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ZUSAMMENFASSUNGDie Borderline-Persönlichkeitsstörung (BPS) und, unabhängig davon, nicht suizidales selbstverletzendes Verhalten (NSSV) sind äußerst prävalente psychiatrische Störungsbilder, welche häufig mit weiteren psychischen Komorbiditäten einhergehen. Dennoch gibt es wenige wissenschaftliche Untersuchungen zu den zugrunde liegenden Mechanismen, die zudem der Verbesserung derzeitiger Behandlungsmöglichkeiten dienen können. Da Cannabiskonsum häufig zur Selbstmedikation bei Patienten mit BPS und NSSV eingesetzt wird und Cannabismissbrauch vermehrt vorkommt, liegt die Untersuchung des Endocannabinoidsystems (ECS) als potenziellen Modulator der Psychopathologie nahe. Des Weiteren sind die Stressverarbeitung als zugrunde liegender Faktor und die Funktionsfähigkeit des endokrinologischen Systems, welches eine zentrale Rolle in der Entwicklung und Aufrechterhaltung der BPS und NSSV spielt, eng mit dem ECS verbunden, welches unter anderem für die Modulation der Hypothalamus-Hypophysen-Nebennierenrinden (HPA)-Achse bekannt ist. Auch wenn mehr Forschung nötig ist, hat das ECS großes Potenzial die Behandlungsmöglichkeiten zu erweitern.

ZUSAMMENFASSUNGDie wissenschaftliche Untersuchung der Herzratenvariabilität im Kontext psychiatrischer Forschungs- und Anwendungsmöglichkeiten hat in den letzten Jahren aufgrund des zunehmenden Verständnisses von psychophysiologischen Vorgängen, aufkommendem Interesse an Biofeedbackverfahren und bestehenden sportmedizinischen Erkenntnissen deutlich zugenommen. Erste translationale Studien erschließen mögliche Zusammenhänge zwischen Herzratenvariabilität und psychischen Störungsbildern sowie anderen neurobiologischen Korrelaten. Hinweise, dass die Herzratenvariabilität eng mit psychologischen Konstrukten wie Emotionsregulation oder Schmerzwahrnehmung verknüpft ist, legen nahe, dass dies auch für psychiatrische Symptome wie selbstverletzendes Verhalten gelten könnte, und dass auf diese Weise neue Interventionsperspektiven erschlossen oder bestehende Therapien ergänzt werden könnten. Studien zur konkreten Interaktion von Herzratenvariabilität und selbstverletzendem Verhalten, die eine Implementierung innerhalb therapeutischer Ansätze ermöglichen würden, stehen noch aus. Die folgende Arbeit stellt eine Übersicht mit Fokus auf der Forschung zur Herzratenvariabilität bei selbstverletzendem Verhalten dar.

ZUSAMMENFASSUNGSymptome einer spielbezogenen Verhaltensstörung (Gaming Disorder) sind in der 11. Auflage der International Classification of Diseases mit validen Kriterien beschrieben. Bei einer Prävalenz von 2–3 % ist nach Einführung der neuen Klassifizierung mit klinischen Vorstellungen entsprechender Patienten zu rechnen. Für die Einschätzung einer behandlungsbedürftigen Störung sind neben den Symptomen und Risikofaktoren auch die Kenntnis der rezipierten Spiele relevant, weil die Art der Bezahlung (Monetarisierungsformen) mit der Entwicklung einer Gaming Disorder in Verbindung gebracht wird.In der vorliegenden Arbeit wurde eine klinische Stichprobe von 151 Spielern auf Symptome der Gaming Disorder (anhand des standardisierten Fragebogens Ten Item Internet Gaming Disorder Test) sowie ihren Spielepräferenzen hin untersucht. Die genannten Spiele wurden hinsichtlich einzelner Merkmale analysiert und für problematische und normale Spieler beschrieben. Neben der weiten Verbreitung potenziell räuberischer Monetarisierungsformen in unserer Stichprobe wurden von problematischen Spielern häufiger Spiele mit zufälligen Belohnungen (Lootboxen) konsumiert, die Ähnlichkeiten zu Glücksspielen aufweisen. Es werden Gründe für Lootbox-Engagement und gesellschaftspolitische Implikationen diskutiert sowie Folgerungen für die Forschung und die Praxis gezogen.

ZUSAMMENFASSUNGObwohl Dissoziation einer der ältesten Forschungsgegenstände der Psychiatrie darstellt, bleibt sie bis heute ein vage definiertes und mannigfaltiges Konstrukt. Ausgeprägte dissoziative Symptome sind für eine Subgruppe von Patienten mit Borderline-Persönlichkeitsstörung (BPS) und posttraumatischer Belastungsstörung (PTBS) charakteristisch und von hoher klinischer Relevanz mit Prävalenzen von 19–34 % bei BPS und bis zu 60 % bei PTBS. Insbesondere Veränderungen der psychischen Integrität mit einer Entfremdung von Selbst und Umwelt (Derealisation/Depersonalisation) gehen mit einer ausgeprägteren BPS- und PTBS-Symptomatik sowie riskanten Verhaltensweisen wie Selbstverletzung und Suizidalität einher. Dissoziative Symptome können nach dem aktuellen Kenntnisstand als eine unwillkürliche und automatische maladaptive Form der Emotionsregulation eingestuft werden, bei welcher subjektiv eine Distanz zu internalen oder externalen bedrohlichen Ereignissen hergestellt wird, die aber objektiv mit einer erhöhten Stressreaktion und autonomer Erregung aufzutreten scheint. Insbesondere bei der BPS wirken sich dissoziative Symptome negativ auf das Behandlungsergebnis aus, während die konkrete Adressierung von Dissoziationen beispielsweise durch Psychoedukation, Achtsamkeit oder Fertigkeitentraining Therapieerfolge verbessert.

ZUSAMMENFASSUNGComputer-, Video- und Mobilespiele (digitale Spiele) sind ein weit verbreitetes Massenmedium, das in allen Altersklassen und sozialen Schichten vertreten ist. Damit im Zusammenhang stehende Krankheitsbilder sind im Abschnitt für Forschungsdiagnosen des Diagnostic and Statistical Manual of Mental Disorders (DSM-5) als Internet Gaming Disorder und den Vorabversionen der International Statistical Classification of Diseases and Related Health Problems (ICD-11) als Gaming Disorder definiert. In der Literatur kontrovers diskutiert wird neben der Notwendigkeit einer möglichen Überpathologisierung von Alltagsverhalten die nosologische Einordnung als Suchterkrankung versus Impulskontrollstörung. Hinweise zur Einordnung als Suchtverhalten geben zum einen Validierungsstudien der Diagnosekriterien, in welchen mit Toleranzentwicklung, Kontrollverlust und Vernachlässigung anderer Aktivitäten allgemeine Suchtkriterien zur Voraussage einer Beeinträchtigung als geeignet eingeschätzt werden. Zum anderen zeigen neurobiologische und bildgebende Befunde eine deutliche Übereinstimmung der Veränderungen bei Konsumenten digitaler Spiele mit denen, wie sie auch bei stoffgebundenen Suchterkrankungen beobachtet wurden. Hilfreich bei einer Risikoeinschätzung für die Entwicklung eines psychiatrisch relevanten Syndroms kann die Kenntnis von Spielmechaniken und Bezahlmodellen digitaler Spiele sein, welche nach lerntheoretischer Konzeption zur Entstehung beitragen können: Gestaffelter Fortschritt im Spiel (Progressionssysteme) mit an saliente Reize gekoppelte Belohnungen zur Charakteraufwertung, der Spieleinstieg ohne Bezahlung (free-to-play), Erwerb von Spielfortschritt und Individualisierungsoptionen (In-Game-Items) durch Kleinstbeträge (Mikrotransaktionen) und an Zufall gekoppelte Belohnungen mit der Möglichkeit, digitale Münzwürfe zu erwerben (Lootboxen) können die Entwicklung von Suchtverhalten fördern.

ZUSAMMENFASSUNGDas wissenschaftliche Interesse am Endocannabinoidsystem hat in den vergangenen Jahren aufgrund der zunehmenden Legalisierung von medizinischem Cannabis und seiner anxiolytischen Wirkung eine breite Basis von Tierexperimenten und erste translationale Studien zu biologischen, genetischen und neurobiologischen Befunden generiert. Besonders die modulatorische Rolle von Endocannabinoiden im Rahmen von Stress- und Angsterkrankungen steht im Vordergrund und weist auf mögliche Interventionspunkte hin, um vorhandene Therapien zu verbessern. Es fehlen jedoch weiterhin Erkenntnisse und Studien zur Wirkweise am Menschen, um die Implementierung dieser therapeutischen Anknüpfungspunkte umzusetzen. Die folgende Arbeit stellt eine Übersicht mit Schwerpunkt auf der Grundlagenforschung zum Endocannabinoidsystem im Rahmen von stressbezogenen Prozessen dar.

An altered processing of negative salient stimuli has been suggested to play a central role in the pathophysiology of major depression (MD). Besides negative affective and social stimuli, physical pain as a subtype of negative sensory stimulation has been investigated in this context. However, the few neuroimaging studies on unpleasant sensory stimulation or pain processing in MD report heterogeneous findings. Here, we investigated 47 young females, 22 with MD and 25 healthy controls (HC) using fMRI (3.0 T). Four levels of increasingly unpleasant electrical stimulation were applied. Ratings of stimulus intensity were assessed by a visual analogue scale. fMRI-data were analyzed using a 2 × 4 ANOVA. Behavioral results revealed no group differences regarding accuracy of unpleasant stimulation level ratings and sensitivity to stimulation. Regarding neural activation related to increasing levels of unpleasant stimulation, we observed increasing activation of brain regions related to the pain and salient stimulus processing corresponding to increasingly unpleasant stimulation in controls. This modulation was significantly smaller in MD compared to controls, particularly in the dorsal anterior cingulate cortex, the somatosensory cortex, and the posterior insula. Overall, brain regions associated with the processing of unpleasant sensory stimulation, but also associated with the salience network, were highly reactive but less modulated in female patients with MD. These results support and extent findings on altered processing of salience and of negative sensory stimuli even of a non-painful quality in female patients with MD. Electronic supplementary material The online version of this article (10.1007/s00406-020-01123-0) contains supplementary material, which is available to authorized users.

Stress underlies the development of various psychiatric disorders. Rodent studies suggest an involvement of the endocannabinoid system in the modulation of the stress response, which needs to be translated to humans. In this study, 22 healthy males (mean age: M = 22.7 years) were exposed to a thermal heat stressor in a fear conditioning paradigm and blood samples of the circulating endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) were assessed. Additionally, electrodermal activity (EDA), task-related anxiety ratings and data on critical life experiences (CLE) were recorded. Interestingly, increases in 2-AG from pre-to-post stress correlated with: smaller stress responses (EDA), by trend more CLE, and greater conditioned anxiety. Smaller stress responses correlated with more CLE. We demonstrate a relation between endocannabinoid level changes from pre-to-post acute stress and the stress response. Our results suggest that investigating the role of 2-AG in the response to stress could be promising in finding treatments in the immediate aftermath of traumatic events.

Gold standard treatments for anxiety- and trauma-related disorders focus on exposure therapy promoting extinction learning and extinction retention. However, its efficacy is limited. Preclinical and particularly animal research has been able to demonstrate that homozygosity for the fatty acid amide hydrolase (FAAH) C385A allele, similar to FAAH inhibition, is associated with elevated concentrations of anandamide (AEA) and facilitates extinction learning and extinction recall. However, in humans, the underlying neurobiological processes are less well understood, and further knowledge might enhance the development of more effective therapies. In this functional magnetic resonance imaging (fMRI) study, a fear conditioning, fear extinction and extinction recall paradigm was conducted with 55 healthy male adults. They were genotyped for the FAAH single-nucleotide polymorphism (SNP) rs324420 to investigate differences related to extinction recall in neural activation and State–Trait Anxiety Inventory (STAI) ratings between AC heterozygotes and CC homozygotes (FAAH C385A SNP). Differential brain activation upon an unextinguished relative to an extinguished stimulus, was greater in AC heterozygotes as compared to CC homozygotes in core neural structures previously related to extinction recall, such as the medial superior frontal gyrus, the dorsal anterior cingulate and the anterior and middle insular cortex. Furthermore, AC heterozygotes displayed higher AEA levels and lower STAI-state ratings. Our data can be interpreted in line with previous suggestions of more successful extinction recall in A-allele carriers with elevated AEA levels. Data corroborate the hypothesis that the endocannabinoid system, particularly AEA, plays a modulatory role in the extinction of aversive memory.

Background: Investigating adolescents and young adults may provide a unique opportunity to understand developmental aspects of the neurobiology of depression. During adolescence, a considerable physiologic reorganization of both grey and white matter of the brain takes place, and it has been suggested that differences in grey-matter volumes during adolescence may reflect different maturational processes. Methods: We investigated grey-matter volumes in a comparatively large sample (n = 103) of adolescents and young adults (aged 12 to 27 years), 60 of them with a diagnosis of current depression. Results: Replicating previous studies, we found a clear whole-brain effect of age: the older the participants, the lower their global grey-matter volumes, particularly in the paracingulate and prefrontal cortices. Contrasting depressed and healthy youth in a whole-brain approach, we found greater grey-matter volumes in the dorsolateral prefrontal cortex of those with depression. Furthermore, a region-of-interest analysis indicated lower grey-matter volumes in the hippocampus in participants with depression compared with healthy controls. Limitations: The present study was limited because of a skewed sex distribution, its cross-sectional design and the fact that some participants were taking an antidepressant. Conclusion: During adolescence, restructuring of the brain is characterized by marked decreases in prefrontal grey-matter volumes, interpreted as a correlate of brain maturation. Findings of greater volumes in the prefrontal cortex, particularly in younger adolescents with depression, may suggest that these participants were more prone to delayed brain maturation or increased neuroplasticity. This finding may represent a risk factor for depression or constitute an effect of developing depression.

Borderline personality disorder (BPD) is characterized by interpersonal disturbances and dysfunctional behavior such as non-suicidal self-injury (NSSI). We recently observed neural alterations in BPD during social inclusion by enhanced activations within the dorsomedial prefrontal cortex (dmPFC) and the posterior cingulate cortex (PCC). To examine the specificity of these neural alterations, we now investigated participants with NSSI but without BPD and compared them to BPD and healthy controls (HC). Considering the association between NSSI and BPD, we further examined neural commonalities during social inclusion. Fifteen females diagnosed with BPD, 16 with NSSI and 17 HC were investigated by fMRI and the cyberball paradigm, focusing on social inclusion (p

Ablehnung in zwischenmenschlichen Situationen oder sozialer Ausschluss wird umgangssprachlich haufig als schmerzhaft beschrieben. Wissenschaftliche Untersuchungen konnten zeigen, dass sozialer Ausschluss in der Tat gleichzeitig mit der Aktivierung von neuronalen Netzwerken einhergeht, die auch bei physischem Schmerz reagieren. Unter experimentellen Bedingungen wird sozialer Ausschluss dabei vorwiegend mit dem Cyberball-Paradigma operationalisiert, das in dem vorliegenden Artikel vorgestellt wird. Da einerseits sozialer Ausschluss als Risikofaktor fur die Entwicklung psychischer Erkrankungen gilt und daruber hinaus Storungen der sozialen Interaktion ein diagnoseubergreifendes Symptom darstellen, ist die Untersuchung neurofunktioneller Korrelate sozialer Zuruckweisung nicht nur von grundlagenwissenschaftlichem, sondern auch von klinischem Interesse. In diesem Artikel werden Befunde zu neuronalen Korrelaten sozialer Zuruckweisung bei Patienten mit psychischen Erkrankungen vorgestellt, die zumeist mit funktionell-magnetresonanztomografischer Untersuchungen erhoben wurden. Wir fokussieren dabei auf Untersuchungen von Patienten mit emotional-instabiler Personlichkeitsstorung vom Borderline-Typ, mit nicht suizidalem selbstverletzendem Verhalten sowie mit depressiver Storung. Social exclusion is perceived as “hurtful” and is not only described by pain words. Research has shown, that social rejection activates neural networks that also react to the experience of physical pain. Under experimental conditions, social exclusion is operationalized by the so-called cyberball-paradigm that we introduce in this article. Considering social exclusion as a risk factor for several psychiatric disorders and dysfunctional social interaction is a frequent symptom across psychiatric diagnoses, the investigation of neural correlates of social exclusion seems not only a topic of interest fo basic research but may be an issue with remarkable clinical implications. In this article, we introduce findings on neural correlates of social exclusion and summarize functional magnetic resonance imaging studies in patients with borderline personality disorder, non-suicidal self-injurious behavior and depressive disorder.

ZusammenfassungDas Interesse an zentralen Korrelaten von Angsterkrankungen und expositionsbasierter Therapie hat in den vergangenen Jahren Hypothesen auf einer breiten Basis von Tierexperimenten generiert. Hier wurden, vor allem in Konditionierungsexperimenten, die genetischen, biologischen und neurobiologischen Komponenten der Angstkonditionierung untersucht. Die Ergebnisse dieser Untersuchungen weisen unter anderem auf eine deutliche Modulation der Effekte durch das Endocannabinoidsystem hin, welche an gewissen Punkten beeinflussbar zu sein scheint. Auch wenn das Endocannabinoidsystem beim Menschen pharmakologischen Interventionen gut zugänglich ist, gelang es bislang nur sehr eingeschränkt, die breite Basis an Ergebnissen von Tierstudien auf die klinische Anwendung am Menschen zu übertragen. Es fehlen vor allem Erkenntnisse, ob und inwiefern das hochvolatile Endocannabinoidsystem beim Menschen tatsächlich vergleichbar zum Nagetier reagiert.

ZusammenfassungPosttraumatische Belastungsstörungen (PTBS) gehen mit Veränderungen der Reagibilität auf neuronaler Ebene einher. Dabei weisen Bildgebungsstudien auf eine erhöhte Aktivität in der Amygdala und eine verminderte Aktivität im präfrontalen Kortex hin. Psychotherapeutische Interventionen gelten als Goldstandard der PTBS-Behandlung. Es wurde eine systematische Literaturrecherche anhand der Datenbanken: PubMed, PsychInfo und dem zentralen Register der kontrollierten Studien der Cochrane Library mit den Suchbegriffen „neural correlates” ODER “fMRI” ODER “SPECT” UND “therapy” UND “PTSD” durchgeführt. 20 Artikel wurden eingeschlossen: 15 verglichen Signalveränderungen von vor zu nach Psychotherapie, sieben verglichen die neuronale Aktivität vor Therapie mit der Symptomreduktion von vor zu nach Therapie und vier Studien verglichen neuronale Korrelate von Therapieansprechen. Erfolgreiche PTBS-Psychotherapie führte über mehrere Studien hinweg zu einer verminderten neuronalen Aktivität in der Amygdala und Insula und zu einer erhöhten Aktivität im dorsalen anterioren zingulären Kortex sowie dem Hippocampus, was im Sinne einer wiedergewonnenen Top-down-Kontrolle interpretiert werden kann.

Human sexual behavior is mediated by a complex interplay of cerebral and spinal centers, as well as hormonal, peripheral, and autonomic functions. Neuroimaging studies identified central neural signatures of human sexual responses comprising neural emotional, motivational, autonomic, and cognitive components. However, empirical evidence regarding the neuromodulation of these neural signatures of human sexual responses was scarce for decades. Pharmacological functional magnetic resonance imaging (fMRI) provides a valuable tool to examine the interaction between neuromodulator systems and functional network anatomy relevant for human sexual behavior. In addition, this approach enables the examination of potential neural mechanisms regarding treatment-related sexual dysfunction under psychopharmacological agents. In this article, we introduce common neurobiological concepts regarding cerebral sexual responses based on neuroimaging findings and we discuss challenges and findings regarding investigating the neuromodulation of neural sexual stimulus processing. In particular, we summarize findings from our research program investigating how neural correlates of sexual stimulus processing are modulated by serotonergic, dopaminergic, and noradrenergic antidepressant medication in healthy males.

Borderline personality disorder (BPD) is characterized by interpersonal disturbances and dysfunctional behavior such as non-suicidal self-injury (NSSI). We recently observed neural alterations in BPD during social inclusion by enhanced activations within the dorsomedial prefrontal cortex (dmPFC) and the posterior cingulate cortex (PCC). To examine the specificity of these neural alterations, we now investigated participants with NSSI but without BPD and compared them to BPD and healthy controls (HC). Considering the association between NSSI and BPD, we further examined neural commonalities during social inclusion. Fifteen females diagnosed with BPD, 16 with NSSI and 17 HC were investigated by fMRI and the cyberball paradigm, focusing on social inclusion (p 0.05; FWE on cluster-level). To examine neural commonalities between BPD and NSSI compared to HC, we computed a conjunction analysis on neural activations under social inclusion. Significant increases in neural activation were observed in BPD within the dmPFC under social inclusion compared to NSSI and HC, whereas neural activations within the PCC did not differ between BPD and NSSI. The conjunction analysis revealed a common neurofunctional increase within the pregenual anterior cingulate cortex and the anterior insula in both, BPD and NSSI. We provide a further evidence regarding a disorder-specific neural reactivity within the dmPFC during social inclusion in BPD, whereas PCC activations may represent an unspecific neural alteration in BPD when compared to NSSI. In contrast, both clinical groups revealed a common neural increase within the salience network that may support the assumptions of a developmental continuum between these two psychiatric conditions.

Humans engage in social interactions and have a fundamental need and motivation to establish and maintain social connections. Neuroimaging studies particularly focused on the neural substrates of social exclusion in healthy subjects (HC), borderline personality disorder (BPD), and major depression (MD). However, there is evidence regarding neural alterations also during social inclusion in BPD that we intended to elucidate in our study. Considering that patients with BPD often have comorbid MD, we investigated patients with BPD, and comorbid MD, patients with MD without BPD, and a sample of HC. By investigating these two clinical samples within one study design, we attempted to disentangle potential confounds arising by psychiatric disorder or medication and to relate neural alterations under social inclusion specifically to BPD. We investigated 48 females (15 BPD and MD, 16 MD, and 17 HC) aged between 18 and 40 years by fMRI (3T), using the established cyberball paradigm with social exclusion, inclusion, and passive watching conditions. Significant group-by-condition interaction effects (p < 0.05, FWE-corrected on cluster level) were observed within the dorsolateral (dlPFC) and dorsomedial prefrontal cortex (dmPFC), the temporo-parietal junction (TPJ), the posterior cingulate cortex (PCC), and the precuneus. Comparisons of estimated neural activations revealed that significant interaction effects were related to a relative increase in neural activations during social inclusion in BPD. In detail, we observed a significant increase in differential (social inclusion vs. passive watching) neural activation within the dmPFC and the PCC in BPD compared to both, MD and HC. However, significant interaction effects within the dlPFC and the TPJ could not specifically be linked to BPD considering that they did not differ significantly between the two clinical groups in post-hoc comparisons. Our study supports previous results on effects of social and inclusion in BPD, and provides further evidence regarding disorder specific neural alterations in BPD for brain regions associated with self-referential and mentalizing processes during social inclusion.

ZusammenfassungSexuelle Funktionsstörungen treten häufig in der Therapie mit monoaminerg wirksamen Antidepressiva, insbesondere unter der Einnahme von selektiven Serotoninwiederaufnahmehemmern auf und beeinträchtigen neben der Lebensqualität in erheblichem Maße die Therapieadhärenz der Betroffenen. Trotz der zunehmenden klinischen Relevanz dieser unerwünschten Arzneimittelwirkung (UAW) konnten die zentralen Mechanismen der sexuellen Dysfunktion unter antidepressiver Medikation nicht hinreichend aufgeklärt werden. In einem umfangreichen Forschungsprogramm untersuchten wir gesunde männliche Probanden mit pharmakologisch gestützter funktioneller Magnetresonanztomografie (pharmako-fMRT) und visueller erotischer Stimulation unter der Einnahme verschiedener antidepressiv wirksamer Substanzen, um die monoaminergen Wirkprinzipien auf neuronalen Korrelate sexueller Stimulation aufzuklären und stellen unsere Ergebnisse in dem folgenden Übersichtsartikel dar.

In adults, trauma imagery has proven to be a useful tool to assess the neural mechanisms of psychological trauma processing. In adolescents, heterogeneous results could be found for other tasks, however, a trauma imagery paradigm has not been evaluated. For this purpose, we investigated a trauma imagery paradigm with control scripts to assess neural correlates of traumatic experiences in youth. 15 adolescents, who had experienced a traumatic interpersonal event in the past and have developed clinically relevant symptoms, underwent an fMRI scan while listening to their individual trauma- versus two control scripts (positive/negative). We analysed a parametric contrast of the imagery phases (trauma > negative > positive) which revealed activity in the thalamus, dorsal anterior cingulate cortex, cuneus, dorsomedial prefrontal cortex and amygdala. Additionally, amygdala-activity correlated positively with depression-symptom-severity. Our data provide evidence for the feasibility of fMRI during a trauma imagery task in adolescents to investigate networks previously related to hyperarousal in adults with PTSD. Further, we demonstrate the specificity of the activated networks for trauma imagery as compared to imagery of other emotional situations. The task might be particularly useful to evaluate neural correlates of treatment in adolescents when hyperarousal is a target symptom.

Borderline Personality Disorder (BPD) is clinically characterized by emotional instability, interpersonal disturbances and dysfunctional behavior such as non-suicidal self-injury (NSSI). During NSSI, patients with BPD typically report analgesic or hypoalgesic phenomena, and pain perception and pain processing in BPD have been repeatedly investigated. Most of the studies so far focused on affective-motivational and cognitive-evaluative neural components of pain within categorial study designs. By contrast, rather basic somatosensory aspects such as neural intensity-encoding of somatosensory stimuli were not examined in further details. Thus, we investigated patients with BPD and healthy controls (HC) by functional magnetic resonance imaging (fMRI) during an unpleasant sensory stimulation task with parametrically increasing stimulus intensities. 15 females diagnosed with BPD and 15 HCs were investigated with fMRI during four individually adjusted levels of electrical stimulus intensities. Ratings of stimulus intensity were assessed by button presses during fMRI. fMRI-data were analyzed by analyses of variances (ANOVA) at a statistical threshold of p < 0.05 FWE-corrected on cluster level. Subjective ratings of stimulus intensities were alike between BPD and HC, and intensity levels identified with equal accuracy. Significant intensity-encoding neural activations were observed within the primary and secondary somtasensory cortex, the posterior insula, the posterior midcingulate cortex (pMCC) and the supplementary motor area (SMA) in both, HC and BPD. Notably, there were no significant between-groups differences in intensity-encoding neural activations, even at lowered significance thresholds. Present results suggest a similar neural somatosensory stimulus intensity encoding in BPD as previously observed on a behavioral level. The alterations in neural affective-motivational or cognitive-evaluative components reported so far may be restricted to pain rather than unpleasant stimulus processing and were absent in our study.

The distinct feeling of wanting to act and thereby causing our own actions is crucial to our self-perception as free human agents. Disturbances of the link between intention and action occur in several disorders. Little is known, however, about the neural correlates of wanting or intending to act. To investigate these for simple voluntary movements, we used a paradigm involving hypnotic paralysis and functional magnetic resonance imaging. Eight healthy women were instructed to sequentially perform left and right hand movements during a normal condition, as well as during simulated weakness, simulated paralysis and hypnotic paralysis of the right hand. Right frontopolar cortex was selectively hypoactivated for attempted right hand movement during simulated paralysis while it was active in all other conditions. Since simulated paralysis was the only condition lacking an intention to move, the activation in frontopolar cortex might be related to the intention or volition to move.

Variations of the µ-opioid receptor gene OPRM1 have been shown to modulate pain perception with some evidence pointing towards a modulation of not only physical but also "psychological pain". In line with suggestions of a common neural network involved in the processing of physical pain and negative and distressing stimuli, like social rejection as a psychologically harmful event, we examined the influence of the A118G polymorphism on the neural processing of physical and non-physical pain. Using fMRI, we investigated a sample of 23 females with the more frequent AA genotype, and eight females with the relatively rare but more pain-sensitive AG genotype during electrical stimulation to the dorsum of the non-dominant hand. Non-physical pain was investigated using Cyberball, a virtual ball-tossing game, to induce experiences of non-self-dependent social rejection. A Go/NoGo task with an increased risk of self-dependent erroneous performance was used as a control task to investigate the effects of negative feedback as a more cognitive form of distress. Relative to A118G homozygous A-allele carriers, G-allele carriers showed significantly increased activation of the supplementary motor area/superior frontal gyrus and the precentral gyrus during electrical stimulation. Increased activation of the secondary sensorimotor cortex (SII) was found during social exclusion and during negative feedback. We demonstrate that brain regions particularly related to the somatosensory component of pain processing are modulated by variations in OPRM1. Influences were evident for both physical and psychological pain processing supporting the assumption of shared neural pathways.

Introduction Non-suicidal self-injury (NSSI) is a symptom of borderline personality disorder (BPD). However, NSSI often occurs independently of BPD. Altered neural processing of social exclusion has been shown in adolescents with NSSI and adults with BPD with additional alterations during social inclusion in BPD patients. Aims of this study were to investigate differences in neural processing of social inclusion and exclusion situations between adolescents with NSSI and young adults with BPD and NSSI. Methods Using fMRI, neural processing of positive and negative social situations (paradigm: “Cyberball”) was explored. Participants were 14 adolescents with NSSI, but without BPD (Mage = 15.4; SD = 1.9), 15 adults with BPD and NSSI (Mage = 23.3; SD = 4.1), as well as 15 healthy adolescents (Mage = 14.5; SD = 1.7), and 16 healthy adults (Mage = 23.2; SD = 4.4). Results Behavioral results showed enhanced feelings of social exclusion in both patient groups as compared to healthy controls but only the NSSI group showed enhanced activation during social exclusion versus inclusion compared to the other groups. While both NSSI and BPD groups showed enhanced activation in the ventral anterior cingulate cortex during social exclusion as compared to their age-matched controls, enhanced activation during social inclusion as compared to a passive watching condition was mainly observed in the BPD group in the dorsolateral and dorsomedial prefrontal cortex, and the anterior insula. Discussion While neural processing of social exclusion was pronounced in adolescents with NSSI, BPD patients also showed increased activity in a per se positive social situation. These results might point toward a higher responsiveness to social exclusion in adolescents with NSSI, which might then develop into a generalized increased sensitivity to all kinds of social situations in adults with BPD.

A number of neuroimaging studies have identified altered regional cerebral blood flow (rCBF) related to major depressive disorder (MDD) in adult samples, particularly in the lateral prefrontal, cingular and temporal regions. In contrast, neuroimaging investigations in adolescents with MDD are rare, although investigating young patients during a significant period of brain maturation might offer valuable insights into the neural mechanisms of MDD. We acquired perfusion images obtained with continuous arterial spin labelling in 21 medication-naive adolescents with MDD before and after a five-session cognitive behavioural group therapy (group CBT). A control group included medication-naive patients under treatment as usual while waiting for the psychotherapy. We found relatively increased rCBF in the right dorsolateral prefrontal cortex (DLPFC; BA 46), the right caudate nucleus and the left inferior parietal lobe (BA 40) after CBT compared with before CBT. Relatively increased rCBF in the right DLPFC postgroup CBT was confirmed by time (post vs. pre)×group (intervention/waiting list) interaction analyses. In the waiting group, relatively increased rCBF was found in the thalamus and the anterior cingulate cortex (BA 24). The relatively small number of patients included in this pilot study has to be considered. Our findings indicate that noninvasive resting perfusion scanning is suitable to identify CBT-related changes in adolescents with MDD. rCBF increase in the DLPFC following a significant reduction in MDD symptoms in adolescents might represent the core neural correlate of changes in 'top-down' cognitive processing, a possible correlate of improved self-regulation and cognitive control.

We recently investigated neuromodulatory effects of the noradrenergic agent reboxetine and the dopamine receptor affine amisulpride in healthy subjects on dynamic erotic stimulus processing. Whereas amisulpride left sexual functions and neural activations unimpaired, we observed detrimental activations under reboxetine within the caudate nucleus corresponding to motivational components of sexual behavior. However, broadly impaired subjective sexual functioning under reboxetine suggested effects on further neural components. We now investigated the same sample under these two agents with static erotic picture stimulation as alternative stimulus presentation mode to potentially observe further neural treatment effects of reboxetine. 19 healthy males were investigated under reboxetine, amisulpride and placebo for 7 days each within a double-blind cross-over design. During fMRI static erotic picture were presented with preceding anticipation periods. Subjective sexual functions were assessed by a self-reported questionnaire. Neural activations were attenuated within the caudate nucleus, putamen, ventral striatum, the pregenual and anterior midcingulate cortex and in the orbitofrontal cortex under reboxetine. Subjective diminished sexual arousal under reboxetine was correlated with attenuated neural reactivity within the posterior insula. Again, amisulpride left neural activations along with subjective sexual functioning unimpaired. Neither reboxetine nor amisulpride altered differential neural activations during anticipation of erotic stimuli. Our results verified detrimental effects of noradrenergic agents on neural motivational but also emotional and autonomic components of sexual behavior. Considering the overlap of neural network alterations with those evoked by serotonergic agents, our results suggest similar neuromodulatory effects of serotonergic and noradrenergic agents on common neural pathways relevant for sexual behavior.

Sexual dysfunction is not only a common symptom in major depression but also a frequent side-effect of antidepressant medication, mainly of the selective serotonin reuptake-inhibitors (SSRI) that are often prescribed as a first line treatment option. Despite of the increasing incidence and prescription rates, neuronal mechanisms underlying SSRI-related sexual dysfunction are poorly understood and investigations on this topic are scarce. Neuroimaging techniques, mainly functional magnetic resonance imaging (fMRI), provide a feasible approach to investigate these mechanisms since SSRI-related sexual dysfunction is most likely related to central nervous processes. This review summarizes the recent literature regarding the basic clinical findings and imaging correlates of antidepressant-related sexual dysfunction linking brain regions and networks potentially involved to phases and subcomponents of sexual processing and antidepressant action. In particular, fMRI studies on SSRI antidepressants including paroxetine and SNRIs including bupropion are highlighted.

Quantitative neuroimaging studies show that different neuroleptics have similar effects on resting metabolism/perfusion in the basal ganglia, but vary in their effect on the cortex, especially in the prefrontal and temporal lobes. These differences may represent signatures of the action of medication on distinctive receptor combinations.This study seeks to determine the effect on cerebral perfusion at rest of low-dose amisulpride, a neuroleptic with a receptor profile relatively selective to dopaminergic D2-receptors and both antidepressant and antipsychotic efficacy.Continuous arterial spin labelling in a placebo-controlled, double blind, crossover study at steady state of N = 20 healthy male adults.Relative to placebo, amisulpride was associated with extensive and significant cortical decrements in resting perfusion levels, particularly in the prefrontal lobes (p = 0.01, corrected). Decrements spared the basal ganglia, where perfusion was slightly increased.In contrast to earlier reports on other neuroleptics, amisulpride was associated with intense cortical perfusion decrements at rest. These results are consistent with an existing model in which dopaminergic blockade is associated not only with metabolism/perfusion increases in the basal ganglia, but also with decreases in the cerebral cortex that in most neuroleptics are compensated by action on other receptor systems. The selective receptor profile of amisulpride may explain the extensive cortical decrements.

Background Current resting state imaging findings support suggestions that the neural signature of depression and therefore also its therapy should be conceptualized as a network disorder rather than a dysfunction of specific brain regions. In this study, we compared neural connectivity of adolescent patients with depression (PAT) and matched healthy controls (HC) and analysed pre-to-post changes of seed-based network connectivities in PAT after participation in a cognitive behavioral group psychotherapy (CBT). Methods 38 adolescents (30 female; 19 patients; 13–18 years) underwent an eyes-closed resting-state scan. PAT were scanned before (pre) and after (post) five sessions of CBT. Resting-state functional connectivity was analysed in a seed-based approach for right-sided amygdala and subgenual anterior cingulate cortex (sgACC). Symptom severity was assessed using the Beck Depression Inventory Revision (BDI-II). Results Prior to group CBT, between groups amygdala and sgACC connectivity with regions of the default mode network was stronger in the patients group relative to controls. Within the PAT group, a similar pattern significantly decreased after successful CBT. Conversely, seed-based connectivity with affective regions and regions processing cognition and salient stimuli was stronger in HC relative to PAT before CBT. Within the PAT group, a similar pattern changed with CBT. Changes in connectivity correlated with the significant pre-to-post symptom improvement, and pre-treatment amygdala connectivity predicted treatment response in depressed adolescents. Limitations Sample size and missing long-term follow-up limit the interpretability. Conclusions Successful group psychotherapy of depression in adolescents involved connectivity changes in resting state networks to that of healthy controls.

Der vorliegende Beitrag versucht, einen Uberblick uber die Neurobiologie der Automatisierung von Willkurbewegungen zu geben. Insbesondere wird aufgezeigt, dass eine zunehmende Bewegungsautomatisierung mit synaptischen Plastizitatsvorgangen im kortikokortikalen und kortikostriatalen System einhergeht, die vermutlich zu Veranderungen in den neuronalen Reprasentationen der geubten Bewegungen fuhren. Sodann wird die Rolle phasischer Dopaminaktivierungen und deren modulatorischer Effekt auf striatale Plastizitatsvorgange bei denjenigen neuronalen Phanomenen diskutiert, die mit fortschreitendem Training beobachtet werden.

Recently, functional interactions between anteroventral prefrontal cortex and nucleus accumbens (NAcc) have been shown to relate to behavior counteracting reward-desiring (Diekhof and Gruber, 2010). Downregulation of the reward system by serotonin has also been suggested as the mode of action accounting for unsatisfactory effects of serotonin reuptake inhibitors (SSRIs) such as insufficient alleviation or even increase of anhedonia, and loss of interest. However, understanding of thein vivomechanisms of SSRI-related alteration of the human reward system is still incomplete. Using functional magnetic resonance imaging (fMRI) within a double-blind cross-over within-subjects study design and administering the SSRI paroxetine, the dopamine/norepinephrine reuptake inhibitor bupropione, and placebo for 7 d each, we investigated a group of 18 healthy male subjects. Under paroxetine, subjects showed significantly decreased activation of the bilateral NAcc during processing of primary rewards (erotic videos), but not under bupropion. Similar to the previous study, analysis of psychophysiological interactions revealed that this downregulation relied on negative interactions between left and right NAcc fMRI signals and the bilateral anteroventral prefrontal cortex that now were significantly enhanced under paroxetine and reduced under bupropion. Individual drug-dependent modulations of interacting brain regions were significantly associated with individual expressions of impulsivity as a personality trait. Our results corroborate and extend previous insights on interregional crosstalk from secondary to primary rewards and demonstrate parallels between active inhibitory control of and serotonergic effects on the dopaminergic reward system's activity.

Investigating the effects of serotonergic antidepressants on neural correlates of visual erotic stimulation revealed decreased reactivity within the dopaminergic reward network along with decreased subjective sexual functioning compared with placebo. However, a global dampening of the reward system under serotonergic drugs is not intuitive considering clinical observations of their beneficial effects in the treatment of depression. Particularly, learning signals as coded in prediction error processing within the dopaminergic reward system can be assumed to be rather enhanced as antidepressant drugs have been demonstrated to facilitate the efficacy of psychotherapeutic interventions relying on learning processes. Within the same study sample, we now explored the effects of serotonergic and dopaminergic/noradrenergic antidepressants on prediction error signals compared with placebo by functional MRI. A total of 17 healthy male participants (mean age: 25.4 years) were investigated under the administration of paroxetine, bupropion and placebo for 7 days each within a randomized, double-blind, within-subject cross-over design. During functional MRI, we used an established monetary incentive task to explore neural prediction error signals within the bilateral nucleus accumbens as region of interest within the dopaminergic reward system. In contrast to diminished neural activations and subjective sexual functioning under the serotonergic agent paroxetine under visual erotic stimulation, we revealed unaffected or even enhanced neural prediction error processing within the nucleus accumbens under this antidepressant along with unaffected behavioural processing. Our study provides evidence that serotonergic antidepressants facilitate prediction error signalling and may support suggestions of beneficial effects of these agents on reinforced learning as an essential element in behavioural psychotherapy.