Astrid Pauls

Methylphenidate effects on prefrontal functioning during attentional-capture and response inhibition

BACKGROUND Methylphenidate improves motor response inhibition, typically assessed with the stop-signal task. The exact underlying mechanism for this, however, remains unknown. In addition, recent studies highlight that stop signals can have a confounding attentional-capture effect because of their low frequency in the task. In the current study, we assessed the effects of methylphenidate on neural networks of inhibitory control and attentional-capture within the context of two inhibitory control tasks. METHODS The effects of methylphenidate (40 mg) were assessed using functional magnetic resonance imaging in 16 healthy volunteers in a within-subject, double-blind, placebo-controlled design. RESULTS Methylphenidate significantly reduced activation of different regions within the right inferior frontal gyrus/insula to infrequent stimuli associated with successful inhibition, failed inhibition, and attentional capture. These inferior frontal gyrus regions showed different interregional connections with inhibitory and attention networks. For failed inhibitions, methylphenidate increased activation within performance-monitoring regions, including the superior frontal, anterior cingulate, and parietal-occipital cortices, but only after controlling for attentional capture. CONCLUSIONS Our findings suggest that the improvement of response inhibition seen following methylphenidate administration is due to its influence on underlying attentional mechanisms linked to response control requirements.

Thalamic neurochemical abnormalities in individuals with prodromal symptoms of schizophrenia — Relationship to auditory event-related potentials

Thalamic neurochemical abnormalities may underlie psychotic symptoms and auditory event-related potential (ERP) abnormalities in schizophrenia. We investigated this hypothesis in subjects at risk of psychosis using magnetic resonance spectroscopy and electroencephalography (EEG). Reduced thalamic glutamate plus glutamine and N-acetyl aspartate levels were associated with abnormal frontal ERPs, supporting a thalamic basis for filtering impairments.

Brain structure in women at risk of postpartum psychosis: an MRI study

Postpartum psychosis (PP) is the most severe psychiatric disorder associated with childbirth. The risk of PP is very high in women with a history of bipolar affective disorder or schizoaffective disorder. However, the neurobiological basis of PP remains poorly understood and no study has evaluated brain structure in women at risk of, or with, PP. We performed a cross-sectional study of 256 women at risk of PP and 21 healthy controls (HC) in the same postpartum period. Among women at risk, 11 who developed a recent episode of PP (PPE) (n = 2 with lifetime bipolar disorder; n = 9 psychotic disorder not otherwise specified) and 15 at risk women who did not develop an episode of PP (NPPE) (n = 10 with lifetime bipolar disorder; n = 1 with schizoaffective disorder; n = 1 with a history of PP in first-degree family member; n = 3 with previous PP). We obtained T1-weighted MRI scans at 3T and examined regional gray matter volumes with voxel-based morphometry and cortical thickness and surface area with Freesurfer. Women with PPE showed smaller anterior cingulate gyrus, superior temporal gyrus and parahippocampal gyrus compared to NPPE women. These regions also showed decreased surface area. Moreover, the NPPE group showed a larger superior and inferior frontal gyrus volume than the HC. These results should be interpreted with caution, as there were between-group differences in terms of duration of illness and interval between delivery and MRI acquisition. Nevertheless, these are the first findings to suggest that MRI can provide information on brain morphology that characterize those women at risk of PP more likely to develop an episode after childbirth.

Poster #S28 IMMUNE RESPONSE TO STRESS IN POSTPARTUM PSYCHOSIS

pregnancy, NDBS taken at the time of birth, and adult plasma samples taken at the time of enrollment. Methods: The study population for this case-control study was selected from individuals born in northern Sweden between 1975 and 1985, identified with the use of Swedish register data. Non-affective psychoses were defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and International Classification of Disease (ICD-9 and -10). Maternal serum samples were available for 138 cases and 394 ageand sex-matched controls. NDBS were available for 100 cases and 196 controls who consented to their collection. 87 cases and 183 controls further consented to have a blood sample taken at the time of enrollment. The concentration of nine different APP were measured in each sample using a magnetic bead-based multiplex panel (Bio-Rad, Hercules, CA, USA): alpha-2 microglobulin (a2m), C-reactive protein (CRP), haptoglobulin, serum amyloid P (SAP), procalcitonin (PCT), ferritin, tissue plasminogen activator (tPA), fibrinogen, and serum amyloid A (SAA). Results: Median values for all APP except ferritin were lower in maternal serum from cases compared to controls. Similarly, median values for a2m, SAP, PCT, and tPA were lower in NDBS from cases compared to controls. However in adult plasma samples, median CRP, tPA, haptoglobin, PCT, and SAA levels were higher in cases compared to controls, while levels of a2m and SAP remained lower in cases compared to controls. Values of APP were not correlated between maternal serum and NDBS, nor were they correlated between NDBS and adult plasma samples. Discussion: To our knowledge, this is the first longitudinal biomarker study in a population diagnosed with non-affective psychoses to include perinatal as well as adult samples. The pattern of lower APP in cases compared to controls in perinatal samples was reversed in samples taken from adults after the time of diagnosis. Findings of lower APP in cases compared to controls in both maternal serum samples as well as NDBS are in contrast to the “Maternal Immune Activation” hypothesis that posits that inflammation during gestation increases risk for schizophrenia and non-affective psychoses later in life. Our study was, however, generally consistent with previous studies in adults, showing that some, but not all, APP were higher in cases compared to controls. Future studies include investigation of cytokines in maternal serum samples, to compare with the APP signature in maternal serum as well as to compare directly to previous studies. Additionally, we plan studies of antibodies to infectious agents and dietary antigens in the longitudinal sample set, in order to study whether exposures during different periods of life are correlated with changes in APP patterns over the life course.