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Background: Deficient information processing in ADHD theoretically results in sensory overload and may underlie the symptoms of the disorder. Mismatch negativity (MMN) and P3a amplitude reflect an individual's detection and subsequent change in attention to stimulus change in their environment. Our primary aim was to explore MMN and P3a amplitude in adult ADHD patients and to examine the effects of methylphenidate (MPH) on these measures. Methods: Forty initially psychostimulant-naïve, adult ADHD patients without comorbid ASD and 42 matched healthy controls (HC) were assessed with an MMN paradigm at baseline. Both groups were retested after 6 weeks, in which patients were treated with MPH. Results: Neither significant group differences in MMN nor P3a amplitude were found at baseline. Although 6-week MPH treatment significantly reduced symptomatology and improved daily functioning of the patients, it did not significantly affect MMN amplitude; however, it did significantly reduce P3a amplitude compared to the HC. Furthermore, more severe ADHD symptoms were significantly associated with larger MMN amplitudes in the patients, both at baseline and follow-up. Conclusion: We found no evidence for early information processing deficits in patients with ADHD, as measured with MMN and P3a amplitude. Six-week treatment with MPH decreased P3a but not MMN amplitude, although more severe ADHD-symptoms were associated with larger MMN amplitudes in the patients. Given that P3a amplitude represents an important attentional process and that glutamate has been linked to both ADHD and MMN amplitude, future research should investigate augmenting MPH treatment of less responsive adults with ADHD with glutamatergic antagonists. [ABSTRACT FROM AUTHOR]

Objectives: Emotion regulation is a predictor of overall life outcome. Problems of emotion regulation are associated with multiple psychiatric disorders and could be a potential treatment target for improving well-being and functioning. Children at familial high risk of severe mental illness have a markedly increased risk of various psychopathology and constitute a group at significant risk of emotion regulation problems. Investigations of emotion regulation in children at familial high risk of severe mental illness are sparse. Methods: We applied an instrument for assessing emotion regulation, the Tangram Emotion Coding Manual (TECM), to a population-based cohort of 522 7-year-old children born to parents diagnosed with either schizophrenia or bipolar disorder and matched controls. The TEC-M is an ecologically valid, clinician-rated observational test measure of spontaneous emotion regulation. We aimed to compare emotion regulation between risk groups and to investigate associations between emotion regulation and psychopathology and daily life functioning, and between emotion regulation and an acknowledged questionnaire-based dysregulation profile. Results: In this early developmental phase, we found no between group differences in emotion regulation. We found a significant but weak negative association between emotion regulation and both child psychopathology and the presence of a dysregulation profile on the Child Behavior Checklist and a weak positive association between emotion regulation and current level of functioning. Conclusions: These findings contribute to the understanding of emotion regulation in familial high-risk children and further studies of emotion regulation in children at familial high risk of severe mental illness are warranted. [ABSTRACT FROM AUTHOR]

Background: Children at familial high‐risk of schizophrenia and bipolar disorder have an elevated prevalence of mental disorders but studies of children within a narrow age range are lacking and there are few conjoint studies of these two groups. Knowledge on their mental health is important for prevention and early intervention. Methods: The authors examined mental disorders and global functioning in children at familial high‐risk of schizophrenia (FHR‐SZ) and bipolar disorder (FHR‐BP) compared with population‐based controls. In a longitudinal cohort study, 450 children (FHR‐SZ, n = 171; FHR‐BP, n = 104; controls, n = 175), were assessed for Axis I disorders at baseline and four‐year follow‐up (mean age 11.9, SD 0.2) with the Kiddie Schedule for Affective Disorders and Schizophrenia for School‐Age Children and for global functioning with Children's Global Assessment Scale. Results: Cumulative incidence of Any Axis I disorder was elevated by age 11 in children at FHR‐SZ (54.4%, OR 3.0, 95% CI 1.9–4.7, p <.001) and children at FHR‐BP (52.9%, OR 2.8, 95% CI 1.7–4.7, p <.001) compared with controls (28.6%). Children at FHR‐SZ and FHR‐BP had higher rates of affective disorders (OR 4.4, 95% CI 1.4–13.5, p =.009; OR 5.1, 95% CI 1.6–16.4, p =.007), anxiety disorders (OR 2.1, 95% CI 1.1–4.0, p =.02; OR 3.0, 95% CI 1.5–6.1, p =.002), and stress and adjustment disorders (OR 3.3, 95% CI 1.4–7.5, p =.006; OR 5.3, 95% CI 2.2–12.4, p <.001). Disruptive behavior disorders (OR 2.8, 95% CI 1.0–7.3, p =.04) and ADHD (OR 2.9, 95% CI 1.6–5.3, p <.001) were elevated in children at FHR‐SZ. Both FHR groups had lower global functioning than controls. Cumulative incidence of disorders increased equally across the three groups from early childhood to preadolescence and level of functioning did not change differentially. Conclusions: Children at FHR‐SZ and FHR‐BP have an elevated prevalence of mental disorders and poorer functioning than controls. Vulnerability in children at FHR manifests early and remains stable throughout childhood. Early attention toward their mental health and identification of those in need of intervention is warranted. [ABSTRACT FROM AUTHOR]

Background: Facing multiple risk factors, relative to single risk factor exposure early in life can have great implications for negative child development. Objective: We aim to examine whether the prevalence of early risk factors is higher among children with familial high risk for schizophrenia or bipolar disorder compared to controls. Further, to investigate the association between number of early risk factors and level of functioning at age seven, and whether this possible association is different in children with familial high risk compared to controls. Method: The Danish High Risk and Resilience Study VIA 7 is a population-based cohort study of children of parents diagnosed with schizophrenia (N = 202), bipolar disorder (N = 120) and controls (N = 200). We conducted a semi-structured anamnestic interview with the child’s primary caregiver to assess early risk factors from pregnancy to age four. We used the Children’s Global Assessment Scale to measure level of functioning at age seven. Results: 13 out of 17 risk factors were more prevalent in children at familial high risk for schizophrenia and 7 out of 17 risk factors were more prevalent in children at familial high risk for bipolar disorder compared to controls. Level of functioning decreased 2.7 (95% CI, 2.2; 3.3)-points per risk factor, but the association was not significantly different across the three groups (p = 0.09). Conclusions: Our results showed that children at age seven with familial high risk for schizophrenia or bipolar disorder experience a greater number of early risk factors. A higher number of early risk factors were associated with lower level of functioning at age seven. However, the association is not different for children with familial high risk or controls. [ABSTRACT FROM AUTHOR]

There is a paucity of evidence on executive functions (EF) as reflected in daily life behaviors in individuals at ultrahigh risk (UHR) for psychosis. This prospective follow-up study investigated the 1-year development in EF in UHR compared to healthy controls (HC) and how this change may relate to change in severity of clinical symptoms, social communication, and functioning. UHR (N = 132) and HC (N = 66) were assessed with the Behaviour Rating Inventory of Executive Function--Adult version (BRIEF-A) self and informant report at baseline and 12 months follow- up comprising the Behavioral Regulation Index (BRI) and the Metacognition Index (MI). Additionally, data on depressive-, negative-, and attenuated psychotic symptoms and everyday social functioning were collected. The study found UHR to display large baseline impairments in EF in real life on both self- and informant reports. UHR and HC showed a significantly different development of EF over time, with UHR displaying greater improvements in EF compared to HC. Change in clinical symptoms did not relate to improvements in EF, except for depressive symptoms negatively associating with the development of the MI. Improvements on the BRI and MI were significantly associated with improvements in social functioning. Findings suggest the potential of UHR individuals displaying a larger ongoing maturational development of daily life EF than HC that seems predominantly independent of development of clinical symptoms. If replicated, this supports a maturational trajectory of daily life EF in UHR that approaches, but do not reach, the level of HC and may indicate a window of opportunity for targeted remediation approaches. [ABSTRACT FROM AUTHOR]

Background: Neurodevelopmental brain disorders such as schizophrenia, autism and attention deficit hyperactivity disorder are complex disorders with heterogeneous etiologies. Schizophrenia and autism are difficult to treat and often cause major individual suffering largely owing to our limited understanding of the disease biology. Thus our understanding of the biological pathogenesis needs to be substantiated to enable development of more targeted treatment options with improved efficacy. Insights into the pre-morbid disease dynamics, the morbid condition and the underlying biological disease mechanisms may come from studies of subjects with homogenous etiologies. Breakthroughs in psychiatric genetics have shown that several genetic anomalies predispose for neurodevelopmental brain disorders. We have established a Danish research initiative to study the common microdeletion at chromosome 22q11.2, which is one of the genetic anomalies that confer high risk of schizophrenia, autism and attention deficit hyperactivity disorder. Methods/design: The study applies a "cause-to-outcome" strategy to identify pre-morbid pathogenesis and underlying biological disease mechanisms of psychosis and secondarily the morbid condition of autism and attention deficit hyperactivity disorder. We use a population based epidemiological design to inform on disease prevalence, environmental risk factors and familial disposition for mental health disorders and a case control study design to map the functional effects across behavioral and neurophysiological traits of the 22q11 deletion in a recruited sample of Danish individuals. Discussion: Identification of predictive pre-morbid clinical, cognitive, functional and structural brain alterations in 22q11 deletion carriers may alter current clinical practice from symptomatic therapy of manifest mental illness into early intervention strategies, which may also be applicable to at risk subjects without known etiology. Hopefully new insights into the biological disease mechanisms, which are mandatory for novel drug developments, can improve the outcome of the pharmacological interventions in psychiatry. [ABSTRACT FROM AUTHOR]

Background: Assortative mating is common in patients with mental disorders, both for specific disorders and across the spectrum of mental disorders. Assortative mating may play a key role in mental disorders because the person with the close relation to an individual with a mental disorder is also likely to have mental disorders, poorer cognitive abilities or lower social functioning, which may further intensify problems for both partners and their offspring. When one parent is ill, the care for the child will often depend on the other parent. Thus, assortative mating will most likely contribute to outcomes in the offspring. Therefore, the objective of this study was to investigate possible diagnoses of a mental illness, cognitive ability and social functioning in individuals who have biological children by partners with schizophrenia or bipolar disorder. Further, we also aimed to explore differences in polygenic risk scores derived from genome-wide association studies for schizophrenia, bipolar disorder, and depression. Methods: This study was based on data from The Danish High Risk and Resilience Study - VIA7, a population-based cohort study conducted in Denmark between 2013 and 2016. Subjects were identified through the Danish Civil registration System and the Danish Psychiatric Central Research register. The VIA7 cohort consists of 522 children aged 7 years with parents diagnosed with schizophrenia or bipolar disorder in the Danish registries (index parents) and their partners (non-index parents). This study focuses on the non-index parents (N = 492) without schizophrenia or bipolar disorder in the Danish registries. All participants were interviewed with a diagnostic interview (SCAN 2.0). Main outcomes were intelligence, processing speed, verbal working memory, and social functioning. A linear mixed effect model was applied for each of the outcomes, including parent status (index parent or non-index parent), group (schizophrenia, bipolar disorder, and control), and interaction between parent status and group. Results: Non-index parents having children by a partner with schizophrenia or bipolar disorder more often fulfilled the criteria for a mental disorder compared to non-index parents in the control group. Non-index parents having children by a partner with schizophrenia or bipolar disorder had lower levels of social functioning compared to non-index parents in the control group and performed poorer on intelligence and processing speed. Discussion: Individuals who have children by partners with schizophrenia or bipolar disorder are more likely to have a mental disorder and to have lower levels of cognitive and social functioning compared to individuals who have children by partners without schizophrenia or bipolar disorder. Assortative mating may have important implications for our understanding of the familial transmission of these disorders. The findings presented in this study should be considered in future genetic research in psychiatry, specifically in the investigation of potential risk factors for children with a parent with schizophrenia or bipolar disorder. [ABSTRACT FROM AUTHOR]

Background: Individuals at ultra-high risk for psychosis (UHR) present with subtle white matter alterations, which have been associated with clinical and functional outcome. The effect of cognitive remediation on white matter (WM) in UHR-individuals has not been investigated. Methods: In a randomized, clinical intervention-trial (FOCUS), UHRindividuals aged 18–40 years were assigned to treatment as usual (TAU) or TAU plus cognitive remediation (CR) for 20 weeks. CR comprised 20 x 2-hour sessions of neurocognitive and social-cognitive training (SCIT). Primary outcome was whole brain fractional anisotropy (FA) derived from diffusion weighted imaging. Secondary outcomes pertained to regions of interest analyses. Planned post-hoc analyses explored dose-response effects of CR on WM. Main analyses of treatment effect of CR on primary and secondary outcomes were conducted using linear mixed models, assessing the interaction of timepoint by group (CR and TAU). Analyses were conducted according to the intention-to-treat principle. Results: 111 UHR-individuals and 59 healthy controls were included. Attrition-rate was 30% at 6 months post-treatment follow-up. The CR group completed a mean of 12 hours of neurocognitive training. We found no effect of CR on whole-brain or regional FA. Planned posthoc analyses revealed significant time*group (high- and low-attendance to CR) interactions in left superior corona radiata (p<0.01), left cingulum cingulate gyrus (P=0.03), and right superior longitudinal fasciculus (P<0,01), corrected. Specifically, when compared to UHR-individuals with high attendance (UHR-high >12 hours), those with low attendance (UHR-low <12 hours) had more co-morbid diagnoses, larger recreational smoking (nicotine and cannabis), more depressive and negative symptoms, and had significantly lower global FA at baseline, and showed a significant increase in FA after treatment. Furthermore, UHR-low displayed large effect-size (ES) improvements on depressive and negative symptoms, and moderate to large ES improvements in several cognitive functions (verbal fluency, verbal working memory, and processing speed). In contrast, UHR-high displayed large ES improvements in UHR-symptoms, and moderate ES improvement on social and occupational functioning. Discussion: Contradicting our main hypothesis, we found no effect of CR on whole-brain or regional FA after six months. This may be explained by both the low number of neurocognitive training sessions and the attrition rate. The average of 12 hours of neurocognitive training is considerably lower than the recommended dosage of 25–30 hours necessary for cognitive improvements. The continuous need to develop feasible interventions and enhance adherence is stressed. Nevertheless, non-specific treatment may improve WM-integrity in UHRindividuals with lower global baseline FA in those with more severe psychopathology. The UHR-low subgroup exhibited improvements with large ES in levels of depressive and negative symptoms, as well as cognitive functions. We speculate, whether our results reflect that UHR-individuals with higher baseline FA (approaching the healthy controls), present with a preserved structural capacity for increased demands and new learning, while UHR-individuals characterized by lower FA at baseline may be more amendable to neuroplastic treatment-effects. The results support the value of subgrouping in a clinically heterogenous UHR-population, which also applies to examining WM integrity. [ABSTRACT FROM AUTHOR]

Attention-deficit hyperactivity disorder (ADHD) is a disabling condition with onset in early childhood. ADHD often co-occurs with educational failure and poor self-esteem. This literature review includes twin studies published in English between 1996 and 2004. Our inclusion criterium was either a quantitative estimate of the heritability of ADHD, or of its inattentive and impulsive-hyperactive symptom-dimensions. This article also contains an introduction to the twin design as a method to estimate the influences from genetic and environmental sources on complex psychological trails. The methodological introduction contains a discussion of the validity of a basic assumption in the twin design referred to as "the equal environment assumption". All together, the studies reviewed include about 38.000 children. Based on parental information. The heritability estimates are generally very high and point to a dominant genetic influence on the symptom-dimensions associated with ADHD and on ADHD defined as a category. In contrast, the non-shared environmental factors are of less influence and the shared environmental factors are of no importance. The theoretical implications of these findings are briefly discussed and support the assumption of ADHD as a developmental disorder. [ABSTRACT FROM AUTHOR]

Background: Neurocognitive impairments are widespread in individuals with schizophrenia both premorbid and post illness onset. Although less pronounced, individuals with bipolar disorder also display various neurocognitive deficits. Owing to the impaired neurocognitive functions in first-degree relatives, neurocognitive deficits are considered endophenotypes of both disorders. Importantly, neurocognitive heterogeneity exists in both disorders. Distinct neurocognitive subgroups in young adults with clinical high risk of psychosis or familial risk of bipolar disorder have been identified with an increased risk of conversion to illness and poorer functioning in the most neurocognitively impaired subgroup. However, neurocognitive heterogeneity remains to be investigated in young children at familial high risk of schizophrenia (FHR-SZ) and bipolar disorder (FHR-BP). The aim of this study was to identify relatively homogeneous neurocognitive subgroups in a cohort of children with FHR-SZ or FHR-BP and to investigate the distribution of high risk status across the neurocognitive subgroups. Exploratively, potential differences between these subgroups on functional outcome and polygenic risk were investigated. Methods: Neurocognition was assessed cross-sectionally with a comprehensive test battery in a population-based cohort of 514 children aged 7 with either FHR-SZ (N=197), FHR-BP (N=118) or no familial high risk of these disorders (N=199). A hierarchical cluster analysis of the neurocognitive data was performed using Ward’s method and followed-up by a K-means cluster analysis. The neurocognitive clusters were further compared on measures of current level of functioning and polygenic risk for educational attainment. Results: Three distinct neurocognitive subgroups were derived from the hierarchical cluster analyses: a 1) significantly impaired, 2) typical, and 3) high functioning subgroup. The three subgroups performed significantly different from each other on the majority of the pairwise comparisons of the neurocognitive functions (Cohen’s d range = 0.33–2.27, p < 0.01). There was a significantly higher percentage of children with FHR-SZ in the significantly impaired subgroup (36%) compared to children with FHR-BP (20%). Importantly, 64% of the children at FHR-SZ and 80% of the children at FHR-BP displayed either typical or high neurocognitive functioning. Finally, the neurocognitive subgroups differed significantly on current level of functioning with the significantly impaired subgroup displaying the lowest level of functioning. Polygenic risk for educational attainment was non-significantly different across neurocognitive subgroups. Discussion: Young children at familial high risk of severe mental disorders (SMD) are neurocognitively heterogenic with three distinct neurocognitive subgroups of varying severity. A higher percentage of children at FHR-SZ was in the significantly impaired subgroup (36%) compared to children at FHR-BP (20%). In this cross-sectional study, being in the significantly impaired neurocognitive subgroup is associated with poorer daily functioning across risk status and in other, longitudinal studies has proven predictive of transition to illness in young adults at clinical high risk. Therefore, neurocognitive profiling in high-risk offspring may guide future intervention programs targeting the neurocognitively impaired subgroup of young children at familial high risk of SMD using e.g. cognitive remediation or other potentially preemptive or ameliorating interventions. [ABSTRACT FROM AUTHOR]

Background: There is evidence of higher rates of insecure and disorganized attachment in infancy in children born to parents with severe mental disorders, but evidence on attachment in middle childhood for these children is lacking. This study aims to explore attachment representations in seven-year-old children born to parents with schizophrenia or bipolar disorder. We also aim to explore possible associations between attachment and psychopathology, level of functioning, and psychotic experiences in these children. - We expect that children at familial high risk will have the highest levels of insecure and disorganized attachment. We expect that population based controls will have the lowest levels of insecure and disorganized attachment and higher levels of security than children at familial high risk. - We expect higher levels of insecure and disorganized attachment to be associated with an increased risk of psychopathology, and psychotic experiences and with lower levels of functioning, whereas we expect higher levels of secure attachment to be associated with a lower risk of psychopathology, and psychotic experiences, and with higher levels of functioning. Methods: The Danish High Risk and Resilience Study VIA 7 is a prospective cohort study of 522 seven-year-old children born in Denmark. The cohort consists of children where one or both parents have been diagnosed with a schizophrenia spectrum disorder (N=202), children where one or both parents have been diagnosed with bipolar affective disorder (N=120) and children where neither of the parents have been diagnosed with these disorders (N=200). Attachment representations were assessed with the Story Stem Assessment Protocol whereas psychopathology, level of functioning, and psychotic experiences were assessed with K-SADS. Results: Data analyses are ongoing but preliminary results indicate that there are no significant differences in attachment representations between the three groups of children, but that there are associations between higher rates of insecure and disorganized attachment and a higher risk of psychopathology. Results will be presented at the SIRS-conference. Discussion: Understanding attachment and its correlates in children at familial high risk of severe mental disorders is important in order to strengthen our understanding of developmental trajectories towards mental disorders in these children. [ABSTRACT FROM AUTHOR]

Background and Hypothesis: Suicide is a leading cause of death in youth and is often preceded by suicidal ideation (SI) and non-suicidal self-injury (NSSI). Identifying early markers of risk for SI and NSSI could improve timely identification of at-risk individuals., Study Design: Children (mean age 11.9, SD 0.2) at familial high risk of schizophrenia (N = 171), or bipolar disorder (N = 104), and controls (N = 174) were assessed for psychotic experiences (PE), SI, NSSI, and Axis I mental disorders in face-to-face interviews in early and middle childhood (age 7 and 11)., Study Results: Having 2 types of early childhood PE predicted middle childhood SI after accounting for previous SI, NSSI, and mental disorders (OR 2.8, 95% CI 1.1-6.9; P = .03). Two PE predicted NSSI (OR 3.0, 95% CI 1.2-7.7; P = .02) in excess of previous SI, NSSI, mental disorders, and familial risk. Persistent and incident PE predicted SI (OR 3.2, 95% CI, 1.1-8.8; P = .03; OR 3.8, 95% CI, 1.3-11.5; P = .02) in the fully adjusted model. Nineteen percent of children with persistent PE reported middle childhood SI vs 3.8% of those who never reported PE. In children with early childhood mental disorders, those who reported 2 PE had 4.4-fold increased odds of later SI (95% CI, 1.2-16.7; P = .03) after adjustments. PE were nondifferentially associated with outcomes across familial risk groups., Conclusions: Early childhood PE index elevated risk for subsequent SI and NSSI beyond what can be attributed to presence of mental disorders. Mental health screenings and clinical assessments should include early childhood PE., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)