scholarly journals Altered kynurenine pathway metabolites in a mouse model of human attention-deficit hyperactivity/autism spectrum disorders: A potential new biological diagnostic marker

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yuki Murakami ◽  
Yukio Imamura ◽  
Kuniaki Saito ◽  
Daisuke Sakai ◽  
Jun Motoyama
Keyword(s):  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Kynurenine Pathway ◽  
Autism Spectrum ◽  
Behavioral Deficits ◽  
Diagnostic Biomarkers ◽  
Hyperactivity Disorder ◽  
Spectrum Disorders ◽  
Almost All ◽  
The Brain

Abstract Deleterious mutations in patchd1 domain containing 1 (PTCHD1) gene have been identified in patients with intellectual disability and/or autism spectrum disorder (ASD). To clarify the causal relationship between Ptchd1 deficiency and behavioral defects relevant to neurodevelopmental disorders, we generated global Ptchd1 knockout (KO) mice. Ptchd1 KO mice displayed hyperlocomotion, increased impulsivity, and lower recognition memory, which resemble attention-deficit hyperactivity disorder (ADHD)-like behaviors. Acute or chronic treatment with atomoxetine ameliorated almost all behavioral deficits in Pthcd1 KO mice. We next determined possible involvement of the kynurenine pathway (KP) metabolites in neurodevelopmental disorders in Ptchd1 KO mice and assessed the potential of KP metabolites as biomarkers for ADHD and/or ASD. Ptchd1 KO mice showed drastic changes in KP metabolite concentrations in the serum and the brain, indicating that the activated KP is associated with ADHD-like behaviors. Our findings indicate that Ptchd1 KO mice can be used as an animal model of human ADHD and/or ASD, and KP metabolites are potential diagnostic biomarkers for neurodevelopmental disorders.

scholarly journals Attention-deficit/hyperactivity disorder and risk for psychiatric and neurodevelopmental disorders in siblings

2018 ◽  
Vol 49 (1) ◽  
pp. 84-91 ◽  
Author(s):  
Elina Jokiranta-Olkoniemi ◽  
Keely Cheslack-Postava ◽  
Petteri Joelsson ◽  
Auli Suominen ◽  
Alan S. Brown ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Population Based ◽  
Autism Spectrum ◽  
Schizophrenia Spectrum Disorders ◽  
Hyperactivity Disorder ◽  
Increased Risk ◽  
Spectrum Disorders

AbstractBackgroundProbands with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for several psychiatric and neurodevelopmental disorders. The risk of these disorders among the siblings of probands has not been thoroughly assessed in a population-based cohort.MethodsEvery child born in Finland in 1991–2005 and diagnosed with ADHD in 1995–2011 were identified from national registers. Each case was matched with four controls on sex, place, and date of birth. The full siblings of the cases and controls were born in 1981–2007 and diagnosed in 1981–2013. In total, 7369 cases with 12 565 siblings and 23 181 controls with 42 753 siblings were included in the analyses conducted using generalized estimating equations.Results44.2% of the cases and 22.2% of the controls had at least one sibling diagnosed with any psychiatric or neurodevelopmental disorder (risk ratio, RR = 2.1; 95% CI 2.0–2.2). The strongest associations were demonstrated for childhood-onset disorders including ADHD (RR = 5.7; 95% CI 5.1–6.3), conduct and oppositional disorders (RR = 4.0; 95% CI 3.5–4.5), autism spectrum disorders (RR = 3.9; 95% CI 3.3–4.6), other emotional and social interaction disorders (RR = 2.7; 95% CI 2.4–3.1), learning and coordination disorders (RR = 2.6; 95% CI 2.4–2.8), and intellectual disability (RR = 2.4; 95% CI 2.0–2.8). Also, bipolar disorder, unipolar mood disorders, schizophrenia spectrum disorders, other neurotic and personality disorders, substance abuse disorders, and anxiety disorders occurred at increased frequency among the siblings of cases.ConclusionsThe results offer potential utility for early identification of neurodevelopmental and psychiatric disorders in at-risk siblings of ADHD probands and also argue for more studies on common etiologies.

scholarly journals Association of maternal diabetes with neurodevelopmental disorders: autism spectrum disorders, attention-deficit/hyperactivity disorder and intellectual disability

2020 ◽  
Author(s):  
Shuyun Chen ◽  
Sixian Zhao ◽  
Christina Dalman ◽  
Håkan Karlsson ◽  
Renee Gardner
Keyword(s):  
Diabetes Mellitus ◽  
Attention Deficit Hyperactivity Disorder ◽  
Autism Spectrum Disorders ◽  
Intellectual Disability ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Maternal Diabetes ◽  
Autism Spectrum ◽  
Hyperactivity Disorder ◽  
Spectrum Disorders

Abstract Background Maternal diabetes has been associated with a risk of neurodevelopmental disorders (NDDs) in offspring, though the common co-occurrence of autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) and intellectual disability (ID) is rarely considered, nor is the potential for confounding by shared familial factors (e.g. genetics). Methods This population-based cohort study used data from Psychiatry Sweden, a linkage of Swedish national registers, to follow 2 369 680 individuals born from 1987 to 2010. We used population-averaged logit models to examine the association between exposure to maternal type 1 diabetes mellitus (T1DM), pre-gestational type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM), and odds of NDDs in offspring. Subgroup analysis was then performed to investigate the timings of GDM diagnosis during pregnancy and its effect on the odds of NDDs in offspring. We compared these results to models considering paternal lifetime T1DM and T2DM as exposures. Results Overall, 45 678 individuals (1.93%) were diagnosed with ASD, 20 823 (0.88%) with ID and 102 018 (4.31%) with ADHD. All types of maternal diabetes were associated with odds of NDDs, with T2DM most strongly associated with any diagnosis of ASD (odds ratioadjusted 1.37, 95% confidence interval 1.03–1.84), ID (2.09, 1.53–2.87) and ADHD (1.43, 1.16–1.77). Considering common co-morbid groups, the associations were strongest between maternal diabetes and diagnostic combinations that included ID. Paternal T1DM and T2DM diagnoses were also associated with offspring NDDs, but these associations were weaker than those with maternal diabetes. Diagnosis of GDM between 27 and 30 weeks of gestation was generally associated with the greatest risk of NDDs in offspring, with the strongest associations for outcomes that included ID. Conclusion The association of maternal diabetes with NDDs in offspring varies depending on the co-morbid presentation of the NDDs, with the greatest odds associated with outcomes that included ID. Results of paternal-comparison studies suggest that the above associations are likely to be partly confounded by shared familial factors, such as genetic liability.

scholarly journals Reduction of cortical parvalbumin expressing GABAergic interneurons in a rodent hyperoxia model of preterm birth brain injury with deficits in social behavior and cognition

Development ◽  
2021 ◽  
Author(s):  
Till Scheuer ◽  
Elena auf dem Brinke ◽  
Sabine Grosser ◽  
Susanne A. Wolf ◽  
Daniele Mattei ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Psychiatric Symptoms ◽  
Autism Spectrum ◽  
Morphological Properties ◽  
Behavioral Deficits ◽  
Hyperactivity Disorder ◽  
Spectrum Disorders ◽  
The Brain ◽  
Psychiatric Problems ◽  
Behavior And Cognition

The inhibitory GABAergic system in the brain is involved in the etiology of various psychiatric problems, including autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and others. These disorders are influenced not only by genetic but also by environmental factors, such as preterm birth, although the mechanisms underlying are not known. In a translational hyperoxia model, exposing mice pups at age P5 to 80% oxygen for 48 hours to mimic a steep rise of oxygen exposure caused by preterm birth from in utero into room air, we documented a persistent reduction of cortical mature parvalbumin expressing interneurons until adulthood. Developmental delay of cortical myelin was observed together with decreased expression of oligodendroglial glial cell-derived neurotrophic factor (GDNF), a factor being involved in interneuronal development. Electrophysiological and morphological properties of remaining interneurons were unaffected. Behavioral deficits were observed for social interaction, learning, and attention. These results elucidate that neonatal oxidative stress can lead to decreased interneuron density and to psychiatric symptoms. The obtained cortical myelin deficit and decreased oligodendroglial GDNF expression indicate an impaired oligodendroglial-interneuronal interplay contributes to interneuronal damage.

Attention-deficit/hyperactivity disorder and other neurodevelopmental disorders in offspring of parents with depression and bipolar disorder

2021 ◽  
pp. 1-8
Author(s):  
L. Propper ◽  
A. Sandstrom ◽  
S. Rempel ◽  
E. Howes Vallis ◽  
S. Abidi ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Attention Deficit Hyperactivity Disorder ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Mood Disorder ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Major Depressive ◽  
Hyperactivity Disorder

Abstract Background Offspring of parents with major mood disorders (MDDs) are at increased risk for early psychopathology. We aim to compare the rates of neurodevelopmental disorders in offspring of parents with bipolar disorder, major depressive disorder, and controls. Method We established a lifetime diagnosis of neurodevelopmental disorders [attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disabilities, specific learning disorders, and motor disorders] using the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version in 400 participants (mean age 11.3 + s.d. 3.9 years), including 93 offspring of parents with bipolar disorder, 182 offspring of parents with major depressive disorder, and 125 control offspring of parents with no mood disorder. Results Neurodevelopmental disorders were elevated in offspring of parents with bipolar disorder [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.23–4.47, p = 0.010] and major depressive disorder (OR 1.87, 95% CI 1.03–3.39, p = 0.035) compared to controls. This difference was driven by the rates of ADHD, which were highest among offspring of parents with bipolar disorder (30.1%), intermediate in offspring of parents with major depressive disorder (24.2%), and lowest in controls (14.4%). There were no significant differences in frequencies of other neurodevelopmental disorders between the three groups. Chronic course of mood disorder in parents was associated with higher rates of any neurodevelopmental disorder and higher rates of ADHD in offspring. Conclusions Our findings suggest monitoring for ADHD and other neurodevelopmental disorders in offspring of parents with MDDs may be indicated to improve early diagnosis and treatment.

scholarly journals Socioemotional profiles of autism spectrum disorders, attention deficit hyperactivity disorder, and disinhibited and reactive attachment disorders: a symptom comparison and network approach

2021 ◽  
pp. 1-10
Author(s):  
Barry Coughlan ◽  
Matt Woolgar ◽  
Marinus H. van IJzendoorn ◽  
Robbie Duschinsky
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Autism Spectrum Disorders ◽  
Attention Deficit ◽  
Autism Spectrum ◽  
Attachment Disorders ◽  
Hyperactivity Disorder ◽  
Children With Asd ◽  
Significant Difference ◽  
Reactive Attachment ◽  
Spectrum Disorders

Abstract Children with autism spectrum disorders (ASDs), attention deficit hyperactivity disorder (ADHD) and disinhibited and reactive attachment disorders (RAD/DAD) often experience socioemotional problems. Elucidating a clear picture of these profiles is essential. Strengths and Difficulties Questionnaires (SDQs) were analysed from cohort of children with ASD (n = 1430), ADHD (n = 1193), and RAD/DAD (n = 39). Kruskal–Wallis Tests and network analytic techniques were used to investigate symptom profiles. Children with ASD experienced more emotional problems, peer problems and fewer prosocial behaviours. Children with ADHD and RAD/DAD had higher levels of hyperactivity and conduct problems. Overall, ASD and ADHD networks were highly correlated (rs = 0.82), and we did not observe a statistically significant difference in terms of global Strength.

scholarly journals Human Plasma Glycome in Attention-Deficit Hyperactivity Disorder and Autism Spectrum Disorders

2010 ◽  
Vol 10 (1) ◽  
pp. M110.004200 ◽  
Author(s):  
Nela Pivac ◽  
Ana Knežević ◽  
Olga Gornik ◽  
Maja Pučić ◽  
Wilmar Igl ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Autism Spectrum Disorders ◽  
Human Plasma ◽  
Attention Deficit ◽  
Autism Spectrum ◽  
Hyperactivity Disorder ◽  
Spectrum Disorders
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