Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases

Abstract A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted

Sensory gating and sensorimotor gating in psychiatric disorders sharing attention deficits

Functional gating is an important function of the brain, preventing it from a sensory overload by filtering out irrelevant stimuli. A deficit in gating is characterized by a general reduction of the ability to gate sensory information. Moreover, a deficit in gating is characterized by a general reduction of the ability to gate intrusive sensory, motor and/or cognitive information. Two widely studied physiological parameters designed to assess central inhibition used in laboratory studies, are prepulse inhibition (PPI) of the acoustic startle response, considered as a form of sensorimotor gating, and suppression of the P50 auditory event-related potential (AEP) in a condition-test paradigm (P50 suppression), considered as a form of sensory gating. While sensory gating and sensorimotor gating have been proposed to be endophenotypic biomarkers for schizophrenia spectrum disorders, deficient gating is not exclusively attributable to schizophrenia. Therefore, psychophysiological alterations like impaired gating have been reported in patients with posttraumatic stress disorder (PTSD), but the findings are still inconsistent, and potential relationships to symptomatology remain unclear. Moreover, even though there is an impaired perceptual capacity in attention-deficit/hyperactivity disorder (ADHD) patients, psychophysiological alterations, such as impaired PPI and P50 suppression, have not been reported in patients suffering from ADHD. Furthermore, there is considerable evidence that schizophrenia patients treated with atypical antipsychotics exhibit relatively less gating deficits than do other patients with schizophrenia. Therefore, recent studies have investigated the effect of antipsychotic medications on gating measures in healthy volunteers exhibiting low levels of gating, rather than in patients. In the present thesis we investigated whether PTSD and ADHD patients exhibit deficits in sensory gating and/or sensorimotor gating compared to healthy control subjects. Furthermore, we investigated the influence of the antipsychotic sertindole vs. placebo in two separate experimental sessions, on both gating measures in male volunteers stratified for low and high baseline gating levels. We showed that PTSD patients as well as ADHD patients showed impaired sensory gating but not sensorimotor gating. Moreover, sertindole increased PPI and P50 suppression in healthy volunteers exhibiting low baseline PPI and low baseline P50 suppression respectively, while sertindole attenuated gating in subjects exhibiting high baseline gating. Furthermore, subjects exhibiting low PPI chose worse strategy in a spatial working memory task. We conclude that deficient P50 gating, neither related to specific psychopathological symptoms nor to specific impairment of cognitive performance, is a robust finding in PTSD and adult ADHD. Consequently, P50 gating is not exclusively associated with a specific disorder. Furthermore, impaired P50 suppression might be a general and common feature of several psychiatric disorders sharing deficits in attention functions. However, the absence of diminished PPI in PTSD patients and adult ADHD patients seems to be a robust finding. Moreover, the influence of antipsychotics on sensory and sensorimotor gating in healthy volunteers seems to be dependent on baseline gating levels. Therefore, mixed D2 / 5-HT2 receptor antagonists modulate PPI as well as P50 suppression in a way to enhance it in healthy subjects with low baseline gating in a way comparable as seen in studies with schizophrenia patients. Thus, sensorimotor and sensory gating measures can be used as informative and independent neurophysiological markers for studies investigating neuropsychiatric disorders and may well constitute separable endophenotypes. While the combined use of PPI and P50 suppression in a single study might represent excellent tools for translational research, it still remains fundamental to assess established parameters for patients’ studies as well as studies with healthy volunteers comparable to those coming from schizophrenia research to achieve constant and comparable and study overlapping data. Eine intakte sensorische Reizfilterleistung, welche für die Ausfilterung irrelevanter Stimuli zuständig ist, schützt das Gehirn vor einer sensorischen Reizüberflutung. Ein Filterleistungsdefizit ist durch eine generelle Reduktion der Fähigkeit, auf das Gehirn eindringende sensorische, motorische oder kognitive Informationen zu filtern, charakterisiert. Zwei in der Forschung häufig verwendete Parameter, welche als Mass für die zentrale Reizfilterleistung des Gehirns gelten, sind die so genannte Präpuls-Inhibition der akustischen Schreckreaktion (PPI) als Mass für die sensomotorische Reizfilterleistung, sowie die durch ein auditorisch evoziertes Potential entstehende P50 Suppressionsleistung, welche als Mass für sie sensorische Reizfilterleistung gilt. Beide Masse wurden als endophänotypische biologische Marker für Erkrankungen aus dem schizophrenen Formenkreis vorgeschlagen; Auffälligkeiten in beiden Massen treten aber nicht nur ausschliesslich im Bereich schizophrener Erkrankungen auf. So wurde eine verminderte Reizfilterleistung auch bei Patienten mit einer posttraumatischen Belastungsstörung (PTBS) gefunden, jedoch sind die Befunde hierzu inkonsistent. Hingegen wurden bei Patienten mit einer Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) keine sensomotorischen und sensorischen Reizfilterleistungsdefizite berichtet, obwohl diese Patientengruppe als Kernmerkmal an einer Beeinträchtigung der Aufmerksamkeit leidet und somit eine Beeinträchtigung der kortikalen Reizfilterleistung in Betracht gezogen werden muss. Zudem gibt es Hinweise, dass Patienten, welche an einer Schizophrenie leiden und mit einer atypischen neuroleptischen Medikation behandelt werden, weniger starke Beeinträchtigungen in ihrer Reizfilterleistung zeigen. Kürzlich haben Studien in gesunden Probanden mit einer tiefen sensorischen und sensomotorischen Reizfilterleistung systematisch die Wirkung einer neuroleptischen Medikation auf beide Masse untersucht. In der vorliegenden Dissertation wurde untersucht, ob Patienten mit einer PTBS und Patienten mit einer ADHS im Vergleich zu gesunden Kontrollprobanden eine verminderte sensomotorische und/oder sensorische Reizfilterleistung aufweisen. Zusätzlich wurde der Einfluss des atypischen Neuroleptikums Sertindol im Vergleich zu Placebo auf die beiden Filtermasse in gesunden Probanden untersucht. Es konnte gezeigt werden, dass sowohl Patienten mit einer PTBS, als auch Patienten mit einer ADHS eine verminderte sensorische Reizfilterleistung aufweisen. Hingegen unterschied sich die sensomotorische Reizfilterleistung in beiden Patientengruppen nicht von der Reizfilterleistung der gesunden Kontrollprobanden. Weiter konnte gezeigt werden, dass Sertindol die Filterleistung in beiden Massen in gesunden Kontrollprobanden mit einer tiefen Baseline erhöhte, während es die Filterleistung von Kontrollprobanden mit einer hohen Baseline verminderte. Probanden mit einer tiefen sensomotorischen Baseline wählten zusätzlich eine schlechtere Strategie in einer Aufgabe zum räumlichen Arbeitsgedächtnis. Die Ergebnisse der Studien weisen darauf hin, dass Patienten mit einer PTBS und Patienten mit einer ADHS eine verminderte sensorische Reizfilterleistung aufweisen, welche nicht an spezifische psychopathologische Symptome oder die Leistung in kognitiven Aufgaben gekoppelt ist. Eine verminderte P50 Suppressionsleistung ist somit nicht an ein spezifisches psychiatrisches Störungsbild gekoppelt, sondern könnte möglicherweise bei verschiedenen Störungsbildern auftreten, welche als Gemeinsamkeit eine Störung der Aufmerksamkeit aufweisen. Der Einfluss einer neuroleptischen Medikation auf die beiden Reizfiltermasse in gesunden Probanden scheint von deren Baseline abhängig zu sein. Es zeigt sich, dass gemischte D2-/5-HT2-Rezeptorantagonisten bei gesunden Probanden mit einer tiefen sensomotorischen als auch sensorischen Baseline zu einer Erhöhung der Reizfilterleistung führen. Diese ist mit den beschriebenen Verbesserungen in Patienten, welche unter einer Schizophrenie leiden und neuroleptisch behandelt werden, vergleichbar. Beide Paradigmen, PPI als auch die P50 Suppression, eignen sich somit als informative und unabhängige neurophysiologische Marker in der Untersuchung von neuropsychiatrischen Störungsbildern und könnten zu einer Endophänotypisierung beitragen. Obwohl sich der kombinierte Einsatz beider Filterleistungsmasse in einer Studie zur translationalen Forschung gut eignet, ist gleichzeitig auf die Einhaltung und Entwicklung von exakten Parametern beider Reizfiltermasse zu achten. Nur so können eine Konstanz der erhobenen Daten vorausgesetzt und die Ergebnisse aus den verschiedenen Studien miteinander verglichen werden. In erster Linie sollten hierfür die Empfehlungen zur Parameterbestimmung aus der Forschung zur Schizophrenie berücksichtig werden

prdl-a, a gene marker for hydra apical differentiation related to triploblastic paired-like head-specific genes

Two homeobox genes, prdl-a and prdl-b, which were isolated from a Hydra vulgaris cDNA library, encode paired-like class homeodomains highly related to that of the aristaless-related genes. In adult polyps, prdl-b is a marker for synchronously dividing nematoblasts while prdl-a displays an expression restricted to the the nerve cell lineage of the head region. During budding and apical regeneration, an early and transient prdl-a expression was observed in endodermal cells of the stump at a time when the head organizer is established. When apical regeneration was delayed upon concomittant budding, prdl-a expression was found to be altered in the stump. Furthermore, a specific anti-prdl-a protein immunoserum revealed that prdl-a was overexpressed in adult polyps of the Chlorohydra viridissima multiheaded mutant, with an expression domain extending below the tentacle ring towards the body column. Accordingly, prdl-a DNA-binding activity was enhanced in nuclear extracts from this mutant. These results suggest that prdl-a responds to apical forming signals and might thus be involved in apical specification. When a marine hydrozoan (Podocorynae carnea) was used, the anti-prdl-a antibody showed cross-reactivity with cells located around the oral region, indicating that prdl-a function is shared by other cnidaria. The ancestral role for prdl-a-related genes in the molecular definition of the head (or oral-surrounding region) is discussed

Sensory and sensorimotor gating in adult attention-deficit/hyperactivity disorder (ADHD)

Even though there is an impaired perceptual capacity in attention-deficit/hyperactivity disorder (ADHD) patients, psychophysiological alterations, such as impaired gating as indexed by prepulse inhibition (PPI) or suppression of P50 auditory event-related potentials, have not been found in patients with ADHD. Hence, potential relationships of psychophysiological measures of gating to psychopathology and cognitive performance remain unclear. The present study investigates two distinct operational measures of gating as well as cognitive performance within adult ADHD patients in order to assess the relationship of these measures to psychopathology. PPI, P50 suppression, cognitive performance, and psychopathologic symptoms were assessed in 26 ADHD patients and 26 healthy control subjects. ADHD patients compared to healthy control subjects exhibited impaired P50 suppression, performed worse in cognitive tasks, and reported more psychopathological symptoms, but were normal in the test of PPI. Thus, P50 gating deficits are not specific to schizophrenia-spectrum disorders. These findings highlight the differences between P50 gating and PPI as measures of the gating construct. In keeping with the lack of correlations between these two putative operational measures of gating seen in both humans and animals, adult ADHD patients exhibit deficient P50 suppression and poor cognitive performance, despite exhibiting normal levels of PPI

The effects of sertindole on sensory gating, sensorimotor gating, and cognition in healthy volunteers

Sensory gating, indexed by P50 suppression, and sensorimotor gating, indexed by prepulse inhibition (PPI), are impaired in schizophrenia spectrum disorders. There is considerable evidence that schizophrenia patients treated with atypical antipsychotics exhibit relatively less gating deficits than do other patients with schizophrenia. Some recent studies have investigated the effects of antipsychotic medications on gating in healthy volunteers exhibiting low levels of gating, rather than in patients. Therefore, the current study investigated the influence of sertindole versus placebo in two separate experimental sessions, on PPI, P50 suppression, and cognition in 30 male volunteers stratified for low and high baseline gating levels. Sertindole increased PPI and P50 suppression in healthy subjects exhibiting low baseline PPI and low baseline P50 suppression, respectively, while sertindole attenuated gating in subjects exhibiting high baseline gating. Furthermore, subjects exhibiting low PPI chose worse strategies in a spatial working memory task. These findings suggest that mixed D(2)/5-HT(2) receptor antagonists enhance both PPI and P50 suppression in a way that enhances it in healthy subjects exhibiting low baseline gating. Furthermore, the results militate in favor of the concomitant assessment of PPI, P50 suppression and cognitive measures while investigating the effect of antipsychotic medication in healthy subjects

Psychotherapy integration under scrutiny: investigating the impact of integrating emotion-focused components into a CBT-based approach: a study protocol of a randomized controlled trial

BACKGROUND This currently recruiting randomized controlled trial investigates the effects of integrating components of Emotion-Focused Therapy (EFT) into Psychological Therapy (PT), an integrative form of cognitive-behavioral therapy in a manner that is directly mirroring common integrative practice in the sense of assimilative integration. Aims of the study are to understand how both, an existing therapy approach as well as the elements to be integrated, are affected by the integration and to clarify the role of emotional processing as a mediator of therapy outcome. METHODS A total of 130 adults with a diagnosed unipolar depressive, anxiety or adjustment disorder (seeking treatment at a psychotherapy outpatient clinic) are randomized to either treatment as usual (PT) with integrated emotion-focused components (TAU + EFT) or PT (TAU). Primary outcome variables are psychopathology and symptom severity at the end of therapy and at follow up; secondary outcome variables are interpersonal problems, psychological wellbeing, quality of life, attainment of individual therapy goals, and emotional competency. Furthermore, process variables such as the quality of the therapeutic relationship are studied as well as aptitude-treatment interactions. Variables are assessed at baseline, after 8 and 16 sessions, at the end of therapy, after 25 ± 3 sessions, and at 6, 12 and 36 month follow-up. Underlying mechanisms of change are investigated. Statistical analyses will be conducted using the appropriate multilevel approaches, mainly two-level regression and growth analysis. DISCUSSION The results of this study will indicate whether the integration of emotion-focused elements into treatment as usual increases the effectiveness of Psychological Therapy. If advantages are found, which may be limited to particular variables or subgroups of patients, recommendations for a systematic integration, and caveats if also disadvantages are detected, can be formulated. On a more abstract level, a cognitive behavioral (represented by PT) and humanistic/experiential (represented by EFT) approach will be integrated. It must be emphasized that mimicking common practice in the development and continued education of psychotherapists, EFT is not integrated as a whole, but only elements of EFT that are considered particularly important, and can be trained in an 8-day training plus supervision of therapies. TRIAL REGISTRATION ClinicalTrials.gov, NCT02822443 , 22 June 2016, retrospectively registered

Characterizing the Protolunar Disk of the Accreting Companion GQ Lupi B

GQ Lup B is a young and accreting, substellar companion that appears to drive a spiral arm in the circumstellar disk of its host star. We report high-contrast imaging observations of GQ Lup B with VLT/NACO at 4-5 $\mu$m and medium-resolution integral field spectroscopy with VLT/MUSE. The optical spectrum is consistent with an M9 spectral type, shows characteristics of a low-gravity atmosphere, and exhibits strong H$\alpha$ emission. The $H-M'$ color is $\gtrsim$1 mag redder than field dwarfs with similar spectral types and a detailed analysis of the spectral energy distribution (SED) from optical to mid-infrared wavelengths reveals excess emission in the $L'$, NB4.05, and $M'$ bands. The excess flux is well described by a blackbody component with $T_\mathrm{disk} \approx 460$ K and $R_\mathrm{disk} \approx 65\,R_\mathrm{J}$ and is expected to trace continuum emission from small grains in a protolunar disk. We derive an extinction of $A_V \approx 2.3$ mag from the broadband SED with a suspected origin in the vicinity of the companion. We also combine 15 yr of astrometric measurements and constrain the mutual inclination with the circumstellar disk to $84 \pm 9$ deg, indicating a tumultuous dynamical evolution or a stellar-like formation pathway. From the measured H$\alpha$ flux and the estimated companion mass, $M_\mathrm{p} \approx 30\,M_\mathrm{J}$, we derive an accretion rate of $\dot{M} \approx 10^{-6.5}\,M_\mathrm{J}\,\mathrm{yr}^{-1}$. We speculate that the disk is in a transitional stage in which the assembly of satellites from a pebble reservoir has opened a central cavity while GQ Lup B is in the final stages of its formation.Comment: 28 pages, 11 figures, accepted for publication in A

SPHERE/ZIMPOL high resolution polarimetric imager

ISSN:0004-6361ISSN:1432-074