Anxiety mediates the relationship between perfectionism and insomnia symptoms: A longitudinal study

Objectives Individuals with insomnia often report aspects of perfectionism and symptoms of anxiety and depression. Investigation of these factors together has been limited. As such, the aim of the present study was to examine the extent to which the association between perfectionism and insomnia symptoms was mediated by anxiety and depression, concurrently and longitudinally. Methods Seventy-six members from the general-population participated at baseline. Data from 57 participants were subsequently analysed at twelve-month follow-up. Insomnia symptoms were assessed using The Insomnia Severity Index (ISI). Perfectionism was assessed using two Multidimensional Perfectionism Scales (F-MPS; HF-MPS). Symptoms of anxiety and depression were assessed using The Hospital Anxiety and Depression Scale (HADS). Correlational analysis examined longitudinal associations between perfectionism and insomnia symptoms. Hierarchical regression analysis examined whether significant associations remained after controlling for anxiety and depression. Results Baseline insomnia symptoms were associated with future doubts about action. Further, this relationship was mediated by preceding symptoms of anxiety and concurrent symptoms of insomnia. Similarly, baseline insomnia symptoms were also associated with future parental criticism. However this relationship was partially mediated by preceding symptoms of anxiety, and was not mediated by concurrent insomnia symptoms. Conclusions Symptoms of insomnia appear to be related to an increase in negative perfectionistic thinking in the form of doubts about action and parental criticism, however these relationships appear to be mediated by symptoms of anxiety. Therefore, treatments for insomnia should address anxiety symptoms with the prospect of preventing the accentuation of aspects of perfectionism due to poor sleep

Association of late-onset postpartum depression of mothers with expressive language development during infancy and early childhood: the HBC study

Background While it has been implied that an infant’s exposure to maternal postpartum depression (PPD) may be associated with delayed development of expressive language, it remains unclear whether such a delay persists into childhood and whether the onset of PPD onset—early (within 4 weeks after childbirth) vs. late (between 5 and 12 weeks postpartum)—is relevant in this context. Objective To examine whether children of mothers with early- or late-onset PPD have reduced expressive language scores during infancy and early childhood (up to 40 months of age). Methods This longitudinal, observational study was conducted as a part of the Hamamatsu Birth Cohort for Mothers and Children (HBC Study), a population-representative sample in Japan. A total of 969 neonates and their mothers were included in the analysis. Exposures Early- and late-onset PPD was measured using the Edinburgh Postnatal Depression Scale. Main Outcomes and Measures Expressive language development was measured using the Mullen Scales of Early Learning. Six points over time were monitored (10, 14, 18, 24, 32, and 40 months postpartum). The relationship between the exposure variable and any change in expressive language score was evaluated using multiple linear regression analysis and growth curve analysis, both adjusted for covariates. Results Results from the adjusted regression analysis showed that children of mothers with late-onset PPD had significantly lower expressive language scores at 18 months of age and beyond, with a score reduction of approximately 0.6 standard deviations from the reference value at 40 months of age (95% CI [−0.888 to −0.265], p < .001). This association was confirmed on growth curve analysis, which revealed a significant, monotonic decline of expressive language development between 10 and 40 months of age among children of mothers with late-onset PPD, but not among children of mothers with early-onset PPD. Conclusion Exposure to late-onset PPD may lead to a persistent decline in the rate of expressive language development in offspring during infancy and early childhood, highlighting the significance of monitoring for late-onset PPD to facilitate early detection and intervention

Association of Genetic Risks with Autism Spectrum Disorder and Early Neurodevelopmental Delays among Children without Intellectual Disability

IMPORTANCE Autism spectrum disorder (ASD) is highly heritable, and modest contributions of common genetic variants to ASD have been reported. However, the association of genetic risks derived from common risk variants with ASD traits in children from the general population is not clear, and the association of these genetic risks with neurodevelopment in infants has not been well understood. OBJECTIVE To test whether a polygenic risk score (PRS) for ASD is associated with neurodevelopmental progress at age 18 months and ASD traits at age 6 years among children from the general population. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, 876 children in the Hamamatsu Birth Cohort for Mothers and Children in Hamamatsu, Japan, underwent testing for the association of an ASD PRS with neurodevelopmental progress and ASD traits. Data collection began in December 2007 and is ongoing. Data analysis was conducted from April to December 2019. MAIN OUTCOMES AND MEASURES Summary data from the largest genome-wide association study were used to generate ASD PRSs, and significance of thresholds was calculated for each outcome. The Autism Diagnostic Observation Schedule 2 was used to measure ASD traits at age 6 years, and the Mullen Scales of Early Learning was used to measure neurodevelopmental progress at age 18 months. RESULTS Of 876 participants (mean [SD] gestational age at birth, 38.9 [1.6] weeks; 438 [50.0%] boys; 868 [99.1%] Japanese), 734 were analyzed. The ASD PRS was associated with ASD traits (R2 = 0.024; β, 0.71; SE, 0.24; P = .03). The association of ASD PRS with infant neurodevelopment was most pronounced in gross motor (R2 = 0.015; β, −1.25; SE, 0.39; P = .01) and receptive language (R2 = 0.014; β, −1.19; SE, 0.39; P = .02) scores on the Mullen Scales of Early Learning. Gene set enrichment analyses found that several pathways, such as cell maturation (R2 = 0.057; β, −5.28; SE, 1.40; P \u3c .001) and adenylyl cyclase activity and cyclic adenosine monophosphate concentration (R2 = 0.064; β, −5.30; SE 1.30; P \u3c .001), were associated with ASD traits. Gene sets associated with inflammation were commonly enriched with ASD traits and gross motor skills (eg, chemokine motif ligand 2 production: R2 = 0.051; β, −6.04; SE, 1.75; P = .001; regulation of monocyte differentiation: R2 = 0.052; β, −6.63; SE, 1.90; P = .001; and B-cell differentiation: R2 = 0.051; β, 7.37; SE, 2.15; P = .001); glutamatergic signaling–associated gene sets were commonly enriched with ASD traits and receptive language skills (eg, regulation of glutamate secretion: R2 = 0.052; β, −5.82; SE, 1.68; P = .001; ionotropic glutamate receptor signaling pathway: R2 = 0.047; β, 3.54; SE, 1.09; P = .001; and negative regulation of glutamate secretion: R2 = 0.045; β, −5.38; SE, 1.74; P = .002). CONCLUSIONS AND RELEVANCE In this study, the ASD PRS was associated with ASD traits among children from the general population. Genetic risks for ASD might be associated with delays in some neurodevelopmental domains, such as gross motor and receptive language skills

Broader autism phenotype as a risk factor for postpartum depression: Hamamatsu Birth Cohort (HBC) Study

AbstractThe broader autism phenotype (BAP), which refers to the expression of behavioral and cognitive propensities that are milder but qualitatively similar to those defining autism spectrum disorder, can play a crucial role in postpartum depression (PPD). We investigated whether pregnant women's BAP would increase the risk for PPD, using a representative birth cohort in Japan. Pregnant women were enrolled in the Hamamatsu Birth Cohort (HBC) Study during their mid-gestation (N=841) and were followed up until 3 months after delivery. BAP was measured mainly during the 2nd trimester of the pregnancy by using the Broader Phenotype Autism Symptoms Scale. Participants scoring 9 points or higher on the Edinburgh Postnatal Depression Scale at least once during the first 3 months after childbirth were diagnosed with PPD. Among participants, 128 (15.2%) women were found to have PPD. Multiple logistic regression analyses showed that BAP were associated with PPD (OR=1.19, 95% CI [1.07–1.31]), even after controlling for other potential confounders. In addition, the association was not moderated by history of depression and/or anxiety disorders, including concurrent depressive and anxiety symptoms during pregnancy. The findings suggest that pregnant women with BAP have an elevated risk for PPD

Voxel-based structural magnetic resonance imaging (MRI) study of patients with early onset schizophrenia

<p>Abstract</p> <p>Background</p> <p>Investigation into the whole brain morphology of early onset schizophrenia (EOS) to date has been sparse. We studied the regional brain volumes in EOS patients, and the correlations between regional volume measures and symptom severity.</p> <p>Methods</p> <p>A total of 18 EOS patients (onset under 16 years) and 18 controls matched for age, gender, parental socioeconomic status, and height were examined. Voxel-based morphometric analysis using the Brain Analysis Morphological Mapping (BAMM) software package was employed to explore alterations of the regional grey (GM) and white matter (WM) volumes in EOS patients. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).</p> <p>Results</p> <p>EOS patients had significantly reduced GM volume in the left parahippocampal, inferior frontal, and superior temporal gyri, compared with the controls. They also had less WM volume in the left posterior limb of the internal capsule and the left inferior longitudinal fasciculus. The positive symptom score of PANSS (higher values corresponding to more severe symptoms) was negatively related to GM volume in the bilateral posterior cingulate gyrus. The negative symptom score was positively correlated with GM volume in the right thalamus. As for the association with WM volume, the positive symptom score of PANSS was positively related to cerebellar WM (vermis region), and negatively correlated with WM in the brain stem (pons) and in the bilateral cerebellum (hemisphere region).</p> <p>Conclusion</p> <p>Our findings of regional volume alterations of GM and WM in EOS patients coincide with those of previous studies of adult onset schizophrenia patients. However, in brain regions that had no overall structural differences between EOS patients and controls (that is, the bilateral posterior cingulate gyrus, the right thalamus, the cerebellum, and the pons), within-subject analysis of EOS patients alone revealed that there were significant associations of the volume in these areas and the symptom severity. These findings suggest that at an early stage of the illness, especially for those with onset before brain maturation, a wide range of disturbed neural circuits, including these brain regions that show no apparent morphological changes, may contribute to the formation of the symptomatology.</p

Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism

<p>Abstract</p> <p>Background</p> <p>Axon-guidance proteins play a crucial role in brain development. As the dysfunction of axon-guidance signaling is thought to underlie the microstructural abnormalities of the brain in people with autism, we examined the postmortem brains of people with autism to identify any changes in the expression of axon-guidance proteins.</p> <p>Results</p> <p>The mRNA and protein expression of axon-guidance proteins, including ephrin (EFN)A4, eEFNB3, plexin (PLXN)A4, roundabout 2 (ROBO)2 and ROBO3, were examined in the anterior cingulate cortex and primary motor cortex of autistic brains (n = 8 and n = 7, respectively) and control brains (n = 13 and n = 8, respectively) using real-time reverse-transcriptase PCR (RT-PCR) and western blotting. Real-time RT-PCR revealed that the relative expression levels of EFNB3, PLXNA4A and ROBO2 were significantly lower in the autistic group than in the control group. The protein levels of these three genes were further analyzed by western blotting, which showed that the immunoreactive values for PLXNA4 and ROBO2, but not for EFNB3, were significantly reduced in the ACC of the autistic brains compared with control brains.</p> <p>Conclusions</p> <p>In this study, we found decreased expression of axon-guidance proteins such as PLXNA4 and ROBO2 in the brains of people with autism, and suggest that dysfunctional axon-guidance protein expression may play an important role in the pathophysiology of autism.</p

Alteration of Plasma Glutamate and Glutamine Levels in Children with High-Functioning Autism

浜松医科大学学位論文　医博第624号（平成24年3月19日

Polygenic Risk Score Analysis Revealed Shared Genetic Background in Attention Deficit Hyperactivity Disorder and Narcolepsy

Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients. Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions. Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use). However, the common biological mechanism for these disorders has not been well understood. Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual. We investigated a possible genetic association between ADHD and narcolepsy traits in the Hamamatsu Birth Cohort for mothers and children (HBC study) (n=876). Gene-set enrichment analyses were used to identify common pathways underlying these disorders. Narcolepsy PRS were significantly associated with ADHD traits both in the hyperactivity domain (e.g.,P-value threshold \u3c 0.05,β[SE], 5.815 [1.774];P=0.002) and inattention domain(e.g.,P-value threshold \u3c 0.05,β[SE], 5.734 [1.761];P=0.004). However, EHS PRS was not significantly associated with either domain of ADHD traits. Gene-set enrichment analyses revealed that pathways related to dopaminergic signaling, immune systems, iron metabolism, and glial cell function involved in both ADHD and narcolepsy. Findings indicate that ADHD and narcolepsy are genetically related, and there are possible common underlying biological mechanisms for this relationship. Future studies replicating these findings would be warranted to elucidate the genetic vulnerability for daytime sleepiness in individuals with ADHD

Targeted prevention of common mental health disorders in university students: randomised controlled trial of a transdiagnostic trait-focused web-based intervention

Background: A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders.&lt;p&gt;&lt;/p&gt; Aims: To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students.&lt;p&gt;&lt;/p&gt; Method: Students were recruited online (n = 1047, age: M = 21.8, SD = 4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n = 519) or a control intervention (n = 528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes.&lt;p&gt;&lt;/p&gt; Results: Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p&#60;.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p = .018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered eating.&lt;p&gt;&lt;/p&gt; Conclusions This study suggests that a transdiagnostic web-based intervention for university students targeting underlying personality risk factors may be a promising way of preventing common mental disorders with a low-intensity intervention

Perinatal Asphyxia Reduces Dentate Granule Cells and Exacerbates Methamphetamine-Induced Hyperlocomotion in Adulthood

Background: Obstetric complications have been regarded as a risk factor for schizophrenia later in life. One of the mechanisms underlying the association is postulated to be a hypoxic process in the brain in the offspring around the time of birth. Hippocampus is one of the brain regions implicated in the late-onset dopaminergic dysfunction associated with hypoxic obstetric complications. Methodology/Principal Findings: We used an animal model of perinatal asphyxia, in which rat pups were exposed to 15 min of intrauterine anoxia during Cesarean section birth. At 6 and 12 weeks after birth, the behavior of the pups was assessed using a methamphetamine-induced locomotion test. In addition, the histopathology of the hippocampus was examined by means of stereology. At 6 weeks, there was no change in the methamphetamine-induced locomotion. However, at 12 weeks of age, we found an elevation in methamphetamine-induced locomotor activity, which was associated with an increase of dopamine release in the nucleus accumbens. At the same age, we also found a reduction of the dentate granule cells of the hippocampus. Conclusions/Significance: These results suggest that the dopaminergic dysregulation after perinatal asphyxia is associated with a reduction in hippocampal dentate granule cells, and this may partly contribute to the pathogenesis of schizophrenia.浜松医科大学学位論文　医博第548号(平成２１年３月１８日