis and systemic inflammation.

BACKGROUND: Higher levels of neurofilament light chain (NfL) and proinflammatory cytokines (i.e., tumor necrosis factor [TNF]-α) were observed in patients with bipolar disorder (BD) and major depressive disorder (MDD). Procollagen type 1 N-terminal propeptide (P1NP), a bone turnover biomarker, is related to MDD. The association among the brain-bone axis, systemic inflammation, and cognitive function remains unclear in severe affective disorders. METHODS: Overall, 25 patients with BD, 24 with MDD, and 29 matched controls were enrolled in the current study and underwent the measurements of the NfL, P1NP, and proinflammatory cytokine levels and 1-back and 2-back working memory tasks. Generalized linear models (GLMs) were used to examine the aforementioned biomarkers between the groups and clarify the association with each other. RESULTS: GLMs showed increased levels of NfL (p = 0.001, p = 0.020) and P1NP (p = 0.050, p = 0.032) in the patients with BD and MDD than in the controls and suggested significant correlations between the NfL level and the mean time of the 2-back working memory task (p = 0.038) and between P1NL and TNF-α levels (p < 0.001). DISCUSSION: Our study revealed the dysregulated brain-bone axis, indicated by elevated NfL and P1NP levels, and related cognitive impairment and systemic inflammation in the patients with BD and MDD. Additional studies are necessary to elucidate definite pathomechanisms underlying those conditions.

Circulating endothelial progenitor cell dysfunction in patients with bipolar disorder.

Dysfunction in circulating endothelial progenitor cells (cEPCs) plays a crucial role in cardiovascular disorders (CVDs). Patients with bipolar disorder (BPD) are at increased risk of developing CVDs. This study examined the associations of the functional properties of cEPCs with BPD and its clinical and cognitive characteristics. We recruited 69 patients with BPD and 41 healthy controls (HCs). The levels of manic, depressive, anxiety, psychosomatic symptoms, subjective cognitive dysfunction, quality of life, and functional disability of the BPD group were evaluated using the Young Mania Rating Scale (YMRS), Clinical Global Impression for BPD (CGI-BP), Hamilton Depression Rating Scale, Montgomery-Åsberg Depression Rating Scale, Hamilton Anxiety Rating Scale, Depression and Somatic Symptoms Scale, Perceived Deficits Questionnaire-Depression, 12-Item Short-Form Health Survey, and Sheehan Disability Scale, respectively. Cognitive function was assessed using 2-back and Go/No-Go tasks. Through in vitro assays, the adhesion to fibronectin and the percentage of apoptosis of cEPCs were examined. Under correction for multiple comparisons, the adhesive function of cEPCs in BPD was significantly lower than that in the HCs (corrected P [Pcorr] = 0.027). The reduced adhesive function of cEPCs correlated significantly with increased scores in the YMRS (Pcorr = 0.0002) and the CGI-BP (Pcorr = 0.0009). A lower percentage of apoptotic cEPC cells was associated with greater commission errors in the 2-back (Pcorr = 0.028) and Go/No-Go tasks (Pcorr = 0.029). The cEPCs of the BPD group exhibited attenuated adhesive function. The altered adhesive and apoptotic functions of cEPCs are associated with manic symptom severity and response inhibition deficits in patients with BPD.