Anya Pedersen

Glial cell dysfunction in schizophrenia indicated by increased S100B in the CSF.

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Neuropeptide S receptor gene—converging evidence for a role in panic disorder

Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn107Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case–control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli.

Glial cell activation in a subgroup of patients with schizophrenia indicated by increased S100B serum concentrations and elevated myo-inositol

Post-mortem and in-vivo studies support the hypothesis that astrocytes might be involved in the pathogenesis of schizophrenia. To further substantiate this hypothesis two markers of astroglial activation (myo-inositol, S100B) acquired with independent methods ((1)H-MRS, quantitative immunoassay) were concomitantly measured in schizophrenic patients. Patients with increased S100B levels showed elevated myo-inositol concentrations. This pilot study demonstrates a concomitant elevation of two markers indicating astrocyte activation in a subgroup of schizophrenic patients.

Craving in Alcohol-Dependent Patients After Detoxification Is Related to Glutamatergic Dysfunction in the Nucleus Accumbens and the Anterior Cingulate Cortex

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.

Learning potential on the WCST in schizophrenia is related to the neuronal integrity of the anterior cingulate cortex as measured by proton magnetic resonance spectroscopy

BACKGROUND In recent years, schizophrenia has increasingly been recognized as a neurocognitive disorder, which has led to a growing literature on cognitive rehabilitation, and suggested several potential enhancements to cognitive function. For instance, it has been shown that executive functioning deficits as measured by the Wisconsin Card Sorting Test (WCST) can be modified in a subgroup of schizophrenic patients. The neurobiological basis of cognitive remediation has not been elucidated so far, although structural, functional and metabolic abnormalities of the prefrontal cortex have been associated with cognitive impairment. METHODS In this study, learning potential was investigated in 43 schizophrenic patients and 37 age- and education-matched healthy controls, using a dynamic version of the WCST, which integrates instructions and feedback into the testing procedure. Performance was related to cerebral metabolism, assessed by single-voxel proton magnetic resonance spectroscopy of the dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC). RESULTS N-acetylaspartate (NAA), a marker of neuronal integrity, was significantly reduced in the DLPFC of schizophrenic patients as compared to the healthy control group. The level of NAA in the DLPFC positively correlated with performance in the dynamic WCST in healthy subjects, whereas in schizophrenic patients a significant correlation was observed between NAA and glutamate/glutamine in the ACC and learning potential. CONCLUSION These data imply a relationship between neuronal plasticity as assessed by learning potential and NAA levels of the prefrontal cortex in schizophrenic patients and healthy subjects, and suggest the involvement of differential neuronal networks in learning for schizophrenic patients compared to healthy controls.

Increased amygdala activation during automatic processing of facial emotion in schizophrenia

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.

Memory impairment correlates with increased S100B serum concentrations in patients with chronic schizophrenia.

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.

Neural correlates of set-shifting: decomposing executive functions in schizophrenia.

BACKGROUND 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. METHODS 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. RESULTS 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. LIMITATIONS All patients were taking neuroleptic medication, which has an impact on cognitive function as well as on dopaminergic and serotonergic prefrontal metabolism. CONCLUSION 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.

The effect of selective REM-sleep deprivation on the consolidation and affective evaluation of emotional memories

Emotion boosts the consolidation of events in the declarative memory system. Rapid eye movement (REM) sleep is believed to foster the memory consolidation of emotional events. On the other hand, REM sleep is assumed to reduce the emotional tone of the memory. Here, we investigated the effect of selective REM-sleep deprivation, SWS deprivation, or wake on the affective evaluation and consolidation of emotional and neutral pictures. Prior to an 9-h retention interval, sixty-two healthy participants (23.5 ± 2.5 years, 32 female, 30 male) learned and rated their affect to 80 neutral and 80 emotionally negative pictures. Despite rigorous deprivation of REM sleep or SWS, the residual sleep fostered the consolidation of neutral and negative pictures. Furthermore, emotional arousal helped to memorize the pictures. The better consolidation of negative pictures compared to neutral ones was most pronounced in the SWS-deprived group where a normal amount of REM sleep was present. This emotional memory bias correlated with REM sleep only in the SWS-deprived group. Furthermore, emotional arousal to the pictures decreased over time, but neither sleep nor wake had any differential effect. Neither the comparison of the affective ratings (arousal, valence) during encoding and recognition, nor the affective ratings of the recognized targets and rejected distractors supported the hypothesis that REM sleep dampens the emotional reaction to remembered stimuli. The data suggest that REM sleep fosters the consolidation of emotional memories but has no effect on the affective evaluation of the remembered contents.

Electrophysiological indices of error monitoring in juvenile and adult attention deficit hyperactivity disorder (ADHD)—A meta-analytic appraisal

Attempts to identify the central disturbed processes explaining the overt symptoms of juvenile and adult ADHD rely heavily on the concept of deficient error monitoring processes. A number of studies have investigated event-related potentials (ERPs) and behavioral performance in tasks traditionally used to probe the interference control and inhibition of motor responses. The inspection of the error negativity (Ne/ERN) and error positivity (Pe) components evoked in these tasks has produced conflicting results with respect to the nature and extent of an error monitoring deficit in ADHD. A meta-analytic aggregation of these single studies should help develop a reliable appraisal of the evidence for the compromised performance monitoring processes in ADHD. Our meta-analysis was confined to studies of adult and juvenile ADHD participants examined in GoNogo and Flanker task studies that also reported the Ne/ERN and Pe ERP components. Only seven studies were suited for the meta-analysis, but their aggregation nevertheless led to clear results: Ne was attenuated in adult and adolescent ADHD participants for both tasks, and Pe was attenuated only in the GoNogo tasks. The ADHD participants made more errors than the controls in both tasks but responded slower only in the Flanker task. To our knowledge, this meta-analysis is the first to compare electrophysiological and behavioral indices of error monitoring in adult and juvenile ADHD patients and healthy controls. Admittedly, the data available for this comparison were sparse and heterogeneous; nevertheless, this meta-analysis produced salient results that indicate a monitoring deficit as a central feature of the ADHD syndrome.