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Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation treatment used as an alternative or complementary treatment for various neuropsychiatric disorders, and could be an alternative or add-on therapy to psychostimulants in attention-deficit hyperactivity disorder (ADHD). Previous studies provided some evidence for improvements in cognition and clinical symptoms in pediatric and adult ADHD patients. However, data from multi-center randomized controlled trials (RCTs) for this condition are lacking. Thus, our aim is to evaluate short- and mid-term effects of tDCS in this multi-center, randomized, double blind, and sham-controlled, parallel group clinical trial with a 1:1 randomization ratio. Primary endpoint is the total score of DSM-IV scale of the internationally established Conners' Adult ADHD Rating Scales (German self-report screening version, CAARS-S-SR), at day 14 post-intervention (p.i.) to detect short-term lasting effects analyzed via analyses of covariance (ANCOVAs). In case of significant between-groups differences at day 14 p.i., hierarchically ordered hypotheses on mid-term lasting effects will be investigated by linear mixed models with visit (5 time points), treatment, treatment by visit interaction, and covariates as fixed categorical effects plus a patient-specific visit random effect, using an unstructured covariance structure to model the residual within-patient errors. Positive results of this clinical trial will expand the treatment options for adult ADHD patients with tDCS and provide an alternative or add-on therapy to psychostimulants with a low risk for side effects. Trial Registration The trial was registered on July 29, 2022 in the German Clinical Trials Register (DRKS00028148). [ABSTRACT FROM AUTHOR]

Aggression occurs across the population ranging on a symptom continuum. Most previous studies have used magnetic resonance imaging in clinical/forensic samples, which is associated with several confounding factors. The present study examined structural brain characteristics in two healthy samples differing only in their propensity for aggressive behavior. Voxel- and surface-based morphometry (SBM) analyses were performed on 29 male martial artists and 32 age-matched male controls. Martial artists had significantly increased mean gray matter volume in two frontal (left superior frontal gyrus and bilateral anterior cingulate cortex) and one parietal (bilateral posterior cingulate gyrus and precuneus) brain clusters compared to controls (whole brain: p < 0.001, cluster level: family-wise error (FWE)-corrected). SBM analyses revealed a trend for greater gyrification indices in martial artists compared to controls in the left lateral orbital frontal cortex and the left pars orbitalis (whole brain: p < 0.001, cluster level: FWE-corrected). The results indicate brain structural differences between martial artists and controls in frontal and parietal brain areas critical for emotion processing/inhibition of emotions as well as empathic processes. The present study highlights the importance of studying healthy subjects with a propensity for aggressive behavior in future structural MRI research on aggression. [ABSTRACT FROM AUTHOR]

Hintergrund: Die Definition von Langzeitverläufen der Depression ist heterogen. Vor allem chronische und therapieresistente Verläufe bedeuten einen hohen Kostenfaktor und reduzieren Lebensqualität stark. Ausgehend von der pharmakotherapeutischen „therapieresistenten Depression“ (TRD) rücken immer mehr systemische Ansätze in den Vordergrund.Dieses narrative Review bietet eine Übersicht zu Langzeitverläufen depressiver Erkrankungen, inklusive verschiedener Definitionen und Einflussfaktoren. Zudem wird eine Übersicht zur Biomarkerforschung des Therapieansprechens mit Fokus auf zentrale Bildgebung vorgestellt.Es erfolgte eine selektive Literaturrecherche in PubMed und Google Scholar für ein narratives Review. Besonders berücksichtigt wurden größere Kohortenstudien, systematische Reviews, Metaanalysen und Studien zur Prädiktion von Therapieansprechen.Chronische und therapieresistente Verläufe bedeuten eine relevante Reduktion von Lebensqualität sowie erhöhte gesundheitliche Risiken. Die Erfassung des Therapieansprechens ist eine definitorische Herausforderung: Eine Alternative zur TRD bietet die systemisch orientierte „schwer zu behandelnde Depression“ („difficult-to-treat depression“, DTD). Der Fokus bewegt sich damit fort von einer Symptomreduktion hin zu einer Kontrolle des Funktionsniveaus. Biomarkerforschung für Therapieansprechen bietet Potenzial, dient derzeit aber hauptsächlich dem theoretischen Erkenntnisgewinn.Die Erfassung von Langzeitverläufen depressiver Erkrankungen ist wichtig, aber auch komplex. Klinische Interventionen sollten daher ein kontinuierliches Monitoring miteinschließen und den Fokus auf den Erhalt von Lebensqualität legen.Ziel der Arbeit: Die Definition von Langzeitverläufen der Depression ist heterogen. Vor allem chronische und therapieresistente Verläufe bedeuten einen hohen Kostenfaktor und reduzieren Lebensqualität stark. Ausgehend von der pharmakotherapeutischen „therapieresistenten Depression“ (TRD) rücken immer mehr systemische Ansätze in den Vordergrund.Dieses narrative Review bietet eine Übersicht zu Langzeitverläufen depressiver Erkrankungen, inklusive verschiedener Definitionen und Einflussfaktoren. Zudem wird eine Übersicht zur Biomarkerforschung des Therapieansprechens mit Fokus auf zentrale Bildgebung vorgestellt.Es erfolgte eine selektive Literaturrecherche in PubMed und Google Scholar für ein narratives Review. Besonders berücksichtigt wurden größere Kohortenstudien, systematische Reviews, Metaanalysen und Studien zur Prädiktion von Therapieansprechen.Chronische und therapieresistente Verläufe bedeuten eine relevante Reduktion von Lebensqualität sowie erhöhte gesundheitliche Risiken. Die Erfassung des Therapieansprechens ist eine definitorische Herausforderung: Eine Alternative zur TRD bietet die systemisch orientierte „schwer zu behandelnde Depression“ („difficult-to-treat depression“, DTD). Der Fokus bewegt sich damit fort von einer Symptomreduktion hin zu einer Kontrolle des Funktionsniveaus. Biomarkerforschung für Therapieansprechen bietet Potenzial, dient derzeit aber hauptsächlich dem theoretischen Erkenntnisgewinn.Die Erfassung von Langzeitverläufen depressiver Erkrankungen ist wichtig, aber auch komplex. Klinische Interventionen sollten daher ein kontinuierliches Monitoring miteinschließen und den Fokus auf den Erhalt von Lebensqualität legen.Material und Methoden: Die Definition von Langzeitverläufen der Depression ist heterogen. Vor allem chronische und therapieresistente Verläufe bedeuten einen hohen Kostenfaktor und reduzieren Lebensqualität stark. Ausgehend von der pharmakotherapeutischen „therapieresistenten Depression“ (TRD) rücken immer mehr systemische Ansätze in den Vordergrund.Dieses narrative Review bietet eine Übersicht zu Langzeitverläufen depressiver Erkrankungen, inklusive verschiedener Definitionen und Einflussfaktoren. Zudem wird eine Übersicht zur Biomarkerforschung des Therapieansprechens mit Fokus auf zentrale Bildgebung vorgestellt.Es erfolgte eine selektive Literaturrecherche in PubMed und Google Scholar für ein narratives Review. Besonders berücksichtigt wurden größere Kohortenstudien, systematische Reviews, Metaanalysen und Studien zur Prädiktion von Therapieansprechen.Chronische und therapieresistente Verläufe bedeuten eine relevante Reduktion von Lebensqualität sowie erhöhte gesundheitliche Risiken. Die Erfassung des Therapieansprechens ist eine definitorische Herausforderung: Eine Alternative zur TRD bietet die systemisch orientierte „schwer zu behandelnde Depression“ („difficult-to-treat depression“, DTD). Der Fokus bewegt sich damit fort von einer Symptomreduktion hin zu einer Kontrolle des Funktionsniveaus. Biomarkerforschung für Therapieansprechen bietet Potenzial, dient derzeit aber hauptsächlich dem theoretischen Erkenntnisgewinn.Die Erfassung von Langzeitverläufen depressiver Erkrankungen ist wichtig, aber auch komplex. Klinische Interventionen sollten daher ein kontinuierliches Monitoring miteinschließen und den Fokus auf den Erhalt von Lebensqualität legen.Ergebnisse: Die Definition von Langzeitverläufen der Depression ist heterogen. Vor allem chronische und therapieresistente Verläufe bedeuten einen hohen Kostenfaktor und reduzieren Lebensqualität stark. Ausgehend von der pharmakotherapeutischen „therapieresistenten Depression“ (TRD) rücken immer mehr systemische Ansätze in den Vordergrund.Dieses narrative Review bietet eine Übersicht zu Langzeitverläufen depressiver Erkrankungen, inklusive verschiedener Definitionen und Einflussfaktoren. Zudem wird eine Übersicht zur Biomarkerforschung des Therapieansprechens mit Fokus auf zentrale Bildgebung vorgestellt.Es erfolgte eine selektive Literaturrecherche in PubMed und Google Scholar für ein narratives Review. Besonders berücksichtigt wurden größere Kohortenstudien, systematische Reviews, Metaanalysen und Studien zur Prädiktion von Therapieansprechen.Chronische und therapieresistente Verläufe bedeuten eine relevante Reduktion von Lebensqualität sowie erhöhte gesundheitliche Risiken. Die Erfassung des Therapieansprechens ist eine definitorische Herausforderung: Eine Alternative zur TRD bietet die systemisch orientierte „schwer zu behandelnde Depression“ („difficult-to-treat depression“, DTD). Der Fokus bewegt sich damit fort von einer Symptomreduktion hin zu einer Kontrolle des Funktionsniveaus. Biomarkerforschung für Therapieansprechen bietet Potenzial, dient derzeit aber hauptsächlich dem theoretischen Erkenntnisgewinn.Die Erfassung von Langzeitverläufen depressiver Erkrankungen ist wichtig, aber auch komplex. Klinische Interventionen sollten daher ein kontinuierliches Monitoring miteinschließen und den Fokus auf den Erhalt von Lebensqualität legen.Diskussion: Die Definition von Langzeitverläufen der Depression ist heterogen. Vor allem chronische und therapieresistente Verläufe bedeuten einen hohen Kostenfaktor und reduzieren Lebensqualität stark. Ausgehend von der pharmakotherapeutischen „therapieresistenten Depression“ (TRD) rücken immer mehr systemische Ansätze in den Vordergrund.Dieses narrative Review bietet eine Übersicht zu Langzeitverläufen depressiver Erkrankungen, inklusive verschiedener Definitionen und Einflussfaktoren. Zudem wird eine Übersicht zur Biomarkerforschung des Therapieansprechens mit Fokus auf zentrale Bildgebung vorgestellt.Es erfolgte eine selektive Literaturrecherche in PubMed und Google Scholar für ein narratives Review. Besonders berücksichtigt wurden größere Kohortenstudien, systematische Reviews, Metaanalysen und Studien zur Prädiktion von Therapieansprechen.Chronische und therapieresistente Verläufe bedeuten eine relevante Reduktion von Lebensqualität sowie erhöhte gesundheitliche Risiken. Die Erfassung des Therapieansprechens ist eine definitorische Herausforderung: Eine Alternative zur TRD bietet die systemisch orientierte „schwer zu behandelnde Depression“ („difficult-to-treat depression“, DTD). Der Fokus bewegt sich damit fort von einer Symptomreduktion hin zu einer Kontrolle des Funktionsniveaus. Biomarkerforschung für Therapieansprechen bietet Potenzial, dient derzeit aber hauptsächlich dem theoretischen Erkenntnisgewinn.Die Erfassung von Langzeitverläufen depressiver Erkrankungen ist wichtig, aber auch komplex. Klinische Interventionen sollten daher ein kontinuierliches Monitoring miteinschließen und den Fokus auf den Erhalt von Lebensqualität legen. [ABSTRACT FROM AUTHOR]

The Habenula is increasingly being investigated in addiction. Reduced volumes of other relevant brain regions in addiction, such as nucleus accumbens, globus pallidus and hypothalamus have been reported. Reduced volumes of the habenula as well as reduced neuronal cell count in the habenula have also been reported in mood disorders and an overlap between mood disorders and addiction is clinically widely recognized. Thus, our aim was to investigate possible volume and neuronal cell count differences in heroin addicts compared to healthy controls. Volumes of the medial (MHB) and lateral habenula (LHB) in heroin addicts (n = 12) and healthy controls (n = 12) were assessed by morphometry of 20 µm serial whole brain sections. Total brain volume was larger in the heroin group (mean 1466.6 ± 58.5 cm3 vs. mean 1331.5 ± 98.8 cm3), possibly because the heroin group was about 15 years younger (p = 0.001). Despite larger mean whole brain volume, the mean relative volume of the MHB was smaller than in healthy non-addicted controls (6.94 ± 2.38 × 10–6 vs.10.64 ± 3.22 × 10−6; p = 0.004). A similar finding was observed regarding relative volumes of the LHB (46.62 ± 10.90 × 10−6 vs. 63.05 ± 16.42 × 10−6p = 0.009). In parallel, neuronal cell numbers were reduced in the MHB of heroin-addicted subjects (395,966 ± 184,178 vs. 644,149 ± 131,140; p < 0.001). These findings were not significantly confounded by age and duration of autolysis. Our results provide further evidence for brain-structural deficits in heroin addiction. [ABSTRACT FROM AUTHOR]

Exercise improves both physical and mental health and increases neurogenesis in the dendate gyrus (DG) of the hippocampus. The aim of this study was to examine whether exercising, as compared to no change in regular physical activity, would impact on hippocampal volume, and in particular the core hippocampal structures, DG and cornu ammonis (CA) subfields, and whether any changes would be moderated by age. Thirty nine previously sedentary healthy participants were randomized to either a standardized progressive aerobic exercise program or to "no change" for 16 weeks. Mental health including profile of mood states (POMS), was assessed before and every 4 weeks during the program. Magnetic resonance imaging to examine hippocampal subfields was carried out before and after the program. Aerobic exercise resulted in a significant improvement of the POMS item 'vigour' compared to those in the control group. Overall left hippocampal and left CA4-DG volumes increased significantly in the exercise group while no significant changes were seen in the control group. Older adults in the control group demonstrated significant reductions in CA4-DG subfields over the study, whereas older adults in the exercise group did not show volume decline. These findings reinforce the literature that exercise has a beneficial effect on mental health and can prevent age-related volume decline. Exercise to Improve Resilience, https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4, NCT02541136, Rec Ref 2011/45/13. [ABSTRACT FROM AUTHOR]

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Deep brain stimulation (DBS) of the globus pallidus internus was recently proposed as a potential new treatment target for opioid addiction. DBS requires computer-assisted-3D planning to implant the stimulation electrode precisely. As volumes of brain regions may differ in addiction compared to healthy controls, our aim was to investigate possible volume differences in addicts compared to healthy controls. Volumes of the globus pallidus externus (PE) and internus (PI) in heroin addicts (n = 14) and healthy controls (n = 12) were assessed using morphometry of serial whole-brain sections. Total brain volume was larger in the heroin group (mean 1479 ± 62 cm3 vs. mean 1352 ± 103 cm3), as the heroin group was more than 10 years younger (p = 0.001). Despite larger mean whole brain volume, the mean relative volume of the PE and PI was smaller in addicted subjects compared to healthy controls (PE 0.658 ± 0.183 × 10−3 vs. 0.901 ± 0.284 × 10−3; ANOVA F(1, 24) = 6.945, p = 0.014, η2 = 0.224; PI 0.253 ± 0.095 × 10−3 vs. 0.345 ± 0.107 × 10−3; ANOVA F(1, 24) = 5.374, p = 0.029, η2 = 0.183). These findings were not significantly confounded by age, duration of autolysis, and fixation time. Our results provide further evidence for structural and not only functional deficits of the globus pallidus in addiction. In the context of previous studies, our findings support the idea of shared pathophysiological processes between comorbid depression and impulsivity in opioid addiction. [ABSTRACT FROM AUTHOR]

The role of monocytes and macrophages in the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD) is poorly understood. Recently, we have shown that the number of CD14+ monocytes remained constant during healthy aging and in AD patients. Although only little is known about the function of activated macrophages and microglia in AD, one important mechanism involves the expression of quinolinic acid (QUIN), an endogenous N-methyl-D-aspartate glutamate receptor (NMDA-R) agonist which mediates excitotoxicity especially in the hippocampus. We used immunofluorescence stainings of PBMCs to determine the expression of quinolinic acid (QUIN) and the MHC class II molecule HLA-DR in peripheral monocytic cells in 51 healthy volunteers aged 22-87 years and 43 patients with AD at diagnosis (0 weeks) and during the course of rivastigmine treatment at 0.25 year (12 weeks), 0.5 year (30 weeks), 1 year, and 1.5 years. The number of QUIN+ HLA-DR+ cells rises in healthy persons aged 30-40 years compared to persons aged 60-70 years, indicating that this cell population increases with aging. AD patients at diagnosis had an increased frequency of QUIN+, QUIN+ HLA-DR+, and QUIN+ HLA-DR+/HLA-DR+ cells compared to aged-matched controls. These cell populations remained increased in AD for up to one year after initiation of treatment with rivastigmine; no alterations were detected in aged healthy persons. We conclude that the expression of the neurotoxic agent QUIN is increased in peripheral monocytes from AD patients. These cells could enter the brain and contribute to excitotoxicity. [ABSTRACT FROM AUTHOR]

N-Methyl-D-aspartate glutamate receptor (NMDA-R) antibodies (Abs) could play a role in neurodegenerative disorders. Since, in these diseases, NMDA-R Abs were detected in serum, but only sporadic in cerebrospinal fluid (CSF), the origin and impact of the Abs are still unresolved. We examined the presence of NMDA-R Abs in serum and CSF using a cell-based immunofluorescence assay as well as the function of the blood-CSF-barrier (B-CSF-B) by determination of Q albumin (ratio of albumin in CSF and serum) in patients with mild cognitive impairment (MCI; N = 59) and different types of dementia, Alzheimer’s disease (AD; N = 156), subcortical ischemic vascular dementia (SIVD; N = 61), and frontotemporal dementia (FTD; N = 34). Serum IgA/IgM NMDA-R Abs and/or a disturbed B-CSF-B were sporadically present in all investigated patients’ groups. In AD, these Abs often developed during the disease course. Patients with either no hippocampal atrophy and/or no AD-related characteristic changes in CSF, referred to “non-classical” AD, were characterized by seropositivity at diagnosis and loss of function of the B-CSF-B showed a progressive decline in cognitive functions and a poor prognosis. Our data indicate that NMDA-R Abs are present in different types of dementia and elderly healthy individuals. In combination with disturbed B-CSF-B integrity, they seem to promote their pathological potential on cognitive decline, and thus, a subgroup of dementia patients with these unique characteristics might inform clinicians. [ABSTRACT FROM AUTHOR]

The hypothalamus is at the core of the stress responses systems of the brain. Most interestingly, even though changes of HPA-function have been observed in opiate addiction not much is known about structural changes of the hypothalamus. Volumes of hypothalamus in heroin addicts (n = 14) and healthy controls (n = 12) were assessed by using morphometry of serial whole-brain sections. Total brain volume was larger in the heroin group (mean 1478.85 ± 62.34 cm3 vs. mean 1352.38 ± 103.24 cm3), as the heroin group was more than 10 years younger (p = 0.001). Thus, diagnosis-related effects in the hypothalamus were assessed using the hypothalamus volume relative to whole brain volume showing reduced volumes of the hypothalamus in the heroin group (0.201 ± 0.074 × 10−3 vs. 0.267 ± 0.048 × 10−3; ANOVA: F(1,23) = 6.211, p = 0.020) with a strong hemispheric effect (left side: about 20% reduction 0.209 ± 0.080 × 10−3 vs. 0.264 ± 0.049 × 10−3; F = 4.109; p = 0.054; right side: about 27% reduction, 0.198 ± 0.069 × 10−3 vs. 0.271 ± 0.050 × 10−3; F = −8.800; p = 0.007). Our results provide further evidence for structural and not only functional deficits of the hypothalamus in addiction. [ABSTRACT FROM AUTHOR]

Oxidative stress and immune dysregulation have been linked to schizophrenia and depression. However, it is unknown whether these factors are related to the pathophysiology or whether they are an epiphenomenon. Inconsistent oxidative stress-related findings in previous studies may have resulted from the use of different biomarkers which show disparate aspects of oxidative stress. Additionally, disease severity, medication, smoking, endocrine stress axis activation and obesity are potential confounders. In order to address some of these shortcomings, we have analyzed a broader set of oxidative stress biomarkers in our exploratory study, including urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), 8-OH-2-deoyxguanosine (8-OH-2-dG), and blood levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione S-transferase (GST) in acutely ill drug-naïve first episode patients with schizophrenia (n = 22), major depression (n = 18), and controls (n = 43). Possible confounding factors were considered, and patients were followed-up after 6 weeks of treatment. No differences were observed regarding 8-OH-2-dG, MDA and GST. At baseline, 8-iso-PGF2α levels were higher in patients with schizophrenia (p = 0.004) and major depression (p = 0.037), with a trend toward higher SOD concentrations in schizophrenia (p = 0.053). After treatment, schizophrenia patients showed a further increase in 8-iso-PGF2α (p = 0.016). These results were not related to age, sex, disease severity, medication or adipose tissue mass. However, 8-iso-PGF2α was associated with smoking, endocrine stress axis activation, C-reactive protein levels and low plasma concentrations of brain-derived neurotrophic factor. This study suggests a role of lipid peroxidation particularly in drug-naïve acutely ill schizophrenia patients and highlights the importance of taking into account other confounding factors in biomarker studies. [ABSTRACT FROM AUTHOR]

Psychiatric disorders are amongst the most prevalent and impairing conditions in childhood and adolescence. Unfortunately, it is well known that general practitioners (GPs) and other frontline health providers (i.e., child protection workers, public health nurses, and pediatricians) are not adequately trained to address these ubiquitous problems (Braddick et al. Child and Adolescent mental health in Europe: infrastructures, policy and programmes, European Communities, 2009; Levav et al. Eur Child Adolesc Psychiatry 13:395-401, 2004). Advances in technology may offer a solution to this problem with clinical decision support systems (CDSS) that are designed to help professionals make sound clinical decisions in real time. This paper offers a systematic review of currently available CDSS for child and adolescent mental health disorders prepared according to the PRISMA-Protocols (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols). Applying strict eligibility criteria, the identified studies ( n = 5048) were screened. Ten studies, describing eight original clinical decision support systems for child and adolescent psychiatric disorders, fulfilled inclusion criteria. Based on this systematic review, there appears to be a need for a new, readily available CDSS for child neuropsychiatric disorder which promotes evidence-based, best practices, while enabling consideration of national variation in practices by leveraging data-reuse to generate predictions regarding treatment outcome, addressing a broader cluster of clinical disorders, and targeting frontline practice environments. [ABSTRACT FROM AUTHOR]

Previous diffusion tensor imaging (DTI) studies have shown that various factors can affect white matter (WM) tract diffusivity. The aim of the present study was to investigate the effects of childhood adversity (CA), age and gender on WM diffusivity in tracts that are thought to be involved in emotional regulation in individuals with major depressive disorder (MDD) and healthy controls (HC). DTI was obtained from 46 subjects with MDD and 46 HC subjects. Data were pre-processed and deterministic tractography was applied in the cingulum, uncinate fasciculus (UF), fornix, superior longitudinal fasciculus (SLF) and fronto-occipital fasciculus (FOF). In subjects with a history of CA, fractional anisotropy (FA) was greater in the rostral cingulum (RC) and dorsal cingulum, whereas radial diffusivity (RD) was smaller in the RC when compared with subjects with no history of CA. In the UF, FOF and parahippocampal cingulum, FA was greater in the left hemisphere in the subjects with CA when compared with those without CA. Age affected FA, longitudinal diffusivity and RD in the UF, fornix, FOF and SLF, reflecting axonal and myelin degeneration with increasing age. Depression or gender did not have any effects on the diffusivity measures. Due to the cross-sectional nature of the study, a recall bias for CA and possible effects of medical treatment on diffusivity measures could have played a role. CA and age could increase the likelihood to develop WM microstructural anomalies in the brain affective network. Moreover, subjects with CA could be more vulnerable to FA changes. [ABSTRACT FROM AUTHOR]