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.

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.

Sexually transmitted infection and teenage pregnancy in adolescents having parents with schizophrenia: a retrospective cohort study of 64,350 participants.

BACKGROUND: The risks of sexually transmitted infections (STIs) and teenage pregnancy in the offspring of parents with schizophrenia remain unknown. METHODS: From the Taiwan National Health Insurance Research Database, 5,850 individuals born between 1980 and 1999 having any parent with schizophrenia and 58,500 age-, sex-, income- and residence-matched controls without parents with severe mental disorders were enrolled in 1996 or on their birthdate and followed up to the end of 2011. Those who contracted any STI or became pregnant in adolescence during the follow-up period were identified. RESULTS: Cox regression analyses demonstrated that offspring of parents with schizophrenia (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.02-1.44), especially daughters (HR: 1.30, 95% CI: 1.06-1.58), were more likely to contract any STI later in life than the control comparisons. In addition, daughters of parents with schizophrenia had an elevated risk of being pregnant in their adolescence (HR: 1.47, 95% CI: 1.29-1.67) compared with those having no parents with severe mental disorders. DISCUSSION: The positive relationship between parental schizophrenia and offspring STIs and teenage pregnancy necessitates clinicians and public health officers to closely monitor the sexual health in the offspring of parents with schizophrenia so that optimal and prompt preventive measures can be taken in the at-risk group.

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.

Role of Appetite Hormone Dysregulation in Symptomology and Executive Function in Adolescents With Attention Deficit Hyperactivity Disorder.

BACKGROUND: Evidence suggests an association of insulin and leptin with attention and executive function. The roles of dysregulated appetite hormones, including insulin and leptin, in the pathomechanisms of attention deficit hyperactivity disorder (ADHD) and associated cognitive function impairment remain unknown. METHODS: In total, 50 adolescents with ADHD were enrolled and age and sex matched with 50 typically developing controls. The parent-reported Swanson, Nolan, and Pelham IV scale and self-reported Barratt Impulsiveness Scale were employed for symptom assessment. The fasting serum concentrations of appetite hormones-leptin, ghrelin, insulin, and adiponectin-were measured. The Wisconsin Card Sorting Test was used to examine executive function. RESULTS: Generalized linear models with adjustment for age, sex, body mass index, and medications indicated that the adolescents with ADHD had higher levels of insulin (P = .039) and leptin (P = .006) than did those in the control group. Self-reported attention and self-control symptoms were negatively associated with insulin level (P = .025 and .018, respectively) and positively associated with leptin level (both P < .001). In addition, insulin level was positively associated with executive function (P = .031). CONCLUSION: Appetite hormone dysregulation was associated with the symptomology and executive function among adolescents with ADHD. Our results may inspire researchers to further examine the role of appetite hormone dysregulation in ADHD pathogenesis.

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.

A longitudinal study of the association between pro-inflammatory cytokines and mood symptoms in bipolar disorder.

BACKGROUND: Because of a relative dearth of longitudinal studies, the directionality of the relationship between mood and inflammation among patients with bipolar disorder (BD) is still unclear. We aimed to investigate the longitudinal associations of pro-inflammatory markers with mood symptom severity in BD. METHODS: Hundred and thirty-two adult patients with BD were enrolled. At the baseline and 1-year follow-up visit, all participants received mood assessment with Montgomery Åsberg depression rating scale (MADRS) and Young mania rating scale, and underwent blood draws to quantify metabolic profile and serum levels of the pro-inflammatory markers, including soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1 (sTNF-αR1), monocyte chemoattractant protein-1, and C-reactive protein. A four-factor model of MADRS, consisting of sadness, negative thoughts, detachment, and neurovegetative symptoms, were applied. RESULTS: At baseline, 65 patients with BD were in depressed state, and 67 patients with BD were in euthymic state. Among patients in depressed state, baseline MADRS total score positively correlated with sTNF-αR1 level at follow-up. While baseline sTNF-αR1 level positively predicted sadness symptom in euthymic patients with BD who later developed depression (n = 22), sadness in patients with bipolar depression predicted later increase in serum sTNF-αR1 level even after remission (n = 17). Moreover, lithium had a stronger effect of lowering peripheral sTNF-αR1 level as compared with other mood stabilizers. CONCLUSION: Our results indicate the bidirectional inflammation-depression relationship in BD.

Antidepressant drugs use and epilepsy risk: A nationwide nested case-control study.

BACKGROUND: To investigate the association between exposure to antidepressants (ADs) and the risk of epilepsy among patients exposed to ADs. METHOD: We conducted a case-control study using Taiwan's National Health Insurance Research Database between 1998 and 2013. A total of 863 patients with epilepsy and 3,452 controls were included. The dose of ADs was categorized according to the cumulative defined daily dose (cDDD). The risk of epilepsy was assessed using conditional logistic regression analysis. RESULTS: Compared with cDDD < 90, ADs exposure with cDDD > 365 (odds ratio [OR]: 1.37, 95% confidence interval [CI]:1.12-1.68) was associated with an increased risk of epilepsy, but not for those with cDDD 90-365 (OR: 1.07,95% CI: 0.87-1.30) after adjustment for several comorbidities and indications of ADs use. Other identified risk factors include cerebrovascular disease, traumatic brain injury, and central nervous system infection. Subgroup analysis of individual ADs showed that escitalopram (OR: 1.93, 95% CI: 1.12-3.31), venlafaxine (OR: 1.62, 95% CI: 1.13-2.31), mirtazapine (OR: 1.56, 95% CI: 1.00-2.43), paroxetine (OR: 1.44, 95% CI: 1.08-1.94), and fluoxetine (OR: 1.25, 95% CI: 1.01-1.56) had a significantly higher risk of epilepsy. Sertraline, fluvoxamine, citalopram, duloxetine, milnacipran, and bupropion did not show any proconvulsant effects. CONCLUSIONS: The study found an increased risk of epilepsy among patients who were exposed to any ADs, particularly longer-term users. Given the nature of observational studies with residual bias, interpretation should be cautious.

Inflammatory cytokines in and cognitive function of adolescents with first-episode schizophrenia, bipolar disorder, or major depressive disorder.

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

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.

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.

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.

Risk of attention deficit hyperactivity and autism spectrum disorders among the children of parents with autoimmune diseases: a nationwide birth cohort study.

Studies have suggested that maternal autoimmune diseases are associated with an increased risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). However, research on the association of paternal autoimmune diseases with ADHD and ASD risk has remained inconclusive. Using the Taiwan National Health Insurance Research Database, we selected 708,517 family triads (father-mother-child) between 2001 and 2008 and followed them until the end of 2011. Parental autoimmune diseases as well as ADHD and ASD in children were identified during the study period. Increased ADHD risk in children in terms of hazard ratios (HRs) and 95% confidence intervals (CIs) was associated with prenatal exposure to paternal autoimmune diseases, including Sjögren's syndrome (HR: 8.41, 95% CI: 2.72-26.05), psoriasis (HR: 1.95, 95% CI: 1.05-3.63), and ankylosing spondylitis (HR: 2.02, 95% CI: 1.29-2.15), as well as maternal autoimmune diseases, such as systemic lupus erythematosus (HR: 1.53, 95% CI: 1.09-2.15), type 1 diabetes mellitus (HR: 1.55, 95% CI: 1.02-2.36), inflammatory bowel disease (HR: 2.37, 95% CI: 1.59-3.52), psoriasis (HR: 1.70, 95% CI: 1.00-2.87), and ankylosing spondylitis (HR: 2.07, 95% CI: 1.11-3.86). However, ASD was only associated with paternal inflammatory bowel disease (HR: 3.08, 95% CI: 1.15-8.28) and ankylosing spondylitis (HR: 2.65, 95% CI: 1.10-6.39). Both paternal and maternal autoimmune diseases were associated with increased likelihood of ADHD in children. However, only paternal autoimmune diseases were related to offspring ASD risk. The precise pathomechanism underlying the correlation between parental autoimmunity and child neurodevelopment requires further investigation.

Risk of teenage pregnancy among adolescents with bipolar disorder: a cohort study of 35,398 adolescent girls.

Teenage pregnancy is a major public health concern. However, few studies have investigated the relationship between pediatric bipolar disorder and early pregnancy, and whether bipolar disorder medications reduce the risk of early pregnancy remains unknown. In total, 3218 adolescent girls with bipolar disorder and 32,180 controls matched for age, family income, residence, and time of enrollment were enrolled in this study from 2001 to 2009. Early pregnancy, defined as pregnancy occurring in patients younger than 20 years old, was identified during the follow-up period from enrollment until the end of 2011. After adjustment for demographic data, psychiatric comorbidities, and bipolar disorder medications, adolescent girls with bipolar disorder had 20 times the risk of early pregnancy (hazard ratio [HR] = 20.63, 95% confidence interval [CI] [15.68, 27.16]) and about 25 times the risk of repeated early pregnancy (HR = 24.59, 95% CI [15.20, 39.78]) compared with those without bipolar disorder. Long-term use of both mood stabilizers (HR = 0.34, 95% CI [0.23, 0.52]) and atypical antipsychotics (HR = 0.32, 95% CI [0.20, 0.51]) was associated with a reduced risk of early pregnancy. Bipolar disorder was associated with an increased risk of early pregnancy in adolescent girls. Bipolar disorder medications reduced this risk. The results suggest that interventions targeting the vulnerable population of adolescent girls with bipolar disorder are warranted to prevent early pregnancies.

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.

Associations of parental mental disorders and age with childhood mental disorders: a population-based cohort study with four million offspring.

This Taiwan study examined the associations of parental age and mental disorders with the offspring risks of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), major depressive disorder (MDD), and bipolar disorder (BD). Children born between January 1991 and December 2004 in Taiwan were enrolled as the birth cohort (n = 4,138,151) and followed up until December 2011. A logistic regression analysis was performed to identify the odds ratio (OR). The advanced age effects were significant in ADHD (range of OR: 1.04 to 1.49) and ASD (range of OR: 1.35 to 2.27). Teenage mothers, teenage fathers, and fathers ≥ 50 years had higher offspring risks of MDD (range of OR: 1.24 to 1.46); and teenage mothers and fathers ≥ 50 years had increased offspring risks of BD (range of OR: 1.23 to 1.87). Both paternal and maternal mental disorders were associated with higher risks of within-disorder transmission for ADHD, ASD, MDD, and BD (range of OR: 2.64 to 30.41). Besides, parents with one of these four mental disorders (ADHD, ASD, MDD, and BD) might have higher risk of cross-disorder transmission to at least one of the other three mental disorders in the offspring (range of OR: 1.35 to 7.15). Parental age and mental disorders had complex and nuanced patterns in association with offspring mental disorders.

Neurofilament Light Chain Is a Novel Biomarker for Major Depression and Related Executive Dysfunction.

BACKGROUND: Evidence suggests that major depressive disorder is related to neuroaxonal injury and that neurofilament light chain (NfL) is a biomarker of neuroaxonal injury. In addition, proinflammatory cytokines have been reported to be associated with major depression and neuroaxonal injury. METHODS: Forty patients with major depression and 40 age- and sex-matched healthy control participants were enrolled for the measurement of NfL and proinflammatory cytokines and assessment of executive function. General linear models were used to examine the association between NfL levels, proinflammatory cytokine levels, and executive function. RESULTS: Patients with major depressive disorder exhibited significantly higher NfL levels (P = .007) than the control participants. NfL levels were positively related to log-transformed levels of tumor necrosis factor-α (P = .004). Higher levels of NfL (P = .002) and tumor necrosis factor-α (P = .013) were associated with greater deficits in executive function. DISCUSSION: NfL was a novel biomarker for major depressive disorder and related executive dysfunction. Further studies are necessary to elucidate the role of NfL in the pathophysiology of major depression and related cognitive impairment.

Familial coaggregation of major psychiatric disorders in first-degree relatives of individuals with autism spectrum disorder: a nationwide population-based study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Identifying common and distinct subcortical volumetric abnormalities in 3 major psychiatric disorders: a single-site analysis of 640 participants.

BACKGROUND: Subcortical volumetric abnormalities in schizophrenia, bipolar disorder and major depressive disorder (MDD) have been consistently found on a single-diagnosis basis in previous studies. However, whether such volumetric abnormalities are specific to a particular disorder or shared by other disorders remains unclear. METHODS: We analyzed the structural MRIs of 160 patients with schizophrenia, 160 patients with bipolar disorder, 160 patients with MDD and 160 healthy controls. We calculated the volumes of the thalamus, hippocampus, amygdala, accumbens, putamen, caudate, pallidum and lateral ventricles using FreeSurfer 7.0 and compared them among the groups using general linear models. RESULTS: We found a significant group effect on the volumes of the thalamus, hippocampus, accumbens and pallidum. Further post hoc analysis revealed that thalamic volumes in patients with schizophrenia, bipolar disorder and MDD were significantly reduced compared to those in healthy controls, but did not differ from one another. Patients with schizophrenia and bipolar disorder also shared a significant reduction in hippocampal volumes. Among the 3 clinical groups, patients with schizophrenia showed significantly lower hippocampal volumes and higher pallidal volumes than patients with bipolar disorder and MDD. LIMITATIONS: Differences in psychotropic use and duration of illness among the patient groups may limit the interpretation of our findings. CONCLUSION: Our findings indicate that decreased thalamic volume is a common feature of schizophrenia, bipolar disorder and MDD. Smaller hippocampal and larger pallidal volumes differentiate schizophrenia from bipolar disorder and MDD and may provide clues to the biological basis for the Kraepelinian distinction between these illnesses.