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ABSTRACT: 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.
Brain and Cognition 05/2012; 79(3):245-51. · 3.17 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Biological Psychiatry 03/2012; 137(1-3):224-9. · 8.28 Impact Factor
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Jun Miyata,
Akihiko Sasamoto, Katja Koelkebeck,
Kazuyuki Hirao,
Keita Ueda,
Ryosaku Kawada,
Shinsuke Fujimoto,
Yusuke Tanaka,
Manabu Kubota,
Hidenao Fukuyama,
Nobukatsu Sawamoto,
Hidehiko Takahashi,
Toshiya Murai
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ABSTRACT: A number of magnetic resonance imaging (MRI) studies have revealed morphological cortical asymmetry in the normal human brain, and reduction or inversion of such hemispheric asymmetry has been reported in schizophrenia. On the other hand, diffusion tensor imaging (DTI) studies have reported inconsistent findings concerning abnormal asymmetry of white matter integrity in schizophrenia. Our aim was to confirm whether there is reduced or inverted asymmetry of white matter integrity in the whole brain in schizophrenia. For this study, 26 right-handed schizophrenia patients, and 32 matched healthy control subjects were investigated. Voxelwise analysis of DTI data was performed using the tract-based spatial statistics. The fractional anisotropy (FA) images were normalized and projected onto the symmetrical white matter skeleton, and the laterality index (LI) of FA, determined by 2 × (left - right)/(left + right), was calculated. The results reveal that schizophrenia patients and healthy controls showed similar patterns of overall FA asymmetries. In the group comparison, patients showed significant reduction of LI in the external capsule (EC), and posterior limb of the internal capsule (PLIC). The EC cluster revealed increased rightward asymmetry, and the PLIC cluster showed reduced leftward asymmetry. Rightward-shift of FA in the EC cluster correlated with negative symptom severity. Considering that the EC cluster includes the uncinate and inferior occipitofrontal fasciculi, which have connections to the orbitofrontal cortex, abnormal asymmetry of white matter integrity in schizophrenia may play a crucial role in the pathogenesis of schizophrenia, through the altered connectivity to the orbitofrontal cortex.
Human Brain Mapping 10/2011; 33(7):1741-9. · 5.88 Impact Factor
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Katja Koelkebeck,
Kazuyuki Hirao,
Ryousaku Kawada,
Jun Miyata,
Teruyasu Saze,
Shiho Ubukata,
Shoji Itakura,
Yasuhiro Kanakogi,
Patricia Ohrmann,
Jochen Bauer,
Anya Pedersen,
Nobukatsu Sawamoto,
Hidenao Fukuyama,
Hidehiko Takahashi,
Toshiya Murai
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ABSTRACT: Theory of mind (ToM) functioning develops during certain phases of childhood. Factors such as language development and educational style seem to influence its development. Some studies that have focused on transcultural aspects of ToM development have found differences between Asian and Western cultures. To date, however, little is known about transcultural differences in neural activation patterns as they relate to ToM functioning. EXPERIMENTAL METHODS: The aim of our study was to observe ToM functioning and differences in brain activation patterns, as assessed by functional magnetic resonance imaging (fMRI). This study included a sample of 18 healthy Japanese and 15 healthy Caucasian subjects living in Japan. We presented a ToM task depicting geometrical shapes moving in social patterns. We also administered questionnaires to examine empathy abilities and cultural background factors.
Behavioral data showed no significant group differences in the subjects' post-scan descriptions of the movies. The imaging results displayed stronger activation in the medial prefrontal cortex (MPFC) in the Caucasian sample during the presentation of ToM videos. Furthermore, the task-associated activation of the MPFC was positively correlated with autistic and alexithymic features in the Japanese sample.
In summary, our results showed evidence of culturally dependent sociobehavioral trait patterns, which suggests that they have an impact on brain activation patterns during information processing involving ToM.
Social neuroscience 09/2011; 6(5-6):615-26. · 3.17 Impact Factor
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ABSTRACT: Although there is considerable evidence that patients with schizophrenia have impaired executive functions, the neural mechanisms underlying these deficits are unclear. Generation and selection is one of the basic mechanisms of executive functioning. We investigated the neural correlates of this mechanism by means of functional magnetic resonance imaging (fMRI) in patients with schizophrenia and healthy controls.
We used the Wisconsin Card Sorting Test (WCST) in an event-related fMRI study to analyze neural activation patterns during the distinct components of the WCST in 36 patients with schizophrenia and 28 controls. We focused our analyses on the process of set-shifting. After participants received negative feedback, they had to generate and decide on a new sorting rule.
A widespread activation pattern encompassing the inferior and middle frontal gyrus, parietal, temporal and occipital cortices, anterior cingulate cortex (ACC), supplementary motor area, insula, caudate, thalamus and brainstem was observed in patients with schizophrenia after negative versus positive feedback, whereas in healthy controls, significant activation clusters were more confined to the cortical areas. Significantly increased activation in the rostral ACC after negative feedback and in the dorsal ACC during matching after negative feedback were observed in schizophrenia patients compared with controls. Controls showed activation in the bilateral dorsolateral prefrontal cortex (Brodmann area 46), whereas schizophrenia patients showed activation in the right dorsolateral prefrontal cortex only.
All patients were taking neuroleptic medication, which has an impact on cognitive function as well as on dopaminergic and serotonergic prefrontal metabolism.
Our data suggest that, in patients with schizophrenia, set-shifting is associated with increased activation in the rostral and dorsal ACC, reflecting higher emotional and cognitive demands, respectively.
Journal of psychiatry & neuroscience: JPN 09/2010; 35(5):321-9. · 5.34 Impact Factor
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Astrid Veronika Rauch,
Maraike Reker,
Patricia Ohrmann,
Anya Pedersen,
Jochen Bauer,
Udo Dannlowski,
Liv Harding, Katja Koelkebeck,
Carsten Konrad,
Harald Kugel,
Volker Arolt,
Walter Heindel,
Thomas Suslow
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ABSTRACT: Schizophrenia patients show abnormalities in the processing of facial emotion. The amygdala is a central part of a brain network that is involved in the perception of facial emotions. Previous functional neuroimaging studies on the perception of facial emotion in schizophrenia have focused almost exclusively on controlled processing. In the present study, we investigated the automatic responsivity of the amygdala to emotional faces in schizophrenia and its relationship to clinical symptomatology by applying an affective priming task. 3-T fMRI was utilized to examine amygdala responses to sad and happy faces masked by neutral faces in 12 schizophrenia patients and 12 healthy controls. The Positive and Negative Syndrome Scale (PANSS) was administered to assess current symptomatology. Schizophrenia patients exhibited greater automatic amygdala responses to sad and happy faces relative to controls. Amygdala responses to masked sad and happy expressions were positively correlated with the negative subscale of the PANSS. Schizophrenia patients appear to be characterized by amygdalar hyperresponsiveness to negative and positive facial expressions on an automatic processing level. Heightened automatic amygdala responsivity could be involved in the development and maintenance of negative symptoms in schizophrenia.
Psychiatry Research 06/2010; 182(3):200-6. · 2.52 Impact Factor
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ABSTRACT: There is substantial evidence for Theory of Mind (ToM) deficits in patients with schizophrenia. Many psychotic symptoms may best be understood in light of an impaired capacity to infer one's own and other persons' mental states and to relate those to executing behavior. The aim of our study was to investigate ToM abilities in first-episode schizophrenia patients and to analyze them in relation to neuropsychological and psychopathological functioning.
A modified Moving Shapes paradigm was used to assess ToM abilities in 23 first-episode patients with schizophrenia and 23 matched healthy controls. Participants had to describe animated triangles which moved (1) randomly, (2) goal-directed, or (3) in complex, socially interactive ways (ToM video sequences). Neuropsychological functioning, psychopathology, autistic and alexithymic features as well as empathetic abilities were correlated with ToM performance.
Compared to healthy controls, first-episode schizophrenia patients gave more incorrect descriptions and used less ToM-related vocabulary when responding to socially complex ToM video sequences. No group differences were revealed for videos with random movements. ToM abilities correlated significantly with positive symptoms, reasoning, verbal memory performance and verbal IQ, but not with empathetic abilities or autistic and alexithymic features. When controlling for reasoning, verbal memory performance and verbal IQ, the correctness of video descriptions was still significantly worse in schizophrenia patients.
The results of our study in first-episode schizophrenia patients underline recent findings on ToM deficits in the early course of schizophrenia. Only a moderate influence of neurocognitive deficits on ToM performance was observed. Impairment in ToM abilities seems to be predominantly independent of clinical state, alexithymia and empathy.
Biological Psychiatry 06/2010; 119(1-3):115-23. · 8.28 Impact Factor
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Anette Kersting,
Patricia Ohrmann,
Anya Pedersen,
Kristin Kroker,
Daniela Samberg,
Jochen Bauer,
Harald Kugel, Katja Koelkebeck,
Johannes Steinhard,
Walter Heindel,
Volker Arolt,
Thomas Suslow
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ABSTRACT: The traumatic loss of an unborn child by induced termination of pregnancy because of fetal malformation is a major life event that causes intense maternal grief. Increasing evidence supports the hypothesis that the same neural structures involved in the experience of physical pain are involved in the experience of social pain and loss.
To investigate neural activation patterns related to acute grief, the authors conducted a functional MRI study of 12 post-termination women and 12 noninduced women who delivered a healthy child. Brain activation was measured while participants viewed pictures of happy baby, happy adult, and neutral adult faces.
Relative to comparison women, post-termination women showed greater activation in the middle and posterior cingulate gyrus, the inferior frontal gyrus, the middle temporal gyrus, the thalamus, and the brainstem in response to viewing happy baby faces. Functional connectivity between the cingulate gyrus and the thalamus during the processing of happy baby faces was significantly stronger in post-termination women.
Overall, acute grief after the loss of an unborn child was closely related to the activation of the physical pain network encompassing the cingulate gyrus, the inferior frontal gyrus, the thalamus, and the brainstem. To the authors' knowledge, the stronger functional thalamocingulate connectivity in post-termination women is the first in vivo demonstration of an involvement of the neural maternal attachment network in grief after the loss of an unborn child.
American Journal of Psychiatry 11/2009; 166(12):1402-10. · 12.54 Impact Factor
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Christa Hohoff,
Gerald Ponath,
Christine M Freitag,
Florian Kästner,
Petra Krakowitzky,
Katharina Domschke, Katja Koelkebeck,
Frank Kipp,
Christof von Eiff,
Jürgen Deckert,
Matthias Rothermundt
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ABSTRACT: Several lines of evidence suggest an important role of the S100B protein and its coding gene in different neuropathological and psychiatric disorders like dementia, bipolar affective disorders and schizophrenia. To clarify whether a direct link exists between gene and gene product, that is, whether S100B variants directly modulate S100B serum concentration, 196 healthy individuals were assessed for S100B serum concentrations and genotyped for five potentially functional S100B SNPs. Functional variants of the serotonergic genes 5-HT1A and 5-HTT possibly modulating S100B serum levels were also studied. Further, publicly available human postmortem gene expression data were re-analyzed to elucidate the impact of S100B, 5-HT1A and 5-HTT SNPs on frontal cortex S100B mRNA expression. Several S100B SNPs, particularly rs9722, and the S100B haplotype T-G-G-A (including rs2186358-rs11542311-rs2300403-rs9722) were associated with elevated S100B serum concentrations (Bonferroni corrected P < 0.05). Of these, rs11542311 was also associated with S100B mRNA expression directly (Bonferroni corrected P = 0.05) and within haplotype G-A-T-C (rs11542311-rs2839356-rs9984765-rs881827; P = 0.004), again with the G-allele increasing S100B expression. Our results suggest an important role of S100B SNPs on S100B serum concentrations and S100B mRNA expression. It hereby links recent evidence for both, the impact of S100B gene variation on various neurological or psychiatric disorders like dementia, bipolar affective disorders and schizophrenia and the strong relation between S100B serum levels and these disorders.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 04/2009; 153B(1):291-7. · 3.70 Impact Factor
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Roohi Abubaker,
Maaike Alaerts,
Ava-Ann Allman,
Jennifer Barnett,
Pauline Belujon,
Robert A Bittner,
Thomas H J Burne,
Wiepke Cahn,
Steven Chance,
Sara Cherkerzian, [......],
LaNina Mompremier,
Barnaby Nelson,
Jonna Perälä,
Anna Rotarska-Jagiela,
Renata Schoeman,
Katharine N Thakkar,
Giuletta Valuri,
Shivarama Varambally,
Clement Zai,
Lynn E DeLisi
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ABSTRACT: The Schizophrenia International Research Society held its first scientific conference in Venice, Italy, June 21 to 25th, 2008. A wide range of controversial topics were presented in overlapping and plenary oral sessions. These included new genetic studies, controversies about early detection of schizophrenia and the prodrome, treatment issues, clinical characteristics, cognition, neuropathology and neurophysiology, other etiological considerations, substance abuse co-morbidity, and animal models for investigating disease etiology and for use as targets in drug studies. Young investigators in the field were awarded travel grants to participate in the congress and one of their roles was to summarize the oral sessions and subsequent discussions. The reports that follow are the culmination of this work produced by 30 young investigators who attended the congress. It is hoped that these summaries will be useful synopses of what actually occurred at the congress for those who did not attend each session or were unable to be present. The abstracts of all presentations, as submitted by the authors a few months prior, were previously published as supplement 2 to volume 102/1-3, June 2008.
Schizophrenia Research 10/2008; 105(1-3):289-383. · 4.75 Impact Factor
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Anya Pedersen,
Markus Diedrich,
Florian Kaestner, Katja Koelkebeck,
Patricia Ohrmann,
Gerald Ponath,
Frank Kipp,
Simone Abel,
Ansgar Siegmund,
Thomas Suslow,
Christof von Eiff,
Volker Arolt,
Matthias Rothermundt
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ABSTRACT: Astrocyte activation indicated by increased S100B is considered a potential pathogenic factor for schizophrenia. To investigate the relationship between astrocyte activation and cognitive performance, S100B serum concentration, memory performance, and psychopathology were assessed in 40 first-episode and 35 chronic schizophrenia patients upon admission and after four weeks of treatment. Chronic schizophrenia patients with high S100B were impaired concerning verbal memory performance (AVLT, Auditory Verbal Learning Test) compared to chronic and first-episode patients with low S100B levels. The findings support the hypothesis that astrocyte activation might contribute to the development of cognitive dysfunction in schizophrenia.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 08/2008; 32(8):1789-92. · 3.25 Impact Factor
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ABSTRACT: Deficits in the Span of Apprehension (SOA) task have been discussed controversially as a trait marker of schizophrenia. The task was administered to 47 schizophrenia and 48 depressed patients as well as to 46 controls. Results indicate a non-specificity of the SOA sum scores but differential abnormalities in spatial visual processing.
European Psychiatry 02/2008; 23(1):29-32. · 2.77 Impact Factor
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ABSTRACT: Hyponatremia is a well-known side effect of antidepressant treatment with serotonin reuptake inhibitors (SSRI) or combined serotonin and noradrenaline reuptake inhibitors (SNRI), and is linked to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in most cases. In contrast, only very few data are available on hyponatremia following treatment with selective noradrenaline reuptake inhibitors (NaRI). In this report, we describe the case of a patient who developed severe hyponatremia after treatment with reboxetine. However, extensive laboratory testing did not reveal inappropriate secretion of ADH, suggesting that SIADH did not account for hyponatremia in our case. Proposing further examination of the underlying pathomechanism of hyponatremia as a side effect of NaRIs, we discuss the importance of careful monitoring of serum sodium levels in patients treated with NaRIs.
The World Journal of Biological Psychiatry 11/2007; 10(4 Pt 2):609-11. · 2.38 Impact Factor
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ABSTRACT: Visual backward masking deficits have been postulated as potential vulnerability markers for schizophrenia. This study investigated the diagnostic specificity of a location and an identification variant of the backward masking task for schizophrenia and analyzed masking performance during the course of the tasks. The influence of schizophrenia patients' intellectual decline on masking performance was also examined. Twenty-eight schizophrenia patients were compared to 28 patients with unipolar depression and 28 healthy controls on a letter location task and a letter identification task applying a low spatial frequency mask. Schizophrenia patients made significantly more detection errors on the location task than depressives at an interstimulus interval (ISI) of 50 ms and healthy controls at ISIs of 16.7, 33.3, 50, and 66.7 ms. Thus, the location masking dysfunction of schizophrenia patients was distinctive at a rather long interstimulus interval (50 ms). On the identification task the performance of schizophrenia patients did not differ from that of the two control groups. Identification but not location masking performance improved during the course of the task for all groups. Intellectual deterioration of schizophrenia patients was not correlated with location or identification masking performance. Schizophrenia patients are characterized by specific impairments in spatial visual processing which appear to be independent of intellectual decline. Potential explanations of the location masking deficit found in schizophrenia are discussed.
Schizophrenia Research 11/2005; 78(2-3):261-8. · 4.75 Impact Factor
