Publications by authors named "Patricia Ohrmann"

77 Publications

Gray matter volume reductions in patients with schizophrenia: A replication study across two cultural backgrounds.

Psychiatry Res Neuroimaging 2019 10 30;292:32-40. Epub 2019 Aug 30.

Department of Psychiatry, University of Kyoto, School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.

Structural gray matter (GM) volume reductions in patients with schizophrenia have rarely been replicated across two different sites, the impact of culture and clinical characteristics remains unresolved. Hence, we assessed GM volume reductions in patients with schizophrenia using 3 T magnetic resonace imaging to replicate results across two independent and culturally different backgrounds (Germany, Japan), and to investigate the impact of brain volume reductions on clinical characteristics. In total, 163 German (80 patients) and 203 Japanese (83 patients) participants were included in the analysis. Voxel-based morphometry (VBM) was used to investigate structural differences between the groups and across the two sites, comparing local GM volumes. Clinical variables were used to analyze effects unrelated to the socio-cultural background. Across both data sets, widespread GM reductions in frontal and temporal cortical parts were found between patients and controls, indicating strong effects of diagnosis and only small effects of site. The investigation of clinical characteristics revealed the strongest effects for chlorpromazine equivalents on GM volume reductions primarily in the Japanese sample. Although the effects of site are small, several brain regions do not overlap between the two groups. Thus, GM may be affected differently at the two sites in patients with schizophrenia.
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http://dx.doi.org/10.1016/j.pscychresns.2019.08.008DOI Listing
October 2019

A Visual Analytics Approach for Comparing Cohorts in Single-Voxel Magnetic Resonance Spectroscopy Data.

Adv Exp Med Biol 2019 ;1138:115-136

Institute of Computer Science, Westfälische Wilhelms-Universität Münster, Münster, Germany.

Single-voxel proton magnetic resonance spectroscopy (H-MRS) is a non-invasive in-vivo technology to measure metabolic concentrations in selected regions of interest in a tissue, e.g., the brain. H-MRS generates spectra of signals with different frequencies and specific intensities which can be assigned to respective metabolites in the investigated tissue and quantified. In studies designed to detect biomarkers of a specific disorder or dysfunction, the overall goal is not just to analyze a single H-MRS data set, but to compare patient cohorts against healthy controls. We propose a visual analytics tool for the comparative analyses of cohorts, i.e., sets of data sets. Each data set can be regarded as a multivariate data sample, in which each variable represents the concentration of a metabolite. While a standard workflow for comparative analyses of two cohorts is routinely deployed by analyzing metabolites individually, our tool allows for comparative cohort analysis in a multivariate setting. Our top-down analysis strategy uses multidimensional data visualization methods combined with statistical plots and statistical analyses. We document and evaluate the effectiveness of our approach for the interactive analysis of metabolite concentrations in three brain regions for a comparative study of an alcohol-dependent patient cohort and a healthy control group.
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http://dx.doi.org/10.1007/978-3-030-14227-8_9DOI Listing
August 2019

Adult patients with ADHD differ from healthy controls in implicit, but not explicit, emotion regulation

J Psychiatry Neurosci 2019 09;44(5):340-349

From the Department of Psychiatry, School of Medicine, University of Münster, Münster, Germany (Materna, Trieloff, Weber, Engell, Ohrmann); Clinical Psychology and Psychotherapy, Department of Psychology, University of Kiel, Kiel, Germany (Wiesner, Shushakova, Pedersen); the Institute for Psychology, University of Münster, Münster, Germany (Schubotz); and the Institute of Clinical Radiology, Medical Faculty, University of Münster, and University Hospital Münster, Münster, Germany (Bauer).

Background: There is increasing evidence that people with attention-deficit/hyperactivity disorder (ADHD) are impaired in emotion regulation, but psychophysiological and functional MRI data on emotion processing in adult patients with ADHD are scarce. We investigated the neural correlates of reappraisal as one of the most efficient emotion-regulation strategies.

Methods: We included 30 adult patients with ADHD and 35 healthy controls in our study. We applied a well-established reappraisal paradigm in functional MRI and assessed behavioural emotion-regulation strategies with standardized questionnaires. We hypothesized that patients with ADHD would demonstrate impaired reappraisal related to reduced activations in the frontoparietal cognitive control network.

Results: Despite our hypothesis, we found no significant activation differences in the neural reappraisal network between patients with ADHD and controls. As well, both groups revealed similar reappraisal success on the immediate behavioural ratings in the scanner. Interestingly, patients with ADHD revealed significantly increased activations in the dorsal and ventral anterior cingulate cortex (ACC) compared to controls when viewing negative > neutral pictures. These ACC activations were significantly correlated with the prevalence of habitual use of reappraisal in patients with ADHD only.

Limitations: Patients withdrew medication only 24 hours before the experiment; we investigated negative, but not positive, emotion processing and regulation.

Conclusion: Although emotion dysregulation is regarded as a core symptom of ADHD, explicit reappraisal does not seem to be impaired in adult patients. However, increased activation of the ACC implies stronger implicit emotion regulation induced by negative stimuli. This might be explained by emotional hyperresponsivity in patients with ADHD compared with controls.
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http://dx.doi.org/10.1503/jpn.180139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710085PMC
September 2019

[Implementation and evaluation of a revised curriculum for psychiatry and psychotherapy].

Nervenarzt 2019 Nov;90(11):1170-1176

Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A 9, 48149, Münster, Deutschland.

Background: Medical education in the discipline of psychiatry and psychotherapy at the University of Münster was traditionally focused on the transfer of knowledge via lectures. According to the current guidelines, the medical curriculum was modified as from the winter semester 2016/2017 to be more competency-based and the changes were evaluated.

Objective: Lectures and seminars were reduced to achieve a better linkage between theoretical and practical knowledge. Moreover, learning goals were formulated based on the German National Competence-based Catalogue of Learning Objectives in Medicine (NKLM) and entrustable professional activities (EPAs).

Material And Methods: Almost all previous lectures are now replaced by an inverted classroom concept with e‑learning. Theoretical knowledge is deepened by immediate multiple choice (MC) examinations and a seminar, which now focusses on specific practical EPAs. At the end of the semester, the students now undergo a practical, formative examination with simulated patients (actors) in addition to the former MC test. For evaluation, a representative sample of a semester cohort which took part in the previous curriculum and a similar cohort which attended the revised curriculum were investigated. Moreover, variables which might have an impact on the results were assessed, e. g. pre-existing psychiatric knowledge and motivation.

Results: Students taught by the modified curriculum showed a significantly better practical performance and no reduction of theoretical knowledge. Relevant influencing factors were not identified.

Conclusion: The results show that a competency-based modification of the curriculum in the discipline of psychiatry and psychotherapy leads to more practical abilities and thus helps future physicians to be more self-determined.
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http://dx.doi.org/10.1007/s00115-019-0677-7DOI Listing
November 2019

Exploring deficient emotion regulation in adult ADHD: electrophysiological evidence.

Eur Arch Psychiatry Clin Neurosci 2018 Jun 2;268(4):359-371. Epub 2017 Aug 2.

Clinical Psychology and Psychotherapy, Department of Psychology, University of Kiel, Olshausenstr. 62, 24118, Kiel, Germany.

Emotional dysregulation (ED) is being increasingly recognized as a core feature of attention-deficit/hyperactivity disorder (ADHD), but the pathophysiological underpinnings remain unclear. In this study, we provide meaningful electrophysiological evidence of ED in adult patients with ADHD (n = 39) compared to healthy controls (n = 40) by exploring the electrophysiological correlates of the emotion regulation strategies reappraisal, distraction, and expressive suppression. Event-related potentials (ERPs) were recorded during passive viewing of neutral and negative images, as well as during emotion regulation. The patients with ADHD exhibited increased frontal late positive potential (LPP) amplitudes during passive viewing of the aversive images and during emotion regulation. Compared with the healthy controls, a subgroup of medication-naïve patients with ADHD (n = 25) also exhibited larger centroparietal LPP amplitudes and provided more negative ratings of the aversive and neutral images. Both the frontal and centroparietal LPP amplitudes were associated with ADHD symptom severity. However, no significant deficit in LPP modulation during emotion regulation was found. These findings strongly support the clinical observation of increased emotional responsivity toward negative stimuli and difficulty during the implementation of emotion regulation strategies and thus encourage the implementation of emotion regulation modules in the treatment of adult patients with ADHD.
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http://dx.doi.org/10.1007/s00406-017-0826-6DOI Listing
June 2018

Hyperactivity and impulsivity in adult attention-deficit/hyperactivity disorder is related to glutamatergic dysfunction in the anterior cingulate cortex.

World J Biol Psychiatry 2018 10 15;19(7):538-546. Epub 2016 Dec 15.

b Department of Psychiatry, School of Medicine , University of Muenster , Germany.

Objectives: Attention-deficit/hyperactivity disorder (ADHD) is closely linked to the dysregulation of dopaminergic and noradrenergic neurotransmission in the fronto-striatal neural network, including the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC). Additionally, increasing evidence supports the involvement of the glutamatergic system in the pathophysiology of ADHD. Impulsivity, a core symptom in patients with ADHD, has been repeatedly associated with glutamatergic neurotransmission, and pharmacological treatment of ADHD has been shown to reduce glutamate levels in the prefrontal cortex.

Methods: We investigated glutamate levels in the ACC and the DLPFC in 30 adults with ADHD and 30 healthy controls using single-voxel proton magnetic resonance spectroscopy on a 3T scanner.

Results: The ADHD group showed a significant increase in glutamate in the ACC compared to controls, no significant differences in metabolites were observed in the DLPFC. Overall, glutamate levels in the ACC were positively correlated with ADHD symptomatology, especially hyperactivity and impulsivity symptoms.

Conclusions: Increased levels of glutamate in the ACC, which were positively correlated with hyperactivity and impulsivity, support the hypothesis that dysfunctional glutamatergic neurotransmission is at least partially responsible for ADHD symptomatology. Modulation of glutamatergic neurotransmission might therefore be a promising avenue for future pharmacological interventions.
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http://dx.doi.org/10.1080/15622975.2016.1262060DOI Listing
October 2018

Risky decision-making under risk in schizophrenia: A deliberate choice?

J Behav Ther Exp Psychiatry 2017 Sep 7;56:57-64. Epub 2016 Aug 7.

Department of Psychiatry, School of Medicine, University of Münster, Germany.

Background And Objectives: Patients with schizophrenia reveal impaired decision-making strategies causing social, financial and health care problems. The extent to which deficits in decision-making reflect intentional risky choices in schizophrenia is still under debate. Based on previous studies we expected patients with schizophrenia to reveal a riskier performance on the GDT and to make more disadvantageous decisions on the IGT.

Methods: In the present study, we investigated 38 patients with schizophrenia and 38 matched healthy control subjects with two competing paradigms regarding feedback: (1) The Game of Dice Task (GDT), in which the probabilities of winning or losing are stable and explicitly disclosed to the subject, to assess decision-making under risk and (2) the Iowa Gambling Task (IGT), which requires subjects to infer the probabilities of winning or losing from feedback, to investigate decision-making under ambiguity.

Results: Patients with schizophrenia revealed an overall riskier performance on the GDT; although they adjusted their strategy over the course of the GDT, they still made significantly more disadvantageous choices than controls. More positive symptoms in patients with schizophrenia indicated by higher PANSS positive scores were associated with riskier choices and less use of negative feedback. Compared to healthy controls, they were not impaired in net score but chose more disadvantageous cards than controls on the first block of the IGT.

Limitations: Effects of medication at the time of testing cannot be ruled out.

Conclusions: Our findings suggest that patients with schizophrenia make riskier decisions and are less able to regulate their decision-making to implement advantageous strategies, even when the probabilities of winning or losing are explicitly disclosed. The dissociation between performance on the GDT and IGT suggests a pronounced impairment of executive functions related to the dorsolateral prefrontal cortex.
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http://dx.doi.org/10.1016/j.jbtep.2016.08.004DOI Listing
September 2017

Disadvantage of Social Sensitivity: Interaction of Oxytocin Receptor Genotype and Child Maltreatment on Brain Structure.

Biol Psychiatry 2016 09 18;80(5):398-405. Epub 2015 Dec 18.

Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia.

Background: Oxytocin has received much attention as a prosocial and anxiolytic neuropeptide. In human studies, the G-allele of a common variant (rs53576) in the oxytocin receptor gene (OXTR) has been associated with protective properties such as reduced stress response and higher receptiveness for social support. In contrast, recent studies suggest a detrimental role of the rs53576 G-allele in the context of childhood maltreatment. To further elucidate the role of OXTR, gene by maltreatment interactions on brain structure and function were investigated.

Methods: Three hundred nine healthy participants genotyped for OXTR rs53576 underwent structural as well as functional magnetic resonance imaging during a common emotional face-matching task. Childhood maltreatment was assessed with the Childhood Trauma Questionnaire (CTQ). Gray matter volumes were investigated by means of voxel-based morphometry across the entire brain.

Results: Structural magnetic resonance imaging data revealed a strong interaction of rs53576 genotype and CTQ scores, mapping specifically to the bilateral ventral striatum. GG homozygotes but not A-allele carriers showed strong gray matter reduction with increasing CTQ scores. In turn, lower ventral striatum gray matter volumes were associated with lower reward dependence, a prosocial trait. Furthermore, the G-allele was associated with increased amygdala responsiveness to emotional facial expressions.

Conclusions: The findings suggest that the G-allele constitutes a vulnerability factor for specific alterations of limbic brain structure in individuals with adverse childhood experiences, complemented by increased limbic responsiveness to emotional interpersonal stimuli. While oxytocinergic signaling facilitates attachment and bonding in supportive social environments, this attunement for social cues may turn disadvantageous under early adverse conditions.
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http://dx.doi.org/10.1016/j.biopsych.2015.12.010DOI Listing
September 2016

Affective Flattening in Patients with Schizophrenia: Differential Association with Amygdala Response to Threat-Related Facial Expression under Automatic and Controlled Processing Conditions.

Psychiatry Investig 2016 Jan 13;13(1):102-11. Epub 2015 Oct 13.

Department of Psychosomatic Medicine, University of Leipzig, Leipzig, Germany.; Department of Psychiatry, University of Münster, Münster, Germany.

Objective: Early neuroimaging studies have demonstrated amygdala hypoactivation in schizophrenia but more recent research based on paradigms with minimal cognitive loads or examining automatic processing has observed amygdala hyperactivation. Hyperactivation was found to be related to affective flattening. In this study, amygdala responsivity to threat-related facial expression was investigated in patients as a function of automatic versus controlled processing and patients' flat affect.

Methods: Functional magnetic resonance imaging was used to measure amygdala activation in 36 patients with schizophrenia and 42 healthy controls. During scanning, a viewing task with masked and unmasked fearful and neutral faces was presented.

Results: Patients exhibited increased amygdala response to unmasked fearful faces. With respect to masked fearful faces, no between-group differences emerged for the sample as a whole but a subsample of patients with flat affect showed heightened amygdala activation. The amygdala response to masked fearful faces was positively correlated with the degree of flat affect. Conversely, amygdala response to unmasked fearful faces was negatively correlated to the severity of affective flattening. In patients, amygdala responses to masked and unmasked fearful faces showed an inverse correlation.

Conclusion: Our findings suggest that amygdala hyperresponsivity to unmasked fearful faces might be a functional characteristic of schizophrenia. Amygdala hyperresponsivity to masked fearful faces might be a specific characteristic of patients with affective flattening. A model of flat affect as a response mechanism to emotional overload is proposed.
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http://dx.doi.org/10.4306/pi.2016.13.1.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701673PMC
January 2016

Linking CSF and cognition in Alzheimer's disease: Reanalysis of clinical data.

Exp Gerontol 2016 Jan 14;73:107-13. Epub 2015 Nov 14.

Evangelisches Krankenhaus Bielefeld, Department of Psychiatry and Psychotherapy Bethel, Remterweg 69-71, D-33617 Bielefeld, Germany.

Objectives: Memory and executive deficits are important cognitive markers of Alzheimer's disease (AD). Moreover, in the past decade, cerebrospinal fluid (CSF) biomarkers have been increasingly utilized in clinical practice. Both cognitive and CSF markers can be used to differentiate between AD patients and healthy seniors with high diagnostic accuracy. However, the extent to which performance on specific mnemonic or executive tasks enables reliable estimations of the concentrations of different CSF markers and their ratios remains unclear.

Methods: To address the above issues, we examined the association between neuropsychological data and CSF biomarkers in 51 AD patients using hierarchical multiple regression analyses. In the first step of these analyses, age, education and sex were entered as predictors to control for possible confounding effects. In the second step, data from a neuropsychological test battery assessing episodic memory, semantic memory and executive functioning were included to determine whether these variables significantly increased (compared to step 1) the explained variance in Aβ42 concentration, p-tau concentration, t-tau concentration, Aβ42/t-tau ratio, and Aβ42/Aβ40 ratio.

Results: The different models explained 52% of the variance in Aβ42/t-tau ratio, 27% of the variance in Aβ42 concentration, and 28% of the variance in t-tau concentration. In particular, Aβ42/t-tau ratio was associated with verbal recognition and code shifting, with Aβ42 being related to verbal recognition and t-tau being related to code shifting. By contrast, the inclusion of neuropsychological data did not allow reliable estimations of Aβ42/Aβ40 ratio or p-tau concentration.

Conclusion: Our results showed that strong associations exist between the cognitive key symptoms of AD and the concentrations and ratios of specific CSF markers. In addition, we revealed a specific combination of neuropsychological tests that may facilitate reliable estimations of CSF concentrations, thereby providing important diagnostic information for non-invasive early AD detection.
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http://dx.doi.org/10.1016/j.exger.2015.11.008DOI Listing
January 2016

Neuropeptide S receptor gene variation modulates anterior cingulate cortex Glx levels during CCK-4 induced panic.

Eur Neuropsychopharmacol 2015 Oct 20;25(10):1677-82. Epub 2015 Jul 20.

Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Germany; kbo-Inn-Salzach-Klinikum, Wasserburg am Inn, Germany; Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University of Munich, Munich, Germany. Electronic address:

An excitatory-inhibitory neurotransmitter dysbalance has been suggested in pathogenesis of panic disorder. The neuropeptide S (NPS) system has been implicated in modulating GABA and glutamate neurotransmission in animal models and to genetically drive altered fear circuit function and an increased risk of panic disorder in humans. Probing a multi-level imaging genetic risk model of panic, in the present magnetic resonance spectroscopy (MRS) study brain glutamate+glutamine (Glx) levels in the bilateral anterior cingulate cortex (ACC) during a pharmacological cholecystokinin tetrapeptide (CCK-4) panic challenge were assessed depending on the functional neuropeptide S receptor gene (NPSR1) rs324981 A/T variant in a final sample of 35 healthy male subjects. The subjective panic response (Panic Symptom Scale; PSS) as well as cortisol and ACTH levels were ascertained throughout the experiment. CCK-4 injection was followed by a strong panic response. A significant time×genotype interaction was detected (p=.008), with significantly lower ACC Glx/Cr levels in T allele carriers as compared to AA homozygotes 5min after injection (p=.003). CCK-4 induced significant HPA axis stimulation, but no effect of genotype was discerned. The present pilot data suggests NPSR1 gene variation to modulate Glx levels in the ACC during acute states of stress and anxiety, with blunted, i.e. possibly maladaptive ACC glutamatergic reactivity in T risk allele carriers. Our results underline the notion of a genetically driven rapid and dynamic response mechanism in the neural regulation of human anxiety and further strengthen the emerging role of the NPS system in anxiety.
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http://dx.doi.org/10.1016/j.euroneuro.2015.07.011DOI Listing
October 2015

Benefits of using culturally unfamiliar stimuli in ambiguous emotion identification: A cross-cultural study.

Psychiatry Res 2015 Jul 14;228(1):39-45. Epub 2015 Apr 14.

Department of Psychology, Kawamura Gakuen Women׳s University, Faculty of Liberal Arts, Abiko, Chiba, Japan.

A novel emotion recognition task that employs photos of a Japanese mask representing a highly ambiguous stimulus was evaluated. As non-Asians perceive and/or label emotions differently from Asians, we aimed to identify patterns of task-performance in non-Asian healthy volunteers with a view to future patient studies. The Noh mask test was presented to 42 adult German participants. Reaction times and emotion attribution patterns were recorded. To control for emotion identification abilities, a standard emotion recognition task was used among others. Questionnaires assessed personality traits. Finally, results were compared to age- and gender-matched Japanese volunteers. Compared to other tasks, German participants displayed slowest reaction times on the Noh mask test, indicating higher demands of ambiguous emotion recognition. They assigned more positive emotions to the mask than Japanese volunteers, demonstrating culture-dependent emotion identification patterns. As alexithymic and anxious traits were associated with slower reaction times, personality dimensions impacted on performance, as well. We showed an advantage of ambiguous over conventional emotion recognition tasks. Moreover, we determined emotion identification patterns in Western individuals impacted by personality dimensions, suggesting performance differences in clinical samples. Due to its properties, the Noh mask test represents a promising tool in the differential diagnosis of psychiatric disorders, e.g. schizophrenia.
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http://dx.doi.org/10.1016/j.psychres.2015.04.005DOI Listing
July 2015

NCAN Cross-Disorder Risk Variant Is Associated With Limbic Gray Matter Deficits in Healthy Subjects and Major Depression.

Neuropsychopharmacology 2015 Oct 24;40(11):2510-6. Epub 2015 Mar 24.

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany.

Genome-wide association studies have reported an association between NCAN rs1064395 genotype and bipolar disorder. This association was later extended to schizophrenia and major depression. However, the neurobiological underpinnings of these associations are poorly understood. NCAN is implicated in neuronal plasticity and expressed in subcortical brain areas, such as the amygdala and hippocampus, which are critically involved in dysfunctional emotion processing and regulation across diagnostic boundaries. We hypothesized that the NCAN risk variant is associated with reduced gray matter volumes in these areas. Gray matter structure was assessed by voxel-based morphometry on structural MRI data in two independent German samples (healthy subjects, n=512; depressed inpatients, n=171). All participants were genotyped for NCAN rs1064395. Hippocampal and amygdala region-of-interest analyses were performed within each sample. In addition, whole-brain data from the combined sample were analyzed. Risk (A)-allele carriers showed reduced amygdala and hippocampal gray matter volumes in both cohorts with a remarkable spatial overlap. In the combined sample, genotype effects observed for the amygdala and hippocampus survived correction for entire brain volume. Further effects were also observed in the left orbitofrontal cortex and the cerebellum/fusiform gyrus. We conclude that NCAN genotype is associated with limbic gray matter alterations in healthy and depressed subjects in brain areas implicated in emotion perception and regulation. The present data suggest that NCAN forms susceptibility to neurostructural deficits in the amygdala, hippocampus, and prefrontal areas independent of disease, which might lead to disorder onset in the presence of other genetic or environmental risk factors.
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http://dx.doi.org/10.1038/npp.2015.86DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569958PMC
October 2015

RGS2 ggenetic variation: association analysis with panic disorder and dimensional as well as intermediate phenotypes of anxiety.

Am J Med Genet B Neuropsychiatr Genet 2015 Apr 4;168B(3):211-22. Epub 2015 Mar 4.

Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.

Accumulating evidence from mouse models points to the G protein-coupled receptor RGS2 (regulator of G-protein signaling 2) as a promising candidate gene for anxiety in humans. Recently, RGS2 polymorphisms were found to be associated with various anxiety disorders, e.g., rs4606 with panic disorder (PD), but other findings have been negative or inconsistent concerning the respective risk allele. To further examine the role of RGS2 polymorphisms in the pathogenesis of PD, we genotyped rs4606 and five additional RGS2 tag single nucleotide polymorphisms (SNPs; rs16834831, rs10801153, rs16829458, rs1342809, rs1890397) in two independent PD samples, comprising 531 matched case/control pairs. The functional SNP rs4606 was nominally associated with PD when both samples were combined. The upstream SNP rs10801153 displayed a Bonferroni-resistant significant association with PD in the second and the combined sample (P = 0.006 and P = 0.017). We furthermore investigated the effect of rs10801153 on dimensional anxiety traits, a behavioral avoidance test (BAT), and an index for emotional processing in the respective subsets of the total sample. In line with categorical results, homozygous risk (G) allele carriers displayed higher scores on the Agoraphobic Cognitions Questionnaire (ACQ; P = 0.015) and showed significantly more defensive behavior during fear provoking situations (P = 0.001). Furthermore, significant effects on brain activation in response to angry (P = 0.013), happy (P = 0.042) and neutral faces (P = 0.032) were detected. Taken together, these findings provide further evidence for the potential role of RGS2 as a candidate gene for PD.
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http://dx.doi.org/10.1002/ajmg.b.32299DOI Listing
April 2015

Influence of repressive coping style on cortical activation during encoding of angry faces.

PLoS One 2014 11;9(12):e112398. Epub 2014 Dec 11.

Department of Psychosomatic Medicine, University of Leipzig, Leipzig, Germany.

Background: Coping plays an important role for emotion regulation in threatening situations. The model of coping modes designates repression and sensitization as two independent coping styles. Repression consists of strategies that shield the individual from arousal. Sensitization indicates increased analysis of the environment in order to reduce uncertainty. According to the discontinuity hypothesis, repressors are sensitive to threat in the early stages of information processing. While repressors do not exhibit memory disturbances early on, they manifest weak memory for these stimuli later. This study investigates the discontinuity hypothesis using functional magnetic resonance imaging (fMRI).

Methods: Healthy volunteers (20 repressors and 20 sensitizers) were selected from a sample of 150 students on the basis of the Mainz Coping Inventory. During the fMRI experiment, subjects evaluated and memorized emotional and neutral faces. Subjects performed two sessions of face recognition: immediately after the fMRI session and three days later.

Results: Repressors exhibited greater activation of frontal, parietal and temporal areas during encoding of angry faces compared to sensitizers. There were no differences in recognition of facial emotions between groups neither immediately after exposure nor after three days.

Conclusions: The fMRI findings suggest that repressors manifest an enhanced neural processing of directly threatening facial expression which confirms the assumption of hyper-responsivity to threatening information in repression in an early processing stage. A discrepancy was observed between high neural activation in encoding-relevant brain areas in response to angry faces in repressors and no advantage in subsequent memory for these faces compared to sensitizers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112398PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263533PMC
September 2015

Abnormal, affect-specific modulatory effects on early auditory processing in schizophrenia: magnetoencephalographic evidence.

Schizophr Res 2015 Feb 10;161(2-3):308-13. Epub 2014 Dec 10.

Department of Psychology, Clinical Psychology and Psychotherapy, University Münster, D-48149 Münster, Germany; Department of Psychology, Clinical Psychology and Psychotherapy, University Kiel, D-24118 Kiel, Germany. Electronic address:

Abnormalities in the perception and identification of emotions have frequently been reported in schizophrenia. Hemodynamic neuroimaging studies found functional abnormalities in cortical and subcortical brain circuits that are involved in normal affective processing, but the temporal dynamics of abnormal emotion processing in schizophrenia remain largely elusive. To investigate this issue, we recorded early auditory evoked field components by means of whole-head magnetoencephalography that were in response to emotion-associated tones in seventeen patients with schizophrenia and in seventeen healthy, matched controls. Forty-two click-like tones (conditioned stimuli; CS) acquired differential emotional meaning through an affective associative learning procedure by pairing each CS three times with either pleasant, unpleasant or neutral auditory scenes. As expected, differential affect-specific modulation in patients vs. controls was evident, starting at the auditory N1m onset latency of approximately 70ms, extending to 230ms. While controls showed the expected enhanced processing of emotion associated CS, patients revealed an inverted pattern with reduced processing of arousal, when compared to neutral stimuli, in the right prefrontal cortex. The present finding suggests impairments in the prioritization of emotionally salient vs. non-salient stimuli in patients with schizophrenia. Dysfunction in higher cognitive processes and behavior in schizophrenia may therefore reflect dysfunction in fundamental, early emotion processing stages.
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http://dx.doi.org/10.1016/j.schres.2014.11.025DOI Listing
February 2015

Insular and hippocampal gray matter volume reductions in patients with major depressive disorder.

PLoS One 2014 22;9(7):e102692. Epub 2014 Jul 22.

Department of Psychiatry, University of Marburg, Marburg, Germany; Department of Psychiatry, University of Münster, Münster, Germany.

Background: Major depressive disorder is a serious psychiatric illness with a highly variable and heterogeneous clinical course. Due to the lack of consistent data from previous studies, the study of morphometric changes in major depressive disorder is still a major point of research requiring additional studies. The aim of the study presented here was to characterize and quantify regional gray matter abnormalities in a large sample of clinically well-characterized patients with major depressive disorder.

Methods: For this study one-hundred thirty two patients with major depressive disorder and 132 age- and gender-matched healthy control participants were included, 35 with their first episode and 97 with recurrent depression. To analyse gray matter abnormalities, voxel-based morphometry (VBM8) was employed on T1 weighted MRI data. We performed whole-brain analyses as well as a region-of-interest approach on the hippocampal formation, anterior cingulate cortex and amygdala, correlating the number of depressive episodes.

Results: Compared to healthy control persons, patients showed a strong gray-matter reduction in the right anterior insula. In addition, region-of-interest analyses revealed significant gray-matter reductions in the hippocampal formation. The observed alterations were more severe in patients with recurrent depressive episodes than in patients with a first episode. The number of depressive episodes was negatively correlated with gray-matter volume in the right hippocampus and right amygdala.

Conclusions: The anterior insula gray matter structure appears to be strongly affected in major depressive disorder and might play an important role in the neurobiology of depression. The hippocampal and amygdala volume loss cumulating with the number of episodes might be explained either by repeated neurotoxic stress or alternatively by higher relapse rates in patients showing hippocampal atrophy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102692PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106847PMC
March 2016

Social alienation in schizophrenia patients: association with insula responsiveness to facial expressions of disgust.

PLoS One 2014 22;9(1):e85014. Epub 2014 Jan 22.

Department of Psychiatry, University of Münster, Münster, Germany ; Department of Psychosomatic Medicine and Psychotherapy, University of Leipzig, Leipzig, Germany.

Introduction: Among the functional neuroimaging studies on emotional face processing in schizophrenia, few have used paradigms with facial expressions of disgust. In this study, we investigated whether schizophrenia patients show less insula activation to macro-expressions (overt, clearly visible expressions) and micro-expressions (covert, very brief expressions) of disgust than healthy controls. Furthermore, departing from the assumption that disgust faces signal social rejection, we examined whether perceptual sensitivity to disgust is related to social alienation in patients and controls. We hypothesized that high insula responsiveness to facial disgust predicts social alienation.

Methods: We used functional magnetic resonance imaging to measure insula activation in 36 schizophrenia patients and 40 healthy controls. During scanning, subjects passively viewed covert and overt presentations of disgust and neutral faces. To measure social alienation, a social loneliness scale and an agreeableness scale were administered.

Results: Schizophrenia patients exhibited reduced insula activation in response to covert facial expressions of disgust. With respect to macro-expressions of disgust, no between-group differences emerged. In patients, insula responsiveness to covert faces of disgust was positively correlated with social loneliness. Furthermore, patients' insula responsiveness to covert and overt faces of disgust was negatively correlated with agreeableness. In controls, insula responsiveness to covert expressions of disgust correlated negatively with agreeableness.

Discussion: Schizophrenia patients show reduced insula responsiveness to micro-expressions but not macro-expressions of disgust compared to healthy controls. In patients, low agreeableness was associated with stronger insula response to micro- and macro-expressions of disgust. Patients with a strong tendency to feel uncomfortable with social interactions appear to be characterized by a high sensitivity for facial expression signaling social rejection. Given the associations of insula responsiveness to covert disgust expression with low agreeableness in healthy individuals, insula responsiveness to expressions of disgust might be in general a neural marker of the personality trait of agreeableness.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0085014PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898910PMC
December 2014

Automatic amygdala response to facial expression in schizophrenia: initial hyperresponsivity followed by hyporesponsivity.

BMC Neurosci 2013 Nov 13;14:140. Epub 2013 Nov 13.

Department of Psychiatry, University of Münster, Albert-Schweitzer-Str, 11, Münster 48149, Germany.

Background: It is well established that the amygdala is crucially involved in the processing of facial emotions. In schizophrenia patients, a number of neuroimaging findings suggest hypoactivation of the amygdala in response to facial emotion, while others indicate normal or enhanced recruitment of this region. Some of this variability may be related to the baseline condition used and the length of the experiment. There is evidence that schizophrenia patients display increased activation of the amygdala to neutral faces and that this is predominantly observed during early parts of the experiment. Recent research examining the automatic processing of facial emotion has also reported amygdala hyperactivation in schizophrenia. In the present study, we focused on the time-course of amygdala activation during the automatic processing of emotional facial expression. We hypothesized that in comparison to healthy subjects, patients would initially show hyperresponsivity of the amygdala to masked emotional and neutral faces. In addition, we expected amygdala deactivation in response to masked facial emotions from the first to the second phase to be more pronounced in patients than in controls.

Results: Amygdala activation in response to angry, happy, neutral, and no facial expression (presented for 33 ms) was measured by functional magnetic resonance imaging in 30 schizophrenia patients and 35 healthy controls. Across all subjects, the bilateral amygdala response to faces (relative to the no facial expression condition) was larger in the initial phase (first half of trials) than in the second phase (second half of trials). During the initial phase, schizophrenia patients exhibited an increased right amygdala response to all faces and an increased left amygdala response to neutral faces compared with controls. During the second phase, controls manifested a higher right amygdala response for all faces and a higher left amygdala response to angry faces than patients.

Conclusions: Schizophrenia patients are characterized by high initial amygdala responsivity to facial expressions at an automatic processing level, which substantially decreases with time. Amygdala deactivation over time might reflect an automatic mechanism by which schizophrenia patients suppress the processing of facial stimuli. This blocking mechanism could help patients avoid overstimulation during social interactions.
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http://dx.doi.org/10.1186/1471-2202-14-140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832234PMC
November 2013

Impact of gray matter reductions on theory of mind abilities in patients with schizophrenia.

Soc Neurosci 2013 18;8(6):631-9. Epub 2013 Sep 18.

a Department of Psychiatry and Psychotherapy, School of Medicine , University of Muenster , Muenster , Germany.

To identify the brain regions involved in the interpretation of intentional movement by patients with schizophrenia, we investigated the association between cerebral gray matter (GM) volumes and performance on a theory of mind (ToM) task using voxel-based morphometry. Eighteen patients with schizophrenia and thirty healthy controls participated in the study. Participants were given a moving shapes task that employs the interpretation of intentional movement. Verbal descriptions were rated according to intentionality. ToM performance deficits in patients were found to be positively correlated with GM volume reductions in the superior temporal sulcus and medial prefrontal cortex. Our findings confirm that divergent brain regions contribute to mentalizing abilities and that GM volume reductions impact behavioral deficits in patients with schizophrenia.
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http://dx.doi.org/10.1080/17470919.2013.837094DOI Listing
June 2014

Acute shift in glutamate concentrations following experimentally induced panic with cholecystokinin tetrapeptide--a 3T-MRS study in healthy subjects.

Neuropsychopharmacology 2013 Aug 5;38(9):1648-54. Epub 2013 Mar 5.

Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.

According to preclinical studies, glutamate has been implicated in the pathogenesis of anxiety. In order to elucidate the role of glutamate in anxiety and panic in humans, brain glutamate+glutamine (Glx) levels were measured during cholecystokinin-tetrapeptide (CCK-4)-induced panic using magnetic resonance spectroscopy (MRS). Eighteen healthy subjects underwent a CCK-4 challenge. MR spectra were obtained from the anterior cingulate cortex (ACC) using a single voxel point-resolved spectroscopy method and analyzed using LCModel. A combined fitting of Glx was performed. Panic was assessed using the Acute Panic Inventory (API) and Panic Symptom Scale (PSS) scores. Moreover, hypothalamic-pituitary-adrenal axis stimulation was monitored throughout the challenge. There was a significant panic response following CCK-4 as revealed by a marked increase in both the panic scores (API: F(1,17)=149.41; p<0.0001; PSS: F(1,17)=88.03; p<0.0001) and heart rate (HR: F(1,17)=72.79; p<0.0001). MRS measures showed a significant increase of brain Glx/creatine (Glx/Cr) levels peaking at 2-10 min after challenge (F(1,17)=15.94; p=0.001). There was also a significant increase in CCK-4-related cortisol release (F(6,11)=8.68; p=0.002). Finally, significant positive correlations were found between baseline Glx/Cr and both APImax (r=0.598; p=0.009) and maximum heart rate (HR(max)) during challenge (r=0.519; p=0.027). Our results suggest that CCK-4-induced panic is accompanied by a significant glutamate increase in the bilateral ACC. The results add to the hypothesis of a disturbance of the inhibitory-excitatory equilibrium and suggest that apart from static alterations rapid and dynamic neurochemical changes might also be relevant for the neural control of panic attacks.
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http://dx.doi.org/10.1038/npp.2013.61DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717541PMC
August 2013

Craving in alcohol-dependent patients after detoxification is related to glutamatergic dysfunction in the nucleus accumbens and the anterior cingulate cortex.

Neuropsychopharmacology 2013 Jul 12;38(8):1401-8. Epub 2013 Feb 12.

Department of Psychiatry, University of Muenster, Muenster, Germany.

The upregulation of glutamatergic excitatory neurotransmission is thought to be partly responsible for the acute withdrawal symptoms and craving experienced by alcohol-dependent patients. Most physiological evidence supporting this hypothesis is based on data from animal studies. In addition, clinical data show that GABAergic and anti-glutamatergic drugs ameliorate withdrawal symptoms, offering indirect evidence indicative of glutamatergic hyperexcitability in alcohol-dependent subjects. We used proton magnetic resonance spectroscopy to quantify the glutamate (Glu) levels in healthy control subjects and in alcohol-dependent patients immediately after detoxification. The volumes of interest were located in the nucleus accumbens (NAcc) and the anterior cingulate cortex (ACC), which are two brain areas that have important functions in reward circuitry. In addition to Glu, we quantified the levels of combined Glu and glutamine (Gln), N-acetylaspartate, choline-containing compounds, and creatine. The Glu levels in the NAcc were significantly higher in patients than in controls. Craving, which was measured using the Obsessive Compulsive Drinking Scale, correlated positively with levels of combined Glu and Gln in the NAcc and in the ACC. The levels of all other metabolites were not significantly different between patients and controls. The increased Glu levels in the NAcc in alcohol-dependent patients shortly after detoxification confirm the animal data and suggest that striatal glutamatergic dysfunction is related to ethanol withdrawal. The positive correlation between craving and glutamatergic metabolism in both key reward circuitry areas support the hypothesis that the glutamatergic system has an important role in the later course of alcohol dependence with respect to abstinence and relapse.
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http://dx.doi.org/10.1038/npp.2013.45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682141PMC
July 2013

High-level, but not low-level, motion perception is impaired in patients with schizophrenia.

Neuropsychology 2013 Jan;27(1):60-8

Institute of Psychology, University of Muenster, Muenster, Germany.

Objective: Smooth pursuit eye movements are compromised in patients with schizophrenia and their first-degree relatives. Although research has demonstrated that the motor components of smooth pursuit eye movements are intact, motion perception has been shown to be impaired. In particular, studies have consistently revealed deficits in performance on tasks specific to the high-order motion area V5 (middle temporal area, MT) in patients with schizophrenia. In contrast, data from low-level motion detectors in the primary visual cortex (V1) have been inconsistent.

Method: To differentiate between low-level and high-level visual motion processing, we applied a temporal-order judgment task for motion events and a motion-defined figure-ground segregation task using patients with schizophrenia and healthy controls. Successful judgments in both tasks rely on the same low-level motion detectors in the V1; however, the first task is further processed in the higher-order motion area MT in the magnocellular (dorsal) pathway, whereas the second task requires subsequent computations in the parvocellular (ventral) pathway in visual area V4 and the inferotemporal cortex (IT). These latter structures are supposed to be intact in schizophrenia.

Results: Patients with schizophrenia revealed a significantly impaired temporal resolution on the motion-based temporal-order judgment task but only mild impairment in the motion-based segregation task.

Conclusions: These results imply that low-level motion detection in V1 is not, or is only slightly, compromised; furthermore, our data restrain the locus of the well-known deficit in motion detection to areas beyond the primary visual cortex.
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http://dx.doi.org/10.1037/a0031300DOI Listing
January 2013

Impaired Behavioral Inhibition in Implicit Sequence Learning in Adult ADHD.

J Atten Disord 2018 Feb 27;22(3):250-260. Epub 2012 Nov 27.

1 University of Muenster, Germany.

Objective: Deficits in explicit learning and memory have consistently been reported in adult ADHD, but it is less clear whether these deficits reflect deficient attentional processes or specific dysfunctions in memory processes. Studies on implicit learning and memory, which are less dependent on the allocation of attention, have rarely been conducted on adult ADHD.

Method: We implemented a modified serial reaction-time task that involves distracting stimuli to investigate implicit sequence learning in 32 adult participants with ADHD and in 32 matched healthy control participants.

Results: The participants with ADHD revealed unimpaired implicit learning performance, but they made significantly more errors than the control participants. There was no evidence for impaired error monitoring in the participants with ADHD reflected by a comparable degree of double errors and post-error slowing in the two groups.

Conclusion: Reduced efficiency of the inhibition of incorrect responses in implicit sequence learning supports previous findings of impaired behavioral inhibition in adult ADHD.
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http://dx.doi.org/10.1177/1087054712464392DOI Listing
February 2018

Neural correlates of affective priming effects based on masked facial emotion: an fMRI study.

Psychiatry Res 2013 Mar 3;211(3):239-45. Epub 2012 Nov 3.

Department of Psychosomatic Medicine, University of Leipzig, Semmelweisstr. 10, 04103 Leipzig, Germany.

Affective priming refers to the phenomenon that subliminal presentation of facial emotion biases subsequent evaluation of a neutral object in the direction of the prime. The aim of the present study was to specify the neural correlates of evaluative shifts elicited by facial emotion shown below the threshold of conscious perception. We tested the hypotheses whether the amygdala is involved in negative priming, whereas the nucleus accumbens participates in positive priming. In addition, exploratory whole brain correlation analyses were conducted. During 3T fMRI scanning, pictures of sad, happy, and neutral facial expression masked by neutral faces were presented to 110 healthy adults who had to judge valence of masks on a four-point scale. There was evidence for significant negative priming based on sad faces. A correlation was observed between amygdala activation and negative priming. Activation in medial, middle, and superior frontal and middle temporo-occipital areas, and insula was also associated with negative priming. No significant priming based on happy faces was found. However, nucleus accumbens activation to happy faces correlated with the positive priming score. The present findings confirm that the amygdala but also other brain regions, especially the medial frontal cortex, appear involved in automatically elicited negative evaluative shifts.
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http://dx.doi.org/10.1016/j.pscychresns.2012.09.008DOI Listing
March 2013

Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain.

J Neuroinflammation 2012 Jul 6;9:125. Epub 2012 Jul 6.

Discipline of Psychiatry, School of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia, Australia.

Background: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated.

Methodology: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs.Principal findings/resultsIn a whole-brain analysis, the polymorphism rs1800795 (-174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = -10, z = -15; F(2,286) = 8.54, p(uncorrected) = 0.0002; p(AlphaSim-corrected) = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses.

Conclusions/significance: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.
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http://dx.doi.org/10.1186/1742-2094-9-125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464888PMC
July 2012

Discriminating unipolar and bipolar depression by means of fMRI and pattern classification: a pilot study.

Eur Arch Psychiatry Clin Neurosci 2013 Mar 26;263(2):119-31. Epub 2012 May 26.

Department of Psychiatry, University of Münster, Albert-Schweitzer-Campus 1 A9, 48149, Münster, Germany.

Bipolar disorders rank among the most debilitating psychiatric diseases. Bipolar depression is often misdiagnosed as unipolar depression, leading to suboptimal therapy and poor outcomes. Discriminating unipolar and bipolar depression at earlier stages of illness could therefore help to facilitate efficient and specific treatment. In the present study, the neurobiological underpinnings of emotion processing were investigated in a sample of unipolar and bipolar depressed patients matched for age, gender, and depression severity by means of fMRI. A pattern-classification approach was employed to discriminate the two samples. The pattern classification yielded up to 90 % accuracy rates discriminating the two groups. According to the feature weights of the multivariate maps, medial prefrontal and orbitofrontal regions contributed to classifications specific to unipolar depression, whereas stronger feature weights in dorsolateral prefrontal areas contribute to classifications as bipolar. Strong feature weights were observed in the amygdala for the negative faces condition, which were specific to unipolar depression, whereas higher amygdala features weights during the positive faces condition were observed, specific to bipolar subjects. Standard univariate fMRI analysis supports an interpretation, where this might be related to a higher responsiveness, by yielding a significant emotion × group interaction within the bilateral amygdala. We conclude that pattern-classification techniques could be a promising tool to classify acutely depressed subjects as unipolar or bipolar. However, since the present approach deals with small sample sizes, it should be considered as a proof-of-concept study. Hence, results have to be confirmed in larger samples preferably of unmedicated subjects.
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http://dx.doi.org/10.1007/s00406-012-0329-4DOI Listing
March 2013

Anterior cingulate cortex activation is related to learning potential on the WCST in schizophrenia patients.

Brain Cogn 2012 Aug 1;79(3):245-51. Epub 2012 May 1.

Department of Psychiatry, School of Medicine, University of Muenster, Germany.

The remediation of executive function in patients with schizophrenia is important in rehabilitation because these skills affect the patient's capacity to function in the community. There is evidence that instructional techniques can improve deficits in the Wisconsin Card Sorting Test (WCST) in some schizophrenia patients. We used a standard test/training phase/standard test format of the WCST to classify 36 schizophrenia patients as high-achievers, learners or non-retainers. All healthy controls performed as high-achievers. An event-related fMRI design assessed neural activation patterns during post-training WCST performance. Patients showed a linear trend between set-shifting related activation in the anterior cingulate cortex and learning potential, i.e. increased activation in high-achievers, a trend for increased activation in learners, and no activation in non-retainers compared to controls. In addition, activation in the temporoparietal cortex was highest in patients classified as learners, whereas in non-retainers activation was increased in the inferior frontal gyrus compared to controls and high-achieving patients. These results emphasize the relevance of the ACC's neural integrity in learning set-shifting strategies for patients with schizophrenia. Also, our results support the hypothesis that compensatory neural activation in patients with schizophrenia helps them to catch up with healthy controls on cognitive tasks.
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http://dx.doi.org/10.1016/j.bandc.2012.03.007DOI Listing
August 2012

Tumor necrosis factor gene variation predicts hippocampus volume in healthy individuals.

Biol Psychiatry 2012 Oct 2;72(8):655-62. Epub 2012 May 2.

Discipline of Psychiatry, School of Medicine, University of Adelaide, North Terrace, Adelaide, Australia.

Background: Cytokines such as tumor necrosis factor (TNF) α have been implicated in neurodegeneration relevant to various neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative properties of cytokine genes on brain function and on hippocampus (HC) function in particular. In this study we investigate the neurodegenerative role of TNF polymorphisms on brain morphology in healthy individuals.

Methods: Voxel-based morphometry was used in a large sample of healthy individuals (n = 303) to analyze the associations between genetic variants of TNF (rs1800629; rs361525) and brain morphology (gray matter concentration).

Results: In a region of interest analysis of the HC, for rs1800629, we observed a strong genotype effect on bilateral HC gray matter concentration. Carriers of one or two A-alleles had significantly smaller volumes compared with GG-homozygotes. For rs361525, a similar effect was observed at almost the same location, with the A-allele resulting in smaller HC volumes compared with GG homozygotes.

Conclusions: The findings suggest a neurodegenerative role of the A-alleles of the TNF single nucleotide polymorphisms rs1800629 (-308G/A) and rs361525 (-238G/A) on hippocampal volumes in healthy individuals. Future imaging studies on the role of these single nucleotide polymorphisms in psychiatric populations of diseases with neurodegenerative components are warranted.
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http://dx.doi.org/10.1016/j.biopsych.2012.04.002DOI Listing
October 2012

Theory of mind in patients with schizophrenia: is mentalizing delayed?

Schizophr Res 2012 May 7;137(1-3):224-9. Epub 2012 Mar 7.

Department of Psychology, University of Muenster, Germany.

Objective: Functional imaging studies have used numerous neurocognitive designs to investigate brain activation during theory of mind (ToM) tasks in patients with schizophrenia. The majority of studies asks participants to retrospectively attribute mental states to others. We used a novel animated task to investigate implicit mentalizing online. Because behavioral studies have revealed slower ToM performance reaction times in patients with schizophrenia, we hypothesized that time would influence functional MRI (fMRI) activation patterns also.

Methods: We applied the "Moving Shapes" paradigm, which involves two interacting triangles, to a functional MRI block design and investigated the neural activation patterns of 15 patients with schizophrenia and 14 healthy controls. We additionally analyzed the first and second halves of each video separately to assess time-related differences.

Results: Overall, patients with schizophrenia showed increased activation in the inferior and middle frontal gyri, the superior temporal gyrus, the precuneus and the cerebellum compared with controls during ToM versus non-ToM videos. Most importantly, patients with schizophrenia had predominantly increased activation in ToM-related brain areas during the second half of the ToM paradigm, whereas the activation in areas of the ToM-network in healthy controls occurred during the first half of the presentation.

Conclusions: Our results confirm recent findings of significantly stronger neural activations that encompass the fronto-temporo-parietal cerebral areas in patients with schizophrenia compared with controls during ToM tasks. The observation of slower cognitive processing in patients with schizophrenia during mentalizing might explain some of the contradictory imaging findings in these patients and have implications for cognitive remediation.
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http://dx.doi.org/10.1016/j.schres.2012.02.022DOI Listing
May 2012