Prenatal maternal Inflammation, childhood cognition and adolescent depressive symptoms.

BACKGROUND: Accumulating evidence indicates that higher prenatal maternal inflammation is associated with increased depression risk in adolescent and adult-aged offspring. Prenatal maternal inflammation (PNMI) may increase the likelihood for offspring to have lower cognitive performance, which, in turn, may heighten risk for depression onset. Therefore, this study explored the potential mediating role of childhood cognitive performance in the relationship between PNMI and adolescent depressive symptoms in offspring. METHODS: Participants included 696 mother-offspring dyads from the Child Health and Development Studies (CHDS) cohort. Biomarkers of maternal inflammation [interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1RA) and soluble TNF receptor-II (sTNF-RII)] were assayed from first (T1) and second trimester (T2) sera. Childhood (ages 9-11) cognitive performance was assessed via standardized Peabody Picture Vocabulary Test (PPVT), a measure of receptive vocabulary correlated with general intelligence. Adolescent (ages 15-17) depressive symptoms were assessed via self-report. RESULTS: There were no significant associations between T1 biomarkers and childhood PPVT or adolescent depressive symptoms. Higher T2 IL1-RA was directly associated with lower childhood PPVT (b = -0.21, SE = 0.08, t = -2.55, p = 0.01), but not with adolescent depressive symptoms. T2 IL-6 was not directly associated with childhood PPVT, but higher T2 IL-6 was directly associated at borderline significance with greater depressive symptoms in adolescence (b = 0.05, SE = 0.03, t = 1.96, p = 0.05). Lower childhood PPVT predicted significantly higher adolescent depressive symptoms (b = -0.07, SE = 0.02, t = -2.99, p < 0.01). There was a significant indirect effect of T2 IL-1RA on adolescent depressive symptoms via childhood PPVT (b = 0.03, 95 % CI = 0.002-0.03) indicating a partially mediated effect. No significant associations were found with T2 sTNF-RII nor IL-8. CONCLUSIONS: Lower childhood cognitive performance, such as that indicated by a lower PPVT score, represents a potential mechanism through which prenatal maternal inflammation contributes to adolescent depression risk in offspring.

Childhood trauma, perceived stress and anhedonia in individuals at clinical high risk for psychosis: multigroup mediation analysis.

BACKGROUND: Evidence suggests that both childhood trauma and perceived stress are risk factors for the development of psychosis, as well as negative symptoms such as anhedonia. Previous findings link increases in perceived stress to anhedonia in individuals at clinical high risk for psychosis (CHR) and depression; however, the role of childhood trauma in this relationship has not yet been explored, despite consistent evidence that it is associated with sensitisation to later stress. AIMS: To examine whether perceived stress mediates the relationship between childhood trauma and anhedonia in a group of youth at CHR as well as in controls (groups with depression and with no diagnosed mental health concerns). METHOD: The study used multigroup mediation to examine the indirect effects of childhood trauma on anhedonia via perceived stress in CHR (n = 117) and depression groups (n = 284) and non-psychiatric controls (n = 124). RESULTS: Perceived stress mediated the relationship between childhood trauma and consummatory anhedonia regardless of group status. Perceived stress mediated the relationship between childhood trauma and anticipatory anhedonia for the CHR and depression groups, but not for non-psychiatric controls. Further, groups differed in the magnitude of this relationship, with the effects trending towards stronger for those in the CHR group. CONCLUSIONS: Our findings suggest a potential transdiagnostic pathway through which childhood trauma contributes to anhedonia across severe mental illness.

Psychosis risk is associated with decreased resting-state functional connectivity between the striatum and the default mode network.

Psychosis is linked to aberrant salience or to viewing neutral stimuli as self-relevant, suggesting a possible impairment in self-relevance processing. Psychosis is also associated with increased dopamine in the dorsal striatum, especially the anterior caudate (Kegeles et al., 2010). Critically, the anterior caudate is especially connected to (a) the cortical default mode network (DMN), centrally involved in self-relevance processing, and (b) to a lesser extent, the cortical frontoparietal network (FPN; Choi, Yeo, & Buckner, 2012). However, no previous study has directly examined striatal-cortical DMN connectivity in psychosis risk. In Study 1, we examined resting-state functional connectivity in psychosis risk (n = 18) and control (n = 19) groups between (a) striatal DMN and FPN subregions and (b) cortical DMN and FPN. The psychosis risk group exhibited decreased connectivity between the striatal subregions and the cortical DMN. In contrast, the psychosis risk group exhibited intact connectivity between the striatal subregions and the cortical FPN. Additionally, recent distress was also associated with decreased striatal-cortical DMN connectivity. In Study 2, to determine whether the decreased striatal-cortical DMN connectivity was specific to psychosis risk or was related to recent distress more generally, we examined the relationship between connectivity and distress in individuals diagnosed with nonpsychotic emotional distress disorders (N = 25). In contrast to Study 1, here we found that distress was associated with evidence of increased striatal-cortical DMN connectivity. Overall, the present results suggest that decreased striatal-cortical DMN connectivity is associated with psychosis risk and could contribute to aberrant salience.

Working memory performance is related to childhood trauma but not psychotic-like experiences in a nonpsychiatric sample.

OBJECTIVE: This project seeks to clarify the impact of childhood trauma and psychotic-like experiences (PLEs) on working memory (WM) and explore gender differences in these relationships. The effect of childhood trauma on WM performance has yet to be explored in individuals with PLEs, despite consistent associations between trauma, psychosis spectrum symptoms, and WM performance. METHOD: In 466 undergraduates, positive PLEs (Prodromal Questionnaire) and trauma (Childhood Trauma Questionnaire) were examined to determine contributions to WM performance on a spatial n-back task. We conducted hierarchical linear regressions on the total sample and stratified by gender to examine the effects of childhood trauma, positive PLEs, and their interaction on WM performance. Supplemental analyses explored attenuated negative and disorganized symptoms. RESULTS: Controlling for age, there were no significant main effects of positive PLEs, childhood trauma, their interaction, or three-way interaction including gender in predicting WM. After stratifying by gender, childhood trauma was significantly associated with poorer WM in females only. Post hoc analyses revealed that in the full sample, physical neglect predicted WM performance and was a trend for females, while sexual abuse trended toward predicting WM in males. Supplemental analyses of attenuated negative and disorganized symptoms revealed childhood trauma significantly predicted WM in the full sample and females only for negative symptoms. CONCLUSIONS: Females who have experienced childhood trauma may be at greater risk for WM problems, irrespective of co-occurring PLEs, suggesting that cognitive difficulties may be partially attributable to history of trauma. These findings have potential implications for intervention strategies in trauma-exposed individuals. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Environmental Risk Factors and Cognitive Outcomes in Psychosis: Pre-, Perinatal, and Early Life Adversity.

Risk for psychosis begins to accumulate as early as the fetal period through exposure to obstetric complications like fetal hypoxia, maternal stress, and prenatal infection. Stressors in the postnatal period, such as childhood trauma, peer victimization, and neighborhood-level adversity, further increase susceptibility for psychosis. Cognitive difficulties are among the first symptoms to emerge in individuals who go on to develop a psychotic disorder. We review the relationship between pre-, perinatal, and early childhood adversities and cognitive outcomes in individuals with psychosis. Current evidence shows that the aforementioned environmental risk factors may be linked to lower overall intelligence and executive dysfunction, beginning in the premorbid period and persisting into adulthood in individuals with psychosis. It is likely that early life stress contributes to cognitive difficulties in psychosis through dysregulation of the body's response to stress, causing changes such as increased cortisol levels and chronic immune activation, which can negatively impact neurodevelopment. Intersectional aspects of identity (e.g., sex/gender, race/ethnicity), as well as gene-environment interactions, likely inform the developmental cascade to cognitive difficulties throughout the course of psychotic disorders and are reviewed below. Prospective studies of birth cohorts will serve to further clarify the relationship between early-life environmental risk factors and cognitive outcomes in the developmental course of psychotic disorders. Specific methodological recommendations are provided for future research.

Examining Specificity of Neural Correlates of Childhood Psychotic-like Experiences During an Emotional n-Back Task.

BACKGROUND: Psychotic-like experiences (PLEs) during childhood are associated with greater risk of developing a psychotic disorder in adulthood, highlighting the importance of identifying neural correlates of childhood PLEs. Furthermore, impairment of cognitive functions, such as working memory and emotion regulation, has also been linked to psychosis risk as well as to disruptions in several brain regions. However, impairments in these domains have also been linked to other disorders, including depression. Therefore, the aim of the current study was to examine whether neural impairments in regions associated with working memory and implicit emotion regulation impairments are specific to PLEs versus depression. METHODS: The current study used an emotional n-back task to examine the relationship between childhood PLEs and neural activation of regions involved in both working memory and implicit emotion regulation using data from 8805 9- to 11-year-olds in the Adolescent Brain Cognitive Development (ABCD) Study 2.0 release. To examine specificity, we also analyzed associations with depressive symptoms. RESULTS: Our results indicated that increased PLEs during middle childhood were associated with decreased activation of the dorsolateral prefrontal cortex, striatum, and pallidum during trials requiring working memory. In contrast, increased activation of the parahippocampus, caudate, nucleus accumbens, and rostral anterior cingulate during face-viewing trials was associated with increased depressive symptoms. CONCLUSIONS: These results support the dimensional view of psychosis across the lifespan, providing evidence that neural correlates of PLEs, such as decreased activation during working memory, are present during middle childhood. Furthermore, these correlates are specific to psychotic-like symptoms as compared with depressive symptoms.

Resting-State Functional Connectivity and Psychotic-like Experiences in Childhood: Results From the Adolescent Brain Cognitive Development Study.

BACKGROUND: Psychotic-like experiences (PLEs) during childhood are associated with greater risk of developing a psychotic disorder (and other mental disorders), highlighting the importance of identifying neural correlates of childhood PLEs. Three major cortical networks-the cingulo-opercular network (CON), default mode network (DMN), and frontoparietal network-are consistently implicated in psychosis and PLEs in adults. However, it is unclear whether variation in functional connectivity is associated with PLEs in school-aged children. METHODS: Using hierarchical linear models, we examined the relationships between childhood PLEs and resting-state functional connectivity of the CON, DMN, and frontoparietal network, as well as the other networks, using an a priori network parcellation, using data from 9- to 11-year-olds (n = 3434) in the ABCD (Adolescent Brain Cognitive Development) study. We examined within-network, between-network, and subcortical connectivity. RESULTS: Decreased CON and DMN connectivity, as well as cinguloparietal (CPAR) network connectivity, were associated with greater PLEs, even after accounting for family history of psychotic disorders, internalizing symptoms, and cognitive performance. Decreased DMN connectivity was more strongly associated with increased delusional ideation, whereas decreased CON connectivity was more strongly associated with increased perceptual distortions. Increased CON-cerebellar and decreased CPAR-cerebellar connectivity were also associated with increased PLEs, and CPAR-cerebellar connectivity was more strongly associated with increased perceptual distortions. CONCLUSIONS: Consistent with hypotheses about the dimensionality of psychosis, our results provide novel evidence that neural correlates of PLEs, such as reduced functional connectivity of higher-order cognitive networks, are present even in school-aged children. The results provide further validation for continuity of PLEs across the life span.