Predictive modeling of optimism bias using gray matter cortical thickness.

People have been shown to be optimistically biased when their future outcome expectancies are assessed. In fact, we display optimism bias (OB) toward our own success when compared to a rival individual's (personal OB [POB]). Similarly, success expectancies for social groups we like reliably exceed those we mention for a rival group (social OB [SOB]). Recent findings suggest the existence of neural underpinnings for OB. Mostly using structural/functional MRI, these findings rely on voxel-based mass-univariate analyses. While these results remain associative in nature, an open question abides whether MRI information can accurately predict OB. In this study, we hence used predictive modelling to forecast the two OBs. The biases were quantified using a validated soccer paradigm, where personal (self versus rival) and social (in-group versus out-group) forms of OB were extracted at the participant level. Later, using gray matter cortical thickness, we predicted POB and SOB via machine-learning. Our model explained 17% variance (R2 = 0.17) in individual variability for POB (but not SOB). Key predictors involved the rostral-caudal anterior cingulate cortex, pars orbitalis and entorhinal cortex-areas that have been associated with OB before. We need such predictive models on a larger scale, to help us better understand positive psychology and individual well-being.

Optimism bias and its relation to scenario valence, gender, sociality, and insecure attachment.

Optimism bias refers to the tendency to display unjustified high/low expectations of future positive/negative events. This study asked 202 participants to estimate the likelihood of 96 different events. We investigated optimism biases for both oneself and the general population, and how these biases are influenced by gender, valence of the event, sociality of the event, as well as attachment anxiety and attachment avoidance. We found that sociality interacted with gender, with the difference in optimism bias for social vs. alone events being larger among women than among men. Attachment anxiety mainly reduced the optimism bias among men deliberating over future alone situations, while attachment avoidance primarily reduced optimism bias among female respondents deliberating over future social interactions. These results may have implications for the well-being and motivation of differently attached men and women and ultimately inspire psychotherapy interventions.

The relationship of maternal and child methylation of the glucocorticoid receptor NR3C1 during early childhood and subsequent child psychopathology at school-age in the context of maternal interpersonal violence-related post-traumatic stress disorder.

Introduction: Interpersonal violent (IPV) experiences when they begin in childhood and continue in various forms during adulthood often lead to chronic post-traumatic stress disorder (PTSD) that is associated in multiple studies with hypocortisolism and lower percentage of methylation of the promoter region of the gene coding for the glucocorticoid receptor (NR3C1). This prospective, longitudinal study examined the relationship of NR3C1 methylation among mothers with IPV-related PTSD and their toddlers and then looked at the relationship of maternal NR3C1 methylation and child psychopathology at school age. Methods: Forty-eight mothers were evaluated for life-events history and post-traumatic stress disorder via structured clinical interview when their children were ages 12-42 months (mean age 26.7 months, SD 8.8). Their children's psychopathology in terms of internalizing symptoms and externalizing behaviors was evaluated using the Child Behavior Checklist at ages 5-9 years (mean age 7 years, SD 1.1). Percentage of methylation for the NR3C1 gene promoter region was assessed from DNA extracted from maternal and child saliva using bisulfite pyrosequencing. Data analysis involved parametric and non-parametric correlations and multiple linear and logistic regression modeling. Results: Logistic regression models using child NR3C1 methylation as the dependent variable and maternal NR3C1 methylation and PTSD group status as predictors, as well as the interaction indicated that all three of these significantly predicted child NR3C1 methylation. These findings remained significant when controlling for child age, sex and maternal child abuse history. Overall, maternal NR3C1 methylation when children were toddlers was negatively and significantly associated with child externalizing behavior severity at school age. Discussion: We found that correlations between mothers and their children of NR3C1 methylation levels overall and at all individual CpG sites of interest were significant only in the IPV-PTSD group. The latter findings support that NR3C1 methylation in mothers positively and statistically significantly correlates with NR3C1 methylation in their children only in presence of IPV-PTSD in the mothers. This maternal epigenetic signature with respect to this glucocorticoid receptor is significantly associated with child behavior that may well pose a risk for intergenerational transmission of violence and related psychopathology.

Families With Violence Exposure and the Intergenerational Transmission of Somatization.

Introduction: Adults who have histories of childhood trauma have been noted to display greater somatization, dissociative symptoms and affect dysregulation. What happens in the parent-child relationship when those traumatized children become parents? A potential link to somatization in the child has been suggested by several prior studies. Children who have early attachment disturbances had more physical complaints if their mothers displayed less maternal sensitivity during observed parent-child interactions. Yet, the intergenerational link between maternal and child somatization has not been sufficiently explored in a longitudinal study in order to understand the potential impact of maternal trauma history and related psychopathology on subsequent child somatization and psychopathology. Methods: This paper examined prospective, longitudinal data of 64 mother-toddler dyads (mean age = 2.4 years, SD = 0.7) who were later studied when children had a mean age of 7 years. Mothers with and without histories of interpersonal violence (IPV; physical/sexual abuse and/or family violence exposure) were included. Mothers with IPV histories were oversampled. Linear and Poisson regression models were used to test the associations between maternal IPV-related post-traumatic stress disorder (PTSD) with maternal somatization severity when children were toddlers, and between maternal somatization and maternal interactive behaviors with child somatization by maternal report and clinician-rated assessment at school-age. Results: Maternal PTSD severity was significantly associated with increased maternal somatization severity (p = 0.031). Maternal somatization severity during the child's early childhood predicted both maternal report of child somatization (p = 0.011) as well as child thought problems (p = 0.007) when children were school-aged. No association was found between maternal somatization and child-reported psychopathology. The study did not find that maternal alexithymia, caregiving behaviors or child exposure to violence contributed significantly to the model examining the association between maternal and child somatization. Conclusion: The results are in line with the hypothesis of intergenerational transmission of somatization in the context of IPV and related maternal PTSD during formative early development. We interpret this as an expression of psychological distress from mother to child, as maternal trauma and pathology affect the caregiving environment and, thus, the parent-child relationship. The authors conclude with a discussion of implications for parent-infant and early childhood intervention.

Impact of mothers' IPV-PTSD on their capacity to predict their child's emotional comprehension and its relationship to their child's psychopathology.

Background: Previous studies demonstrated that when the violence-exposed child becomes a mother and interacts with her own child during early sensitive periods for social-emotional development, she may have difficulties providing sensitive responsiveness to the child's emotional communication. Such difficulties place the child's development of emotional comprehension (EC) and related self-regulation at risk. The aim of this study was to examine how mothers' interpersonal violence-related posttraumatic disorder (IPV-PTSD) would affect their children's EC and their own ability to predict their children's EC. We also investigated how mothers' predictive ability would correlate with child psychopathology. Methods: Sixty-one mother-child dyads (36 with IPV-PTSD) participated in this study. Children's (mean age = 7.0 years, SD = 1.1) EC was assessed with the Test of Emotion Comprehension (child TEC) and their psychopathology as reported by the mother was assessed with the Child Behaviour Checklist (CBCL) and as evaluated by a clinician using selected modules of the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Mothers were measured for IPV-PTSD with the Clinician Administered PTSD Scale (CAPS) and for their capacity to predict their child's emotional comprehension (mother-responding-as-child TEC; mTEC). Results: We found no significant between-group differences in children's level of EC. Maternal PTSD was associated with lower scores on the mTEC, however. Reduced maternal scores on the mTEC were significantly associated with maternal report of increased aggressive child behaviour and with depression symptoms on the K-SADS. Further, scores on the mTEC interacted with maternal report of child aggression on child oppositional defiant disorder (ODD) symptoms on the K-SADS. Conclusion: These findings support that improving maternal emotional comprehension may help reduce child risk for psychiatric morbidity in this population.

Antecedentes: Los estudios previos demostraron que cuando la niña expuesta a violencia llega a ser madre e interactúa con su propio hijo durante periodos críticos tempranos para el desarrollo socioemocional, ella podría tener dificultades para brindar una respuesta sensible a la comunicación emocional del niño. Tales dificultades podrían poner en riesgo el desarrollo de la comprensión emocional del niño (CE) y la autorregulación asociada a ella. El objetivo de este estudio fue evaluar cómo el trastorno de estrés postraumático por violencia interpersonal de las madres (TEPT-VIF) podría afectar tanto la CE de sus hijos como su propia capacidad de predecir la CE en sus hijos. También investigamos cómo la capacidad predictiva de las madres podría correlacionarse con psicopatología infantil.Métodos: En este estudio participaron sesenta y una diadas madre-hijo (36 con TEPT-VIF). La CE de los niños (edad media = 7.0 años, DE = 1.1) fue evaluada mediante la prueba de Comprensión Emocional (TEC en sus siglas en inglés) del niño. Asimismo, la psicopatología del niño, según lo reportado por la madre, fue evaluada con la Lista de Chequeo Conductual del Niño (CBCL en sus siglas en inglés) y según la evaluación de un médico utilizando módulos seleccionados de la Escala Infantil para Trastornos Afectivos y Esquizofrenia (K-SADS por sus siglas en inglés). En las madres, se midió tanto el TEPT-VIF mediante la Escala para el Trastorno de Estrés Postraumático Administrada por el Clínico (CAPS en sus siglas en ingles) como su capacidad de predecir la comprensión emocional del niño mediante la prueba de Comprensión Emocional en la que la madre responde como el niño (mTEC en sus siglas en inglés).Resultados: No encontramos diferencias significativas entre los grupos en los niveles de CE de los niños. Sin embargo, el trastorno de estrés postraumático materno estuvo asociado a puntajes más bajos en el mTEC. Los puntajes maternos bajos en el mTEC estuvieron significativamente asociados en la K-SADS a un reporte materno de un aumento de la conducta agresiva del niño y a síntomas depresivos. Adicionalmente, los puntajes en el mTEC estuvieron relacionados en la K-SADS con un reporte materno de agresión del niño dentro de los síntomas del trastorno oposicionista desafiante (TOD).Conclusión: Estos hallazgos respaldan que el mejorar la comprensión emocional materna podría ayudar a disminuir el riesgo infantil de morbilidad psiquiátrica en esta población.

Multivariate patterns of brain-behavior associations across the adult lifespan.

The nature of brain-behavior covariations with increasing age is poorly understood. In the current study, we used a multivariate approach to investigate the covariation between behavioral-health variables and brain features across adulthood. We recruited healthy adults aged 20-73 years-old (29 younger, mean age = 25.6 years; 30 older, mean age = 62.5 years), and collected structural and functional MRI (s/fMRI) during a resting-state and three tasks. From the sMRI, we extracted cortical thickness and subcortical volumes; from the fMRI, we extracted activation peaks and functional network connectivity (FNC) for each task. We conducted canonical correlation analyses between behavioral-health variables and the sMRI, or the fMRI variables, across all participants. We found significant covariations for both types of neuroimaging phenotypes (ps = 0.0004) across all individuals, with cognitive capacity and age being the largest opposite contributors. We further identified different variables contributing to the models across phenotypes and age groups. Particularly, we found behavior was associated with different neuroimaging patterns between the younger and older groups. Higher cognitive capacity was supported by activation and FNC within the executive networks in the younger adults, while it was supported by the visual networks' FNC in the older adults. This study highlights how the brain-behavior covariations vary across adulthood and provides further support that cognitive performance relies on regional recruitment that differs between older and younger individuals.

Shared Neural Phenotypes for Mood and Anxiety Disorders A Meta-Analysis of 226 Task-Related Functional Imaging Studies.

(Appeared originally in JAMA Psychiatry 2020;77(2):172-179).

Associations Between Maternal Post-traumatic Stress Disorder and Traumatic Events With Child Psychopathology: Results From a Prospective Longitudinal Study.

Introduction: Exposure to interpersonal violence (IPV) can lead to post-traumatic stress disorder (PTSD) in mothers, and in turn adversely affect the mother-child relationship during early development, as well as the mental health of their children. Our objectives are to assess: (1) the association of maternal IPV-PTSD to child psychopathology, (2) the association of maternal IPV independently of PTSD to child psychopathology, and (3) the relationship between child exposure to violence to the psychopathology of these children. Methods: We used data from the longitudinal Geneva Early Childhood Stress Project. The sample included 64 children [mean age at Phase 1 = 2.4 (1.0-3.7) years] of mothers with or without IPV-PTSD. Data on mothers was collected during Phase 1, using the Clinical Administered PTSD Scale (CAPS), the Brief Physical and Sexual Abuse Questionnaire (BPSAQ) and the Conflict Tactics Scale (CTS2). Modules of a semi-structured diagnostic interview, and the Violence Exposure Scale were used to collect information on child at Phase 2, when children were older [mean age = 7.02 (4.7-10)]. Results: A higher CAPS score in mothers when children were toddler-age was associated with an increased risk of symptoms of attention deficit/hyperactivity disorder (ADHD; ß = 0.33, p = 0.014) and PTSD in school-age children. The association between maternal IPV-PTSD and child PTSD (ß = 0.48, p < 0.001) symptoms remained significant after adjustment for potential confounders. Among children, exposure to violence was associated with an increased risk of symptoms of generalized anxiety (ß = 0.37, p = 0.006), major depressive (ß = 0.24, p = 0.039), ADHD (ß = 0.27, p = 0.040), PTSD (ß = 0.52, p < 0.001), conduct (ß = 0.58, p = 0.003) and oppositional defiant (ß = 0.34, p = 0.032) disorders. Conclusion: Our longitudinal findings suggest that maternal IPV-PTSD during the period of child development exert an influence on the development of psychopathology in school-aged children. Mothers' IPV was associated with child psychopathology, independently of PTSD. Child lifetime exposure to violence had an additional impact on the development of psychopathology. Careful evaluation of maternal life-events is essential during early childhood to reduce the risk for the development of child psychopathology. Early efforts to curb exposure to violence in children and early intervention are both needed to reduce further risk for intergenerational transmission of trauma, violence, and related psychopathology.

Enhanced sensitivity to optimistic cues is manifested in brain structure: a voxel-based morphometry study.

Recent research shows that congruent outcomes are more rapidly (and incongruent less rapidly) detected when individuals receive optimistic rather than pessimistic cues, an effect that was termed optimism robustness. In the current voxel-based morphometry study, we examined whether optimism robustness has a counterpart in the brain structure. The participants' task was to detect two different letters (symbolizing monetary gain or loss) in a visual search matrix. Prior to each onset of the search matrix, two different verbal cues informed our participants about a high probability to gain (optimistic expectancy) or lose (pessimistic expectancy) money. The target presented was either congruent or incongruent with these induced expectancies. Optimism robustness revealed in the participants' reaction times correlated positively with gray matter volume (GMV) in brain regions involved in selective attention (medial visual association area, intraparietal sulcus), emphasizing the strong intertwinement of optimistic expectancies and attention deployment. In addition, GMV in the primary visual cortex diminished with increasing optimism robustness, in line with the interpretation of optimism robustness arising from a global, context-oriented perception. Future studies should address the malleability of these structural correlates of optimism robustness. Our results may assist in the identification of treatment targets in depression.

Linked patterns of biological and environmental covariation with brain structure in adolescence: a population-based longitudinal study.

Adolescence is a period of major brain reorganization shaped by biologically timed and by environmental factors. We sought to discover linked patterns of covariation between brain structural development and a wide array of these factors by leveraging data from the IMAGEN study, a longitudinal population-based cohort of adolescents. Brain structural measures and a comprehensive array of non-imaging features (relating to demographic, anthropometric, and psychosocial characteristics) were available on 1476 IMAGEN participants aged 14 years and from a subsample reassessed at age 19 years (n = 714). We applied sparse canonical correlation analyses (sCCA) to the cross-sectional and longitudinal data to extract modes with maximum covariation between neuroimaging and non-imaging measures. Separate sCCAs for cortical thickness, cortical surface area and subcortical volumes confirmed that each imaging phenotype was correlated with non-imaging features (sCCA r range: 0.30-0.65, all PFDR < 0.001). Total intracranial volume and global measures of cortical thickness and surface area had the highest canonical cross-loadings (|ρ| = 0.31-0.61). Age, physical growth and sex had the highest association with adolescent brain structure (|ρ| = 0.24-0.62); at baseline, further significant positive associations were noted for cognitive measures while negative associations were observed at both time points for prenatal parental smoking, life events, and negative affect and substance use in youth (|ρ| = 0.10-0.23). Sex, physical growth and age are the dominant influences on adolescent brain development. We highlight the persistent negative influences of prenatal parental smoking and youth substance use as they are modifiable and of relevance for public health initiatives.

Years of life lost due to the psychosocial consequences of COVID-19 mitigation strategies based on Swiss data.

BACKGROUND: The pandemic caused by coronavirus disease 2019 (COVID-19) has forced governments to implement strict social mitigation strategies to reduce the morbidity and mortality from acute infections. These strategies, however, carry a significant risk for mental health, which can lead to increased short-term and long-term mortality and is currently not included in modeling the impact of the pandemic. METHODS: We used years of life lost (YLL) as the main outcome measure, applied to Switzerland as an example. We focused on suicide, depression, alcohol use disorder, childhood trauma due to domestic violence, changes in marital status, and social isolation, as these are known to increase YLL in the context of imposed restriction in social contact and freedom of movement. We stipulated a minimum duration of mitigation of 3 months based on current public health plans. RESULTS: The study projects that the average person would suffer 0.205 YLL due to psychosocial consequence of COVID-19 mitigation measures. However, this loss would be entirely borne by 2.1% of the population, who will suffer an average of 9.79 YLL. CONCLUSIONS: The results presented here are likely to underestimate the true impact of the mitigation strategies on YLL. However, they highlight the need for public health models to expand their scope in order to provide better estimates of the risks and benefits of mitigation.

The effect of optimistic expectancies on attention bias: Neural and behavioral correlates.

Optimism bias and positive attention bias are important features of healthy information processing. Recent findings suggest dynamic bidirectional optimism-attention interactions, but the underlying neural mechanisms remain to be identified. The current functional magnetic resonance imaging (fMRI) study, therefore, investigated the neural mechanisms underlying causal effects of optimistic expectancies on attention. We hypothesized that expectancies guide attention to confirmatory evidence in the environment, with enhanced salience and executive control network (SN/ECN) activity for unexpected information. Moreover, based on previous findings, we anticipated optimistic expectancies to more strongly impact attention and SN/ECN activity than pessimistic expectancies. Expectancies were induced with visual cues in 50 participants; subsequent attention to reward and punishment was assessed in a visual search task. As hypothesized, cues shortened reaction times to expected information, and unexpected information enhanced SN/ECN activity. Notably, these effects were stronger for optimistic than pessimistic expectancy cues. Our findings suggest that optimistic expectancies involve particularly strong predictions of reward, causing automatic guidance of attention to reward and great surprise about unexpected punishment. Such great surprise may be counteracted by visual avoidance of the punishing evidence, as revealed by prior evidence, thereby reducing the need to update (over)optimistic reward expectancies.

Group membership dictates the neural correlates of social optimism biases.

Optimism bias, i.e. expecting the future to hold more desirable than undesirable outcomes, also extends to people that we like or admire. However, it remains unknown how the brain generates this social optimism bias. In this study, respondents estimated the likelihood of future desirable and undesirable outcomes for an in-group and three out-groups: warm-incompetent, cold-competent, and cold-incompetent. We found a strong social optimism bias for the in-group and the warm out-group and an inverted pattern for the cold-incompetent out-group. For all groups, scores of social optimism bias correlated with the brain activity in structures that respondents differentially engaged depending on the target social group. In line with our hypotheses, evaluating the in-group recruited the ventromedial prefrontal cortex and the precuneus/posterior cingulate cortex, whereas evaluating the warm out-group engaged the posterior insula, mid cingulate cortex, and somatosensory cortices. These findings suggest different underlying cognitive mechanisms of social optimism bias for these groups, despite similar behavioural patterns. Thinking about the cold out-groups recruited the right anterior temporal lobe, and temporoparietal junction. Evaluating the cold-incompetent out-group additionally recruited the anterior insula, inferior frontal cortex and dorsomedial frontal cortex. We discuss these neuroimaging findings with respect to their putative cognitive functions.

Baseline brain structural and functional predictors of clinical outcome in the early course of schizophrenia.

Although schizophrenia is considered a brain disorder, the role of brain organization for symptomatic improvement remains inadequately defined. We investigated the relationship between baseline brain morphology, resting-state network connectivity and clinical response after 24-weeks of antipsychotic treatment in patients with schizophrenia (n = 95) using integrated multivariate analyses. There was no significant association between clinical response and measures of cortical thickness (r = 0.37, p = 0.98) and subcortical volume (r = 0.56, p = 0.15). By contrast, we identified a strong mode of covariation linking functional network connectivity to clinical response (r = 0.70; p = 0.04), and particularly to improvement in positive (weight = 0.62) and anxious/depressive symptoms (weight = 0.49). Higher internal cohesiveness of the default mode network was the single most important positive predictor. Key negative predictors involved the functional cohesiveness of central executive subnetworks anchored in the frontoparietal cortices and subcortical regions (including the thalamus and striatum) and the inter-network integration between the default mode and sensorimotor networks. The present findings establish links between clinical response and the functional organization of brain networks involved both in perception and in spontaneous and goal-directed cognition, thereby advancing our understanding of the pathophysiology of schizophrenia.

Shared Neural Phenotypes for Mood and Anxiety Disorders: A Meta-analysis of 226 Task-Related Functional Imaging Studies.

Importance: Major depressive disorder, bipolar disorder, posttraumatic stress disorder, and anxiety disorders are highly comorbid and have shared clinical features. It is not yet known whether their clinical overlap is reflected at the neurobiological level. Objective: To detect transdiagnostic convergence in abnormalities in task-related brain activation. Data Source: Task-related functional magnetic resonance imaging articles published in PubMed, Web of Science, and Google Scholar during the last decade comparing control individuals with patients with mood, posttraumatic stress, and anxiety disorders were examined. Study Selection: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines, articles were selected if they reported stereotactic coordinates of whole-brain-based activation differences between adult patients and control individuals. Data Extraction and Synthesis: Coordinates of case-control differences coded by diagnosis and by cognitive domain based on the research domain criteria were analyzed using activation likelihood estimation. Main Outcomes and Measures: Identification of transdiagnostic clusters of aberrant activation and quantification of the contribution of diagnosis and cognitive domain to each cluster. Results: A total of 367 experiments (major depressive disorder, 149; bipolar disorder, 103; posttraumatic stress disorder, 55; and anxiety disorders, 60) were included comprising observations from 4507 patients and 4755 control individuals. Three right-sided clusters of hypoactivation were identified centered in the inferior prefrontal cortex/insula (volume, 2120 mm3), the inferior parietal lobule (volume, 1224 mm3), and the putamen (volume, 888 mm3); diagnostic differences were noted only in the putamen (χ23 = 8.66; P = .03), where hypoactivation was more likely in bipolar disorder (percentage contribution = 72.17%). Tasks associated with cognitive systems made the largest contribution to each cluster (percentage contributions >29%). Clusters of hyperactivation could only be detected using a less stringent threshold. These were centered in the perigenual/dorsal anterior cingulate cortex (volume, 2208 mm3), the left amygdala/parahippocampal gyrus (volume, 2008 mm3), and the left thalamus (volume, 1904 mm3). No diagnostic differences were observed (χ23 < 3.06; P > .38), while tasks associated with negative valence systems made the largest contribution to each cluster (percentage contributions >49%). All findings were robust to the moderator effects of age, sex, and magnetic field strength of the scanner and medication. Conclusions and Relevance: In mood disorders, posttraumatic stress disorder, and anxiety disorders, the most consistent transdiagnostic abnormalities in task-related brain activity converge in regions that are primarily associated with inhibitory control and salience processing. Targeting these shared neural phenotypes could potentially mitigate the risk of affective morbidity in the general population and improve outcomes in clinical populations.

Person-Based Brain Morphometric Similarity is Heritable and Correlates With Biological Features.

The characterization of the functional significance of interindividual variation in brain morphometry is a core aim of cognitive neuroscience. Prior research has focused on interindividual variation at the level of regional brain measures thus overlooking the fact that each individual brain is a person-specific ensemble of interdependent regions. To expand this line of inquiry we introduce the person-based similarity index (PBSI) for brain morphometry. The conceptual unit of the PBSI is the individual person's brain structural profile which considers all relevant morphometric measures as features of a single vector. In 2 independent cohorts (total of 1756 healthy participants), we demonstrate the foundational validity of this approach by affirming that the PBSI scores for subcortical volume and cortical thickness in healthy individuals differ between men and women, are heritable, and robust to variation in neuroimaging parameters, sample composition, and regional brain morphometry. Moreover, the PBSI scores correlate with age, body mass index, and fluid intelligence. Collectively, these results suggest that the person-based measures of brain morphometry are biologically and functionally meaningful and have the potential to advance the study of human variation in multivariate brain imaging phenotypes in healthy and clinical populations.

EEG recording during an emotional face-matching task in children of mothers with interpersonal violence-related posttraumatic stress disorder.

The aim of this study was to examine the effects of maternal interpersonal violence-related posttraumatic disorder (IPV-PTSD) on child appraisal of emotion, as measured by high-density electroencephalography (HD-EEG) during an Emotional Face-matching Task (EFMT). We recorded HD-EEG in 47 children of mothers with and without IPV-PTSD during an Emotional Face-matching Task (EFMT). Mothers and children each performed the EFMT. Behavioral results demonstrated that both mothers who were directly exposed to violent events, and their children, presented attentional bias toward negative emotions when processing facial stimuli. EEG findings confirmed differences in emotion appraisal between children of IPV-PTSD mothers and non-PTSD controls at scalp-level and in terms of source localization upon which children of IPV-PTSD mothers demonstrated decreased activation of the right dorsolateral prefrontal cortex (dlPFC) in response to angry and fearful faces as compared to non-PTSD children with respect to the N170 component. Our study, to our knowledge, is the first to show that maternal IPV-PTSD significantly affects a mother's own and her child's neural activity in response to facial expressions of negative emotion. These findings are potentially important to the development and study of effective interventions to interrupt intergenerational cycles of violence and trauma.

Initial Evidence for Brain Plasticity Following a Digital Therapeutic Intervention for Depression.

BACKGROUND: Digital therapeutics such as cognitive-emotional training have begun to show promise for the treatment of major depressive disorder. Available clinical trial data suggest that monotherapy with cognitive-emotional training using the Emotional Faces Memory Task is beneficial in reducing depressive symptoms in patients with major depressive disorder. The aim of this study was to investigate whether Emotional Faces Memory Task training for major depressive disorder is associated with changes in brain connectivity and whether changes in connectivity parameters are related to symptomatic improvement. METHODS: Fourteen major depressive disorder patients received Emotional Faces Memory Task training as monotherapy over a six-week period. Patients were scanned at baseline and posttreatment to identify changes in resting-state functional connectivity and effective connectivity during emotional working memory processing. RESULTS: Compared to baseline, patients showed posttreatment reduced connectivity within resting-state networks involved in self-referential and salience processing and greater integration across the functional connectome at rest. Moreover, we observed a posttreatment increase in the Emotional Faces Memory Task-induced modulation of connectivity between cortical control and limbic brain regions, which was associated with clinical improvement. DISCUSSION: These findings provide initial evidence that cognitive-emotional training may be associated with changes in short-term plasticity of brain networks implicated in major depressive disorder. CONCLUSION: Our findings pave the way for the principled design of large clinical and neuroimaging studies.

Multivariate Associations Among Behavioral, Clinical, and Multimodal Imaging Phenotypes in Patients With Psychosis.

Importance: Alterations in multiple neuroimaging phenotypes have been reported in psychotic disorders. However, neuroimaging measures can be influenced by factors that are not directly related to psychosis and may confound the interpretation of case-control differences. Therefore, a detailed characterization of the contribution of these factors to neuroimaging phenotypes in psychosis is warranted. Objective: To quantify the association between neuroimaging measures and behavioral, health, and demographic variables in psychosis using an integrated multivariate approach. Design, Setting, and Participants: This imaging study was conducted at a university research hospital from June 26, 2014, to March 9, 2017. High-resolution multimodal magnetic resonance imaging data were obtained from 100 patients with schizophrenia, 40 patients with bipolar disorder, and 50 healthy volunteers; computed were cortical thickness, subcortical volumes, white matter fractional anisotropy, task-related brain activation (during working memory and emotional recognition), and resting-state functional connectivity. Ascertained in all participants were nonimaging measures pertaining to clinical features, cognition, substance use, psychological trauma, physical activity, and body mass index. The association between imaging and nonimaging measures was modeled using sparse canonical correlation analysis with robust reliability testing. Main Outcomes and Measures: Multivariate patterns of the association between nonimaging and neuroimaging measures in patients with psychosis and healthy volunteers. Results: The analyses were performed in 92 patients with schizophrenia (23 female [25.0%]; mean [SD] age, 27.0 [7.6] years), 37 patients with bipolar disorder (12 female [32.4%]; mean [SD] age, 27.5 [8.1] years), and 48 healthy volunteers (20 female [41.7%]; mean [SD] age, 29.8 [8.5] years). The imaging and nonimaging data sets showed significant covariation (r = 0.63, P < .001), which was independent of diagnosis. Among the nonimaging variables examined, age (r = -0.53), IQ (r = 0.36), and body mass index (r = -0.25) were associated with multiple imaging phenotypes; cannabis use (r = 0.23) and other substance use (r = 0.33) were associated with subcortical volumes, and alcohol use was associated with white matter integrity (r = -0.15). Within the multivariate models, positive symptoms retained associations with the global neuroimaging (r = -0.13), the cortical thickness (r = -0.22), and the task-related activation variates (r = -0.18); negative symptoms were mostly associated with measures of subcortical volume (r = 0.23), and depression/anxiety was associated with measures of white matter integrity (r = 0.12). Conclusions and Relevance: Multivariate analyses provide a more accurate characterization of the association between brain alterations and psychosis because they enable the modeling of other key factors that influence neuroimaging phenotypes.

Maternal PTSD and corresponding neural activity mediate effects of child exposure to violence on child PTSD symptoms.

The aim of this study was to examine the relationship of maternal interpersonal violence-related posttraumatic stress disorder (IPV-PTSD), associated neural activity in response to mother-child relational stimuli, and child psychopathology indicators at child ages 12-42 months and one year later. The study tested the hypothesis that decreased maternal neural activity in regions that subserve emotion regulation would be associated with child symptoms associated with emotional dysregulation at both time points. Functional magnetic resonance imaging of 42 mothers with or without violence-exposure and associated IPV-PTSD were assessed. Their child's life-events and symptoms/behaviors indicative of high-risk subsequent PTSD diagnosis on a maternal-report questionnaire were measured one year later. Maternal IPV-PTSD severity was significantly associated with decreased ventromedial prefrontal cortex (vmPFC) activation in response to mother-child relational stimuli. Maternal IPV-PTSD severity and decreased vmPFC activation were then significantly associated with a child attachment disturbance at 12-42 months and symptoms/behaviors one year later, that were correlated with emotional dysregulation and risk for child PTSD. Maternal IPV-PTSD and child exposure to IPV were both predictive of child PTSD symptoms with maternal IPV-PTSD likely mediating the effects of child IPV exposure on child PTSD symptoms. These findings suggest that maternal IPV-PTSD severity and associated decreased vmPFC activity in response to mother-child relational stimuli are predictors of child psychopathology by age 12-42 months and one-year later. Significant findings in this paper may well be useful in understanding how maternal top-down cortico-limbic dysregulation promotes intergenerational transmission of IPV and related psychopathology and, thus should be targeted in treatment.