Trauma exposure and disclosure in Hispanic youth at clinical high risk for psychosis: A retrospective review study.

AIM: This exploratory study aimed to examine differences in rates of self and clinician-reports of trauma in youth at clinical high risk for psychosis (CHR) and whether rates of reporting differed by ethnicity. METHODS: Self-reported history of trauma was collected at intake amongst youth at CHR enrolled in Coordinated Specialty Care (CSC) services (N = 52). A structured chart review was conducted for the same sample to identify clinician-reported history of trauma throughout treatment in CSC. RESULTS: For all patients, frequency of self-reported trauma at intake to CSC (56%) was lower compared to clinician-reports of trauma throughout treatment (85%). Hispanic patients self-reported trauma at intake (35%) less frequently than non-Hispanics (69%) (p = .02). No differences were found in clinician reported exposure to trauma by ethnicity throughout treatment. CONCLUSION: Whilst further research is needed, these findings suggest the need for formalised, repeated, and culturally appropriate assessments of trauma within CSC.

In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group.

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.

Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group.

BACKGROUND: Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD. METHODS: Longitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables. RESULTS: Compared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18

Characteristics of Hispanics Referred to Coordinated Specialty Care for First-Episode Psychosis and Factors Associated With Enrollment.

OBJECTIVE: The primary objectives of this study were to examine referral sources and demographic, clinical, and socioenvironmental characteristics of Hispanics referred to and enrolled in a program of coordinated specialty care (Early CSC program) for first-episode psychosis, to compare them with characteristics of other referred and enrolled racial-ethnic groups, and to identify factors associated with enrollment in the program. METHODS: A retrospective review was conducted for all individuals referred to and enrolled in the Early CSC program over a 2-year period. Extracted data included referral sources and demographic and clinical characteristics. Zip code-level data from publicly available sources were cross-referenced with individual records. Nonparametric tests and appropriate secondary analysis were used to determine significant differences across racial-ethnic groups referred to (N=180) or enrolled in (N=75) the Early CSC program. A random forest model was used to determine which factors or interacting factors were associated with enrollment among the eligible referrals (N=114). RESULTS: Hispanic individuals were more likely to be referred from inpatient or outpatient mental health providers and not from other community sources. Among eligible Hispanic referrals, those who lived in areas with a lower percentage of Spanish speaking in the home were more likely to enroll in services, compared with those who lived in areas with a higher percentage of Spanish speaking. CONCLUSIONS: Continued exploration of factors associated with referral and enrollment in CSC programs for the growing Hispanic ethnic group in the United States can help determine best steps for developing these programs.

Cortical mediation of relationships between dopamine receptor D2 and cognition is absent in youth at risk of bipolar disorder.

Bipolar disorder is associated with cognitive deficits and cortical changes for which the developmental dynamics are not well understood. The dopamine D2 receptor (DRD2) gene has been associated with both psychiatric disorders and cognitive variability. Here we examined the mediating role of brain structure in the relationship between DRD2 genomic variation and cognitive performance, with target cortical regions selected based on evidence of association with DRD2, bipolar disorder and/or cognition from prior literature. Participants (n = 143) were aged 12-30 years and comprised 62 first-degree relatives of bipolar patients (deemed 'at-risk'), 55 controls, and 26 patients with established bipolar disorder; all were unrelated Caucasian individuals with complete data across the three required modalities (structural magnetic resonance imaging, neuropsychological and genetic data). A DRD2 haplotype was derived from three functional polymorphisms (rs1800497, rs1076560, rs2283265) associated with alternative splicing (i.e., D2-short/-long isoforms). Moderated mediation analyses explored group differences in relationships between this DRD2 haplotype, three structural brain networks which subsume the identified cortical regions of interest (frontoparietal, dorsal-attention, and ventral-attention), and three cognitive indices (intelligence, attention, and immediate memory). Controls who were homozygous for the DRD2 major haplotype demonstrated greater cognitive performance as a result of dorsal-attention network mediation. However, this association was absent in the 'at-risk' group. This study provides the first evidence of a functional DRD2-brain-cognition pathway. The absence of typical brain-cognition relationships in young 'at-risk' individuals may reflect biological differences that precede illness onset. Further insight into early pathogenic processes may facilitate targeted early interventions.

Using structural MRI to identify bipolar disorders - 13 site machine learning study in 3020 individuals from the ENIGMA Bipolar Disorders Working Group.

Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47-67.00, ROC-AUC = 71.49%, 95% CI = 69.39-73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70-60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen's Kappa = 0.83, 95% CI = 0.829-0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data.

The Impact of Childhood Adversity on Cognitive Development in Schizophrenia.

Childhood adversity, such as physical, sexual, and verbal abuse, as well as neglect and family conflict, is a risk factor for schizophrenia. Such adversity can lead to disruptions of cognitive function during development, undermining intellectual capabilities and academic achievement. Schizophrenia is a neurodevelopmental disorder that is associated with cognitive impairments that may become evident during childhood. The Australian Schizophrenia Research Bank database comprises a large community cohort (N = 1169) in which we previously identified 3 distinct cognitive groups among people with schizophrenia: (1) Compromised, current, and estimated premorbid cognitive impairment; (2) Deteriorated, substantial decline from estimated premorbid function; and (3) Preserved, performing in the normal cognitive range without decline. The compromised group displayed the worst functional and symptom outcomes. Here, we extend our previous work by assessing the relationship among these categories of cognitive abilities and reported childhood adversity in 836 patients and healthy controls. Exploratory factor analysis of the Childhood Adversity Questionnaire revealed 3 factors (lack of parental involvement; overt abuse; family breakdown and hardship). People with schizophrenia reported significantly more childhood adversity than healthy controls on all items and factors. People with schizophrenia in the compromised group reported significantly more lack of parental involvement and family breakdown and hardship and lower socioeconomic status than those in the deteriorated group. The cognitive groups were not related to family history of psychosis. These findings identify specific social and family factors that impact cognition, highlighting the important role of these factors in the development of cognitive and functional abilities in schizophrenia.

Cognitive reserve attenuates age-related cognitive decline in the context of putatively accelerated brain ageing in schizophrenia-spectrum disorders.

BACKGROUND: In schizophrenia, relative stability in the magnitude of cognitive deficits across age and illness duration is inconsistent with the evidence of accelerated deterioration in brain regions known to support these functions. These discrepant brain-cognition outcomes may be explained by variability in cognitive reserve (CR), which in neurological disorders has been shown to buffer against brain pathology and minimize its impact on cognitive or clinical indicators of illness. METHODS: Age-related change in fluid reasoning, working memory and frontal brain volume, area and thickness were mapped using regression analysis in 214 individuals with schizophrenia or schizoaffective disorder and 168 healthy controls. In patients, these changes were modelled as a function of CR. RESULTS: Patients showed exaggerated age-related decline in brain structure, but not fluid reasoning compared to controls. In the patient group, no moderation of age-related brain structural change by CR was evident. However, age-related cognitive change was moderated by CR, such that only patients with low CR showed evidence of exaggerated fluid reasoning decline that paralleled the exaggerated age-related deterioration of underpinning brain structures seen in all patients. CONCLUSIONS: In schizophrenia-spectrum illness, CR may negate ageing effects on fluid reasoning by buffering against pathologically exaggerated structural brain deterioration through some form of compensation. CR may represent an important modifier that could explain inconsistencies in brain structure - cognition outcomes in the extant literature.

ParentWorks: Evaluation of an Online, Father-Inclusive, Universal Parenting Intervention to Reduce Child Conduct Problems.

Evidence-based parenting interventions are effective in reducing conduct problems, yet these interventions have limited reach, and few involve the participation of fathers. This paper describes the outcomes of an open trial of ParentWorks, a universal, online, father-inclusive parenting intervention aiming to decrease childhood behavioural problems and promote positive parenting in mothers and fathers. A total of 388 families (456 individual parents; 36.6% fathers) were included in the study. Mixed model analyses showed significant decreases in child emotional/behavioural problems, dysfunctional parenting, interparental conflict, and parental mental health problems. The baseline severity of child behavioural problems significantly moderated the effects on child outcomes so that children with higher levels of problems benefitted more from the program. Participation of both caregivers in two-parent families, as well as parent sex, did not significantly affect the program outcomes. Results provide initial empirical support for the universal, self-directed, online parenting intervention, in addressing both child behavioural problems and parenting outcomes. Trial registration: ACTRN12616001223426, registered 05/09/2016.

Increased plasma Brain-Derived Neurotrophic Factor (BDNF) levels in females with schizophrenia.

Brain-Derived Neurotrophic Factor (BDNF) acts as a critical regulator of synaptogenesis and synaptic plasticity. Sex differences have been demonstrated in many aspects of schizophrenia. This study tested for sex-specific differences in peripheral BDNF levels in people with schizophrenia and healthy controls. We measured circulating plasma BDNF levels in 95 people with schizophrenia and 80 healthy controls. Plasma BDNF levels were significantly elevated in females with schizophrenia compared to males with schizophrenia and to female healthy controls. These results suggest that sex differences in peripheral BDNF levels may contribute to other sex related differences in schizophrenia.

Proton magnetic resonance spectroscopic imaging of gray and white matter in bipolar-I and schizophrenia.

BACKGROUND: Glutamine plus glutamate (Glx), as well as N-acetylaspartate compounds, (NAAc), a marker of neuronal viability, are quantified with proton magnetic resonance spectroscopy (1H-MRS) and have been reported altered in psychotic disorders. However, few studies have compared these neurometabolites in bipolar disorder and schizophrenia. METHODS: Used 1H-MRS imaging from an axial supraventricular slab of gray matter (GM; medial-frontal and medial-parietal) and white matter (WM; bilateral-frontal and bilateral-parietal) voxels. Bipolar-I with history of psychosis (N = 43), schizophrenia (N = 41) and healthy controls (HC; N = 45) were studied (age range: 17-65). RESULTS: Amongst younger (age ≤40 years-median split) bipolar-I vs HC subjects Glx was increased (p < 0.001), while NAAc was reduced in WM (p < 0.001). In GM, NAAc (p < 0.001) and myo-inositol (p = 0.002) were reduced. Amongst older bipolar-I (vs HC) in WM regions we found reductions in: NAAc (p < 0.001), glycerophospho-choline + phospho-choline (p < 0.001), creatine + phospho-creatine (p < 0.001) and myo-inositol (p < 0.001); in GM only Glx was increased (p < 0.005). Contrasts between bipolar-I and schizophrenia produced fewer results: amongst younger subjects, reduced NAAc (p < 0.001) in WM and lower myo-inositol in GM (p = 0.04) in bipolar-I vs schizophrenia. In the older patients, bipolar-I had lower GM NAAc (p = 0.009) than schizophrenia. LIMITATIONS: First, differential exposure to antipsychotic and mood stabilizing medication across the groups. Second, differences in substance use histories among the groups. Third, neglect of peripheral and ventral cortical and subcortical regions. Finally, limited power to detect bipolar/schizophrenia differences. CONCLUSIONS: Chronically-treated bipolar-I have increased Glx and reduced NAAc, suggestive of neuronal dysfunction. The NAAc reductions are more severe in bipolar-I than in schizophrenia patients.

Keeping Parents Involved: Predicting Attrition in a Self-Directed, Online Program for Childhood Conduct Problems.

Positive parenting programs have a strong evidence base for improving parent-child relationships, strengthening families, and reducing childhood behavior disturbances. Their reach is less than optimal however, with only a minority of families in need of help participating. Father involvement is particularly low. Online, self-directed programs have the potential to improve participation rates. This article examines risk factors for dropout/attrition from a free, evidence-based, self-directed, father-inclusive parenting program, Parentworks, which was made available across Australia. Parents (N = 2,967) enrolled in the program and completed preintervention questionnaires. There was a steady and consistent loss of participants through the sequence of core program modules, until a final sample of 218 completed the postintervention questionnaire. A range of demographic and parent and child variables were tested as predictors of 3 subgroups: nonstarters, partial completers, and full completers. Nonstarters (n = 1,625) tended to have older children with fewer behavioral problems and report higher psychopathology and dysfunctional parenting than those who partially (n = 1,124) or fully completed. Contrary to findings from face-to-face research, single parents had the highest completion rates. Coparticipation of partners and interparental conflict had no impact on completion rates. Fathers participated at relatively high levels. Results show that parents with the greatest need tend to engage with online programs, and online programs may be particularly useful for fathers, single parents, and those in conflicted relationships. Directions for future program design and research are discussed.

The promise of functional near-infrared spectroscopy in autism research: What do we know and where do we go?

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique that has been gaining increasing interest as a method to investigate the brain function of individuals on the autism spectrum. It is a non-invasive, portable and relatively motion-tolerant method of measuring haemodynamic activity in the brain. fNIRS can be particularly effective for quantifying brain function in challenging clinical populations. In light of this, there is a growing body of fNIRS literature focusing on individuals on the autism spectrum. The aim of this review is to evaluate and summarise key studies from the literature and discuss their implications for the field. Potential limitations of the fNIRS approach and resolution of these issues based on emerging fNIRS research are also discussed.

Evaluation of 'The Father Effect' Media Campaign to Increase Awareness of, and Participation in, an Online Father-Inclusive Parenting Program.

There is substantial evidence that parenting programs are effective in improving parenting and child mental health outcomes. While there is increasing focus on delivering parenting interventions online to increase their reach and dissemination, fathers are underrepresented in all formats of parenting programs. However, research suggests that father participation is important for intervention effectiveness. This study evaluated the effectiveness of a media campaign for increasing awareness of, and participation in, an online father-inclusive parenting program called 'ParentWorks'. An 8-week campaign was conducted in Australia via social media channels, digital display advertising, digital television, and radio. To assess the impact of the campaign, data were obtained from caregivers registering for ParentWorks during the campaign period (n = 848) and an 8-week comparison period that occurred 3 months later (n = 254). Additionally, a nationally representative sample of 2021 caregivers of children aged 2-16 years completed an online survey. Survey questions asked about exposure to the campaign, registration for participation in ParentWorks, and knowledge of the importance of father participation in parenting programs. Three times as many caregivers registered during the 8-week media campaign compared to the comparison period, and a significantly greater proportion of male caregivers registered in the campaign versus the comparison period. The online survey found that 11% of caregivers reported exposure to the campaign, and significantly more fathers than mothers reported exposure. Results showed that those who were exposed to the campaign were significantly more likely to endorse the importance of father participation in parenting programs, than those not exposed to the campaign. The findings indicate that media campaigns appear to be an effective method of increasing awareness of online parenting programs and enhancing rates of father involvement.

Spatial dynamics within and between brain functional domains: A hierarchical approach to study time-varying brain function.

The analysis of time-varying activity and connectivity patterns (i.e., the chronnectome) using resting-state magnetic resonance imaging has become an important part of ongoing neuroscience discussions. The majority of previous work has focused on variations of temporal coupling among fixed spatial nodes or transition of the dominant activity/connectivity pattern over time. Here, we introduce an approach to capture spatial dynamics within functional domains (FDs), as well as temporal dynamics within and between FDs. The approach models the brain as a hierarchical functional architecture with different levels of granularity, where lower levels have higher functional homogeneity and less dynamic behavior and higher levels have less homogeneity and more dynamic behavior. First, a high-order spatial independent component analysis is used to approximate functional units. A functional unit is a pattern of regions with very similar functional activity over time. Next, functional units are used to construct FDs. Finally, functional modules (FMs) are calculated from FDs, providing an overall view of brain dynamics. Results highlight the spatial fluidity within FDs, including a broad spectrum of changes in regional associations, from strong coupling to complete decoupling. Moreover, FMs capture the dynamic interplay between FDs. Patients with schizophrenia show transient reductions in functional activity and state connectivity across several FDs, particularly the subcortical domain. Activity and connectivity differences convey unique information in many cases (e.g., the default mode) highlighting their complementarity information. The proposed hierarchical model to capture FD spatiotemporal variations provides new insight into the macroscale chronnectome and identifies changes hidden from existing approaches.

Development and Psychometric Evaluation of the Father Engagement Questionnaire.

While there has been increasing interest in promoting father engagement in parenting interventions for child wellbeing, both research and practice endeavors have been hindered by a lack of a measure of father engagement practices. This paper reports the development and evaluation of a comprehensive, practitioner-report measure of father engagement practices--the Father Engagement Questionnaire (FEQ). Practitioners (N = 589; 84.5% females; mean age = 38.56) involved in delivering parenting interventions in Australia completed the FEQ, along with background demographics and questions regarding their own and organization's practice. A separate sample of 28 practitioners completed the FEQ twice, with a two-week interim, to assess test-retest stability of the measure. Exploratory factor analysis revealed five factors corresponding to the measure's five intended content areas: Confidence in Working with Fathers, Competence in Using Engagement Strategies, Perceived Effectiveness of Engagement Strategies, Frequency of Strategy Use, and Organizational Practices for Father Engagement. Each of these scales demonstrated adequate internal consistency reliability and test-retest stability. As the five scales appear to be related but distinct, it is recommended that the FEQ is used as a multidimensional measure of father engagement. In terms of predictive validity, higher scores on the Confidence in Working with Fathers, Frequency of Strategy Use, and Organizational Practices for Father Engagement scales were associated with a higher likelihood of practitioner-reported father attendance. The results provide support for adequate psychometric properties of the FEQ as a research and clinical tool for assessing and monitoring father engagement practices.

Exploring the moderating effects of dopaminergic polymorphisms and childhood adversity on brain morphology in schizophrenia-spectrum disorders.

Genetic and environmental etiologies may contribute to schizophrenia and its associated neurobiological profile. We examined the interaction between dopaminergic polymorphisms, childhood adversity and diagnosis (schizophrenia/schizoaffective disorder) on dopamine-related brain structures. Childhood adversity histories and structural MRI data were obtained from 249 (153 schizophrenia/schizoaffective, 96 controls) participants registered in the Australian Schizophrenia Research Bank. Polymorphisms in DRD2 and COMT were genotyped and a dopaminergic risk allelic load (RAL) was calculated. Regression analysis was used to test the main and interaction effects of RAL, childhood adversity and diagnosis on volumes of dopamine-related brain structures (caudate, putamen, nucleus accumbens, dorsolateral prefrontal cortex and hippocampus). A schizophrenia/schizoaffective diagnosis showed significant main effects on bilateral hippocampus, left dorsolateral prefrontal cortex and bilateral putamen volumes. RAL showed a significant main effect on left putamen volumes. Furthermore, across the whole sample, a significant two-way interaction between dopaminergic RAL and childhood adversity was found for left putamen volumes. No brain structure volumes were predicted by a three-way interaction that included diagnosis. Our finding suggests the left putamen may be particularly sensitive to dopaminergic gene-environment interactions regardless of diagnosis. However, larger studies are needed to assess whether these interactions are more or less pronounced in those with schizophrenia/schizoaffective disorders.

The effects of a muscarinic receptor 1 gene variant on cortical thickness and surface area in schizophrenia.

Individuals with schizophrenia who are homozygous at the c.267C>A single nucleotide polymorphism (rs2067477) within the cholinergic muscarinic M1 receptor gene have been reported to perform less well on the Wisconsin Card Sorting Test and demonstrate reduced grey matter volume in the right precentral gyrus. We investigated if rs2067477 genotype variation influenced cortical thickness and cortical surface area in a sample of 176 schizophrenia/schizoaffective disorder patients using FreeSurfer. We were unable to detect any significant changes to either surface-based measure of brain structure across genotype. Future studies should expand the focus and include SNPs that are in linkage disequilibrium with rs2067477.