Psychiatric disorders in individuals with neurofibromatosis 1 in Denmark: A nationwide register-based cohort study.

The aim of this study was to assess the risks of psychiatric disorders in a large cohort of 905 individuals with NF1 and 7614 population comparisons matched on sex and year of birth. The cohort was linked to the Danish Psychiatric Central Research Register to ascertain information on hospital contacts for psychiatric disorders based on the International Classification of Diseases version 8 and 10. The hazard ratio (HR) for a first psychiatric hospital contact was higher in girls (4.19, 95% confidence interval [CI] 1.81-9.69) and boys with NF1 (5.02, 95% CI 3.27-7.69) <7 years of age than in the population comparisons. Both sexes had increased HRs for developmental disorders, including attention deficit/hyperactivity disorders, autism spectrum disorders, and intellectual disabilities in childhood. Females with NF1 had also increased HRs for unipolar depression, other emotional and behavioral disorders, and severe stress reaction and adjustment disorders in early adulthood. The HRs for psychoses, schizophrenia, bipolar disorders, and substance abuse were similar in individuals with NF1 and the population comparisons. Finally, the cumulative incidence of a first hospital contact due to any psychiatric disorder by age 30 years was 35% (95% CI 29-41) in females and 28% (95% CI 19-37) in males with NF1. Thus, screening for psychiatric disorders may be important for early diagnosis and facilitation of appropriate and effective treatment in individuals with NF1.

Fish Oil Supplementation in Pregnancy and Neurodevelopment in Childhood-A Randomized Clinical Trial.

A double-blind randomized controlled trial of n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation or matching placebo during third trimester of pregnancy was conducted within the COPSAC2010 mother-child cohort consisting of 736 women and their children. The objective was to determine if maternal n-3 LCPUFA pregnancy supplementation affects offspring neurodevelopment until 6 years. Neurodevelopment was evaluated in 654 children assessing age of motor milestone achievement, language development, cognitive development, general neurodevelopment, and emotional and behavioral problems. Maternal n-3 LCPUFA supplementation during pregnancy improved early language development and reduced the impact of emotional and behavioral problems. The n-3 LCPUFA supplementation was in boys associated with the earlier achievement of gross motor milestones, improved cognitive development, and a reduced impact of emotional and behavioral problems.

Quality of life and self-esteem in 7-year-old children with familial high risk of schizophrenia or bipolar disorder: the Danish High Risk and Resilience Study-VIA 7-a population-based cohort study.

It is well established that children with familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) have a higher risk of developing mental disorders, however, little is known of to what degree the genetic and environmental vulnerabilities affect the quality of life and self-esteem of these children. We aimed to compare the quality of life and self-esteem between children with FHR-SZ or FHR-BP and controls. We used Danish nationwide registers to retrieve a cohort of 522 7-year-old children with FHR-SZ or FHR-BP and controls. Quality of life was assessed with the 'Health-related Quality of Life Screening Instrument', KIDSCREEN-27, and the scale 'Social Acceptance (Bullying)' from the KIDSCREEN-52. Self-esteem was assessed with the self-report scale 'I think I am'. Assessors were blind to familial risk status of the children. Children with FHR-SZ displayed lower levels of the general quality of life, as well as lower scores on the 'Psychological Well-being' scale and the 'School Environment' scale of the KIDSCREEN-27 compared with controls. Both children with FHR-SZ and FHR-BP reported more bullying victimization compared with controls. Children with FHR-SZ reported lower self-esteem on the total scale of 'I think I am', as well as on the 'Skills and talents', the 'Psychological well-being', and the 'Relationships with others' subscales compared with controls. The findings of lower quality of life and self-esteem in children with FHR-SZ together with more bullying victimization in both familial high-risk groups call for studies on low risk, early intervention strategies towards this group of vulnerable children.

Attention-deficit/hyperactivity disorder symptoms in children with surgically corrected Ventricular Septal Defect, Transposition of the Great Arteries, and Tetralogy of Fallot.

BACKGROUND: Children with complex CHD are at risk for psychopathology such as severe attention-deficit/hyperactivity disorder symptoms after congenital heart surgery. OBJECTIVE: The aim of this study was to investigate if children with Ventricular Septal Defect, Transposition of Great Arteries, or Tetralogy of Fallot have an increased occurrence of attention-deficit/hyperactivity disorder symptoms compared with the background population and to investigate differences between the three CHDs in terms of occurrence and appearance of attention-deficit/hyperactivity disorder symptoms. METHOD: A national register-based survey was conducted, including children aged 10-16 years with surgically corrected CHDs without genetic abnormalities and syndromes. The Attention-Deficit/Hyperactivity Disorder-Rating Scale questionnaires were filled in by parents and school teachers. RESULTS: In total, 159 out of 283 questionnaires were completed among children with CHDs and compared with age- and sex-matched controls. Children with CHDs had significantly increased inattention scores (p = 0.009) and total attention-deficit/hyperactivity disorder scores (p = 0.008) compared with controls. Post hoc analyses revealed that children with Tetralogy of Fallot had significantly higher inattention scores compared with children both with Ventricular Septal Defect (p = 0.043) and controls (p = 0.004). CONCLUSION: Attention-deficit/hyperactivity disorder symptoms and inattention symptoms were significantly more frequent among children aged 10-16 years with CHDs, in particular in children with corrected Tetralogy of Fallot.

Cognitive remediation plus standard treatment versus standard treatment alone for individuals at ultra-high risk of developing psychosis: Results of the FOCUS randomised clinical trial.

BACKGROUND: Individuals at ultra-high risk (UHR) for psychosis have significant cognitive deficits that can impede functional recovery. Applying cognitive remediation (CR) before the onset of frank psychosis may improve the cognitive and functional prognosis of UHR individuals, however, little is known about the feasibility and efficacy of CR for this population. METHODS: In this randomised, clinical trial 146 individuals at UHR for psychosis aged 18-40 years were randomly assigned to treatment as usual (TAU) or TAU plus cognitive remediation. The CR targeted neurocognitive and social cognitive remediation. Assessments were carried out at 6- and 12-months post baseline. RESULTS: A total of 73 UHR individuals were assigned to TAU and 73 assigned to TAU + cognitive remediation. Compared to the control group, cognitive remediation did not result in significant improvement on the primary outcome; the Brief Assessment of Cognition in Schizophrenia composite score at 6-month follow-up (b = -0.125, 95%CI: -0.23 to 0.172, p = 0.41). Nor did the intervention improve secondary outcomes in clinical symptoms or functioning. Exploratory analyses found emotion recognition latencies to be significantly more reduced in the intervention group at 6-months. At 12-months, the intervention group exhibited significantly better performance on two measures of executive function and visual memory. CONCLUSION: The 20-session treatment protocol was not well received in the UHR group, and unsurprisingly global measures did not improve. The benefit found in isolated neuro- and social cognitive measures after even a few sessions points to a potential for cognitive malleability if people can be engaged sufficiently to practice the skills. Trial registration ClinicalTrial.gov identifier: NCT02098408.

Social Cognition, Language, and Social Behavior in 7-Year-Old Children at Familial High-Risk of Developing Schizophrenia or Bipolar Disorder: The Danish High Risk and Resilience Study VIA 7-A Population-Based Cohort Study.

OBJECTIVE: To characterize social cognition, language, and social behavior as potentially shared vulnerability markers in children at familial high-risk of schizophrenia (FHR-SZ) and bipolar disorder (FHR-BP). METHODS: The Danish High-Risk and Resilience Study VIA7 is a multisite population-based cohort of 522 7-year-old children extracted from the Danish registries. The population-based controls were matched to the FHR-SZ children on age, sex, and municipality. The FHR-BP group followed same inclusion criteria. Data were collected blinded to familial high-risk status. Outcomes were social cognition, language, and social behavior. RESULTS: The analysis included 202 FHR-SZ children (girls: 46%), 120 FHR-BP children (girls: 46.7%), and 200 controls (girls: 46.5%). FHR-SZ children displayed significant deficits in language (receptive: d = -0.27, P = .006; pragmatic: d = -0.51, P < .001), social responsiveness (d = -0.54, P < .001), and adaptive social functioning (d = -0.47, P < .001) compared to controls after Bonferroni correction. Compared to FHR-BP children, FHR-SZ children performed significantly poorer on adaptive social functioning (d = -0.29, P = .007) after Bonferroni correction. FHR-BP and FHR-SZ children showed no significant social cognitive impairments compared to controls after Bonferroni correction. CONCLUSION: Language, social responsiveness, and adaptive social functioning deficits seem associated with FHR-SZ but not FHR-BP in this developmental phase. The pattern of results suggests adaptive social functioning impairments may not be shared between FHR-BP and FHR-SZ in this developmental phase and thus not reflective of the shared risk factors for schizophrenia and bipolar disorder.

Non-pharmacological modulation of cerebral white matter organization: A systematic review of non-psychiatric and psychiatric studies.

OBJECTIVE: Neuroplasticity is a well-described phenomenon, but effects of non-pharmacological interventions on white matter (WM) are unclear. Here we review associations between active non-pharmacological interventions and WM organization in healthy subjects and in psychiatric patients. METHOD: A systematic review of non-psychiatric and psychiatric studies in MEDLINE and EMBASE databases. We included longitudinal, controlled studies in human participants aged 18-60 years published in peer-reviewed journals between 2000 and 2017. Studies required active interventions lasting between one day and one year, targeting cognitive-, motor- or sensory domains. The primary outcome was intervention-related brain changes in diffusion-weighted imaging (DWI) derived measures. RESULTS: We included 25 studies. Twenty studies reported positive findings. Five studies investigated psychiatric patients. Nine randomized, controlled trials (RCTs) reported DWI changes following cognitive interventions. Interventions were too heterogeneous to perform a meta-analysis. Intervention duration of at least eight weeks appeared required to induce consistent WM changes. CONCLUSIONS: Non-pharmacological interventions can induce changes in WM. DWI is a relevant correlate of e.g. cognitive training in prospective, long-term RCTs of psychiatric patients.

Social cognition in patients at ultra-high risk for psychosis: What is the relation to social skills and functioning?

OBJECTIVE: Patients at ultra-high risk (UHR) for psychosis show significant impairments in functioning. It is essential to determine which factors influence functioning, as it may have implications for intervention strategies. This study examined whether social cognitive abilities and clinical symptoms are associated with functioning and social skills. METHODS: The study included 65 UHR patients and 30 healthy controls. Social cognitive function, social skills, and a broad range of functioning measures were assessed. RESULTS: The UHR patients demonstrated significant decrements on The Awareness of Social Inferences Task total score (p = .046, d = .51), and on the CANTAB emotion recognition task total percent correct (p = .023, d = .54) displaying particular difficulties in negative affect recognition. The patients exhibited significant impairments in social skills measured with the High Risk Social Challenge (p˂.001, d = 1.05). Aspects of emotion recognition were associated with role functioning and social skill performance. The level of attributional bias was associated with overall functioning, and theory of mind ability was associated with self-reported functioning. Negative symptoms were associated with all measures of functioning (p ≤ .05). CONCLUSION: Significant impairments in social cognition and social skills were found in UHR patients. The patients' social cognitive function was associated with overall functioning and social skills. Negative symptoms appear to play an important role for functioning. Research is needed to investigate how the relations between social cognition, social skills and functioning develop from the UHR state to the stage of manifest illness. Research into how deficits in social cognition and social skills can be ameliorated in UHR patients is warranted.

A Psychometric Evaluation of the Danish Version of the Theory of Mind Storybook for 8-14 Year-Old Children.

BACKGROUND: Theory-of-Mind (ToM) keeps on developing in late childhood and early adolescence, and the study of ToM development later in childhood had to await the development of sufficiently sensitive tests challenging more mature children. The current study aimed to investigate the psychometric properties of the Danish version of the Theory-of-Mind Storybook Frederik (ToM-Frederik). METHODS: We assessed whether ToM-Frederik scores differed between a group of 41 typically developing (TD) children and a group of 33 children with High Functioning Autism Spectrum Disorder (HFASD). A lower mean ToM-Frederik score was expected in the HFASD group. To determine the convergent validity of ToM-Frederik, potential associations with Strange Stories and Animated Triangles (AT) were analyzed. Furthermore, potential associations between ToM-Frederik and the Social Responsiveness Scale (SRS) and between ToM-Frederik and the Social Emotional Evaluation (SEE) Total score were analyzed. RESULTS: A significantly higher ToM-Frederik score was observed in the TD group compared to the HFASD group. Furthermore, the convergent validity of ToM-Frederik as a measure of ToM was supported by significant and positive associations with the Strange Stories and the AT scores in the HFASD group, whereas ToM-Frederik was significantly correlated with Strange Stories, but not with AT in the TD group. ToM-Frederik was not significantly associated with SRS in neither the HFASD nor the TD group. CONCLUSION: The findings are supportive of ToM-Frederik as a valid indicator of deficits at the group level in children with HFASD between 7 and 14 years of age. Furthermore, the convergent validity is supported.

The association between working alliance and clinical and functional outcome in a cohort of 400 patients with first-episode psychosis: a cross-sectional study.

OBJECTIVE: Working alliance between patients with a first-episode psychosis and their case manager is regarded as a key element in specialized early intervention services. The impact of this patient-case manager dyad on functional and clinical outcome is unknown. We aimed to investigate if a strong working alliance was associated with fewer clinical symptoms and better social functioning. METHOD: In a cross-sectional design, patients with first-episode schizophrenia spectrum disorders (ICD-10, F20-29) were included after 18 months of treatment (N = 400). Baseline data were collected between June 2009 and December 2011. Symptoms were assessed using Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), Global Assessment of Functioning (GAF), Brief Assessment of Cognition in Schizophrenia (BACS), Working Alliance Inventory (WAI), and General Self-Efficacy (GSE). Linear regression analyses were adjusted for age, sex, cognition, and self-efficacy. RESULTS: Results revealed significant associations between working alliance and fewer negative (ß = -0.12; 95% CI, -0.19 to -0.04) and disorganized symptoms (ß = -0.06; 95% CI, -0.11 to -0.01), and between working alliance and better social functioning (ß = 1.45; 95% CI, 0.55 to 2.36). General self-efficacy mediated the effect of working alliance, explaining 14%-18% of the variance in associated outcomes. Global level of cognitive functioning, compliance, and self-efficacy influenced clinical and functional outcome more strongly than working alliance. CONCLUSIONS: Better working alliance was weakly associated with fewer negative and disorganized symptoms and better social functioning. A strong working alliance may be a prerequisite for adherence to the specialized early intervention services treatment, providing the basis for positive treatment outcome. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00914238.