Gregor Peikert

Association of a functional −1019C>G 5-HT1A receptor gene polymorphism with panic disorder with agoraphobia

Panic disorder is a common anxiety disorder which frequently co-occurs with agoraphobia. A functional promoter polymorphism in the serotonin receptor 1A (5-HT1A) gene has been found to be associated with major depression as well as anxiety- and depression-related personality traits. We investigated a possible association between this 5-HT1A gene promoter polymorphism and panic disorder by genotyping the 1019C>G single nucleotide polymorphism in 134 panic-disorder patients with and without agoraphobia and matched 134 controls. In our sample no significant evidence of allelic association in the combined panic-disorder group was found. However, our results show a significant association with the G allele in patients with panic disorder with agoraphobia (p=0.03, n=101). In conclusion, our findings do not support a major contribution of this polymorphism to the pathogenesis of panic disorder, but provide evidence for a possible role in the subgroup with agoraphobia.

Fronto-Cingulate Effective Connectivity in Obsessive Compulsive Disorder: A Study With fMRI and Dynamic Causal Modeling

Evidence suggests that obsessive compulsive disorder (OCD) is associated with an overactive error control system. A key role in error detection and control has been ascribed to the fronto‐cingulate system. However, the exact functional interplay between the single components of this network in OCD is largely unknown. Therefore, the present study combined a univariate data analysis and effective connectivity analysis using dynamic causal modeling (DCM) to examine error control in 21 patients with OCD and 21 matched healthy controls. All subjects performed an adapted version of the Stroop color‐word task while undergoing fMRI scans. Enhanced activation in the fronto‐cingulate system could be detected in OCD patients during the incongruent task condition. Additionally, task‐related modulation of effective connectivity from the dorsal ACC to left DLPFC was significantly stronger in OCD patients. These findings are consistent with an overactive error control system in OCD subserving suppression of prepotent responses during decision‐making. Hum Brain Mapp, 2010.

Temporal and right frontal lobe alterations in panic disorder: a quantitative volumetric and voxel-based morphometric MRI study

BACKGROUND With regard to current neurobiological theories, the aim of our study was to examine possible alterations of temporal and frontal lobe volume in panic disorder (PD). METHOD Seventeen in-patients with PD and a group of healthy control subjects (HC) matched for age and gender were investigated by quantitative volumetric magnetic resonance imaging (MRI). Structures of interest were: the temporal lobe, the amygdala-hippocampus complex (AHC) and the frontal lobe. In addition, a voxel-based morphometry (VBM) analysis implemented in Statistical Parametric Mapping 5 (SPM5) was used for a more detailed assessment of possible volume alterations. Modulated grey matter (GM) images were used to test our a priori hypotheses and to present the volumetric results. RESULTS Quantitative volumetric MRI revealed a bilateral reduction in temporal lobe volume in patients with PD compared to HC subjects. The AHC was normal. The right frontal lobe volume was also decreased. Using VBM we detected a significant GM volume reduction in the right middle temporal gyrus [Brodmann area (BA) 21] in patients with PD. In addition, there was a reduction in GM volume in the medial part of the orbitofrontal cortex (BA 11). CONCLUSIONS Our results of reduced temporal and frontal lobe volume in PD are in agreement with prior studies. By using a recent VBM approach we were able to assess the abnormalities more precisely. The location of GM volume reduction in the right middle temporal gyrus and medial orbitofrontal cortex lends further support to recent aetiological models of PD.

The novel brain-specific tryptophan hydroxylase-2 gene in panic disorder

Panic disorder is a common psychiatric disorder characterized by recurrent anxiety attacks and anticipatory anxiety. Due to the severity of the symptoms of the panic attacks and the frequent additional occurrence of agoraphobia, panic disorder is an often debilitating disease. Elevation of central serotonin levels by drugs such as clomipramine represents one of the most effective treatment options for panic disorder. This points to an important role of dysregulation of the serotonergic system in the genetic etiology of panic disorder. The novel brain-specific 5-HT synthesizing enzyme, tryptophan hydroxylase-2 (TPH2), which represents the rate-limiting enzyme of 5-HT production in the brain, may therefore be of particular importance in panic disorder. We focused on the putative transcriptional control region of TPH2 and identified two novel common single nucleotide polymorphisms (SNPs) of TPH2 in and close to this region. Moreover, a recently described loss-of-function mutation of TPH2 which results in an 80% reduction of serotonin production, was assessed. In an analysis of the putative transcriptional control region SNPs in a sample of panic disorder patients and controls no association of the disorder with the TPH2 SNPs or haplotypes was found. Moreover, the loss-of-function R441H mutation of TPH2 was not present in the panic disorder patients. The results of this first study of TPH2 in panic disorder argue against an importance of allelic variation of TPH2 in the pathogenesis of panic disorder with or without agoraphobia.

White matter structure and symptom dimensions in obsessive–compulsive disorder

There is evidence that the different symptom dimensions in obsessive-compulsive disorder (OCD) may be mediated by partially distinct neural systems. This DTI study investigated the relationship between symptom dimensions and white matter microstructure. Fractional anisotropy (FA), axial and radial diffusivity was analyzed in relation to the main OCD symptom dimensions. Symptom severity on the obsessing dimension was negatively correlated with FA in the corpus callosum and the cingulate bundle. Severity on the ordering dimension was negatively correlated with FA in, amongst others, the right inferior fronto-occipital fasciculus and the right optic radiation. All correlations were ascribable to alterations in radial diffusivity while there was no association between symptoms and axial diffusivity. Present results illustrate an association between alterations in visual processing tracts and ordering symptoms which are characterized by altered visual processing and increased attention towards irrelevant detail. They also indicate an association between obsessive thoughts and alterations in structures known to be relevant for cognitive control and inhibition. Hence, different symptom dimensions must be taken into account in order to disentangle the neurobiological underpinnings of OCD.

Aberrant anterior cingulate activation in obsessive–compulsive disorder is related to task complexity

OBJECTIVES Evidence for working memory (WM) deficits in obsessive-compulsive disorder (OCD) is increasing. However, findings regarding the underlying neural substrates are heterogeneous. Moreover, the influence of cognitive demand on the severity of these deficits and associated activation alterations is a matter of debate. METHODS To further address this question the present fMRI study examined a sample of 21 predominantly medication-free inpatients with OCD and 21 matched healthy volunteers using a parametric verbal n-back task. RESULTS In agreement with earlier studies patients exhibited focused activation alterations that could be found to be critically dependent on WM demands: There were no differences in activation between patients and healthy volunteers under low cognitive demands. However, patients exhibited a significantly decreased activation in the dorsal anterior cingulate cortex (dACC) in association with increasing task demands. While dACC activation in controls showed a linear increase with increasing task demands, this linearity was not detectable in patients with OCD. CONCLUSIONS Present findings provide further support for the relevance of the anterior cingulate in OCD and illustrate that both task demands and task processes are of major influence in this context.

Self-referential processing influences functional activation during cognitive control: an fMRI study

Rostral anterior cingulate cortex (rACC) plays a central role in the pathophysiology of major depressive disorder (MDD). As we reported in our previous study (Wagner et al., 2006), patients with MDD were characterized by an inability to deactivate this region during cognitive processing leading to a compensatory prefrontal hyperactivation. This hyperactivation in rACC may be related to a deficient inhibitory control of negative self-referential processes, which in turn may interfere with cognitive control task execution and the underlying fronto-cingulate network activation. To test this assumption, a functional magnetic resonance imaging study was conducted in 34 healthy subjects. Univariate and functional connectivity analyses in statistical parametric mapping software 8 were used. Self-referential stimuli and the Stroop task were presented in an event-related design. As hypothesized, rACC was specifically engaged during negative self-referential processing (SRP) and was significantly related to the degree of depressive symptoms in participants. BOLD signal in rACC showed increased valence-dependent (negative vs neutral SRP) interaction with BOLD signal in prefrontal and dorsal anterior cingulate regions during Stroop task performance. This result provides strong support for the notion that enhanced rACC interacts with brain regions involved in cognitive control processes and substantiates our previous interpretation of increased rACC and prefrontal activation in patients during Stroop task.

The neural basis of the abnormal self-referential processing and its impact on cognitive control in depressed patients.

Persistent pondering over negative self‐related thoughts is a central feature of depressive psychopathology. In this study, we sought to investigate the neural correlates of abnormal negative self‐referential processing (SRP) in patients with Major Depressive Disorder and its impact on subsequent cognitive control‐related neuronal activation. We hypothesized aberrant activation dynamics during the period of negative and neutral SRP in the rostral anterior cingulate cortex (rACC) and in the amygdala in patients with major depressive disorder. Additionally, we assumed abnormal activation in the fronto‐cingulate network during Stroop task execution. 19 depressed patients and 20 healthy controls participated in the study. Using an event‐related functional magnetic resonance imaging (fMRI) design, negative, positive and neutral self‐referential statements were displayed for 6.5 s and followed by incongruent or congruent Stroop conditions. The data were analyzed with SPM8. In contrast to controls, patients exhibited no significant valence‐dependent rACC activation differences during SRP. A novel finding was the significant activation of the amygdala and the reward‐processing network during presentation of neutral self‐referential stimuli relative to baseline and to affective stimuli in patients. The fMRI analysis of the Stroop task revealed a reduced BOLD activation in the right fronto‐parietal network of patients in the incongruent condition after negative SRP only. Thus, the inflexible activation in the rACC may correspond to the inability of depressed patients to shift their attention away from negative self‐related stimuli. The accompanying negative affect and task‐irrelevant emotional processing may compete for neuronal resources with cognitive control processes and lead thereby to deficient cognitive performance associated with decreased fronto‐parietal activation. Hum Brain Mapp 36:2781–2794, 2015.

Wie effektiv sind Ausbildungstherapien? Vergleichsstudie zur Effektivität von Ausbildungs- und Regeltherapien

Hintergrund: Psychotherapeuten in Ausbildung (PiA) leisten in Deutschland einen bedeutenden Beitrag zur psychotherapeutischen Versorgung. Bisher wurde kaum untersucht, wie effektiv die während der Ausbildung durchgeführten Therapien im Vergleich zu Behandlungen durch erfahrene Psychotherapeuten sind. Patienten und Methoden: Sämtliche im Jahr 2007 an der Ambulanz eines verhaltenstherapeutischen Ausbildungsinstituts abgeschlossenen Behandlungen («Ausbildungstherapien», n = 487) wurden mit abgeschlossenen Behandlungen durch niedergelassene psychologische Psychotherapeuten («Regeltherapien», n = 224) verglichen. Dazu wurden klinische und soziodemographische Daten aus den Patientenakten erhoben, zudem wurden Patienten und Therapeuten retrospektiv befragt. Als zentrales Erfolgsmaß wurde der Fragebogen zur Beurteilung der Behandlung (FBB) in einer Patienten- und einer Therapeutenversion eingesetzt. Ergebnisse: Ausbildungstherapien erwiesen sich als ebenso effektiv wie Regeltherapien, erstrecken sich bei vergleichbaren Stundenzahlen aber über signifikant kürzere Zeiträume. Schlussfolgerungen: Unter Supervision durchgeführte Ausbildungstherapien sind in der Versorgungspraxis durchschnittlich ebenso effektiv wie Behandlungen durch erfahrene Psychotherapeuten. Damit wird die Validität von Psychotherapiestudien unterstützt, in denen PiA die Behandlungen durchführen. Zudem wird belegt, dass Ausbildungstherapien nicht nur quantitativ, sondern auch qualitativ einen wesentlichen Beitrag zur psychotherapeutischen Versorgung der Bevölkerung leisten.

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Offizielles Mitteilungsorgan von AFKV – Ausbildungsinstitut für Klinische Verhaltenstherapie in NW gem. e.V., Gelsenkirchen APV – Gesellschaft für Angewandte Psychologie und Verhaltensmedizin mbH, Münster AVM (CH) – Arbeitsgemeinschaft für Verhaltensmodifikation, Ostermundingen (Schweiz) AVM (D) – Arbeitsgemeinschaft für Verhaltensmodifikation, Bamberg (Deutschland) AVM (Ö) – Arbeitsgemeinschaft für Verhaltensmodifikation, Salzburg (Österreich) AVT – Akademie für Verhaltenstherapie GmbH, Köln BAP – Bayerische Private Akademie für Psychotherapie GmbH, München CIP – Centrum für Integrative Psychotherapie, München DÄVT – Deutsche Ärztliche Gesellschaft für Verhaltenstherapie e.V., Bad Pyrmont – Deutsche PsychotherapeutenVereinigung, Berlin DGESS – Deutsche Gesellschaft für Essstörungen e.V. DGPM – Deutsche Gesellschaft für Psychosomatische Medizin und Ärztliche Psychotherapie e.V., Berlin DGVM – Deutsche Gesellschaft für Verhaltensmedizin und Verhaltensmodifikation DKPM – Deutsches Kollegium für Psychosomatische Medizin DVT – Deutscher Fachverband für Verhaltenstherapie e.V. GAP – Gesellschaft für Ausbildung in Psychotherapie, Frankfurt/M. IFKV – Institut für Fortund Weiterbildung in Klinischer Verhaltenstherapie, Bad Dürkheim IVB – Institut für Verhaltenstherapie Berlin e.V., Berlin ÖGVT – Österreichische Gesellschaft für Verhaltenstherapie, Wien SGVT – Schweizerische Gesellschaft für Verhaltenstherapie, Bern TAVT – Private Tübinger Akademie für Verhaltenstherapie – GmbH, Tübingen VFKV – Verein zur Förderung der Klinischen Verhaltenstherapie, München Herausgeber