Volume In Schizophrenia Research Articles

The involvement of the cerebellar vermis across the psychotic-affective spectrum in enriched samples of recent-onset schizophrenia, bipolar disorder, and major depressive disorder

BackgroundThe cerebellar vermis is implicated in cognition and emotion, two key components of the psychotic-affective spectrum that includes schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). MethodsVolumes [N= 391; 97 SCZ, 78 BD, 103 MDD, and 113 healthy controls (HC)] and seed-to-whole brain functional connectivity (FC) [N= 136; 33 SCZ, 23 BD, 51 MDD, and 29 HC] of total vermis and its subregions, V1 (anterior), V2 (posterior superior), and V3 (posterior inferior), were examined across SCZ, BD, MDD, and HC in samples enriched for first episode individuals. The relationship between vermis volumes and FC and cognitive measures were explored. ResultsSignificant diagnosis (p= 0.05) and diagnosis by subregion (p= 0.02) effects on vermis volumes were observed across the four groups, particularly in V2 (p= 0.01) with decreased V2 volumes in SCZ compared to BD (pFDR=0.01). SCZ, BD, and MDD had significant effects on vermis FC, with SCZ having the greatest effects. SCZ had effects on FC of V1, V2, and V3 with broadly distributed cortical and subcortical regions, while BD and MDD effects were observed in FC of V2 and V3 with frontotemporal regions. Exploratory analyses found significant canonical correlation between V3 FC and WM and visual learning for SCZ and MDD. No significant associations were shown between vermis volumes and cognitive measures. ConclusionsStructural and functional alterations of the vermis appear to vary across the psychotic-affective spectrum of SCZ, BD, and MDD. Posterior vermis may be a key neural intersection between affective and psychotic psychopathology.

Effects of web-based adapted physical activity on hippocampal plasticity, cardiorespiratory fitness, symptoms, and cardiometabolic markers in patients with schizophrenia: a randomized, controlled study.

Among the lifestyle interventions, the physical activity (PA) has emerged as an adjuvant non-pharmacological treatment improving mental and physical health in patients with schizophrenia (SZPs) and increasing the hippocampus (HCP) volume. Previously investigated PA programs have been face-to-face, and not necessary adapted to patients' physiological fitness. We propose an innovative 16-week adapted PA program delivered by real-time videoconferencing (e-APA), allowing SZPs to interact with a coach and to manage their physical condition. The primary goal was to demonstrate a greater increase of total HCP volumes in SZPs receiving e-APA compared to that observed in a controlled group. The secondary objectives were to demonstrate the greater effects of e-APA compared to a controlled group on HCP subfields, cardiorespiratory fitness, clinical symptoms, cognitive functions, and lipidic profile. Thirty-five SZPs were randomized to either e-APA or a controlled group receiving a health education program under the same conditions (e-HE). Variables were assessed at pre- and post-intervention time-points. The dropout rate was 11.4%. Compared to the e-HE group, the e-APA group did not have any effect on the HCP total volumes but increased the left subiculum volume. Also, the e-APA group significantly increased cardiorespiratory fitness (VO2max), improved lipidic profile and negative symptoms but not cognitive functions. This study demonstrated the high feasibility and multiple benefits of a remote e-APA program for SZPs. e-APA may increase brain plasticity and improve health outcomes in SZPs, supporting that PA should be an add-on therapeutic intervention. ClinicalTrial.gov on 25 august 2017 (NCT03261817).

Hypothalamic Subunit Volumes in Schizophrenia and Bipolar Spectrum Disorders.

The hypothalamus is central to many hormonal and autonomous nervous system pathways. Emerging evidence indicates that these pathways may be disrupted in schizophrenia and bipolar disorder. Yet, few studies have examined the volumes of hypothalamic subunits in these patient groups. We compared hypothalamic subunit volumes in individuals with psychotic disorders to healthy controls. We included 344 patients with schizophrenia spectrum disorders (SCZ), 340 patients with bipolar disorders (BPD), and 684 age- and-sex-matched healthy controls (CTR). Total hypothalamus and five hypothalamic subunit volumes were extracted from T1-weighted magnetic resonance imaging (MRI) using an automated Bayesian segmentation method. Regression models, corrected for age, age2, sex, and segmentation-based intracranial volume (sbTIV), were used to examine diagnostic group differences, interactions with sex, and associations with clinical symptoms, antipsychotic medication, antidepressants and mood stabilizers. SCZ had larger volumes in the left inferior tubular subunit and smaller right anterior-inferior, right anterior-superior, and right posterior hypothalamic subunits compared to CTR. BPD did not differ significantly from CTR for any hypothalamic subunit volume, however, there was a significant sex-by-diagnosis interaction. Analyses stratified by sex showed smaller right hypothalamus and right posterior subunit volumes in male patients, but not female patients, relative to same-sex controls. There was a significant association between BPD currently taking antipsychotic medication and the left inferior tubular subunits volumes. Our results show regional-specific alterations in hypothalamus subunit volumes in individuals with SCZ, with relevance to HPA-axis dysregulation, circadian rhythm disruption, and cognition impairment.

Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification.

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

A Study on the Measurement of Subcortical Volume in Schizophrenia Using Magnetic Resonance Imaging

A Study on the Measurement of Subcortical Volume in Schizophrenia Using Magnetic Resonance Imaging

Thalamic nuclei volumes in schizophrenia and bipolar spectrum disorders - Associations with diagnosis and clinical characteristics.

The thalamus is central to brain functions ranging from primary sensory processing to higher-order cognition. Structural deficits in thalamic association nuclei such as the pulvinar and mediodorsal nuclei have previously been reported in schizophrenia. However, the specificity with regards to clinical presentation, and whether or not bipolar disorder (BD) is associated with similar alterations is unclear. We investigated thalamic nuclei volumes in 334 patients with schizophrenia spectrum disorders (SSD) (median age 29years, 59% male), 322 patients with BD (30years, 40% male), and 826 healthy controls (HC) (34years, 54% male). Volumes of 25 thalamic nuclei were extracted from T1-weighted magnetic resonance imaging using an automated Bayesian segmentation method and compared between groups. Furthermore, we explored associations with clinical characteristics across diagnostic groups, including psychotic and mood symptoms and medication use, as well as diagnostic subtype in BD. Significantly smaller volumes were found in the mediodorsal, pulvinar, and lateral and medial geniculate thalamic nuclei in SSD. Similarly, smaller volumes were found in BD in the same four regions, but mediodorsal nucleus volume alterations were limited to its lateral part and pulvinar alterations to its anterior region. Smaller volumes in BD compared to HC were seen only in BD type I, not BD type II. Across diagnoses, having more negative symptoms was associated with smaller pulvinar volumes. Structural alterations were found in both SSD and BD, mainly in the thalamic association nuclei. Structural deficits in the pulvinar may be of relevance for negative symptoms.

Fitness is positively associated with hippocampal formation subfield volumes in schizophrenia: a multiparametric magnetic resonance imaging study

Hippocampal formation (HF) volume loss is a well-established finding in schizophrenia, with select subfields, such as the cornu ammonis and dentate gyrus, being particularly vulnerable. These morphologic alterations are related to functional abnormalities and cognitive deficits, which are at the core of the insufficient recovery frequently seen in this illness. To counteract HF volume decline, exercise to improve aerobic fitness is considered as a promising intervention. However, the effects of aerobic fitness levels on HF subfields are not yet established in individuals with schizophrenia. Therefore, our study investigated potential associations between aerobic fitness and HF subfield structure, functional connectivity, and related cognitive impact in a multiparametric research design. In this cross-sectional study, 53 participants diagnosed with schizophrenia (33 men, 20 women; mean [SD] age, 37.4 [11.8] years) underwent brain structural and functional magnetic resonance imaging and assessments of aerobic fitness and verbal memory. Multivariate multiple linear regressions were performed to determine whether aerobic fitness was associated with HF subfield volumes and functional connections. In addition, we explored whether identified associations mediated verbal memory functioning. Significant positive associations between aerobic fitness levels and volumes were demonstrated for most HF subfields, with the strongest associations for the cornu ammonis, dentate gyrus, and subiculum. No significant associations were found for HF functional connectivity or mediation effects on verbal memory. Aerobic fitness may mitigate HF volume loss, especially in the subfields most affected in schizophrenia. This finding should be further investigated in longitudinal studies.Clinical Trials Registration: The study on which the manuscript is based was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Clinical correlates of regional gray matter volumes in schizophrenia: A structural magnetic resonance imaging study.

The objective of this study is to investigate the correlation between the regional gray matter volumes and length of Para Cingulate Sulcus (PCS) with the clinical profile of patients with schizophrenia. In this hospital-based, cross-sectional study, thirty consecutive in-patients diagnosed with schizophrenia and equal number of healthy volunteers matched for age- and sex- were recruited as controls. Detailed clinical assessment and magnetic resonance imaging (MRI) of the brain were carried out within 2 days for controls and within 2 weeks of hospitalization for patients. The Positive and Negative Syndrome Scale and Montreal Cognitive Assessment were applied to schizophrenia patients to assess symptoms and cognitive function, respectively. Schizophrenia patients had significant volume deficit in bilateral amygdalae, bilateral superior temporal gyri, anterior cingulate cortex and bilateral hippocampi, along with a highly significant reduction in the length of right PCS. Schizophrenia patients with the duration of untreated psychosis (DUP) of 6-12 months showed a significantly greater volume of the right superior temporal gyrus (STG). First-episode schizophrenia patients had a significant reduction in the length of the left PCS. The volume of bilateral superior temporal gyri in schizophrenia patients showed a significant direct correlation with positive symptoms and an inverse correlation with negative symptoms. Schizophrenia patients have significant volume deficit in some brain regions. DUP of 6-12 months is associated with significantly greater volume of the right STG. First-episode schizophrenia patients have a significant reduction in the length of the left PCS. In schizophrenia patients, the volume of bilateral superior temporal gyri showed a significant direct correlation with the positive symptoms and an inverse correlation with the negative symptoms.

Relationships between cognitive performance, clinical insight and regional brain volumes in schizophrenia

Impairments in cognitive performance are common in schizophrenia, and these contribute to poor awareness of symptoms and treatment (‘clinical insight’), which is an important predictor of functional outcome. Although relationships between cognitive impairment and reductions in regional brain volumes in patients are relatively well characterised, less is known about the brain structural correlates of clinical insight. To address this gap, we aimed to explore brain structural correlates of cognitive performance and clinical insight in the same sample. 108 patients with schizophrenia (SZH) and 94 age and gender-matched controls (CON) (from the Northwestern University Schizophrenia Data and Software Tool (NUSDAST) database) were included. SZH had smaller grey matter volume across most fronto-temporal regions and significantly poorer performance on all cognitive domains. Multiple regression showed that higher positive symptoms and poorer attention were significant predictors of insight in SZH; however, no significant correlations were seen between clinical insight and regional brain volumes. In contrast, symptomology did not contribute to cognitive performance, but robust positive relationships were found between regional grey matter volumes in fronto-temporal regions and cognitive performance (particularly executive function). Many of these appeared to be unique to SZH as they were not observed in CON. Findings suggest that while there exists a tight link between cognitive functioning and neuropathological processes affecting gross brain anatomy in SZH, this is not the case for clinical insight. Instead, clinical insight levels seem to be influenced by symptomology, attentional performance and other subject-specific variables.

Abnormal corneal nerve morphology and brain volume in patients with schizophrenia

Neurodevelopmental and neurodegenerative pathology occur in Schizophrenia. This study compared the utility of corneal confocal microscopy (CCM), an ophthalmic imaging technique with MRI brain volumetry in quantifying neuronal pathology and its relationship to cognitive dysfunction and symptom severity in schizophrenia. Thirty-six subjects with schizophrenia and 26 controls underwent assessment of cognitive function, symptom severity, CCM and MRI brain volumetry. Subjects with schizophrenia had lower cognitive function (P ≤ 0.01), corneal nerve fiber density (CNFD), length (CNFL), branch density (CNBD), CNBD:CNFD ratio (P < 0.0001) and cingulate gyrus volume (P < 0.05) but comparable volume of whole brain (P = 0.61), cortical gray matter (P = 0.99), ventricle (P = 0.47), hippocampus (P = 0.10) and amygdala (P = 0.68). Corneal nerve measures and cingulate gyrus volume showed no association with symptom severity (P = 0.35–0.86 and P = 0.50) or cognitive function (P = 0.35–0.86 and P = 0.49). Corneal nerve measures were not associated with metabolic syndrome (P = 0.61–0.64) or diabetes (P = 0.057–0.54). The area under the ROC curve distinguishing subjects with schizophrenia from controls was 88% for CNFL, 84% for CNBD and CNBD:CNFD ratio, 79% for CNFD and 73% for the cingulate gyrus volume. This study has identified a reduction in corneal nerve fibers and cingulate gyrus volume in schizophrenia, but no association with symptom severity or cognitive dysfunction. Corneal nerve loss identified using CCM may act as a rapid non-invasive surrogate marker of neurodegeneration in patients with schizophrenia.

Altered asymmetries in cortical and subcortical brain volume in schizophrenia

Altered asymmetries in cortical and subcortical brain volume in schizophrenia

Relation between season of birth and left superior temporal gyrus volume in schizophrenia

Relation between season of birth and left superior temporal gyrus volume in schizophrenia

Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia

A potential pathophysiological mechanism of cognitive difficulties in schizophrenia is a dysregulated cholinergic system. Particularly, the cholinergic basal forebrain nuclei (BFCN), the source of cortical cholinergic innervation, support multiple cognitive functions, ranging from attention to decision-making. We hypothesized that BFCN structural integrity is altered in schizophrenia and associated with patients’ attentional deficits. We assessed gray matter (GM) integrity of cytoarchitectonically defined BFCN region-of-interest in 72 patients with schizophrenia and 73 healthy controls, matched for age and gender, from the COBRE open-source database, via structural magnetic resonance imaging (MRI)–based volumetry. MRI-derived measures of GM integrity (i.e., volumes) were linked with performance on a symbol coding task (SCT), a paper-pencil-based metric that assesses attention, by correlation and mediation analysis. To assess the replicability of findings, we repeated the analyses in an independent dataset comprising 26 patients with schizophrenia and 24 matched healthy controls. BFCN volumes were lower in patients (t(139)=2.51, p = 0.01) and significantly associated with impaired SCT performance (r = 0.31, p = 0.01). Furthermore, lower BFCN volumes mediated the group difference in SCT performance. When including global GM volumes, which were lower in patients, as covariates-of-no-interest, these findings disappeared, indicating that schizophrenia did not have a specific effect on BFCN relative to other regional volume changes. We replicated these findings in the independent cohort, e.g., BFCN volumes were lower in patients and mediated patients’ impaired SCT performance. Results demonstrate lower BFCN volumes in schizophrenia, which link with patients’ attentional deficits. Data suggest that a dysregulated cholinergic system might contribute to cognitive difficulties in schizophrenia via impaired BFCN.

Absence of negative associations of insular and medial frontal gray matter volume with dissociative symptoms in schizophrenia

BackgroundDissociative symptoms have been constantly found in schizophrenia (SCZ). Traumatic experience seems to relate to dissociative symptoms and brain volume alterations in SCZ. The current study aimed to clarify the inter-relations of dissociative symptoms, traumatic experience, and brain volume in SCZ. MethodsWe employed voxel-based morphometry to compare the distributions of gray matter volumes (GMV) in 37 SCZ patients and 26 healthy volunteers (HV). All participants underwent T1-weighted images on a 1.5 T MRI system. Traumatic experience was examined by the Brief Betrayal Trauma Survey. Pathological and non-pathological dissociation were measured by the Dissociative Symptoms Scale and the Dissociative Experiences Scale, respectively. ResultsA GMV reduction was found in SCZ patients in the right thalamus. Importantly, a significant group by pathological dissociation interaction was observed in the medial frontal cortex (MFC), bilateral anterior insular area, and precuneus. A negative correlation between MFC/insular GMV and pathological dissociation was observed in HV; higher non-pathological dissociation and smaller volume in MFC/insula were associated with pathological dissociation. In contrast, higher traumatic experience, higher non-pathological dissociation, and larger volume in MFC/insula were associated with pathological dissociation in SCZ. ConclusionThe negative association between MFC/insula GMV and pathological dissociation in HV was not observed in SCZ patients. The absent negative association in SCZ suggests a unique neural underpinning in SCZ with dissociative pathology, in which medial frontal and temporal regions play crucial roles.

The association of matrix metalloproteinase 9 (MMP9) with hippocampal volume in schizophrenia: a preliminary MRI study.

Matrix metalloproteinases 9 (MMP9) are enzymes involved in regulating neuroplasticity in the hippocampus. This, combined with evidence for disrupted hippocampal structure and function in schizophrenia, has prompted our current investigation into the relationship between MMP9 and hippocampal volumes in schizophrenia. 34 healthy individuals (mean age = 32.50, male = 21, female = 13) and 30 subjects with schizophrenia (mean age = 33.07, male = 19, female = 11) underwent a blood draw and T1-weighted magnetic resonance imaging. The hippocampus was automatically segmented utilizing FreeSurfer. MMP9 plasma levels were measured with ELISA. ANCOVAs were conducted to compare MMP9 plasma levels (corrected for age and sex) and hippocampal volumes between groups (corrected for age, sex, total intracranial volume). Spearman correlations were utilized to investigate the relationship between symptoms, medication, duration of illness, number of episodes, and MMP9 plasma levels in patients. Last, we explored the correlation between MMP9 levels and hippocampal volumes in patients and healthy individuals separately. Patients displayed higher MMP9 plasma levels than healthy individuals (F(1, 60) = 21.19, p < 0.0001). MMP9 levels correlated with negative symptoms in patients (R = 0.39, p = 0.035), but not with medication, duration of illness, or the number of episodes. Further, patients had smaller left (F(1,59) = 9.12, p = 0.0040) and right (F(1,59) = 6.49, p = 0.013) hippocampal volumes. Finally, left (R = -0.39, p = 0.034) and right (R = -0.37, p = 0.046) hippocampal volumes correlated negatively with MMP9 plasma levels in patients. We observe higher MMP9 plasma levels in SCZ, associated with lower hippocampal volumes, suggesting involvement of MMP9 in the pathology of SCZ. Future studies are needed to investigate how MMP9 influences the pathology of SCZ over the lifespan, whether the observed associations are specific for schizophrenia, and if a therapeutic modulation of MMP9 promotes neuroprotective effects in SCZ.

Birth asphyxia and its implications for neuropsychology and brain volume in schizophrenia

IntroductionNewborn infants can suffer permanent brain damage as a result of birth asphyxia (ASP), a severe obstetric complication (OC). However, effects of OCs on cognitive abilities and brain structure in schizophrenia (SZ) are unknown.ObjectivesThe main goals of this study were to investigate putative effects of a history of OCs on adult cognition and brain structure in SZ.MethodsWe utilized prospective data from the Medical Birth Registry of Norway to identify incidences of severe OCs in adult healthy controls (HC; n = 622) and patients with SZ (n = 607). IQ was assessed, and a subset of participants (n= 414) underwent magnetic resonance imaging.ResultsSevere OCs (27%) and ASP (14%) were equally common in SZ and HC. SZ patients with OCs had lower IQ than patients without OCs, a difference not found in HC (p = .023). Having experienced more than one co-occurring severe OC was associated with lower IQ in both groups, wherein 81% of co-occurring OCs involved ASP. ASP was related to smaller intracranial volume and brain volumes in both groups. Smaller caudate volumes were found in SZ patients with ASP compared to patients without ASP, a difference not found in HC (p = .009).ConclusionsOur findings give support for an effect of birth ASP on brain development in both patients with SZ and HC. OC history specifically impacts IQ in SZ. Smaller caudate volumes might be particularly related to disease development. These results warrant replication in an independent sample.DisclosureNo significant relationships.

Reduced Hippocampal Subfield Volume in Schizophrenia and Clinical High-Risk State for Psychosis.

Magnetic resonance imaging (MRI) studies in schizophrenia demonstrated volume reduction in hippocampal subfields divided on the basis of specific cytoarchitecture and function. However, it remains unclear whether this abnormality exists prior to the onset of psychosis and differs across illness stages. MRI (3 T) scans were obtained from 77 patients with schizophrenia, including 24 recent-onset and 40 chronic patients, 51 individuals with an at-risk mental state (ARMS) (of whom 5 subsequently developed psychosis within the follow-up period), and 87 healthy controls. Using FreeSurfer software, hippocampal subfield volumes were measured and compared across the groups. Both schizophrenia and ARMS groups exhibited significantly smaller volumes for the bilateral Cornu Ammonis 1 area, left hippocampal tail, and right molecular layer of the hippocampus than the healthy control group. Within the schizophrenia group, chronic patients exhibited a significantly smaller volume for the left hippocampal tail than recent-onset patients. The left hippocampal tail volume was positively correlated with onset age, and negatively correlated with duration of psychosis and duration of medication in the schizophrenia group. Reduced hippocampal subfield volumes observed in both schizophrenia and ARMS groups may represent a common biotype associated with psychosis vulnerability. Volumetric changes of the left hippocampal tail may also suggest ongoing atrophy after the onset of schizophrenia.

In Vivo Amygdala Nuclei Volumes in Schizophrenia and Bipolar Disorders.

Abnormalities in amygdala volume are well-established in schizophrenia and commonly reported in bipolar disorders. However, the specificity of volumetric differences in individual amygdala nuclei is largely unknown. Patients with schizophrenia disorders (SCZ, N = 452, mean age 30.7 ± 9.2 [SD] years, females 44.4%), bipolar disorders (BP, N = 316, 33.7 ± 11.4, 58.5%), and healthy controls (N = 753, 34.1 ± 9.1, 40.9%) underwent T1-weighted magnetic resonance imaging. Total amygdala, nuclei, and intracranial volume (ICV) were estimated with Freesurfer (v6.0.0). Analysis of covariance and multiple linear regression models, adjusting for age, age2, ICV, and sex, were fitted to examine diagnostic group and subgroup differences in volume, respectively. Bilateral total amygdala and all nuclei volumes, except the medial and central nuclei, were significantly smaller in patients relative to controls. The largest effect sizes were found for the basal nucleus, accessory basal nucleus, and cortico-amygdaloid transition area (partial η2 > 0.02). The diagnostic subgroup analysis showed that reductions in amygdala nuclei volume were most widespread in schizophrenia, with the lateral, cortical, paralaminar, and central nuclei being solely reduced in this disorder. The right accessory basal nucleus was marginally smaller in SCZ relative to BP (t = 2.32, P = .05). Our study is the first to demonstrate distinct patterns of amygdala nuclei volume reductions in a well-powered sample of patients with schizophrenia and bipolar disorders. Volume differences in the basolateral complex (lateral, basal, and accessory basal nuclei), an integral part of the threat processing circuitry, were most prominent in schizophrenia.

Cortisol-dehydroepiandrosterone ratios are inversely associated with hippocampal and prefrontal brain volume in schizophrenia

While high levels of glucocorticoids are generally neuro-damaging, a related adrenal steroid, dehydroepiandrosterone (DHEA), has anti-glucocorticoid and neuroprotective properties. Previous work has shown increased circulating levels of DHEA and abnormal cortisol/DHEA ratios in people with schizophrenia, however reports are limited and their relationship to neuropathology is unclear. We performed the largest study to date to compare levels of serum DHEA and cortisol/DHEA ratios in people with schizophrenia and healthy controls, and investigated the extent to which cortisol/DHEA ratios predict brain volume. Serum cortisol and DHEA were assayed in 94 people with schizophrenia and 81 healthy controls. T1-weighted high-resolution anatomical scans were obtained using a 3 T Achieva scanner on a subset of 59 people with schizophrenia and 60 healthy controls. Imaging data were preprocessed and analyzed using SPM12. People with schizophrenia had significantly increased serum DHEA levels (p = 0.002), decreased cortisol/DHEA ratios (p = 0.02) and no difference in cortisol levels compared to healthy controls. Cortisol/DHEA ratios were inversely correlated with hippocampal (r = -0.33 p = 0.01) and dorsolateral prefrontal cortex (r = -0.30, p = 0.02) volumes in patients. Our findings suggest that the cortisol/DHEA ratio may be a molecular blood signature of hippocampal and cortical damage. These results further implicate the role of DHEA and hypothalamic-pituitary-adrenal axis dysfunction in the pathophysiology of schizophrenia.

Systemic inflammation and grey matter volume in schizophrenia and bipolar disorder: Moderation by childhood trauma severity

BackgroundElevated levels of systemic inflammation are consistently reported in both schizophrenia (SZ) and bipolar-I disorder (BD), and are associated with childhood trauma exposure. We tested whether childhood trauma exposure moderates associations between systemic inflammation and brain morphology in people with these diagnoses. MethodsParticipants were 55 SZ cases, 52 BD cases and 59 healthy controls (HC) who underwent magnetic resonance imaging. Systemic inflammation was measured using a composite z-score derived from serum concentrations of interleukin 6, tumor necrosis factor alpha and C-reactive protein. Indices of grey matter volume covariation (GMC) were derived from independent component analysis. Childhood trauma was measured using the Childhood Trauma Questionnaire (CTQ Total score). ResultsA series of moderated moderation analyses indicated that increased systemic inflammation were associated with increased GMC in the striatum and cerebellum among all participants. Severity of childhood trauma exposure moderated the relationship between systemic inflammation and GMC in one component, differently among the groups. Specifically, decreased GMC in the PCC/precuneus, parietal lobule and postcentral gyrus, and increased GMC in the left middle temporal gyrus was associated with increased systemic inflammation in HC individuals exposed to high (but not low or average) levels of trauma and in SZ cases exposed to low (but not average or high) levels of trauma, but not in BD cases. ConclusionsIncreased systemic inflammation is associated with grey matter changes in people with psychosis, and these relationships may be partially and differentially moderated by childhood trauma exposure according to diagnosis.