Significant Main Effect Of Diagnosis Research Articles

Abnormal resting-state functional connectivity in subregions of amygdala in adults and adolescents with major depressive disorder

BackgroundThe different symptoms of major depressive disorder (MDD) in adolescents compared to adults suggested there may be differences in the pathophysiology between adolescents and adults with MDD. However, despite the amygdala being considered critical in the pathophysiology, there was limited knowledge about the commonalities and differences in the resting-state functional connectivity (rsFC) of amygdala subregions in MDD patients of different age groups.MethodsIn the current study, 65 adolescents (46 with MDD and 19 controls) and 91 adults (35 with MDD and 56 controls) were included. A seed-based functional connectivity analysis was performed for each of the amygdala subregions. A 2 × 2 ANOVA was used to analyze the main effect of age, diagnosis, and their interaction on the rsFC of each subregion.ResultsA significant main effect of age was revealed in the rsFC of bilateral centromedial (CM) subregions and right laterobasal (LB) subregion with several brain regions in the limbic system and frontoparietal network. The significant main effect of diagnosis showed MDD patients of different ages showed higher connectivity than controls between the right LB and left middle frontal gyrus (MFG).ConclusionsThe rsFC of specific amygdala subregions with brain regions in the limbic system and frontoparietal network is affected by age, indicating a distinct amygdala connectivity profile in adolescents. The decreased rsFC between the right LB and the left MFG in adolescents and adults with MDD could serve as a diagnostic biomarker and a target of nonpharmacological treatment for MDD.

Early auditory processing abnormalities alter individual learning trajectories and sensitivity to computerized cognitive training in schizophrenia.

Auditory system plasticity is a promising target for neuromodulation, cognitive rehabilitation and therapeutic development in schizophrenia (SZ). Auditory-based targeted cognitive training (TCT) is a 'bottom up' intervention designed to enhance the speed and accuracy of auditory information processing, which has been shown to improve neurocognition in certain SZ patients. However, the dynamics of TCT learning as a function of training exercises and their impact on neurocognitive functioning and therapeutic outcomes are unknown. Forty subjects (SZ, n = 21; healthy subjects (HS), n = 19) underwent comprehensive clinical, cognitive, and auditory assessments, including measurements of auditory processing speed (APS) at baseline and after 1-h of TCT. SZ patients additionally completed 30-hours of TCT and repeated assessments ~10-12 weeks later. SZ patients were deficient in APS at baseline (d = 0.96, p < 0.005) relative to HS. After 1-h of TCT, analyses revealed significant main effects of diagnosis (d = 1.75, p = 0.002) and time (d = 1.04, p < 0.001), and a diagnosis × time interaction (d = 0.85, p = 0.02) on APS. APS learning effects were robust after 1-h in SZ patients (d = 1.47, p < 0.001) and persisted throughout the 30-h of training. Baseline APS was associated with verbal learning gains after 30-h of TCT (r = 0.51, p = 0.02) in SZ. TCT learning metrics may have prognostic utility and aid in the prospective identification of individuals likely to benefit from TCT. Future experimental medicine studies may advance predictive algorithms that enhance TCT-related clinical, cognitive and functional outcomes.

Soccer Skill Performance and Retention Following an 8-Week Adapted Soccer Intervention in Adults With Disabilities

This study evaluated the efficacy of an 8-week (two sessions/week; 60 min/session) adapted soccer intervention on skill performance and retention in 30 adults (18 men and 12 women) ages 17–40 years with autism spectrum disorder, Down syndrome, and intellectual disability. Of these 30 participants, 18 completed a 1-month retention test. The program included behavior supports and adaptations for participants with varying levels of behavioral needs. Dribbling, kicking a moving ball, kicking a stationary ball, throw-ins, trapping, and a composite skill score were examined. Linear mixed-effect regression revealed a significant time main effect with improvements from pretest to posttest and pretest to retention for all skills. In addition, modest offline gains (i.e., posttest &lt; retention) were observed for throw-ins, kicking a moving ball, and the composite skill score. A significant main effect of diagnosis was observed such that participants with autism spectrum disorder had better performance on kicking a moving ball than those with Down syndrome and intellectual disability. Finally, a significant main effect of level of function was observed. This program enabled adults with various disabilities to acquire fundamental soccer skills that may lead to meaningful participation in community soccer programs.

Visual processing deficits in patients with schizophrenia spectrum and bipolar disorders and associations with psychotic symptoms, and intellectual abilities

ObjectiveLow-level sensory disruption is hypothesized as a precursor to clinical and cognitive symptoms in severe mental disorders. We compared visual discrimination performance in patients with schizophrenia spectrum disorder or bipolar disorder with healthy controls, and investigated associations with clinical symptoms and IQ. MethodsPatients with schizophrenia spectrum disorder (n = 32), bipolar disorder (n = 55) and healthy controls (n = 152) completed a computerized visual discrimination task. Participants responded whether the latter of two consecutive grids had higher or lower spatial frequency, and discrimination thresholds were estimated using an adaptive maximum likelihood procedure. Case-control differences in threshold were assessed using linear regression, F-test and post-hoc pair-wise comparisons. Linear models were used to test for associations between visual discrimination threshold and psychotic symptoms derived from the PANSS and IQ assessed using the Matrix Reasoning and Vocabulary subtests from the Wechsler Abbreviated Scale of Intelligence (WASI). ResultsRobust regression revealed a significant main effect of diagnosis on discrimination threshold (robust F = 6.76, p = .001). Post-hoc comparisons revealed that patients with a schizophrenia spectrum disorder (mean = 14%, SD = 0.08) had higher thresholds compared to healthy controls (mean = 10.8%, SD = 0.07, β = 0.35, t = 3.4, p = .002), as did patients with bipolar disorder (12.23%, SD = 0.07, β = 0.21, t = 2.42, p = .04). There was no significant difference between bipolar disorder and schizophrenia (β = −0.14, t = −1.2, p = .45). Linear models revealed negative associations between IQ and threshold across all participants when controlling for diagnostic group (β = −0.3, t = −3.43, p = .0007). This association was found within healthy controls (t = −3.72, p = .0003) and patients with bipolar disorder (t = −2.53, p = .015), and no significant group by IQ interaction on threshold (F = 0.044, p = .97). There were no significant associations between PANSS domain scores and discrimination threshold. ConclusionPatients with schizophrenia spectrum or bipolar disorders exhibited higher visual discrimination thresholds than healthy controls, supporting early visual deficits among patients with severe mental illness. Discrimination threshold was negatively associated with IQ among healthy controls and bipolar disorder patients. These findings elucidate perception-related disease mechanisms in severe mental illness, which warrants replication in independent samples.

Positron Emission Tomography Assessments of Phosphodiesterase 10A in Patients With Schizophrenia.

Phosphodiesterase 10A (PDE10A) is a highly expressed enzyme in the basal ganglia, where cortical glutamatergic and midbrain dopaminergic inputs are integrated. Therapeutic PDE10A inhibition effects on schizophrenia have been reported previously, but the status of this molecule in the living patients with schizophrenia remains elusive. Therefore, this study aimed to investigate the central PDE10A status in patients with schizophrenia and examine its relationship with psychopathology, cognition, and corticostriatal glutamate levels. This study included 27 patients with schizophrenia, with 5 antipsychotic-free cases, and 27 healthy controls. Positron emission tomography with [18F]MNI-659, a specific PDE10A radioligand, was employed to quantify PDE10A availability by measuring non-displaceable binding potential (BPND) of the ligand in the limbic, executive, and sensorimotor striatal functional subregions, and in the pallidum. BPND estimates were compared between patients and controls while controlling for age and gender. BPND correlations were examined with behavioral and clinical measures, along with regional glutamate levels quantified by the magnetic resonance spectroscopy. Multivariate analysis of covariance demonstrated a significant main effect of diagnosis on BPND (p = .03). A posthoc test showed a trend-level higher sensorimotor striatal BPND in patients, although it did not survive multiple comparison corrections. BPND in controls in this subregion was significantly and negatively correlated with the Tower of London scores, a cognitive subtest. Striatal or dorsolateral prefrontal glutamate levels did not correlate significantly with BPND in either group. The results suggest altered striatal PDE10A availability and associated local neural dysfunctions in patients with schizophrenia.

Compassion focused therapy for pain management: '3 systems approach' to understanding why striving and self-criticism are key psychological barriers to regulating activity and improving self-care for people living with persistent pain.

This paper describes the development of an eight-week Compassion Focused Therapy for Pain Management (CFT-PM) group. This group was specifically designed for 'strivers' a sub-group of people with persistent pain who tend to engage in over-activity and resist making reasonable adjustments to their activity levels to accommodate their persistent pain. 'Strivers' tend to cope by ignoring their pain and pushing on through, in the shorter term leading to 'boom and bust' activity-related exacerbations of their pain. They also risk the development of additional persistent fatigue and burnout in the longer term. 117 people completed the CFT-PM group; The group was delivered in person (n = 84) but in online format from July 2020 (n = 33). 162 people started the CFT-PM group but 45 dropped-out (27.43%). There was a significant effect for time across all measures: significant improvement was found for depression, self-compassion, pain-related disability, pain-related anxiety and pain self-efficacy. Pain numeric rating scores were approaching significance. There was a significant main effect of diagnosis; post-hoc t-test analysis found significant improvement for all diagnoses on all measures with the exception of spinal. There was also a significant interaction between time and format: post-hoc t-test analysis found greater improvement for virtual format on self-compassion and pain-related anxiety. Findings suggests that CFT-PM may be a clinically effective group intervention with virtual format showing superior improvement. This approach might be less suitable for certain diagnoses; the spinal group may benefit more from traditional CBT-based PMPs. Limitations include the lack of random selection or allocation to treatment group. Future studies should adopt an experimental design to be able to draw firm conclusions regarding causation and efficacy. Despite these limitations, present findings suggest that CFT-PM may be an effective group intervention worthy of further investigation and clinical application.

Familial risk for major depression: differential white matter alterations in healthy and depressed participants.

Major depressive disorder (MDD) has been associated with alterations in brain white matter (WM) microstructure. However, diffusion tensor imaging studies in biological relatives have presented contradicting results on WM alterations and their potential as biomarkers for vulnerability or resilience. To shed more light on associations between WM microstructure and resilience to familial risk, analyses including both healthy and depressed relatives of MDD patients are needed. In a 2 (MDD v. healthy controls, HC) × 2 (familial risk yes v. no) design, we investigated fractional anisotropy (FA) via tract-based spatial statistics in a large well-characterised adult sample (N = 528), with additional controls for childhood maltreatment, a potentially confounding proxy for environmental risk. Analyses revealed a significant main effect of diagnosis on FA in the forceps minor and the left superior longitudinal fasciculus (ptfce-FWE = 0.009). Furthermore, a significant interaction of diagnosis with familial risk emerged (ptfce-FWE = 0.036) Post-hoc pairwise comparisons showed significantly higher FA, mainly in the forceps minor and right inferior fronto-occipital fasciculus, in HC with as compared to HC without familial risk (ptfce-FWE < 0.001), whereas familial risk played no role in MDD patients (ptfce-FWE = 0.797). Adding childhood maltreatment as a covariate, the interaction effect remained stable. We found widespread increased FA in HC with familial risk for MDD as compared to a HC low-risk sample. The significant effect of risk on FA was present only in HC, but not in the MDD sample. These alterations might reflect compensatory neural mechanisms in healthy adults at risk for MDD potentially associated with resilience.

Age-Related Decrease in Default-Mode Network Functional Connectivity Is Accelerated in Patients With Major Depressive Disorder.

Major depressive disorder (MDD) is a common psychiatric disorder which is associated with an accelerated biological aging. However, little is known whether such process would be reflected by a more rapid aging of the brain function. In this study, we tested the hypothesis that MDD would be characterized by accelerated aging of the brain’s default-mode network (DMN) functions. Resting-state functional magnetic resonance imaging data of 971 MDD patients and 902 healthy controls (HCs) was analyzed, which was drawn from a publicly accessible, multicenter dataset in China. Strength of functional connectivity (FC) and temporal variability of dynamic functional connectivity (dFC) within the DMN were calculated. Age-related effects on FC/dFC were estimated by linear regression models with age, diagnosis, and diagnosis-by-age interaction as variables of interest, controlling for sex, education, site, and head motion effects. The regression models revealed (1) a significant main effect of age in the predictions of both FC strength and dFC variability; and (2) a significant main effect of diagnosis and a significant diagnosis-by-age interaction in the prediction of FC strength, which was driven by stronger negative correlation between age and FC strength in MDD patients. Our results suggest that (1) both healthy participants and MDD patients experience decrease in DMN FC strength and increase in DMN dFC variability along age; and (2) age-related decrease in DMN FC strength may occur at a faster rate in MDD patients than in HCs. However, further longitudinal studies are still needed to understand the causation between MDD and accelerated aging of brain.

Emotion dysregulation across the span of eating disorder symptoms: Findings from a community sample of adolescents.

Emotion dysregulation is proposed as a key factor within eating disorder pathology. However, less is known about specific emotion regulation difficulties experienced by adolescents with varying levels of eating disorders symptoms. The present study examined the relationship between eating disorder behaviors and specific facets of emotion dysregulation, and differences in emotion dysregulation between eating disorder diagnostic groups. Participants were 2,783 adolescents, 11-19 years (M=14 years, 9months, SD=1year, 6months), who completed self-report measures as part of the EveryBODY study. Adolescents were identified as not having eating disorder symptoms (n=2,122) or meeting diagnostic criteria for symptoms of specific eating disorder, including: anorexia nervosa or atypical anorexia nervosa (n=57), bulimia nervosa (n=136), binge-eating disorder (n=57), other specified feeding or eating disorder characterized by binge eating or purging (n=381), and unspecified feeding or eating disorder (n=30). Binge eating, driven exercise, and fasting were each uniquely associated with emotion dysregulation, whereas purging was not. Similar findings were obtained within specific domains of emotion dysregulation. Findings from diagnostic groups showed a significant main effect of diagnosis on overall emotion dysregulation and most domains of emotion dysregulation. Adolescents with eating disorder symptoms consistently reported higher emotion dysregulation compared to those without these symptoms. Findings indicate that emotion dysregulation is a key factor across eating disorder pathology, and potential treatment target across the spectrum of eating disorder diagnoses in adolescents.

Towards robust and replicable sex differences in the intrinsic brain function of autism

BackgroundMarked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data.MethodsWe addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7–18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z > 3.1, cluster-level P < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research.ResultsDiscovery analyses in ABIDE revealed significant main effects of diagnosis and sex across the intrinsic functional connectivity of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples—EU-AIMS LEAP.LimitationsGiven the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability.ConclusionsAtypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies.

Brain-derived neurotrophic factor Val66Met polymorphism affects cortical thickness of rostral anterior cingulate in patients with major depressive disorder.

The neuro-anatomical substrates of major depressive disorder (MDD) remain poorly understood. Brain-derived neurotrophic factor (BDNF) gene polymorphism (Val66Met/rs6265) is associated with neuro-plasticity and development. In the present study, we explore the influence of BDNF gene polymorphism on cortical thickness in nonelderly, first episode, drug-naive patients with MDD. Two hundred and sixteen participants (105 MDD patients and 111 healthy controls) were divided into subgroups based on the BDNF genotype. High-resolution MRI was obtained in all participants. A relationship of BDNF Val66Met gene polymorphism and cortical thickness was investigated. The significant main effect of diagnosis was identified in the left rostal anterior cingulate (rACC), right inferior temporal and right lateral orbitofrontal (lOFC). The main effect of the genotype was observed in the left posterior cingulate cortex. The diagnosis-by-genotype interaction effect was found located in the left rACC. MDD patients who were Met-carriers exhibited thinner cortical thickness in the left rACC than healthy controls Met-carriers. Neither the symptom severity nor the illness duration was correlated significantly with cortical thickness. Our findings suggested that the BDNF gene polymorphism was associated with cortical thickness alterations of the left rACC in MDD patients, and genotype that carries Met may serve as a vulnerability factor in MDD regarding the cortical thickness loss in the left rACC. This finding can be considered as a supportive evidence for the neurotrophic factor hypothesis of depression.

Association of cortical thickness with age of onset in first-episode, drug-naïve major depression.

We previously showed differences in brain grey matter volume changes between patients with early-onset adult depression (EOD) and late-onset adult depression (LOD). Here, we aim to identify whether cortical thickness (CT) is affected by the age of onset in patients with depression. High-resolution MRI images were obtained for 54 major depressive disorder (MDD) patients with EOD, 58 patients with LOD, 57 young healthy controls (HCs), and 58 aged HCs. Depression severity was assessed using the Hamilton Depression Rating Scale 17-item (HDRS17). Associations between CT of patients and clinical scores were analyzed. There was a significant main effect of diagnosis for the left rostal anterior cingulate (rACC), right inferior temporal, right lateral orbitofrontal cortex (lOFC), and bilateral pericalcarine. A remarkable onset age-group effect on CT was observed in the rACC and bilateral caudal anterior cingulate (cACC). The diagnosis-by-onset age interaction effect was found in bilateral rACC and right lOFC. Thinning CT in bilateral rACC was observed in EOD patients compared to young HCs. Compared to older HCs, thicker CT in lOFC was seen in the LOD patient group. Compared with the LOD group, the EOD group showed cortical thinning of the right cACC and posterior cingulate cortex (PCC). There were no significant associations between CT in right cACC or PCC with symptom severity or illness duration. MDD patients with different age at onset show distinct CT alterations, suggesting potentially divergent pathological mechanisms of EOD and LOD.

Temporal dynamic changes of intrinsic brain activity in schizophrenia with cigarette smoking

Mounting evidence from multimodal neuroimaging studies has supported a neurobiological basis for schizophrenia-nicotine dependence comorbidity. However, this evidence comes exclusively from studies measuring static intrinsic activity/connectivity of the brain, while the dynamic effects of this comorbidity remain poorly understood. The current study therefore sought to examine whether temporal dynamic intrinsic brain activity interacted with diagnosis (schizophrenics vs. healthy controls) and smoking status (smokers vs. non-smokers). We used a mixed sample design and included the following four groups: i) schizophrenic smokers (n = 22), ii) schizophrenic non-smokers (n = 27), iii) healthy control smokers (n = 22), and iv) healthy control non-smokers (n = 21). All subjects underwent functional magnetic resonance imaging during the resting state. The temporal variability in intrinsic brain activity among the four groups was compared using a novel dynamic amplitude of low-frequency fluctuation (dALFF) method. A significant main effect of diagnosis was found in the left superior parietal gyrus (SPG; F(1, 88) = 142.1, P < 0.0001). Moreover, the dALFF strength in the SPG was positively correlated with disease duration in patients with schizophrenia (Rho(46) = 0.43, P = 0.002). In addition, a significant interaction between diagnosis and smoking status was observed in the left dorsolateral prefrontal cortex (DLPFC; F(1, 88) = 7.39, P = 0.008), which was consistent with the self-medication hypothesis. Together, this study has demonstrated for the first time that nicotine restores dynamic intrinsic brain activity in the left DLPFC in patients with schizophrenia. This interaction may be a clinical neuromarker for increased comorbid smoking in schizophrenia.

Increased Serum Levels of α-Synuclein in Patients With Major Depressive Disorder

ObjectiveEpidemiologic studies have demonstrated that depression is a risk factor for dementia. In particular, dementia with Lewy bodies (DLB) has been noted to be highly relevant to depression. It has been suggested that α-synuclein (α-syn), a major component of Lewy bodies, is related to the onset and progression of DLB. To investigate the relationship between depression and DLB, we compared serum α-syn levels of patients with depression to those of healthy subjects. MethodsThe subjects were 103 inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), or DSM-5 major depressive disorder (MDD) and 132 healthy comparisons. Patients were recruited from Juntendo Koshigaya Hospital, Saitama, Japan, between June 2010 and November 2016. Serum α-syn levels were measured using an enzyme-linked immunosorbent assay kit. Serum α-syn levels were compared using a 2 (age group [<60 years versus ≥60 years]) × 2 (diagnosis [MDD versus comparison]) analysis of variance. ResultsThere was no significant main effect of age (F = 1.167, df = 1, 231, p = 0.281). There was a significant main effect of diagnosis (F = 44.657, df = 1, 231, p <0.001), with higher α-syn levels in the MDD group versus the healthy comparison group, regardless of age. ConclusionThe present results suggest that depression may affect the metabolism of α-syn; there is a possibility that depression is not only a prodromal symptom of DLB but also a causal risk factor for DLB.

T22. PITUITARY GLAND VOLUME DIFFERENCES IN INDIVIDUALS WITH PSYCHOSIS: RESULTS FROM THE BIPOLAR-SCHIZOPHRENIA NETWORK ON INTERMEDIATE PHENOTYPES (B-SNIP) STUDY

BackgroundWhen exposed to stress, the hypothalamic-pituitary-adrenal axis is hyperactivated, which can cause the enlargement of the pituitary gland. Hence, pituitary gland volume could be a biomarker of stress present in psychosis. However, it remains unclear if individuals with psychosis have larger pituitary gland than healthy people. Previous studies investigating this question used small samples and reported inconsistent results. In the current study, we used an automated multi-atlas segmentation method to investigate the differences between pituitary gland volumes in a large sample of individuals on the psychosis spectrum.MethodsData collection was completed across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium with a total of 755 participants included in the study - 174 individuals with schizophrenia (SZ), 115 with schizoaffective disorder (SZA), 167 with psychotic bipolar disorder (PBD), and 299 healthy controls (HC). Structural magnetic resonance images were acquired and pituitary gland volumes were obtained using the automated MAGeT-Brain algorithm. General linear model and post-hoc independent t-tests were used to analysis the differences between subgroups of patients using clinical diagnosis and agnostic Biotype classification (Biotype 1 being the most cognitively impaired). We also explored potential effect of antipsychotic intake, symptoms severity and duration of illness. In all analyses, we used Bonferroni correction for multiple comparisons and entered confounds as covariates (age, sex, race, intracranial volume, and site).ResultsOverall, the pituitary gland volumes were not significantly different between patients and HC. No significant main effect of diagnosis was observed, but SZ patients had trending larger pituitary volume compared to HC (p=.033, uncorrected). We observed a significant main effect of Biotype (p=.003), with Biotype 1 having significantly larger pituitary gland than HC and Biotype 2 (p=.004 and p=.013). In the patients group, no significant relationship between the pituitary gland and the amount of antipsychotic intake was observed (r=.02, p=.68). Significant correlations with the pituitary gland volume were observed with symptoms severity (r=.22, p=.000), and with the duration of illness (r=-.18, p=.002). Importantly, Biotypes did not significantly differ in terms of symptoms severity nor duration of illness.DiscussionAs a group, individuals with psychosis do not have abnormal pituitary gland volume, but larger pituitary gland is related to shorter duration of illness and greater symptoms severity. Therefore, larger pituitary gland volume could be a state-related biomarker of psychosis. Moreover, while we did not observe any significant subgroup differences using clinical diagnosis, our results suggest an increase in pituitary volume in biotype 1 patients compared to HC. These findings clarify previous inconsistent reports, and encourage further investigation of stress biomarkers in individual with psychosis with lower cognitive abilities. In the future, this could lead to the development of more targeted treatments for this specific subgroup of patients.

Calibrating actigraphy to improve sleep efficiency estimates.

Actigraphy (ACT) can enhance treatment for insomnia by providing objective estimates of sleep efficiency; however, only two studies have assessed the accuracy of actigraphy-based estimates of sleep efficiency (ACT-SE) in sleep-disordered samples studied at home. Both found poor correspondence with polysomnography-based estimates (PSG-SE). The current study tested that concordance in a third sample and piloted a method for improving ACT-SE. Participants in one of four diagnostic categories (panic disorder, post-traumatic stress disorder, comorbid post-traumatic stress and panic disorder and controls without sleep complaints) underwent in-home recording of sleep using concurrent ambulatory PSG and actigraphy. Precisely synchronized PSG and ACT recordings were obtained from 41 participants. Sleep efficiency was scored independently using conventional methods, and ACT-SE/PSG-SE concordance examined. Next, ACT data recorded initially at 0.5Hz were resampled to 30-s epochs and rescaled on a per-participant basis to yield optimized concordance between PSG- and ACT-based sleep efficiency estimates. Using standard scoring of ACT, the correlation between ACT-SE and PSG-SE across participants was statistically significant (r=0.35, P<0.025), although ACT-SE failed to replicate a main effect of diagnosis. Individualized calibration of ACT against a night of PSG yielded a significantly higher correlation between ACT-SE and PSG-SE (r=0.65, P<0.001; z=1.692, P=0.0452, one-tailed) and a significant main effect of diagnosis that was highly correspondent with the effect on PSG-SE. ACT-based estimates of sleep efficiency in sleep-disordered patients tested at home can be improved significantly by calibration against a single night of concurrent PSG.

Atypical developmental trajectory of local spontaneous brain activity in autism spectrum disorder

Autism spectrum disorder (ASD) is marked by atypical trajectory of brain maturation, yet the developmental abnormalities in brain function remain unclear. The current study examined the effect of age on amplitude of low-frequency fluctuations (ALFF) in ASD and typical controls (TC) using a cross-sectional design. We classified all the participants into three age cohorts: child (<11 years, 18ASD/20TC), adolescent (11–18 years, 28ASD/26TC) and adult (≥18 years, 18ASD/18TC). Two-way analysis of variance (ANOVA) was performed to ascertain main effects and interaction effects on whole brain ALFF maps. Results exhibited significant main effect of diagnosis in ASD with decreased ALFF in the right precuneus and left middle occipital gyrus during all developmental stages. Significant diagnosis-by-age interaction was observed in the medial prefrontal cortex (mPFC) with ALFF lowered in autistic children but highered in autistic adolescents and adults. Specifically, remarkable quadratic change of ALFF with increasing age in mPFC presented in TC group was absent in ASD. Additionally, abnormal ALFF values in diagnosis-related brain regions predicted the social deficits in ASD. Our findings indicated aberrant developmental patterns of spontaneous brain activity associated with social deficits in ASD and highlight the crucial role of the default mode network in the development of disease.

Nicotine restores functional connectivity of the ventral attention network in schizophrenia

While previous work has suggested that nicotine may transiently improve attention deficits in schizophrenia, the neuronal mechanisms are poorly understood. This study is the first to examine the effects of nicotine on connectivity within the ventral attention network (VAN) during a selective attention task in schizophrenia. Using a crossover design, 17 nonsmoking patients with schizophrenia and 20 age/gender-matched nonsmoking healthy controls performed a go/no-go task with environmental noise distractors during application of a 7 mg nicotine or placebo patch. Psychophysiological interaction analysis was performed to analyze task-associated changes in connectivity between a ventral parietal cortex (VPC) seed and the inferior frontal gyrus (IFG), key components of the human VAN. Effects of nicotine on resting state VAN connectivity were also examined. A significant diagnosis × drug interaction was observed on task-associated connectivity between the VPC seed and the left IFG (F(1,35) = 8.03, p < 0.01). This effect was driven by decreased connectivity after placebo in patients and greater connectivity after nicotine. Resting state connectivity analysis showed a significant main effect of diagnosis between the seed and right IFG (F = 4.25, p = 0.023) due to increased connectivity in patients during placebo, but no drug × diagnosis interactions or main effects of drug. This study is the first to demonstrate that 1) the VAN is disconnected in schizophrenia during selective attention, and 2) nicotine may normalize this pathological state.

Using the Circumplex Model of Affect to Study Valence and Arousal Ratings of Emotional Faces by Children and Adults with Autism Spectrum Disorders

The affective circumplex model holds that emotions can be described as linear combinations of two underlying, independent neurophysiological systems (arousal, valence). Given research suggesting individuals with autism spectrum disorders (ASD) have difficulty processing emotions, we used the circumplex model to compare how individuals with ASD and typically-developing (TD) individuals respond to facial emotions. Participants (51 ASD, 80 TD) rated facial expressions along arousal and valence dimensions; we fitted closed, smooth, 2-dimensional curves to their ratings to examine overall circumplex contours. We modeled individual and group influences on parameters describing curve contours to identify differences in dimensional effects across groups. Significant main effects of diagnosis indicated the ASD-group’s ratings were constricted for the entire circumplex, suggesting range constriction across all emotions. Findings did not change when covarying for overall intelligence.

Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease

Ancillary to decline in cognitive abilities, patients with Alzheimer’s disease (AD) frequently suffer from behavioural and psychological symptoms of dementia (BPSD). Hypothalamic polypeptides such as melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF) levels were measured in 33 patients with AD and 33 healthy subjects (HS) using a fluorescence immunoassay (FIA). A significant main effect of diagnosis (F(1,62) = 8.490, p<0.01) on MCH levels was found between AD (93.76±13.47 pg/mL) and HS (84.65±11.40 pg/mL). MCH correlated with T-tau (r = 0.47; p<0.01) and P-tau (r = 0.404; p<0.05) in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r = −0.362, p<0.05) and was increased in more severely affected patients (MMSE≤20) compared to HS (p<0.001) and BPSD-positive patients compared to HS (p<0.05). In CSF-HCRT-1, a significant main effect of sex (F(1,31) = 4.400, p<0.05) with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL) was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD.