Introduction Attention-deficit/hyperactivity disorder (ADHD, OMIM #143 465) represents one of the most prevalent psychiatric disorders with 2 – 8% affected children and adolescents worldwide. The characteristic symptoms are diverse, ranging from hyperactivity and impulsivity over inattention to emotional dysregulation. Previous studies claimed a genetic heritability of 60 – 90% and thereby led to several genomic studies focusing on the identification of genetic variants contributing to ADHD susceptibility.

Introduction The 22q11.2 deletion syndrome (22q11.2DS) is a rare chromosomal syndrome with a prevalence of approximately 0.025%. Affected individuals show a wide range of somatic features, most commonly congenital heart defects, immunodeficiency, hypoparathyroidism and palatal abnormalities. Furthermore, the syndrome is highly comorbid with psychiatric disorders. Among potential biomarkers in a range of modalities are substantia nigra (SN) hyperechogenity (reported in adult 22q11.2DS) and compromised olfactory function (reported in pediatric 22q11.2DS). Regarding fear conditioning and fear generalization, there is a scarcity of research despite the high number of comorbid anxiety disorders.

Introduction Attention-deficit-hyperactivity disorder (ADHD), the most common neurodevelopmental disorder, is characterized by an early childhood-onset and the core symptoms comprise inattention, hyperactivity and impulsivity. Profound research on the identification of potential causes revealed both environmental factors and a strong genetic component as contributors to an increased ADHD susceptibility (Biederman & Faraone, 2005) which helped to identify a number of potential risk genes (Demontis et al., 2019, Elia et al., 2015).

Abstract Objectives: During the last two decades transcranial sonography (TCS) of the brain parenchyma evolved from a pure research tool to a clinical relevant neuroimaging method especially in Parkinson’s disease and related movement disorders. The aim of this systematic review is to update and summarise the published TCS findings in psychiatric disorders and critically address the question whether TCS may be a valuable tool for the diagnosis or differential diagnosis of psychiatric disorders similarly to the field of movement disorders. Methods: This paper provides detailed information about the perspectives and limitations of TCS, including guidelines for the scanning procedures, assessment of midbrain structures and discusses the potential causes of the ultrasound abnormalities in psychiatric disorders. Results: Changes in the echogenicity of subcortical brain structures were detected in different disorders, such as obsessive-compulsive disorder, autism spectrum disorder, schizophrenia, panic disorder, attention-deficit/hyperactivity (ADHD), bipolar disorder and depressive disorder. Although the physical properties of brain tissue underlying the echogenic features in TCS are largely unknown, no alternative technique provides the same insight into the specific central nervous structural characteristics. Conclusions: Urgent research questions to further clarify the underlying pathophysiological and structural alterations are further outlined to bring this promising technique to the clinic.

Alpha-motoneurons and muscle fibres are structurally and functionally interdependent. Both cell types particularly rely on endoplasmic reticulum (ER/SR) functions. Mutations of the ER proteins VAPB, SigR1 and HSP27 lead to hereditary motor neuron diseases (MNDs). Here, we determined the expression profile and localization of these ER proteins/chaperons by immunohistochemistry and immunoblotting in biopsy and autopsy muscle tissue of patients with amyotrophic lateral sclerosis (ALS) and other neurogenic muscular atrophies (NMAs) and compared these patterns to mouse models of neurogenic muscular atrophy. Postsynaptic neuromuscular junction staining for VAPB was intense in normal human and mouse muscle and decreased in denervated Nmd(2J) mouse muscle fibres. In contrast, VAPB levels together with other chaperones and autophagy markers were increased in extrasynaptic regions of denervated muscle fibres of patients with MNDs and other NMAs, especially at sites of focal myofibrillar disintegration (targets). These findings did not differ between NMAs due to ALS and other causes. G93A-SOD1 mouse muscle fibres showed a similar pattern of protein level increases in denervated muscle fibres. In addition, they showed globular VAPB-immunoreactive structures together with misfolded SOD1 protein accumulations, suggesting a primary myopathic change. Our findings indicate that altered expression and localization of these ER proteins and autophagy markers are part of the dynamic response of muscle fibres to denervation. The ER is particularly prominent and vulnerable in both muscle fibres and alpha-motoneurons. Thus, ER pathology could contribute to the selective build-up of degenerative changes in the neuromuscular axis in MNDs.

In rodents, the five-choice serial reaction time task (5-CSRTT) has been established as a reliable measure of waiting impulsivity being defined as the ability to regulate a response in anticipation of reinforcement. Key brain structures are the nucleus accumbens (NAcc) and prefrontal regions (for example, pre- and infralimbic cortex), which are, together with other transmitters, modulated by serotonin. In this functional magnetic resonance imaging study, we examined 103 healthy males while performing the 5-CSRTT measuring brain activation in humans by means of a paradigm that has been widely applied in rodents. Subjects were genotyped for the tryptophan hydroxylase-2 (TPH2; G-703T; rs4570625) variant, an enzyme specific for brain serotonin synthesis. We addressed neural activation patterns of waiting impulsivity and the interaction between the NAcc and the ventromedial prefrontal cortex (vmPFC) using dynamic causal modeling. Genetic influence was examined via interaction analyses between the TPH2 genotype (GG homozygotes vs T allele carriers) and the degree of impulsivity as measured by the 5-CSRTT. We found that the driving input of the vmPFC was reduced in highly impulsive T allele carriers (reflecting a reduced top-down control) in combination with an enhanced response in the NAcc after correct target processing (reflecting an augmented response to monetary reward). Taken together, we found a high overlap of our findings with reports from animal studies in regard to the underlying cognitive processes, the brain regions associated with waiting impulsivity and the neural interplay between the NAcc and vmPFC. Therefore, we conclude that the 5-CSRTT is a promising tool for translational studies.