Exploring the relationship between circulating inflammatory markers and the brain

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Residual negative symptoms differentiate cognitive performance in clinically stable patients with schizophrenia and bipolar disorder

Cognitive deficits in various domains have been shown in patients with bipolar disorder and schizophrenia. The purpose of the present study was to examine if residual psychopathology explained the difference in cognitive function between clinically stable patients with schizophrenia and bipolar disorder. We compared the performance on tests of attention, visual and verbal memory and executive function of 25 patients with schizophrenia in remission and 25 euthymic bipolar disorder patients with that of 25 healthy controls. Mediation analysis was used to see if residual psychopathology could explain the difference in cognitive function between the patient groups. Both patient groups performed significantly worse than healthy controls on most cognitive tests. Patients with bipolar disorder displayed cognitive deficits that were milder but qualitatively similar to those of patients with schizophrenia. Residual negative symptoms mediated the difference in performance on cognitive tests between the two groups. Neither residual general psychotic symptoms nor greater antipsychotic doses explained this relationship. The shared variance explained by the residual negative and cognitive deficits that the difference between patient groups may be explained by greater frontal cortical neurophysiological deficits in patients with schizophrenia, compared to bipolar disorder. Further longitudinal work may provide insight into pathophysiological mechanisms that underlie these deficits

Mild inflammation causes a reduction in resting-state amplitude of low-frequency fluctuation in healthy adult males

Systemic inflammation has been associated with negative mood states and human sickness behaviour. Previous studies have shown an association between systemic inflammation and changes in task-related blood-oxygen-level-dependent activity and functional connectivity within large-scale networks. However, no study has examined the effect of inflammation on the magnitude of blood-oxygen-level-dependent low-frequency fluctuations at rest. We used a double-blind placebo-controlled crossover design to randomise 20 male subjects (aged 20–50 years) to receive either a Salmonella typhi vaccine or a placebo saline injection at two separate sessions. All participants underwent a resting-state functional magnetic resonance scan and a measure of inflammation (interleukin 6) and mood (Profile of Mood States) 3 h after injection. We compared the whole brain amplitude of low-frequency fluctuations between the vaccine and placebo conditions using a repeated measures design. Vaccine condition was associated with greater interleukin 6 levels (p < 0.001). Vaccine condition was also associated with lower amplitude of low-frequency fluctuations in the right and left frontal pole, superior frontal gyrus, paracingulate gyrus (Cluster 1) and the right mid and inferior frontal gyrus (Cluster 2) (p < 0.001, false discovery rate corrected). Lower amplitude of low-frequency fluctuations pertaining to first cluster correlated with greater total Profile of Mood States score (worse mood) (r = −0.38; p = 0.04). These results imply possible excitation/inhibition imbalance mechanisms during inflammation that may be a relevant target in psychiatric disease, especially mood disorders

Resting state connectivity and cognitive performance in adults with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Cognitive impairment is an inevitable feature of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), affecting executive function, attention and processing speed from an early stage. Impairment is associated with structural markers such as lacunes, but associations with functional connectivity have not yet been reported. Twenty-two adults with genetically-confirmed CADASIL (11 male; aged 49.8 ± 11.2 years) underwent functional magnetic resonance imaging at rest. Intrinsic attentional/executive networks were identified using group independent components analysis. A linear regression model tested voxel-wise associations between cognitive measures and component spatial maps, and Pearson correlations were performed with mean intra-component connectivity z-scores. Two frontoparietal components were associated with cognitive performance. Voxel-wise analyses showed an association between one component cluster and processing speed (left middle temporal gyrus; peak −48, −18, −14; ZE = 5.65, pFWEcorr = 0.001). Mean connectivity in both components correlated with processing speed (r = 0.45, p = 0.043; r = 0.56, p = 0.008). Mean connectivity in one component correlated with faster Trailmaking B minus A time (r = −0.77, p < 0.001) and better executive performance (r = 0.56, p = 0.011). This preliminary study provides evidence for associations between cognitive performance and attentional network connectivity in CADASIL. Functional connectivity may be a useful biomarker of cognitive performance in this population

Incidence and correlates of delirium in a West African mental health clinic

Objective: <br/> <br/> To determine the incidence of delirium in those patients presenting to a psychiatric clinic in Nigeria and to examine if any demographic or clinical variables were correlated with this diagnosis. <br/> <br/> Method <br/> <br/> A prospective survey design; 264 consecutive new referrals to a psychiatric clinic in Nigeria were assessed for the presence of delirium using a standardised diagnostic scale. Data was analysed for normality and appropriate statistical test employed to examine the relationships between the presence of delirium and demographic and clinical variables. <br/> <br/> Results <br/> <br/> Of individuals presenting to the mental health clinics, 18.2% had delirium. No demographic variable was significant regarding the presence or absence of delirium. With regard to clinical variables duration of current symptoms, referral source and the presence of comorbid physical illness were significantly associated with the presence of delirium. Most delirium was due to infections. Nearly all patients with delirium were prescribed psychotropic medication (95.2%), and most attributed their symptoms to a spiritual cause.Conclusion(s) Delirium presents more commonly to psychiatry services in the less developed world compared to the West. Development efforts should focus on recognition and management of delirium to improve outcomes and maximise resource

Intact mismatch negativity responses in clinical high-risk for psychosis and first-episode psychosis: evidence from source-reconstructed event-related fields and time-frequency data

Background: To examine whether Mismatch Negativity (MMN) Responses are impaired in participants at clinical high-risk for psychosis (CHR-P) and first episode psychosis (FEP) patients and whether MMN-deficits predict clinical outcomes in CHR-Ps. Methods: Magnetoencephalography (MEG) data were collected during a duration-deviant MMN-paradigm for a group of 116 CHR-P participants, 33 FEP patients, (15 antipsychotic-naïve), a psychosis-risk-negative group (CHR-N: n=38) with substance abuse and affective disorder and 49 healthy controls (HC). Analysis of group differences of source-reconstructed event-related fields as well as time-frequency and inter-trial-phase-coherence (ITPC) focused on bilateral Heschl’s gyri and superior temporal gyri. Results: Significant MMNm responses were found across participants in bilateral Heschl’s gyrus and superior temporal gyri. However, MMN-amplitude as well as time-frequency and ITPC-responses were intact in CHR-P and FEP-patients relative to HC. Furthermore, MMN-deficits were not related to persistent attenuated psychotic symptoms nor transitions to psychosis in CHR-Ps. Conclusions: Our data suggest that MMNm responses in MEG-data are not impaired in early-stage psychosis and may not predict clinical outcomes in CHR-P participants

Structural and functional brain changes in acute takotsubo syndrome

Background: Takotsubo syndrome mimics an acute myocardial infarction, typically in the aftermath of mental or physical stress. Objectives: The mechanism by which emotional processing in the context of stress leads to significant cardiac injury is poorly understood, so a full exploration of brain structure and function in takotsubo syndrome patients merits investigation. Methods: Twenty-five acute (<5 days) takotsubo patients and 25 control subjects were recruited into this observational cross-sectional study. Surface-based morphometry was carried out on magnetic resonance imaging (MRI) brain scans to extract cortical morphology based on volume, thickness, and surface area with the use of Freesurfer. Cortical morphology general linear models were corrected for age, sex, photoperiod, and total brain volume. Resting-state functional MRI and diffusion tensor tractography images were preprocessed and analyzed with the use of the Functional Magnetic Resonance Imaging of the Brain Diffusion Toolbox and Functional Connectivity Toolbox. Results: There was significantly smaller total white matter and subcortical gray matter volumes in takotsubo (P < 0.001), with smaller total brain surface area but increased total cortical thickness (both P < 0.001). Individual gray matter regions (hippocampus and others) were significantly smaller in takotsubo (P < 0.001); only thalamus and insula were larger (P < 0.001). There was significant hyperfunctional and hypofunctional connectivity in multiple areas, including thalamus-amygdala-insula and basal ganglia (P < 0.05). All structural tractography connections were increased in takotsubo (P < 0.05). Conclusions: The authors showed smaller gray and white matter volumes driven by smaller cortical surface area, but increased cortical thickness and structural tractography connections with bidirectional changes in functional connectivity linked to emotion, language, reasoning, perception, and autonomic control. These are interventional targets in takotsubo patients’ rehabilitation