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Franziska Degenhardt,
Lutz Priebe,
Jana Strohmaier,
Stefan Herms,
Per Hoffmann,
Manuel Mattheisen,
Rainald Mössner, Igor Nenadic,
Heinrich Sauer,
Dan Rujescu,
Wolfgang Maier,
Thomas G Schulze,
Marcella Rietschel,
Markus M Nöthen,
Sven Cichon
Psychiatric genetics 02/2013; 23(1):45-46. · 2.33 Impact Factor
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ABSTRACT: Antipsychotic drug action might include mechanisms related to normalising phospholipid and high-energy metabolism. We applied brain metabolic imaging with (31) P magnetic resonance spectroscopy ((31) P MRS) and two-dimensional chemical shift imaging to assess changes of metabolism of phospholipids and high-energy phosphates in schizophrenia patients at baseline (four antipsychotic-naïve and three off antipsychotics) and at follow-up, after 6 weeks of treatment with olanzapine. Results indicate a significant increase of adenosine-triphosphate (ATP) in the right inferior temporal cortex and a trend towards ATP decrease in the left cerebellum. This suggests a shift in high-energy phosphates (rather than phospholipids), possibly related to normalisation of functioning in these areas. Copyright © 2012 John Wiley & Sons, Ltd.
Human Psychopharmacology Clinical and Experimental 12/2012; · 2.48 Impact Factor
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Igor Nenadic,
Raka Maitra,
Sigrid Scherpiet,
Christian Gaser,
C Christoph Schultz,
Claudia Schachtzabel,
Stefan Smesny,
Jürgen R Reichenbach,
Jens Treutlein,
Thomas W Mühleisen,
Thomas Deufel,
Sven Cichon,
Marcella Rietschel,
Markus M Nöthen,
Heinrich Sauer,
Ralf G M Schlösser
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ABSTRACT: Common genetic variation in the promoter region of the glutamate receptor delta 1 (GRID1) gene has recently been shown to confer increased risk for schizophrenia in several independent large samples. We analysed high-resolution magnetic resonance imaging (MRI) data from 62 patients with schizophrenia and 54 healthy controls using voxel-based morphometry (VBM) to assess the effect of single nucleotide polymorphism rs3814614 (located in the GRID1 promoter region), of which the T allele was identified as a risk factor in a previous association study. There were no effects of genotype or group × genotype interactions on total brain grey matter or white matter, but on regional grey matter. In healthy subjects, we identified a significant effect of rs3814614 genotype in the anterior thalamus (bilaterally), superior prefrontal cortex, and orbitofrontal cortex - in all cases with the homozygous risk genotype TT resulting in higher grey matter density. We did not find this association within the schizophrenia sample, where rs3814614 variation was only associated with grey matter reduction in TT homozygous subjects in medial parietal cortex and increased grey matter in right medial cerebellum. For white matter, we did not find significant genotype effects in healthy controls, and only minor effects within schizophrenia patients in the posterior temporal lobe white matter. Our data indicate that GRID1 rs3814614 genotype is related to grey matter variation in prefrontal and anterior thalamic brain areas in healthy subjects, but not in patients indicating a potential role of this schizophrenia candidate gene in thalamo-cortical functioning.
Journal of psychiatric research 09/2012; · 3.72 Impact Factor
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Manuel Mattheisen,
Thomas W Mühleisen,
Jana Strohmaier,
Jens Treutlein, Igor Nenadic,
Margrieta Alblas,
Sandra Meier,
Franziska Degenhardt,
Stefan Herms,
Per Hoffmann,
Stephanie H Witt,
Ina Giegling,
Heinrich Sauer,
Thomas G Schulze,
Dan Rujescu,
Markus M Nöthen,
Marcella Rietschel,
Sven Cichon
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ABSTRACT: Convergent evidence from pharmacological and animal studies suggests a possible role for the synaptic vesicle glycoprotein 2A gene (SV2A) in schizophrenia susceptibility. To test systematically all common variants in the SV2A gene region for an association with schizophrenia, we used a HapMap-based haplotype tagging approach and tested five SNPs in 794 patients and 843 controls. The SNP rs15931 showed evidence for an association with schizophrenia and was followed-up in an independent sample of 2581 individuals (overall p-value=0.0042, OR=0.779). Our study in the German population provides evidence, at a genetic level, for the involvement of the SV2A gene region in schizophrenia.
Biological Psychiatry 09/2012; 141(2-3):262-5. · 8.28 Impact Factor
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Stefan Smesny,
Christian E H Schmelzer,
Anke Hinder,
Alexandra Köhler,
Christiane Schneider,
Maria Rudzok,
Ulrike Schmidt,
Berko Milleit,
Christine Milleit, Igor Nenadic,
Heinrich Sauer,
Reinhard H H Neubert,
Joachim W Fluhr
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ABSTRACT: There is considerable evidence for specific pathology of lipid metabolism in schizophrenia, affecting polyunsaturated fatty acids and in particular sphingolipids. These deficits are assumed to interfere with neuronal membrane functioning and the development and maintenance of myelin sheaths. Recent studies suggest that some of these lipid pathologies might also be detected in peripheral skin tests. In this study, we examined different skin lipids and their relation to schizophrenia. We assessed epidermal lipid profiles in 22 first-episode antipsychotic-naïve schizophrenia patients and 22 healthy controls matched for age and gender using a hexan/ethanol extraction technique and combined high-performance thin-layer chromatography/gas-chromatography. We found highly significant increase of ceramide AH and NH/AS classes in patients and decrease of EOS and NP ceramide classes. This is the first demonstration of specific peripheral sphingolipid alterations in schizophrenia. The results support recent models of systemic lipid pathology and in particular of specific sphingolipids, which are crucial in neuronal membrane integrity. Given recent findings showing amelioration of psychopathology using fatty acid supplementation, our findings also bear relevance for sphingolipids as potential biomarkers of the disease.
Schizophrenia Bulletin 05/2012; · 8.80 Impact Factor
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Gianluca Mingoia,
Gerd Wagner,
Kerstin Langbein,
Raka Maitra,
Stefan Smesny,
Maren Dietzek,
Hartmut P Burmeister,
Jürgen R Reichenbach,
Ralf G M Schlösser,
Christian Gaser,
Heinrich Sauer, Igor Nenadic
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ABSTRACT: Alterations in brain function in schizophrenia and other neuropsychiatric disorders are evident not only during specific cognitive challenges, but also from functional MRI data obtained during a resting state. Here we apply probabilistic independent component analysis (pICA) to resting state fMRI series in 25 schizophrenia patients and 25 matched healthy controls. We use an automated algorithm to extract the ICA component representing the default mode network (DMN) as defined by a DMN-specific set of 14 brain regions, resulting in z-scores for each voxel of the (whole-brain) statistical map. While goodness of fit was found to be similar between the groups, the region of interest (ROI) as well as voxel-wise analysis of the DMN showed significant differences between groups. Healthy controls revealed stronger effects of pICA-derived connectivity measures in right and left dorsolateral prefrontal cortices, bilateral medial frontal cortex, left precuneus and left posterior lateral parietal cortex, while stronger effects in schizophrenia patients were found in the right amygdala, left orbitofrontal cortex, right anterior cingulate and bilateral inferior temporal cortices. In patients, we also found an inverse correlation of negative symptoms with right anterior prefrontal cortex activity at rest and negative symptoms. These findings suggest that aberrant default mode network connectivity contributes to regional functional pathology in schizophrenia and bears significance for core symptoms.
Biological Psychiatry 05/2012; 138(2-3):143-9. · 8.28 Impact Factor
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Thomas W Mühleisen,
Manuel Mattheisen,
Jana Strohmaier,
Franziska Degenhardt,
Lutz Priebe,
C Christoph Schultz,
René Breuer,
Sandra Meier,
Per Hoffmann,
Fernando Rivandeneira, [......],
Heinrich Sauer,
Rainald Mössner,
Wolfgang Maier,
Dan Rujescu,
Christoph Lange,
Roel A Ophoff,
Thomas G Schulze,
Marcella Rietschel,
Markus M Nöthen,
Sven Cichon
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ABSTRACT: A recent study found genome-wide significant association between common variation in the gene neurocan (NCAN, rs1064395) and bipolar disorder (BD). In view of accumulating evidence that BD and schizophrenia partly share genetic risk factors, we tested this single-nucleotide polymorphism for association with schizophrenia in three independent patient-control samples of European ancestry, totaling 5061 patients and 9655 controls. The rs1064395 A-allele, which confers risk for BD, was significantly over-represented in schizophrenia patients compared to controls (p=2.28×10(-3); odds ratio=1.11). Follow-up in non-overlapping samples from the Schizophrenia Psychiatric GWAS Consortium (5537 patients, 8043 controls) provided further support for our finding (p=0.0239, odds ratio=1.07). Our data suggest that genetic variation in NCAN is a common risk factor for BD and schizophrenia.
Biological Psychiatry 04/2012; 138(1):69-73. · 8.28 Impact Factor
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ABSTRACT: Schizophrenia is often assumed to comprise a group of biologically distinct disorders, yet it has been difficult to dissect subgroups using biological markers. We review recent brain imaging morphometry studies addressing the issue of heterogeneity within the diagnostic category of schizophrenia. Studies of subgroups of schizophrenia patients have mostly used either symptom structure or clinical course for the delineation of potentially meaningful subgroups. Studies defining subgroups according to outcome, i.e. good versus poor outcome (or 'non-Kraepelinian' vs. 'Kraepelinian', respectively) have shown that while these two subgroups might overlap in the extent (and possibly also strength) of prefrontal deficits, they differ in temporal and occipital areas, where poor-outcome patients show stronger deficits. More recent studies have investigated subgroups of schizophrenia based on factor analysis of psychopathology. They have demonstrated a complex pattern of regional changes, where the typical three subgroups might overlap in prefrontal changes, but show divergence in structural deficits in other areas such as the thalamus, hippocampus, or cerebellum. Altogether, these studies demonstrate that brain structure per se is not a uniform endophenotype, but rather a combination of regional deficits highly heterogeneous in both meeting endophenotype criteria as well as in their distribution within the disease category.
Neuropsychobiology 01/2012; 66(1):44-9. · 2.67 Impact Factor
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ABSTRACT: In light of bottom-up models of disrupted cognition in schizophrenia, visual processing deficits became a key feature for the pathophysiology of schizophrenia. However, morphometric studies focusing on the visual cortex are limited. Thus, the present study sought to provide a combined cortical shape analysis (cortical thickness, folding) of visual areas, which were implicated to be involved in disturbed visual processing in schizophrenia. A group of 72 patients with schizophrenia according to DSM-IV and 72 age- and gender-matched healthy control subjects were included. All participants underwent high-resolution T1-weighted MRI scans on a 1.5-T scanner. Cortical thickness and mean curvature of the V1, V2 and V5/MT+ visual cortex were estimated using an automated computerized algorithm (Freesurfer Software). A GLM controlling for the effect of age was used to estimate differences of cortical shape parameters between the study groups. Significantly increased gyrification of the V1, V2 and the V5/MT+ visual area bilaterally was detected. Conversely, cortical thickness was reduced in patients with schizophrenia only for the V5/MT+ area. This study is the first providing direct in vivo evidence for a disturbed cortical shape of central visual areas in schizophrenia. The present findings of hypergyria are highly indicative for a disrupted corticogenesis of these visual key regions and might constitute a relevant anatomical basis for visual processing deficits in schizophrenia.
Brain Structure and Function 12/2011; · 5.63 Impact Factor
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Biological Psychiatry 11/2011; 134(2-3):296-7. · 8.28 Impact Factor
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ABSTRACT: The anterior cingulate cortex plays a central role in altered processes of cognitive control in schizophrenia. However, the cortical foundations of disturbed anterior cingulate cognitive activation are poorly understood. Therefore, this study investigated the association of anterior cingulate cognitive activation and cortical thickness in schizophrenia combining functional magnetic resonance imaging (fMRI) and surface-based morphometry.
Fifty-three patients with schizophrenia according to DSM-IV and 53 age- and sex-matched healthy subjects were included and underwent fMRI and high-resolution T1-weighted MRI. fMRI data was analyzed using SPM5. Cortical thickness was calculated using an automated computerized algorithm (Freesurfer Software). Statistical cortical maps were created correlating anterior cingulate activation and cortical thickness on a node-by-node basis covering the entire cortex in schizophrenia and healthy control subjects.
Patients demonstrated a significantly reduced anterior cingulate cognitive activation. Significantly differing associations of anterior cingulate activation and cortical thickness were found in a pattern of dorsolateral prefrontal, superior frontal-anterior cingulate, and superior temporal cortical regions, where patients but not healthy control subjects demonstrated a significant association of reduced anterior cingulate activation and cortical thinning. A direct comparison of cortical thickness between the diagnostic groups revealed a significantly reduced cortical thickness of these prefrontotemporal regions in schizophrenia.
To our best knowledge, this is the first study indicating that prefrontotemporal cortical thinning constitutes a relevant cortical pathomechanism for altered cognitive activation in schizophrenia. Our data additionally reveal a profound disruption of structural and functional integration in the prefrontotemporal system in schizophrenia.
Biological psychiatry 10/2011; 71(2):146-53. · 8.93 Impact Factor
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ABSTRACT: Habituation is a basic process of learning evident in a decrement in neuronal/behavioral responses to repeated sensory stimulation. It is generally accepted that habituation affects all sensory systems in the human brain, including the somatosensory network. However, it is not clear where habituation originates within this hierarchically organized network. In this study, we examined whether habituation effects increase relatively uniformly along the processing hierarchy or rather distinctly at a particular processing stage. We addressed these questions by performing functional magnetic resonance imaging (fMRI) on 43 healthy subjects during unilateral electrical median nerve stimulation using a block design. We found a time-dependent decrease in the positive BOLD response (indicative of habituation) in all areas of the somatosensory network with the exception of Brodmann area (BA) 3b. The increase in habituation within the presumed processing stream was most pronounced between subareas of the primary somatosensory cortex (BA3b, BA1, BA2), and no further increase in habituation effects was observed in the subsequent processing stages within either the secondary somatosensory cortex or the insula. Moreover, we found a relatively strong habituation effect within the thalamus. These findings indicate that the increase in habituation along the processing hierarchy is measurable primarily between subareas of the primary somatosensory cortex, and we hypothesize that this increase originates in thalamocortical interactions early in the processing stream.
Behavioural brain research 08/2011; 225(2):432-6. · 3.22 Impact Factor
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C Christoph Schultz, Igor Nenadic,
Kathrin Koch,
Gerd Wagner,
Martin Roebel,
Claudia Schachtzabel,
Thomas W Mühleisen,
Markus M Nöthen,
Sven Cichon,
Thomas Deufel,
Michael Kiehntopf,
Marcella Rietschel,
Jürgen R Reichenbach,
Heinrich Sauer,
Ralf G M Schlösser
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ABSTRACT: In light of current etiological concepts the glutamatergic system plays an essential role for the pathophysiology of the disorder, offering multiple options for new treatment strategies. The D-amino oxidase activator (DAOA) gene is closely connected to the glutamatergic system and its therapeutic and pathophysiological relevance for schizophrenia is therefore intensively debated. In a further step to shed light on the role of DAOA in schizophrenia, we aimed to investigate the association of the functional DAOA Arg30Lys (rs2391191) variant and cortical thickness in schizophrenia. Cortical thickness was computed by an automated surface-based technique (FreeSurfer) in 52 genotyped patients with schizophrenia and 42 healthy controls. Cortical thickness of the entire cortex was compared between risk carriers and non-risk carriers regarding the Arg30Lys polymorphism in patients and healthy controls on the basis of a node-by-node procedure and an automated clustering approach. Risk carriers with schizophrenia show significantly thinner cortex in two almost inversely arranged clusters on the left and right hemisphere comprising middle temporal, inferior parietal, and lateral occipital cortical areas. The clusters encompass an area of 1174 mm(2) (left) and 1156 mm(2) (right). No significant effect was observed in healthy controls.The finding of our study that the Arg30Lys risk variant is associated with a distinct cortical thinning provides new evidence for the pathophysiological impact of DAOA in schizophrenia. The affected areas are mostly confined to cortical regions with a crucial role in the ToM network and visual processing, which both can be influenced by glutamatergic modulation. Our finding thus underlines the importance of DAOA and related glutamatergic processes as a putative target for therapeutic interventions in schizophrenia.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 07/2011; 36(8):1747-53. · 6.99 Impact Factor
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Igor Nenadic,
Gerd Wagner,
Daniel Güllmar,
Claudia Schachtzabel,
Katrin von Consbruch,
Sabine Köhler,
Kathrin Koch,
Martin Roebel,
C Christoph Schultz,
Jürgen R Reichenbach,
Heinrich Sauer,
Ralf G M Schlösser
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ABSTRACT: Studies using diffusion tensor imaging (DTI) have shown multifocal reduction in anisotropy of white matter fibre tracts in schizophrenia, and a few of these also suggest changes in apparent diffusion coefficient (ADC). In this study, we assessed ADC in 18 patients with schizophrenia and 18 healthy controls using a voxel-based approach. We did not find evidence of statistically significant changes in ADC in either direction at P < 0.05 (FDR corrected) using different smoothing filter sizes; only at an uncorrected threshold of P < 0.001 did we find an increase in a small right prefrontal area close to our previous FA finding. Our findings therefore do not support ADC changes to be a marker of white matter or grey matter abnormalities in schizophrenia. Changes in other parameters like fractional anisotropy (FA) might be a more sensitive indicator of white matter pathology in this disorder.
Archiv f ur Psychiatrie und Nervenkrankheiten 04/2011; 261(3):213-6. · 2.75 Impact Factor
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ABSTRACT: Altered cortical surface complexity and gyrification differences may be a potentially sensitive marker for several neurodevelopmental disorders. We propose to use spherical harmonic (SPH) constructions to measure cortical surface folding complexity. First, we demonstrate that the complexity measure is accurate, by applying our SPH approach and the more traditional box-counting method to von Koch fractal surfaces with known fractal dimension (FD) values. The SPH approach is then applied to study complexity differences between 87 patients with DSM-IV schizophrenia (with stable psychopathology and treated with antipsychotic medication; 48 male/39 female; mean age=35.5 years, SD=11.0) and 108 matched healthy controls (68 male/40 female; mean age=32.1 years, SD=10.0). The global FD for the right hemisphere in the schizophrenia group was significantly reduced. Regionally, reduced complexity was also found in temporal, frontal, and cingulate regions in the right hemisphere, and temporal and prefrontal regions in the left hemisphere. These results are discussed in terms of previously published findings. Finally, the anatomical implications of a reduced FD are highlighted through comparison of two subjects with vastly different complexity maps.
NeuroImage 02/2011; 56(3):961-73. · 5.89 Impact Factor
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Thomas W Mühleisen,
F Buket Basmanav,
Andreas J Forstner,
Manuel Mattheisen,
Lutz Priebe,
Stefan Herms,
Rene Breuer,
Susanne Moebus, Igor Nenadic,
Heinrich Sauer,
Rainald Mössner,
Wolfgang Maier,
Dan Rujescu,
Michael Ludwig,
Marcella Rietschel,
Markus M Nöthen,
Sven Cichon
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ABSTRACT: Large rare deletions in NRXN1 increase the risk for schizophrenia. The aim of the present study was to determine whether small rare sequence changes in exons and splice sites contribute to the development of schizophrenia in a high-penetrance manner. Complete coding regions and splice sites were resequenced in 94 patients and 94 controls. Among the 16 rare sequence variants, two missense substitutions (E201G and I1068V) were observed in single patients but not in controls. Investigation of DNA samples from family members and in silico analysis of possible effects on protein function produced no evidence of high-penetrance genetic effects. Follow-up genotyping of the most promising findings (E201G and I1068V) in an independent sample of >1400 patients and >1100 controls revealed no overrepresentation in patients compared to controls (E201G: 0/1 and I1068V: 0/0). Since I1068V was observed in a single patient, it is impossible to exclude the possibility that I1068V makes a minor contribution to schizophrenia susceptibility. Overall, however, the results do not suggest the existence of rare, highly penetrant NRXN1 mutations in patients with schizophrenia.
Biological Psychiatry 01/2011; 127(1-3):35-40. · 8.28 Impact Factor
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Stefan Smesny,
Christina Kunstmann,
Sebastian Kunstmann,
Ingo Willhardt,
Juergen Lasch,
Rachel A Yotter,
Tina-Marie Proffitt,
Melissa Kerr,
Conny Marculev,
Berko Milleit,
Christine Milleit, Igor Nenadic,
Paul Amminger,
Patrick D McGorry,
Heinrich Sauer,
Gregor E Berger
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ABSTRACT: Intracellular phospholipases A₂ (inPLA₂) are activated during monoaminergic neurotranismision and act as key enzymes in cell membrane repair and remodelling, neuroplasticity, neurodevelopment, apoptosis, synaptic pruning, neurodegenerative processes and neuroinflammation. Several independent studies found increased inPLA₂ activity in drug-naïve first episode and chronic schizophrenia. This study investigates if inPLA₂ activity is associated with symptoms severity and treatment response in first episode schizophrenia (FES).
InPLA₂ activity was measured in serum of 35 young FES patients (mean age: 19.36 ± 3.32, mean duration of illness: 7.53 ± 6.28 months, 16 neuroleptic-naïve) before and after 12 weeks of treatment with second-generation antipsychotic medications (olanzapine, quetiapine or risperidone), as well as in 22 healthy controls matched for age. Psychopathology and social functioning were assessed at the same time points.
Baseline inPLA₂ activity was significantly increased in drug-naïve and treated FES patients compared to healthy controls. Baseline inPLA₂ activity was also associated with severity of negative symptoms and lower functioning at baseline. Furthermore, baseline inPLA₂ activity was associated with improvement in negative symptoms and functioning within the first 12 weeks of treatment.
Intracellular PLA₂ activity is increased in first episode schizophrenia and associated with symptom severity and outcome after 12 weeks of treatment. Future studies should investigate the implications of inPLA₂ activity as a potential predictor of treatment response for different antipsychotic agents.
The World Journal of Biological Psychiatry 12/2010; 12(8):598-607. · 2.38 Impact Factor
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ABSTRACT: Cerebral gyrification is attributed to a large extent to genetic and intrauterine/perinatal factors. Hence, investigating gyrification might offer important evidence for disturbed neurodevelopmental mechanisms in schizophrenia. As an extension of recent ROI analyses of gyrification in schizophrenia the present study is the first to compare on a node-by-node basis mean curvature as a sensitive parameter for the identification of local gyrification changes of the whole cortex in first-episode schizophrenia.
A group of 54 patients with first-episode schizophrenia according to DSM-IV and 54 age and gender matched healthy control subjects were included. All participants underwent high-resolution T1-weighted MRI scans on a 1.5 T scanner. Mean curvature was calculated dividing the sum of the principal curvatures by two at each point of the curved surface as implemented in the Freesurfer Software package. Statistical cortical maps were created to estimate gyrification differences between groups based on a clustering approach.
A significantly increased gyrification was observed in first-episode schizophrenia patients relative to controls in a right parahippocampal-lingual cortex area. The cluster encompassed a surface area of 750 mm². A further analysis of cortical thickness of this cluster demonstrated concurrent significant reduced cortical thickness of this area.
This is the first study to reveal an aberrant gyrification of the medial surface in first-episode schizophrenia. This finding is in line with substantial evidence showing medial temporal lobe abnormalities in schizophrenia. The present morphometric data provide further support for an early disruption of cortical maturation in schizophrenia.
Biological Psychiatry 11/2010; 123(2-3):137-44. · 8.28 Impact Factor
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ABSTRACT: Regional structural brain changes are among the most robust biological findings in schizophrenia, yet the underlying pathophysiological changes remain poorly understood. Recent evidence suggests that abnormal neuronal/dendritic plasticity is related to alterations in membrane lipids. We examined whether serum activity of membrane lipid remodelling/repairing cytosolic phospholipase A(2) (PLA(2)) were related to regional brain structure in magnetic resonance images (MRI). The study involved 24 schizophrenia patients, who were either drug-naïve or off antipsychotic medication, and 25 healthy controls. Using voxel-based morphometry (VBM) analysis of T1-high-resolution MRI-images, we correlated both gray matter and white matter changes with serum PLA(2)-activity. PLA(2) activity was increased in patients, consistent with previous findings. VBM group comparison of patients vs. controls showed abnormalities of frontal and medial temporal cortices/hippocampus, and left middle/superior temporal gyrus in first-episode patients. Group comparison of VBM/PLA(2)-correlations revealed a distinct pattern of disease-related interactions between gray/white matter changes in patients and PLA(2)-activity: in first-episode patients (n=13), PLA(2)-activity was associated with structural alterations in the left prefrontal cortex and the bilateral thalamus. Recurrent-episode patients (n=11) showed a wide-spread pattern of associations between PLA(2)-activity and structural changes in the left (less right) prefrontal and inferior parietal cortex, the left (less right) thalamus and caudate nucleus, the left medial temporal and orbitofrontal cortex and anterior cingulum, and the cerebellum. Our findings demonstrate a potential association between membrane lipid biochemistry and focal brain structural abnormalities in schizophrenia. Differential patterns in first-episode vs. chronic patients might be related to PLA(2)-increase at disease-onset reflecting localized regenerative activity, whereas correlations in recurrent-episode patients might point to less specific neurodegenerative aspects of disease progression.
NeuroImage 10/2010; 52(4):1314-27. · 5.89 Impact Factor
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ABSTRACT: Skin flushing after niacin (methylnicotinate, vitamin B(3)) stimulation is a biological marker of availability of polyunsaturated fatty acids (PUFA). Decreased PUFA levels have been reported in depressive disorder, while add-on supplementation of omega-3 PUFA has been suggested to improve depressive symptoms. This study aimed to clarify whether a disturbance of niacin skin flushing occurs also in depression, and to identify patient characteristics for those who might benefit from PUFA supplementation.
We studied 30 patients with recurrent unipolar depressive disorder during a major depressive episode (treated with antidepressants), and 30 healthy volunteers matched for age and gender. Aqueous methylnicotinate was applied in three dilution steps (0.001M, 0.01M, and 0.1M) onto the inner forearm skin. Skin flushing was assessed in three-minute intervals over 15min using optical reflection spectroscopy.
While there was no overall difference in skin flushing between patients and controls, niacin sensitivity was inversely correlated with severity of symptoms, and flush deficits were significantly associated with depressed mood, feelings of anxiety and somatic symptoms (loss of appetite and weight loss).
Results are suggestive of a subgroup of depressive patients characterised by a specific symptom cluster and disturbed niacin skin flushing.
Journal of affective disorders 08/2010; 124(3):335-40. · 3.76 Impact Factor
