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A still expanding body of evidence unequivocally supports the superior efficacy of clozapine compared to other antipsychotics for a considerable number of outcome measures in the treatment of schizophrenia including positive symptoms, negative symptoms, aggression and suicidality. Therefore, clozapine remains the gold standard not only for treatment-resistant schizophrenia but also for a larger number of patients with a poor course of illness. Furthermore, recent meta-analytical evidence clearly demonstrates the superiority of clozapine for reducing all-cause mortality. This finding indicates that clozapine is one of the most potent means to reduce the outrageous mortality gap faced by patients with schizophrenia. Despite its unmatched and wide-ranging efficacy as well as its cost effectiveness, clozapine remains alarmingly underutilized throughout the industrialized world even though patients’ acceptance of clozapine treatment is surprisingly high. While limited, existing evidence indicates that this is primarily due to psychiatrists’ concerns regarding safety and side effect management possibly resulting from insufficient clinical training in using clozapine. This would imply that many patients are never offered clozapine in the first place despite a clear indication. We argue that psychiatrists have an urgent obligation to address this issue and ensure sufficient availability of this vital treatment option. If our fields’ commitment to shared decision-making is to be genuine, we must not exclude patients from the potentially life-changing decision to initiate clozapine treatment. Therefore, concerted research and mental-health policy efforts should focus on identifying barriers for clozapine utilization and effective measures to overcome them. On the one hand, this will require structural changes to clinical training and care systems. On the other and hand – and at least as important – it will require a continued commitment of individual psychiatrists to align their attitudes and clinical practices more closely with the existing evidence and patient preference. The benefits for patients, their families, clinical psychiatry and society will be substantial.

Schizophrene Psychosen sind durch einen hohen Grad an durch Behinderung beeinträchtigter Lebensjahre aber auch deutlich beeinträchtigter Lebensqualität ge-kennzeichnet. Bei ca. 30 % der Patienten zeigt sich im Krankheitsverlauf eine The-rapieresistenz, d.h., eine unzureichende Response auf mehrere lege artis durchge-führte antipsychotische Standardtherapieversuche. Bei therapieresistenter Schizo-phrenie (TRS) ist Clozapin noch immer die einzige wirksame medikamentöse Be-handlungsoption. Hierbei ist Clozapin durch eine gute Wirksamkeit in verschiede-nen Symptomdimensionen charakterisiert. Neben der überlegenen Wirksamkeit bei Positivsymptomatik bestehen positive Effekte auf Negativsymptomatik. Weiterhin senkt Clozapin das Risiko für Suizidversuche und aggressives Verhalten stärker als andere Antipsychotika, gleiches gilt auch für komorbiden Substanzkonsum. Zudem weist Clozapin die stärkste Mortalitätsreduktion aller Antipsychotika auf. Von hoher Relevanz für eine optimale Wirksamkeit ist hierbei der frühzeitige Einsatz von Clo-zapin nach Feststellung einer Therapieresistenz. Trotz der nachgewiesenen Effekte wird Clozapin bei TRS weiterhin zu selten und meist Jahre zu spät verordnet. Haupthinderungsrund ist hierbei wahrscheinlich neben der unzureichenden An-wendung der Therapieresistenzkriterien und der damit verbundenen Leitlinienemp-fehlungen die noch immer weiter verbreitete Furcht vor Nebenwirkungen wie Agra-nulozytose und Myokarditis. Das Ziel dieser Übersichtsarbeit ist es, der ungerecht-fertigten Zurückhaltung beim Einsatz von Clozapin entgegen zu wirken, indem ak-tuelle Erkenntnisse zu den umfassenden positiven Effekten von Clozapin und evi-denzbasierte Handlungsempfehlungen für ein optimales Nebenwirkungsmanage-ments dargestellt werden. Weiterhin werden evidenzbasierte Augmentationsstrate-gien für den Fall einer unzureichenden Therapieresponse unter Clozapin darge-legt.

Studying the visual system with fMRI often requires using localizer paradigms to define regions of interest (ROIs). However, the considerable interindividual variability of the cerebral cortex represents a crucial confound for group-level analyses. Cortex-based alignment (CBA) techniques reliably reduce interindividual macroanatomical variability. Yet, their utility has not been assessed for visual field localizer paradigms, which map specific parts of the visual field within retinotopically organized visual areas. We evaluated CBA for an attention-enhanced visual field localizer, mapping homologous parts of each visual quadrant in 50 participants. We compared CBA with volume-based alignment and a surface-based analysis, which did not include macroanatomical alignment. CBA led to the strongest increase in the probability of activation overlap (up to 86%). At the group level, CBA led to the most consistent increase in ROI size while preserving vertical ROI symmetry. Overall, our results indicate that in addition to the increased signal-to-noise ratio of a surface-based analysis, macroanatomical alignment considerably improves statistical power. These findings confirm and extend the utility of CBA for the study of the visual system in the context of group analyses. CBA should be particularly relevant when studying neuropsychiatric disorders with abnormally increased interindividual macroanatomical variability.

Background Patients with schizophrenia suffer from profound impairments of working memory and selective attention. These cognitive domains show a considerable overlap on both the behavioral and neurophysiological level. Importantly, selective attention appears to be crucial for the selection of information to be encoded into working memory. A number of studies have demonstrated that the efficiency of this “gatekeeper” function influences working memory performance. Furthermore, behavioural evidence indicates, that patients with schizophrenia have a specific deficit when required to suppress irrelevant but highly salient visual information during working memory encoding. Therefore, elucidating the neurophysiological mechanisms underlying the “gatekeeper” function of selective attention for working memory is highly relevant for understanding this deficit in schizophrenia. The aim of the current study was to investigate the neurophysiological correlates of encoding either salient or non-salient information in the presence of distractors of opposite saliency using functional magnetic resonance imaging (fMRI). Furthermore, we wanted to study the impact of additional top-down information guiding the selection of task relevant information. Methods 35 healthy volunteers underwent fMRI in a 3 T Siemens Trio scanner. During a change detection task four Gabor patches (two flickering and two non-flickering) with varying orientations were shown and participants had to memorise the orientations of the Gabor patches. A colored fixation cross was displayed before the stimuli either cueing two (predictive cue) or four (non-predictive cue) Gabor patch locations resulting in a 2 x 2 design of four conditions with the factors salience (flickering vs. non-flickering) and cue (predictive cue vs. non-predictive cue). During retrieval a single Gabor patch was displayed, and participants reported if the orientation was the same or had changed in that location. At the beginning of each block participants were instructed to either encode the flickering or non-flickering patches (targets) whose location could either be cued or uncued. In 80 % of trials, a target was probed during retrieval. Data analysis in Brain Voyager included standard data preprocessing. Additionally, a multiscale curvature driven cortex based alignment procedure was used to minimise macro-anatomical variability between subjects. Subsequently, functional data were analysed using a random-effects multi-subject general linear model (p