Early-Onset Schizophrenia: Exploring the Contribution of the Thought Disorder Index to Clinical Assessment

Background: Differentiating diagnostically between schizophrenia and emotional and personality disorders with psychotic or psychotic-like symptoms is a challenging task. It is especially difficult when working with adolescent patients, because their symptoms tend to manifest at lower levels as compared with adult patients. Thought disorder is a core symptom of schizophrenia, and the Rorschach Inkblot Method is widely used for the assessment of formal thought disorder. Objective: In this study, which is situated within ongoing clinical practice, we investigated whether the Rorschach test is helpful for assessing early-onset schizophrenia due to its ability to detect thought disorder. We also wanted to examine whether the Thought Disorder Index (TDI) is superior to the Comprehensive System (CS) for differentiating between patients with early-onset schizophrenia and non-psychotic patients experiencing auditory and visual hallucinations. An additional aim was to examine whether the TDI correlated with the Positive and Negative Syndrome Scale (PANSS). Methods: Twenty-three subjects between the ages of 12 and 18 years were examined with the use of the Rorschach test, and the protocols were scored according to both the TDI and the CS. All subjects were also assessed with the Positive and Negative Syndrome Scale. The sample included 14 subjects who fulfilled the criteria for schizophrenia and 9 subjects who were experiencing hallucinations that emanated from severe emotional and relational problems but who had different non-psychotic disorders. Results: Although the two groups could not be distinguished with regard to their total scores for thought disorder, the identification of specific thought disorder types proved useful for differential diagnosis. Verbalizations that were categorized by the TDI as “absurd responses,” “fluidity,” “contamination,” “autistic logic,” and “word-finding difficulty” were only given by patients who had been diagnosed with schizophrenia. When patients’ responses were scored with the use of the CS, the “contamination” score was the only one found to be specific to schizophrenia. Conclusions: Although the sample size limits the conclusions that can be drawn, the results indicate that the TDI may be superior to the CS for the identification of thought disorder specific to—but not always present in—adolescents with schizophrenia. In other words, the absence of severe thought disorder is not synonymous with the absence of severe psychopathology, but the presence of the most severe thought disorder types (i.e., “absurd responses,” “fluidity,” “incoherence,” “contamination,” and “autistic logic”) seems to be a strong indicator of schizophrenic psychopathology

Effects of exercise on cognitive performance in children and adolescents with ADHD:Potential mechanisms and evidence-based recommendations

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with a complex symptomatology, and core symptoms as well as functional impairment often persist into adulthood. Recent investigations estimate the worldwide prevalence of ADHD in children and adolescents to be ~7%, which is a substantial increase compared to a decade ago. Conventional treatment most often includes pharmacotherapy with central nervous stimulants, but the number of non-responders and adverse effects call for treatment alternatives. Exercise has been suggested as a safe and low-cost adjunctive therapy for ADHD and is reported to be accompanied by positive effects on several aspects of cognitive functions in the general child population. Here we review existing evidence that exercise affects cognitive functions in children with and without ADHD and present likely neurophysiological mechanisms of action. We find well-described associations between physical activity and ADHD, as well as causal evidence in the form of small to moderate beneficial effects following acute aerobic exercise on executive functions in children with ADHD. Despite large heterogeneity, meta-analyses find small positive effects of exercise in population-based control (PBC) children, and our extracted effect sizes from long-term interventions suggest consistent positive effects in children and adolescents with ADHD. Paucity of studies probing the effect of different exercise parameters impedes finite conclusions in this regard. Large-scale clinical trials with appropriately timed exercise are needed. In summary, the existing preliminary evidence suggests that exercise can improve cognitive performance intimately linked to ADHD presentations in children with and without an ADHD diagnosis. Based on the findings from both PBC and ADHD children, we cautiously provide recommendations for parameters of exercise

Early-Onset Schizophrenia: Exploring the Contribution of the Thought Disorder Index to Clinical Assessment

Background: Differentiating diagnostically between schizophrenia and emotional and personality disorders with psychotic or psychotic-like symptoms is a challenging task. It is especially difficult when working with adolescent patients, because their symptoms tend to manifest at lower levels as compared with adult patients. Thought disorder is a core symptom of schizophrenia, and the Rorschach Inkblot Method is widely used for the assessment of formal thought disorder. Objective: In this study, which is situated within ongoing clinical practice, we investigated whether the Rorschach test is helpful for assessing early-onset schizophrenia due to its ability to detect thought disorder. We also wanted to examine whether the Thought Disorder Index (TDI) is superior to the Comprehensive System (CS) for differentiating between patients with early-onset schizophrenia and non-psychotic patients experiencing auditory and visual hallucinations. An additional aim was to examine whether the TDI correlated with the Positive and Negative Syndrome Scale (PANSS). Methods: Twenty-three subjects between the ages of 12 and 18 years were examined with the use of the Rorschach test, and the protocols were scored according to both the TDI and the CS. All subjects were also assessed with the Positive and Negative Syndrome Scale. The sample included 14 subjects who fulfilled the criteria for schizophrenia and 9 subjects who were experiencing hallucinations that emanated from severe emotional and relational problems but who had different non-psychotic disorders. Results: Although the two groups could not be distinguished with regard to their total scores for thought disorder, the identification of specific thought disorder types proved useful for differential diagnosis. Verbalizations that were categorized by the TDI as “absurd responses,” “fluidity,” “contamination,” “autistic logic,” and “word-finding difficulty” were only given by patients who had been diagnosed with schizophrenia. When patients’ responses were scored with the use of the CS, the “contamination” score was the only one found to be specific to schizophrenia. Conclusions: Although the sample size limits the conclusions that can be drawn, the results indicate that the TDI may be superior to the CS for the identification of thought disorder specific to—but not always present in—adolescents with schizophrenia. In other words, the absence of severe thought disorder is not synonymous with the absence of severe psychopathology, but the presence of the most severe thought disorder types (i.e., “absurd responses,” “fluidity,” “incoherence,” “contamination,” and “autistic logic”) seems to be a strong indicator of schizophrenic psychopathology

Increased risk of somatic diseases following anorexia nervosa in a controlled nationwide cohort study

OBJECTIVE: To assess the risk of somatic diseases in connection with anorexia nervosa (AN). METHOD: This matched cohort study was based on Danish registries of all patients born 1961-2008 with a first-time diagnosis of AN in 1994-2018 at age 8-32 and matched controls without an eating disorder. For 13 somatic disease categories, time from inclusion date to time of first somatic diagnosis, accounting for censoring, was studied by use of time-stratified Cox models. RESULTS: A total of 9985 AN patients born 1961-2008 and 49,351 controls were followed for a median (interquartile range) of 9.0 (4.4-15.7) years. During the first 2 years after entry there was a 60% higher hazard for any somatic disease among patients with AN than among controls, while the ratio from three to 11 years was reduced to 1.18. Regardless of age at diagnosis, the hazard among patients and controls were no different at approximately a decade after diagnosis of AN and the cumulative risk for patients for 12 of 13 disease categories was always higher or no less that for controls. For all disease categories, the hazard ratio (HR) was higher when close to entry. For most disease categories, age at diagnosis of AN did not modify the effect. DISCUSSION: While around 90% of all individuals had any somatic disease at the end of follow-up, the cumulative incidence over time was higher for patients with AN than for controls. Large HRs were seen in the early years after diagnosis during which patients require extensive medical interventions. PUBLIC SIGNIFICANCE: Based on Danish registries, a large sample of almost 10,000 patients with AN born 1961-2008 and almost 50,000 matched controls were followed for a median of 9 years. While around 90% of all individuals had any somatic disease at the end of follow-up, the cumulative incidence over time was higher for patients with AN than for controls

Enrichment of megabase-sized DNA molecules for single-molecule optical mapping and next-generation sequencing

Abstract Next-generation sequencing (NGS) has caused a revolution, yet left a gap: long-range genetic information from native, non-amplified DNA fragments is unavailable. It might be obtained by optical mapping of megabase-sized DNA molecules. Frequently only a specific genomic region is of interest, so here we introduce a method for selection and enrichment of megabase-sized DNA molecules intended for single-molecule optical mapping: DNA from a human cell line is digested by the NotI rare-cutting enzyme and size-selected by pulsed-field gel electrophoresis. For demonstration, more than 600 sub-megabase- to megabase-sized DNA molecules were recovered from the gel and analysed by denaturation-renaturation optical mapping. Size-selected molecules from the same gel were sequenced by NGS. The optically mapped molecules and the NGS reads showed enrichment from regions defined by NotI restriction sites. We demonstrate that the unannotated genome can be characterized in a locus-specific manner via molecules partially overlapping with the annotated genome. The method is a promising tool for investigation of structural variants in enriched human genomic regions for both research and diagnostic purposes. Our enrichment method could potentially work with other genomes or target specified regions by applying other genomic editing tools, such as the CRISPR/Cas9 system

Sequencing of human genomes extracted from single cancer cells isolated in a valveless microfluidic device

Sequencing the genomes of individual cells enables the direct determination of genetic heterogeneity amongst cells within a population. We have developed an injection-moulded valveless microfluidic device in which single cells from colorectal cancer derived cell lines (LS174T, LS180 and RKO) and fresh colorectal tumors have been individually trapped, their genomes extracted and prepared for sequencing using multiple displacement amplification (MDA). Ninety nine percent of the DNA sequences obtained mapped to a reference human genome, indicating that there was effectively no contamination of these samples from non-human sources. In addition, most of the reads are correctly paired, with a low percentage of singletons (0.17 ± 0.06%) and we obtain genome coverages approaching 90%. To achieve this high quality, our device design and process shows that amplification can be conducted in microliter volumes as long as the lysis is in sub-nanoliter volumes. Our data thus demonstrates that high quality whole genome sequencing of single cells can be achieved using a relatively simple, inexpensive and scalable device. Detection of genetic heterogeneity at the single cell level, as we have demonstrated for freshly obtained single cancer cells, could soon become available as a clinical tool to precisely match treatment with the properties of a patient's own tumor

Parental rating of sleep in children with attention deficit/hyperactivity disorder

Objective: Sleep problems have often been associated with attention deficit/hyperactivity disorder (ADHD). Parents of those with ADHD and children with ADHD report sleep difficulties more frequently than healthy children and their parents. The primary objective of this paper is to describe sleep patterns and problems of 5 to 11-year-old children suffering from ADHD as described by parental reports and sleep questionnaires. Method: The study included 321 children aged 5–11 years (average age 8.4 years); 45 were diagnosed with ADHD, 64 had other psychiatric diagnoses, and 212 were healthy. One hundred and ninety-six of the test subjects were boys and 125 were girls. A semi-structured interview (Kiddie-SADS-PL) was used to DSM-IV diagnose ADHD and comorbidity in the clinical group. Sleep difficulties were rated using a structured sleep questionnaire (Children Sleep Behaviour Scale). Results: Children diagnosed with ADHD had a significantly increased occurrence of sleep problems. Difficulties relating to bedtime and unsettled sleep were significantly more frequent in the ADHD group than in the other groups. Children with ADHD showed prolonged sleep onset latency, but no difference was shown regarding numbers of awakenings per night and total sleep time per night. Comorbid oppositional defiant disorder appeared not to have an added effect on problematic behaviour around bedtime. Conclusion: Parents of children with ADHD report that their children do not sleep properly more often than other parents. The ADHD group report problems with bedtime resistance, problems with sleep onset latency, unsettled sleep and nightmares more often than the control groups. It may therefore be relevant for clinicians to initiate a closer examination of those cases reporting sleep difficulties

International comparisons of behavioral and emotional problems in preschool children: parents’ reports from 24 societies

International comparisons were conducted of preschool children’s behavioral and emotional problems as reported on the Child Behavior Checklist for Ages 1½–5 by parents in 24 societies (N¼19,850). Item ratings were aggregated into scores on syndromes; Diagnostic and Statistical Manual of Mental Disorders–oriented scales; a Stress Problems scale; and Internalizing, Externalizing, and Total Problems scales. Effect sizes for scale score differences among the 24 societies ranged from small to medium (3–12%). Although societies differed greatly in language, culture, and other characteristics, Total Problems scores for 18 of the 24 societies were within 7.1 points of the omnicultural mean of 33.3 (on a scale of 0–198). Gender and age differences, as well as gender and age interactions with society, were all very small (effect sizes<1%). Across all pairs of societies, correlations between mean item ratings averaged .78, and correlations between internal consistency alphas for the scales averaged .92, indicating that the rank orders of mean item ratings and internal consistencies of scales were very similar across diverse societies