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Pawley, Adam D. ; Mayer, Jutta ; Medda, Juliane ; Brandt, Geva A. ; Agnew-Blais, Jessica C. ; Asherson, Philip ; Rommel, Anna-Sophie ; Ramos-Quiroga, J. Antoni ; Palacio Sanchez, Judit ; Bergsma, Douwe ; Buitelaar, Jan K. ; Ortega, Francisco B. ; Muntaner-Mas, Adrià ; Grimm, Oliver ; Reif, Andreas ; Freitag, Christine M. ; Kuntsi, Jonna
Beyond well-established difficulties with working memory in individuals with attention deficit hyperactivity disorder (ADHD), evidence is emerging that other memory processes may also be affected. We investigated, first, which memory processes show differences in adults and adolescents with ADHD in comparison to control participants, focusing on working and short-term memory, initial learning, interference, delayed and recognition memory. Second, we investigated whether ADHD severity, co-occurring depressive symptoms, IQ and physical fitness are associated with the memory performance in the individuals with ADHD.
We assessed 205 participants with ADHD (mean age 25.8 years, SD 7.99) and 50 control participants (mean age 21.1 years, SD 5.07) on cognitive tasks including the digit span forward (DSF) and backward (DSB), the Rey Auditory Verbal Learning Test (RAVLT), and the vocabulary and matrix reasoning subtests of the Wechsler Abbreviated Scale of Intelligence. Participants with ADHD were additionally assessed on ADHD severity, depression symptoms and cardiorespiratory fitness. A series of regressions were run, with sensitivity analyses performed when variables were skewed.
ADHD-control comparisons were significant for DSF, DSB, delayed and recognition memory, with people with ADHD performing less well than the control participants. The result for recognition memory was no longer significant in sensitivity analysis. Memory performance was not associated with greater ADHD or depression symptoms severity. IQ was positively associated with all memory variables except DSF. Cardiorespiratory fitness was negatively associated with the majority of RAVLT variables.
Individuals with ADHD showed difficulties with working memory, short-term memory and delayed memory, as well as a potential difficulty with recognition memory, despite preserved initial learning.
Koromina, Maria ; Ravi, Ashvin ; Panagiotaropoulou, Georgia ; Schilder, Brian M. ; Humphrey, Jack ; Braun, Alice ; Bidgeli, Tim ; Chatzinakos, Chris ; Coombes, Brandon ; Kim, Jaeyoung ; Liu, Xiaoxi ; Terao, Chikashi ; O'Connell, Kevin S. ; Adams, Mark ; Adolfsson, Rolf ; Alda, Martin ; Alfredsson, Lars ; Andlauer, Till ; Andreassen, Ole A. ; Antoniou, Anastasia ; Baune, Bernhard T. ; Bengesser, Susanne ; Biernacka, Joanna ; Boehnke, Michael ; Bosch, Rosa ; Cairns, Murray ; Carr, Vaughan J. ; Casas Brugué, Miquel ; Catts, Stanley ; Cichon, Sven ; Corvin, Aiden ; Craddock, Nicholas ; Dafnas, Konstantinos ; Dalkner, Nina ; Dannlowski, Udo ; Degenhardt, Franziska ; Di Florio, Arianna ; Dikeos, Dimitris ; Fellendorf, Frederike Tabea ; Ferentinos, Panagiotis ; Forstner, Andreas Josef ; Forty, Liz ; Frye, Mark ; Fullerton, Janice M. ; Gawlik, Micha ; Gizer, Ian R. ; Gordon-Smith, Katherine ; Green, Melissa J. ; Grigoroiu-Serbanescu, Maria ; Guzman-Parra, José ; Hahn, Tim ; Henskens, Frans ; Hillert, Jan ; Jablensky, Assen V. ; Jones, Lisa ; Jones, Ian ; Jonsson, Lina ; Kelsoe, John R. ; Kircher, Tilo ; Kirov, George ; Kittel-Schneider, Sarah ; Kogevinas, Manolis ; Landén, Mikael ; Leboyer, Marion ; Lenger, Melanie ; Lissowska, Jolanta ; Lochner, Christine ; Loughland, Carmel ; MacIntyre, Donald ; Martin, Nicholas G. ; Maratou, Eirini ; Mathews, Carol A. ; Mayoral, Fermı́n ; McElroy, Susan L. ; McGregor, Nathaniel W. ; McIntosh, Andrew M. ; McQuillin, Andrew ; Michie, Patricia ; Milanova, Vihra ; Mitchell, Philip B. ; Moutsatsou, Paraskevi ; Mowry, Bryan ; Müller-Myhsok, Bertram ; Myers, Richard M. ; Nenadić, Igor ; Nöthen, Markus Maria ; O'Donovan, Claire ; O'Donovan, Michael ; Ophoff, Roel André ; Owen, Michael J. ; Pantelis, Christos ; Pato, Carlos ; Pato, Michele T. ; Patrinos, George P. ; Pawlak, Joanna M. ; Perlis, Roy H. ; Porichi, Evgenia ; Posthuma, Danielle ; Ramos-Quiroga, Josep Antoni ; Reif, Andreas ; Reininghaus, Eva Z. ; Ribasés, Marta ; Rietschel, Marcella ; Schall, Ulrich ; Schulze, Thomas Gerd ; Scott, Laura J. ; Scott, Rodney J. ; Serretti, Alessandro ; Shannon Weickert, Cynthia ; Smoller, Jordan W. ; Soler Artigas, Marı́a ; Stein, Dan J. ; Streit, Fabian ; Toma, Claudio ; Tooney, Paul ; Vieta, Eduard ; Vincent, John B. ; Waldman, Irwin D. ; Weickert, Thomas ; Witt, Stephanie H. ; Hong, Kyung Sue ; Ikeda, Masashi ; Iwata, Nakao ; Świątkowska, Beata ; Won, Hong-Hee ; Edenberg, Howard J. ; Ripke, Stephan ; Raj, Towfique ; Coleman, Jonathan R. I. ; Mullins, Niamh
Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).
Bruckner, Franz ; Gruber, Judith R. ; Ruf, Alea ; Edwin Thanarajah, Sharmili ; Reif, Andreas ; Matura, Silke
Lifestyle factors—such as diet, physical activity (PA), smoking, and alcohol consumption—have a significant impact on mortality as well as healthcare costs. Moreover, they play a crucial role in the development of type 2 diabetes mellitus (DM2). There also seems to be a link between lifestyle behaviours and insulin resistance, which is often a precursor of DM2. This study uses an enhanced Healthy Living Index (HLI) integrating accelerometric data and an Ecological Momentary Assessment (EMA) to explore differences in lifestyle between insulin-sensitive (IS) and insulin-resistant (IR) individuals. Moreover, it explores the association between lifestyle behaviours and inflammation. Analysing data from 99 participants of the mPRIME study (57 women and 42 men; mean age 49.8 years), we calculated HLI scores—ranging from 0 to 4— based on adherence to specific low-risk lifestyle behaviours, including non-smoking, adhering to a healthy diet, maximally moderate alcohol consumption, and meeting World Health Organization (WHO) PA guidelines. Insulin sensitivity was assessed using a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and C-reactive protein (CRP) levels were used as a proxy for inflammation. Lifestyle behaviours, represented by HLI scores, were significantly different between IS and IR individuals (U = 1529.0; p = 0.023). The difference in the HLI score between IR and IS individuals was mainly driven by lower adherence to PA recommendations in the IR group. Moreover, reduced PA was linked to increased CRP levels in the IR group (r = −0.368, p = 0.014). Our findings suggest that enhancing PA, especially among individuals with impaired insulin resistance, holds significant promise as a preventive strategy.
O’Connell, Kevin S. ; Koromina, Maria ; van der Veen, Tracey ; Boltz, Toni ; David, Friederike S. ; Kay Yang, Jessica Mei ; Lin, Keng-Han ; Wang, Xin ; Coleman, Jonathan R. I. ; Mitchell, Brittany L. ; McGrouther, Caroline C. ; Rangan, Aaditya V. ; Lind, Penelope A. ; Koch, Elise ; Harder, Arvid ; Parker, Nadine ; Bendl, Jaroslav ; Adorjan, Kristina ; Agerbo, Esben ; Albani, Diego ; Alemany, Silvia ; Alliey-Rodriguez, Ney ; Als, Thomas D. ; Andlauer, Till F. M. ; Antoniou, Anastasia ; Ask, Helga ; Bass, Nicholas ; Bauer, Michael ; Beins, Eva C. ; Bigdeli, Tim B. ; Pedersen, Carsten Bøcker ; Boks, Marco P. ; Børte, Sigrid ; Bosch, Rosa ; Brum, Murielle ; Brumpton, Ben M. ; Brunkhorst-Kanaan, Nathalie ; Budde, Monika ; Bybjerg-Grauholm, Jonas ; Byerley, William ; Cabana-Domínguez, Judit ; Cairns, Murray J. ; Carpiniello, Bernardo ; Casas, Miquel ; Cervantes, Pablo ; Chatzinakos, Chris ; Chen, Hsi-Chung ; Clarence, Tereza ; Clarke, Toni-Kim ; Claus, Isabelle ; Coombes, Brandon ; Corfield, Elizabeth C. ; Cruceanu, Cristiana ; Cuellar-Barboza, Alfredo ; Czerski, Piotr M. ; Dafnas, Konstantinos ; Dale, Anders M. ; Dalkner, Nina ; Degenhardt, Franziska ; DePaulo, J. Raymond ; Djurovic, Srdjan ; Drange, Ole Kristian ; Escott-Price, Valentina ; Fanous, Ayman H. ; Fellendorf, Frederike T. ; Ferrier, I. Nicol ; Forty, Liz ; Frank, Josef ; Frei, Oleksandr ; Freimer, Nelson B. ; Fullard, John F. ; Garnham, Julie ; Gizer, Ian R. ; Gordon, Scott D. ; Gordon-Smith, Katherine ; Greenwood, Tiffany A. ; Grove, Jakob ; Guzman-Parra, José ; Ha, Tae Hyon ; Hahn, Tim ; Haraldsson, Magnus ; Hautzinger, Martin ; Havdahl, Alexandra ; Heilbronner, Urs ; Hellgren, Dennis ; Herms, Stefan ; Hickie, Ian B. ; Hoffmann, Per ; Holmans, Peter A. ; Huang, Ming-Chyi ; Ikeda, Masashi ; Jamain, Stéphane ; Johnson, Jessica S. ; Jonsson, Lina ; Kalman, Janos L. ; Kamatani, Yoichiro ; Kennedy, James L. ; Kim, Euitae ; Kim, Jaeyoung ; Kittel-Schneider, Sarah ; Knowles, James A. ; Kogevinas, Manolis ; Kranz, Thorsten M. ; Krebs, Kristi ; Kushner, Steven A. ; Lavebratt, Catharina ; Lawrence, Jacob ; Leber, Markus ; Lee, Heon-Jeong ; Liao, Calwing ; Lucae, Susanne ; Lundberg, Martin ; MacIntyre, Donald J. ; Maier, Wolfgang ; Maihofer, Adam X. ; Malaspina, Dolores ; Manchia, Mirko ; Maratou, Eirini ; Martinsson, Lina ; Mattheisen, Manuel ; McGregor, Nathaniel W. ; McInnis, Melvin G. ; McKay, James D. ; Medeiros, Helena ; Meyer-Lindenberg, Andreas ; Millischer, Vincent ; Morris, Derek W. ; Moutsatsou, Paraskevi ; Mühleisen, Thomas W. ; O’Donovan, Claire ; Olsen, Catherine M. ; Panagiotaropoulou, Georgia ; Papiol, Sergi ; Pardiñas, Antonio F. ; Park, Hye Youn ; Perry, Amy ; Pfennig, Andrea ; Pisanu, Claudia ; Potash, James B. ; Quested, Digby ; Rapaport, Mark H. ; Regeer, Eline J. ; Rice, John P. ; Rivera, Margarita ; Schulte, Eva C. ; Senner, Fanny ; Shadrin, Alexey ; Shilling, Paul D. ; Sigurdsson, Engilbert ; Sindermann, Lisa ; Sirignano, Lea ; Siskind, Dan ; Slaney, Claire ; Sloofman, Laura G. ; Smeland, Olav B. ; Smith, Daniel J. ; Sobell, Janet L. ; Soler Artigas, Maria ; Stein, Dan J. ; Stein, Frederike ; Su, Mei-Hsin ; Sung, Heejong ; Świątkowska, Beata ; Terao, Chikashi ; Tesfaye, Markos ; Tesli, Martin ; Thorgeirsson, Thorgeir E. ; Thorp, Jackson G. ; Toma, Claudio ; Tondo, Leonardo ; Tooney, Paul A. ; Tsai, Shih-Jen ; Tsermpini, Evangelia Eirini ; Vawter, Marquis P. ; Vedder, Helmut ; Vreeker, Annabel ; Walters, James T. R. ; Winsvold, Bendik S. ; Witt, Stephanie H. ; Won, Hong-Hee ; Ye, Robert ; Young, Allan H. ; Zandi, Peter P. ; Zillich, Lea ; Adolfsson, Rolf ; Alda, Martin ; Alfredsson, Lars ; Backlund, Lena ; Baune, Bernhard T. ; Bellivier, Frank ; Bengesser, Susanne ; Berrettini, Wade H. ; Biernacka, Joanna M. ; Boehnke, Michael ; Børglum, Anders D. ; Breen, Gerome ; Carr, Vaughan J. ; Catts, Stanley ; Cichon, Sven ; Corvin, Aiden ; Craddock, Nicholas ; Dannlowski, Udo ; Dikeos, Dimitris ; Etain, Bruno ; Ferentinos, Panagiotis ; Frye, Mark ; Fullerton, Janice M. ; Gawlik, Micha ; Gershon, Elliot S. ; Goes, Fernando S. ; Green, Melissa J. ; Grigoroiu-Serbanescu, Maria ; Hauser, Joanna ; Henskens, Frans A. ; Hjerling-Leffler, Jens ; Hougaard, David M. ; Hveem, Kristian ; Iwata, Nakao ; Jones, Ian ; Jones, Lisa A. ; Kahn, René S. ; Kelsoe, John R. ; Kircher, Tilo ; Kirov, George ; Kuo, Po-Hsiu ; Landén, Mikael ; Leboyer, Marion ; Li, Qingqin S. ; Lissowska, Jolanta ; Lochner, Christine ; Loughland, Carmel ; Luykx, Jurjen J. ; Martin, Nicholas G. ; Mathews, Carol A. ; Mayoral, Fermin ; McElroy, Susan L. ; McIntosh, Andrew M. ; McMahon, Francis J. ; Medland, Sarah E. ; Melle, Ingrid ; Milani, Lili ; Mitchell, Philip B. ; Morken, Gunnar ; Mors, Ole ; Mortensen, Preben Bo ; Müller-Myhsok, Bertram ; Myers, Richard M. ; Myung, Woojae ; Neale, Benjamin M. ; Nievergelt, Caroline M. ; Nordentoft, Merete ; Nöthen, Markus M. ; Nurnberger, John I. ; O’Donovan, Michael C. ; Oedegaard, Ketil J. ; Olsson, Tomas ; Owen, Michael J. ; Paciga, Sara A. ; Pantelis, Christos ; Pato, Carlos N. ; Pato, Michele T. ; Patrinos, George P. ; Pawlak, Joanna M. ; Ramos-Quiroga, Josep Antoni ; Reif, Andreas ; Reininghaus, Eva Z. ; Ribasés, Marta ; Rietschel, Marcella ; Ripke, Stephan ; Rouleau, Guy A. ; Roussos, Panos ; Saito, Takeo ; Schall, Ulrich ; Schalling, Martin ; Schofield, Peter R. ; Schulze, Thomas G. ; Scott, Laura J. ; Scott, Rodney J. ; Serretti, Alessandro ; Smoller, Jordan W. ; Squassina, Alessio ; Stahl, Eli A. ; Stefansson, Hreinn ; Stefansson, Kari ; Stordal, Eystein ; Streit, Fabian ; Sullivan, Patrick F. ; Turecki, Gustavo ; Vaaler, Arne E. ; Vieta, Eduard ; Vincent, John B. ; Waldman, Irwin D. ; Weickert, Cynthia S. ; Weickert, Thomas W. ; Werge, Thomas ; Whiteman, David C. ; Zwart, John-Anker ; Edenberg, Howard J. ; McQuillin, Andrew ; Forstner, Andreas J. ; Mullins, Niamh ; Di Florio, Arianna ; Ophoff, Roel A. ; Andreassen, Ole A.
Changes in glutamatergic neuroplasticity has been proposed as one of the core mechanisms underlying the pathophysiology of depression. In consequence components of the glutamatergic synapse have been explored as potential targets for antidepressant treatment. The rapid antidepressant effect of the NMDA receptor antagonist ketamine and subsequent approval of its S-enantiomer (i.e. esketamine), have set the precedent for investigation into other glutamatergic rapid acting antidepressants (RAADs). In this review, we discuss the potential of the different glutamatergic targets for antidepressant treatment. We describe important clinical outcomes of several key molecules targeting components of the glutamatergic synapse and their applicability as RAADs. Specifically, here we focus on substances beyond (es)ketamine, for which meaningful data from clinical trials are available, including arketamine, esmethadone, nitrous oxide and other glutamate receptor modulators. Molecules only successful in preclinical settings and case reports/series are only marginally discussed. With this review, we aim underscore the critical role of glutamatergic modulation in advancing antidepressant therapy, thereby possibly enhancing clinical outcomes but also to reducing the burden of depression through faster therapeutic effects.
Highlights
• Up-to-date overview on developing new medications including candidates with novel bioloigical targets for the treatment of anxiety disorders and PTSD.
• Targeting glutamatergic, cholinergic and neurosteroid mechanisms can produce acute anxiolytic effects.
• Drugs, including psychedelics, are hypothesized to produce neuroplasticity to cause enduring clinical effects.
• Combining medication with psychological approaches may augment therapeutic efficacy.
• Advances in circuit neuroscience can be leveraged to inform the design of rationale drug targets.
Abstract
Psychiatric disorders associated with psychological trauma, stress and anxiety are a highly prevalent and increasing cause of morbidity worldwide. Current therapeutic approaches, including medication, are effective in alleviating symptoms of anxiety disorders and posttraumatic stress disorder (PTSD), at least in some individuals, but have unwanted side-effects and do not resolve underlying pathophysiology. After a period of stagnation, there is renewed enthusiasm from public, academic and commercial parties in designing and developing drug treatments for these disorders. Here, we aim to provide a snapshot of the current state of this field that is written for neuropharmacologists, but also practicing clinicians and the interested lay-reader. After introducing currently available drug treatments, we summarize recent/ongoing clinical assessment of novel medicines for anxiety and PTSD, grouped according to primary neurochemical targets and their potential to produce acute and/or enduring therapeutic effects. The evaluation of putative treatments targeting monoamine (including psychedelics), GABA, glutamate, cannabinoid, cholinergic and neuropeptide systems, amongst others, are discussed. We emphasize the importance of designing and clinically assessing new medications based on a firm understanding of the underlying neurobiology stemming from the rapid advances being made in neuroscience. This includes harnessing neuroplasticity to bring about lasting beneficial changes in the brain rather than – as many current medications do – produce a transient attenuation of symptoms, as exemplified by combining psychotropic/cognitive enhancing drugs with psychotherapeutic approaches. We conclude by noting some of the other emerging trends in this promising new phase of drug development.
Luderer, Mathias ; Seidt, Johanna ; Gerhardt, Sarah ; Hoffmann, Sabine ; Vollstädt-Klein, Sabine ; Reif, Andreas ; Sobanski, Esther
Rationale: Attention deficit/hyperactivity disorder (ADHD) is common in alcohol use disorder (AUD). Continuous performance tests (CPTs) allow to measure ADHD related deficits in a laboratory setting. Most studies on this topic focused on CPTs measuring inattention or impulsivity, disregarding hyperactivity as one of the core symptoms of ADHD.
Methods: We examined N = 47 in three groups (ADHD N = 19; AUD N = 16; ADHD + AUD N = 12) with questionnaires on ADHD core symptoms, executive functioning (EF), mind wandering, and quality of life (QoL). N = 46 (ADHD N = 16; AUD N = 16; ADHD + AUD N = 14) were examined with a CPT (QbTest®) that also measures motor activity objectively.
Results: Inattention and impulsivity were significantly increased in AUD vs. ADHD and in AUD vs. ADHD + AUD. Hyperactivity was significantly higher in ADHD + AUD vs. ADHD and ADHD + AUD vs. AUD, but not in ADHD vs. AUD. EF was lower in both ADHD groups vs. AUD. Mind wandering was increased in both ADHD groups vs. AUD. QoL was significantly lower in ADHD + AUD compared to AUD. In contrast, results of the QbTest were not significantly different between groups.
Conclusion: Questionnaires are more useful in assessing ADHD core symptoms than the QbTest®. Hyperactivity appears to be a relevant symptom in ADHD + AUD, suggesting a possible pathway from ADHD to AUD. The lower QoL in ADHD + AUD emphasizes the need for routine screening, diagnostic procedures and treatment strategies for this patient group.
Aichholzer, Mareike ; Schiweck, Carmen ; Uckermark, Carmen ; Hamzehloiya, Tirage ; Reif-Leonhard, Christine ; Golbach, Rejane ; Reif, Andreas ; Edwin Thanarajah, Sharmili
Background: The COVID-19 pandemic led to a higher incidence of depression and a worsening of psychiatric conditions, while pre-existing constraints of the healthcare system and safety regulations limited psychiatric care.
Aims: We investigated the impact of the pandemic on the clinical care of patients with a single episode (SE-MDD) or major depressive disorder (MDD) in Germany.
Methods: Nationwide inpatient data were extracted from the German Institute for Hospital Remuneration System for 2020 and 2021 (depression data) and the Robert Koch Institute (COVID-19 incidence). Changes in inpatients were tested with linear regression models. Local cases of depression in our department compared to 2019 were explored with one-way ANOVA and Dunnett's test.
Results: Across Germany, the inpatient numbers with both SE-MDD and MDD declined by more than 50% during three out of four COVID-19 waves. Higher COVID-19 incidence correlated with decreased inpatient numbers. In our department, fewer MDD inpatients were treated in 2020 (adj. p < 0.001) and 2021 (adj. p < 0.001) compared to 2019, while the number of SE-MDD inpatients remained stable. During this period fewer elective and more emergency inpatients were admitted. In parallel, MDD outpatient admissions increased in 2021 compared to 2019 (adj. p = 0.002) and 2020 (adj. p = 0.003).
Conclusion: During high COVID-19 infection rates, MDD patients received less inpatient care, which might cause poor outcomes in the near future. These data highlight the necessity for improved infrastructure in the in- and outpatient domains to facilitate accessibility to adequate care.
Cabana-Domínguez, Judit ; Antón-Galindo, Ester ; Fernàndez-Castillo, Noèlia ; Singgih, Euginia L. ; O'Leary, Aet ; Norton, William H. G. ; Strekalova, Tatyana ; Schenck, Annette ; Reif, Andreas ; Lesch, Klaus-Peter J. ; Slattery, David A. ; Cormand, Bru
Highlights
• Overview on functional work performed in rodent, zebrafish and fruit fly models of ADHD and its comorbidities.
• Comprehensive search for new genetically modified mouse models to study ADHD-related and comorbid traits.
• Review of behavioral assays available in animal models to test ADHD-related and comorbid traits.
• Animal models to assess environmental effects contributing to the epigenetic mechanisms of ADHD and comorbidities.
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder resulting from the interaction between genetic and environmental risk factors. It is well known that ADHD co-occurs frequently with other psychiatric disorders due, in part, to shared genetics factors. Although many studies have contributed to delineate the genetic landscape of psychiatric disorders, their specific molecular underpinnings are still not fully understood. The use of animal models can help us to understand the role of specific genes and environmental stimuli-induced epigenetic modifications in the pathogenesis of ADHD and its comorbidities. The aim of this review is to provide an overview on the functional work performed in rodents, zebrafish and fruit fly and highlight the generated insights into the biology of ADHD, with a special focus on genetics and epigenetics. We also describe the behavioral tests that are available to study ADHD-relevant phenotypes and comorbid traits in these models. Furthermore, we have searched for new models to study ADHD and its comorbidities, which can be useful to test potential pharmacological treatments.
Einführung: Seit 20 Jahren ist die Vagusnervstimulation (VNS) eine europaweit zugelassene invasive Therapieoption für therapieresistente Depressionen (TRD). Im Gegensatz zu geläufigeren Behandlungen wie EKT sind Kenntnisse über VNS sowohl in der Allgemeinbevölkerung als auch in Fachkreisen gering.
Methoden: In diesem narrativen Review geben wir eine klinisch und wissenschaftlich fundierte Übersicht über die VNS. Hypothesen zum Wirkmechanismus sowie die aktuelle Evidenzlage zur Wirksamkeit werden dargestellt. Das perioperative Management, das Nebenwirkungsprofil und die Nachbetreuung einschließlich Dosistitration werden beschrieben. Ein Vergleich über internationale Leitlinienempfehlungen zur VNS findet sich ebenfalls. Ferner formulieren wir Kriterien, die bei der Auswahl geeigneter Patienten hilfreich sind.
Ergebnisse: Die elektrischen Impulse werden über den N. vagus afferent weitergeleitet und stimulieren über verschiedene Wege ein neuromodulatorisches zerebrales Netzwerk. Viele Studien und Fallserien zeigten die Wirksamkeit von VNS als adjuvantes Verfahren bei TRD. Der Effekt tritt mit einer Latenz von 3 bis 12 Monaten ein und steigt möglicherweise mit der Dauer der VNS. Unter der Beachtung der Stimulationsempfehlungen sind die Nebenwirkungen für die meisten Patienten tolerabel.
Fazit: Die VNS ist eine zugelassene, wirksame und gut verträgliche Langzeittherapie für chronische und therapieresistente Depressionen. Weitere Sham-kontrollierte Studien über einen längeren Beobachtungszeitraum sind zur Verbesserung der Evidenz wünschenswert.