Longitudinal Functional Connectome in Pediatric Concussion: An Advancing Concussion Assessment in Pediatrics Study.

Advanced magnetic resonance imaging (MRI) techniques indicate that concussion (i.e., mild traumatic brain injury) disrupts brain structure and function in children. However, the functional connectivity of brain regions within global and local networks (i.e., functional connectome) is poorly understood in pediatric concussion. This prospective, longitudinal study addressed this gap using data from the largest neuroimaging study of pediatric concussion to date to study the functional connectome longitudinally after concussion as compared with mild orthopedic injury (OI). Children and adolescents (n = 967) 8-16.99 years with concussion or mild OI were recruited from pediatric emergency departments within 48 h post-injury. Pre-injury and 1-month post-injury symptom ratings were used to classify concussion with or without persistent symptoms based on reliable change. Subjects completed a post-acute (2-33 days) and chronic (3 or 6 months via random assignment) MRI scan. Graph theory metrics were derived from 918 resting-state functional MRI scans in 585 children (386 concussion/199 OI). Linear mixed-effects modeling was performed to assess group differences over time, correcting for multiple comparisons. Relative to OI, the global clustering coefficient was reduced at 3 months post-injury in older children with concussion and in females with concussion and persistent symptoms. Time post-injury and sex moderated group differences in local (regional) network metrics of several brain regions, including degree centrality, efficiency, and clustering coefficient of the angular gyrus, calcarine fissure, cuneus, and inferior occipital, lingual, middle occipital, post-central, and superior occipital gyrus. Relative to OI, degree centrality and nodal efficiency were reduced post-acutely, and nodal efficiency and clustering coefficient were reduced chronically after concussion (i.e., at 3 and 6 months post-injury in females; at 6 months post-injury in males). Functional network alterations were more robust and widespread chronically as opposed to post-acutely after concussion, and varied by sex, age, and symptom recovery at 1-month post-injury. Local network segregation reductions emerged globally (across the whole brain network) in older children and in females with poor recovery chronically after concussion. Reduced functioning between neighboring regions could negatively disrupt specialized information processing. Local network metric alterations were demonstrated in several posterior regions that are involved in vision and attention after concussion relative to OI. This indicates that functioning of superior parietal and occipital regions could be particularly susceptibile to the effects of concussion. Moreover, those regional alterations were especially apparent at later time periods post-injury, emerging after post-concussive symptoms resolved in most and persisted up to 6 months post-injury, and differed by biological sex. This indicates that neurobiological changes continue to occur up to 6 months after pediatric concussion, although changes emerge earlier in females than in males. Changes could reflect neural compensation mechanisms.

iCOPE With COVID-19: A Brief Telemental Health Intervention for Children and Adolescents During the COVID-19 Pandemic.

The COVID-19 pandemic has prompted extensive disruptions to the daily lives of children and adolescents worldwide, which has been associated with an increase in anxiety and depressive symptoms in youth. However, due to public health measures, in-person psychosocial care was initially reduced, causing barriers to mental health care access. This study investigated the feasibility, acceptability and preliminary effectiveness of iCOPE with COVID-19, a brief telemental health intervention for children and adolescents to address anxiety symptoms. Sessions were provided exclusively using videoconferencing technology. Feasibility and acceptability were measured with client satisfaction data. The main outcome measure for effectiveness was anxiety symptom severity measured using the Screen for Child Anxiety and Related Disorders (SCARED). Results indicated that the treatment was well accepted by participants. Significant reductions in anxiety were noted for social anxiety, and were observed to be trending towards a mean decrease for total anxiety. The findings suggest that this brief telemental health intervention focused on reducing anxiety related to COVID-19 is acceptable and feasible to children and adolescents. Future research using a large sample and with a longer follow-up period could inform whether symptom decreases are sustained over time.

Pragmatic Language Comprehension After Pediatric Traumatic Brain Injury: A Scoping Review.

OBJECTIVE: This scoping review aims to examine the literature pertaining to pragmatic language comprehension in pediatric traumatic brain injury (TBI), in order to summarize the current evidence and to identify areas for further research. METHODS: We searched MEDLINE Ovid and PsycINFO Ovid using search terms to identify all articles that examined pragmatic language comprehension in children and adolescents with TBI published until November 2017. RESULTS: A total of 13 articles met our inclusion criteria. The studies included examined a number of pragmatic domains including knowledge-based and pragmatic inferences, detection and judgment of ambiguous sentences, comprehension of humor, understanding of figurative language (eg, metaphors and idioms), and comprehension of irony and deceptive praise. CONCLUSION: The research suggests that children and adolescents with TBI, as compared with healthy or orthopedically injured controls, display deficits in comprehension of pragmatic language. Children with severe TBI demonstrate more widespread deficits in pragmatic comprehension abilities, whereas children with mild TBI show relatively intact pragmatic comprehension. Limitations and gaps identified in the literature warrant further research in this area.

Theory of Mind and Parental Nurturance as Predictors of Peer Relationships After Childhood Traumatic Brain Injury: A Test of Moderated Mediation.

OBJECTIVE: Traumatic brain injury (TBI) sustained in childhood is associated with poor social outcomes. This study investigated the role of theory of mind (ToM) as a mediator of the relation between TBI and peer rejection/victimization and reciprocated friendships, as well as the moderating effect of parental nurturance on those relationships. METHOD: Participants were children of 8-13 years old (M = 10.45, SD = 1.47), including 13 with severe TBI, 39 with complicated mild/moderate TBI, and 32 children with orthopedic injuries. Data on peer rejection/victimization and friendship were collected in school classrooms using the Extended Class Play and friendship nominations. Parents rated parental nurturance using the Child-Rearing Practices Report. Finally, ToM was measured based on children's average performance across three tasks measuring different aspects of ToM. RESULTS: Severe TBI was associated with poorer ToM, greater peer rejection/victimization, and fewer reciprocated friendships. ToM mediated the relation between severe TBI and peer rejection/victimization (i.e., severe TBI predicted poorer ToM, which in turn predicted greater rejection/victimization). Parental nurturance significantly moderated this relation, such that the mediating effect of ToM was significant only at low and average levels of parental nurturance, for both severe and complicated mild/moderate TBI groups. Neither the mediating effect of ToM nor the moderating effect of parental nurturance was significant for reciprocated friendships. CONCLUSION: High parental nurturance may mitigate the negative effects of ToM deficits on risk of peer rejection/victimization among children with TBI. Interventions designed to increase parental nurturance or ToM may promote better social outcomes among children with TBI.

Changes in symptom content from a clinical high-risk state to conversion to psychosis.

AIM: There is an interest in the transition to psychosis for those at clinical high risk of developing psychosis. This transition is typically determined by a change in severity of the attenuated symptoms as they reach a psychotic level. However, any concomitant change in the content of such symptoms has not been examined. The current study aimed to examine potential qualitative changes in the symptom content from a clinical high-risk state to a first episode of psychosis. METHODS: Sixty-seven individuals, who had been identified as meeting the attenuated psychotic syndrome based on the Structured Interview of Psychosis-Risk Syndromes and who later developed a full-blown psychosis were included in the study. Comprehensive clinical vignettes were written and raters were trained using the Content of Attenuated Psychotic Symptoms codebook to code for the presence of specific symptom content found within the attenuated psychotic symptoms of unusual thought content, suspicious ideas, grandiose ideas and perceptual abnormalities. RESULTS: Two main changes in symptom content from baseline to conversion were observed. First, content that was vague and lacked intensity progressed to being more specific, concrete and severe. Second, new symptoms appeared whose onset occurred for the first time at conversion. CONCLUSION: A change in symptom content should be monitored by clinicians, as changes in content may be indications of a possible transition to psychosis.

Biomarkers of adverse childhood experiences: A scoping review.

Adverse Childhood Experiences (ACEs) are stressful and/or traumatic experiences that occur during childhood. Research has demonstrated a link between ACEs and risk of physical and mental health disorders, where early life adversity may become "biologically embedded" and have wide-ranging effects on various physiological systems. The aim of this study was to identify the extent and breadth of recent research activity relating to biological measures of ACEs in adulthood. We undertook a scoping review including published research articles. Medline and PsycINFO were searched for articles from 2007 to July 2017. Articles were eligible if they included adult participants, were written in English, and reported on a biomarker of childhood adversity in adulthood. Forty articles met our inclusion criteria. Studies investigated a range of ACEs that were often measured retrospectively. The studies identified biomarkers related to inflammation (e.g., CRP), cardio/metabolic systems (e.g., BMI), genetics (e.g., telomere length), and endocrine systems (e.g., cortisol), as well as composites of multiple physiological systems. However, not every study identified found significant associations. Health behaviours, emotional distress, social relationships, and socioeconomic factors may help explain some of these associations. Further research is needed to better understand biomarkers of ACEs in adulthood and their relationship to health conditions.

Mapping structural covariance networks of facial emotion recognition in early psychosis: A pilot study.

People with psychosis show deficits recognizing facial emotions and disrupted activation in the underlying neural circuitry. We evaluated associations between facial emotion recognition and cortical thickness using a correlation-based approach to map structural covariance networks across the brain. Fifteen people with an early psychosis provided magnetic resonance scans and completed the Penn Emotion Recognition and Differentiation tasks. Fifteen historical controls provided magnetic resonance scans. Cortical thickness was computed using CIVET and analyzed with linear models. Seed-based structural covariance analysis was done using the mapping anatomical correlations across the cerebral cortex methodology. To map structural covariance networks involved in facial emotion recognition, the right somatosensory cortex and bilateral fusiform face areas were selected as seeds. Statistics were run in SurfStat. Findings showed increased cortical covariance between the right fusiform face region seed and right orbitofrontal cortex in controls than early psychosis subjects. Facial emotion recognition scores were not significantly associated with thickness in any region. A negative effect of Penn Differentiation scores on cortical covariance was seen between the left fusiform face area seed and right superior parietal lobule in early psychosis subjects. Results suggest that facial emotion recognition ability is related to covariance in a temporal-parietal network in early psychosis.

A pilot study of cognitive insight and structural covariance in first-episode psychosis.

Cognitive insight is described as a balance between one's self-reflectiveness (recognition and correction of dysfunctional reasoning), and self-certainty (overconfidence). Neuroimaging studies have linked the ventrolateral prefrontal cortex (VLPFC) to cognitive insight in people with psychosis. However, the relationship between cognitive insight and structural connectivity between the VLPFC and other brain areas is unknown. Here, we investigated the modulation of cognitive insight on structural covariance networks involving the VLPFC in a first-episode psychosis sample. Fifteen patients with a first-episode psychosis provided magnetic resonance (MR) scans and completed the Beck Cognitive Insight Scale (BCIS). MR scans were also available for 15 historical controls. Seed-based analysis of structural covariance was conducted using the Mapping Anatomical Correlations Across the Cerebral Cortex (MACACC) methodology, whereby Pearson correlation coefficients were extracted between seed regions in left and right VLPFC and cortical thickness across the brain. Structural covariance maps between groups were compared at each vertex. In first-episode subjects, we evaluated the modulation of BCIS scores on cortical covariance between VLPFC and every other vertex. Findings showed no significant group difference between first-episode psychosis subjects and controls in thickness covariance seeded from left or right VLPFC. However, in first-episode psychosis subjects, a positive association with self-certainty was found in networks seeded from both left and right VLPFC with thickness in medial frontal cortex and right pars triangularis. No significant associations were found for self-reflectiveness. These results suggest that self-certainty, but not self-reflectiveness, positively modulated cortical covariance in a frontal network in patients with a first-episode psychosis.

The Violent Content in Attenuated Psychotic Symptoms.

The relationship between psychosis and violence has typically focused on factors likely to predict who will commit violent acts. One unexplored area is violence in the content of subthreshold positive symptoms. The current aim was to conduct an exploratory analysis of violent content in the attenuated psychotic symptoms (APS) of those at clinical high risk of psychosis (CHR) who met criteria for attenuated psychotic symptom syndrome (APSS). The APS of 442 CHR individuals, determined by the Structured Interview for Prodromal Syndromes, were described in comprehensive vignettes. The content of these symptoms were coded using the Content of Attenuated Positive Symptoms Codebook. Other measures included clinical symptoms, functioning, beliefs and trauma. Individuals with violent content had significantly higher APS, greater negative beliefs about the self and others, and increased bullying. The same findings and higher ratings on anxiety symptoms were present when participants with self-directed violence were compared to participants with no violent content. Individuals reporting violent content differ in their clinical presentation compared to those who do not experience violent content. Adverse life events, like bullying, may impact the presence of violent content in APS symptoms. Future studies should explore violent content in relation to actual behavior.

Traumatic brain injury in individuals at clinical high risk for psychosis.

BACKGROUND: Recent research suggests that a traumatic brain injury (TBI) can significantly increase the risk of later development of psychosis. However, it is unknown whether people at clinical high risk (CHR) of psychosis have experienced TBI at higher rates, compared to otherwise healthy individuals. This study evaluated the prevalence of mild TBI, whether it was related to past trauma and the relationship of mild TBI to later transition to psychosis. METHODS: Seven-hundred forty-seven CHR and 278 healthy controls (HC) were assessed on past history of mild TBI, age at first and last injury, severity of worst injury and number of injuries using the Traumatic Brain Injury Interview. Attenuated psychotic symptoms were assessed with the Scale of Psychosis-risk Symptoms. IQ was estimated using the Wechsler Abbreviated Scale of Intelligence and past trauma and bullying were recorded using the Childhood Trauma and Abuse Scale. RESULTS: CHR participants experienced a mild TBI more often than the HC group. CHR participants who had experienced a mild TBI reported greater total trauma and bullying scores than those who had not, and those who experienced a mild TBI and later made the transition to psychosis were significantly younger at the age at first and most recent injury than those who did not. CONCLUSION: A history of mild TBI is more frequently observed in CHR individuals than in HC. Inclusion or study of CHR youth with more severe TBI may provide additional insights on the relationship between TBI and later transition to psychosis in CHR individuals.

Cognitive insight is associated with cortical thickness in first-episode psychosis.

Compared to non-clinical subjects, people with psychosis show poor cognitive insight as reflected in low Self-Reflectiveness and high Self-Certainty. Neuroimaging studies have reported that 1) low Self-Reflectiveness is associated with volumetric reductions in ventrolateral prefrontal cortex (VLPFC), 2) higher Self-Certainty is associated with volumetric reductions in hippocampus, and 3) higher Self-Certainty is associated with fractional anisotropy in the fornix, in people with psychosis. The aims of the current study were to expand on this research by 1) performing an exploratory whole-brain cortical thickness analysis of the neural correlates of cognitive insight, to reveal whether regions outside the VLPFC are important for cognitive insight, and 2) to evaluate associations between cognitive insight and subfields of the hippocampus, which are distinct, interacting, and have different functions. We also aimed to replicate previous research documenting associations between cognitive insight and 3) total hippocampal volumes and 4) fornix fractional anisotropy. Fifteen people with a first-episode psychosis completed the Beck Cognitive Insight Scale and provided magnetic resonance and diffusion tensor imaging scans. Cortical thickness and hippocampal volumes were analyzed in FreeSurfer, and fornixfractional anisotropy was analyzed in Diffusion Toolkit/TrackVis. Higher Self-Reflectiveness and lower Self-Certainty significantly associated with thickness and thinness in VLPFC, respectively, as well as thickness and thinness in widespread frontal, parietal and temporal cortices. No associations emerged between Self-Reflectiveness or Self-Certainty and hippocampal total or sub-field volumes, or fornix fractional anisotropy. Results suggest that the neural correlates of cognitive insight involve a network of frontal, temporal and parietal brain regions.

The natural history of early versus late disability accumulation in primary progressive MS.

BACKGROUND: Primary progressive multiple sclerosis (PPMS) is the least common MS disease course and carries the worst prognosis. In relapsing-remitting multiple sclerosis (RRMS) disability accumulation occurs in two distinct phases, but it is unclear whether this is also true for PPMS. Here we investigate factors associated with early and late disability accumulation in PPMS. METHODS: We used Kaplan-Meier survival analyses and Cox regression to investigate the influence of sex, age at disease onset and onset symptoms on time to, and age at, Expanded Disability Status Scale (EDSS) 4 and 6, as well as the time from EDSS 4 to 6 in patients with PPMS. RESULTS: We identified 500 patients with PPMS. The analyses on time to EDSS 4 included 358 patients, and those on time to EDSS 6 included 392 patients. The median times to EDSS 4 and EDSS 6 were 5 and 9 years. The analyses on age at EDSS 4 included 360 patients, and those on age at EDSS 6 included 402 patients. The median ages at EDSS 4 and EDSS 6 were 51 and 55 years. Older age at onset and bilateral motor onset symptoms were independently associated with a shorter time to both EDSS 4 and EDSS 6. Sex and other onset symptoms were not associated with time to, or age at, landmark disability. Only age at onset was significantly associated with the time from EDSS 4 to EDSS 6. CONCLUSIONS: Age at disease onset is the most important predictor of disability accumulation in PPMS. Bilateral motor onset symptoms were associated with quicker disease progression. In contrast to RRMS, we found no evidence for distinct phases of disability accumulation in PPMS. Disability accumulation in PPMS appears to be affected by the same factors throughout its course.

Exercise practices in individuals at clinical high risk of developing psychosis.

AIM: Recent research suggests aerobic exercise has a positive impact on symptoms and cognition in psychosis. Because individuals with psychosis are at risk of weight gain and the resultant metabolic side-effects, developing effective exercise programmes is of interest. Furthermore, this may be a useful intervention for those who are at risk of developing psychosis, that is, those at clinical high risk (CHR). The aim of this initial exploratory project was to examine the role of exercise in participants at CHR for psychosis. METHODS: A comprehensive questionnaire was developed to assess current physical activity involvement; exercise levels in terms of frequency, intensity and duration; and perceived fitness levels. Reported barriers to exercise and reasons for exercising were also considered. Eighty participants, 40 CHR and 40 healthy controls, were assessed with this questionnaire. RESULTS: Overall, both groups were involved in a wide range of physical activity. Healthy controls reported higher levels of participation in indoor/outdoor activities and strength and/or flexibility training. They also exercised more frequently, more intensely and reported higher perceived fitness levels than CHR participants. Levels of exercise were unrelated to clinical symptoms and functioning in CHR participants. CHR youth reported more barriers to exercise and less positive reasons for exercising that were related to self-perception. CONCLUSION: The results suggest that exercise should be investigated further in the CHR population as it may have treatment implications.

Treating young individuals at clinical high risk for psychosis.

BACKGROUND: Typically, studies investigating those at clinical high risk for psychosis have focused on predictors of conversion and treatments that might prevent conversion to full-blown psychosis. Few studies have followed those who do not go on to develop a psychotic illness. METHODS: Participants were 48 young people who were at risk for developing psychosis based on the Structured Interview for Prodromal Symptoms criteria and participated in a treatment programme where they were offered up to 6 months of psychosocial treatment and psychiatric management. Attenuated psychotic symptoms, negative symptoms, depression, anxiety, social functioning, alcohol and drug use, and meta-cognitive beliefs were assessed at baseline, 6, 12 and 18 months. Personality characteristics were assessed at baseline. Medication use was tracked and psychiatric visits were logged over the 18-month study period. RESULTS: On average, participants attended 12 sessions of psychosocial treatment and had one meeting with the psychiatrist every 6 months. Only 24% were ever prescribed any psychotropic medications, and antipsychotics were not used. Significant improvements were found over time in attenuated positive symptoms, negative symptoms, depression, anxiety, meta-cognitions and social functioning with most improvement occurring in the first 6 months. There was no change in the level of substance use. For personality assessment, participants generally scored high on neuroticism and openness and had low scores on extraversion, agreeableness and conscientiousness. CONCLUSION: With minimal treatment and no antipsychotics, young people who present as being at risk for developing a psychotic disorder demonstrate clinical improvement over time. However, a few continued to have the liability of ongoing attenuated psychotic symptoms.