The hippocampus is a complex structure consisting of subregions with specialized cytoarchitecture and functions. Magnetic resonance imaging (MRI) studies in psychotic disorders show hippocampal ...subfield abnormalities, but affected regions differ between studies. We here present an overview of hippocampal anatomy and function relevant to psychosis, and the first systematic review and meta-analysis of MRI studies of hippocampal subfield morphology in schizophrenia and bipolar disorder. Twenty-one MRI studies assessing hippocampal subfield volumes or shape in schizophrenia or bipolar disorder were included (n 15–887 subjects). Nine volumetric group comparison studies (total n = 2593) were included in random effects meta-analyses of group differences. The review showed mixed results, with volume reductions reported in most subfields in schizophrenia and bipolar disorder. Volumetric studies using ex-vivo based image analysis templates corresponded best with the shape studies, with CA1 as the most affected region. The meta-analyses showed volume reductions in all subfields in schizophrenia and bipolar disorder compared to healthy controls (all p < .005; schizophrenia: d = 0.28-0.49, bipolar disorder: d = 0.20-0.35), and smaller left CA2/3 and right subiculum in schizophrenia than bipolar disorder. In conclusion, the hippocampal subfields appear to be differently affected in psychotic disorders. However, due to the lack of control for putative confounders such as medication, alcohol and illicit substance use, and illness stage, the results from the meta-analysis should be interpreted with caution. Methodological subfield segmentation weaknesses should be addressed in future studies.
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•Review (21 MRI-studies): widespread volume reductions and shape alterations.•Changes were in part related to clinical symptoms and lithium use.•Meta-analysis (8 studies): larger reductions in schizophrenia than bipolar disorder.•Methodological differences may confound the results.•Future studies using newer protocols in larger subject samples are warranted.
Schizophrenia is associated with decreased life expectancy (15-25 y) compared to the general population, with comorbid somatic diseases and in particular cardiovascular diseases being a major cause. ...Life style and medication probably account for much of the increased mortality risk due to somatic diseases in schizophrenia, but the evidence implicating biological pathways potentially affecting both body and brain is increasing. This includes overlapping genes between schizophrenia and somatic diseases, prenatal risk factors such as hypoxia and infections, and increased cardiovascular disease risk in drug-naïve patients at illness onset. Although environmental bias increases throughout the disease course, there are also some studies on chronic schizophrenia and postmortem brain samples that warrant further attention. In the following, we will attempt to move beyond environmental impact and explore some of the shared pathophysiological mechanisms potentially underlying both schizophrenia and somatic diseases.
Abstract Background Hippocampal dysfunction and volume reductions have been reported in patients with schizophrenia and bipolar disorder. The hippocampus consists of anatomically distinct subfields. ...We investigated to determine whether in vivo volumes of hippocampal subfields differ between clinical groups and healthy control subjects. Methods Clinical examination and magnetic resonance imaging were performed in 702 subjects (patients with schizophrenia spectrum n = 210; mean age, 32.0 ± 9.3 (SD) years; 59% male, patients with bipolar spectrum n = 192; mean age, 35.5 ± 11.5 years; 40% male and healthy control subjects n = 300; mean age, 35.3 ± 9.9 years; 53% male). Hippocampal subfield volumes were estimated with FreeSurfer. General linear models were used to explore diagnostic differences in hippocampal subfield volumes, covarying for age, intracranial volume, and medication. Post hoc analyses of associations to psychosis symptoms (Positive and Negative Syndrome Scale) and cognitive function (verbal memory California Verbal Learning Test, second edition and IQ Wechsler Abbreviated Scale of Intelligence) were performed. Results Patient groups had smaller cornu ammonis (CA) subfields CA2/3 (left, p = 7.2 × 10−6 ; right, p = 2.3 × 10−6 ), CA4/dentate gyrus (left, p = 1.4 × 10−5 ; right, p = 2.3 × 10−6 ), subiculum (left, p = 3.7 × 10−6 ; right, p = 2.8 × 10−8 ), and right CA1 ( p = .006) volumes than healthy control subjects, but smaller presubiculum volumes were found only in patients with schizophrenia (left, p = 6.7 × 10−5 ; right, p = 1.6 × 10−7 ). Patients with schizophrenia had smaller subiculum (left, p = .035; right, p = .031) and right presubiculum ( p = .002) volumes than patients with bipolar disorder. Smaller subiculum volumes were related to poorer verbal memory in patients with bipolar disorder and healthy control subjects and to negative symptoms in patients with schizophrenia. Conclusions Hippocampal subfield volume reductions are found in patients with schizophrenia and bipolar disorder. The magnitude of reduction is greater in patients with schizophrenia, particularly in the hippocampal outflow regions presubiculum and subiculum.
Persons with schizophrenia have a small but significant increase in risk of violence, which remains after controlling for known environmental risk factors.
MRI-studies may point toward the biological ...underpinnings of psychotic violence, and neuroimaging has increasingly been used in forensic and legal settings despite unclear relevance.
(1) To present the first systematic review, following standardized guidelines, of MRI studies of violence with schizophrenia. (2) To critically discuss the promises and pitfalls of using this literature to understand violence in schizophrenia in clinical, forensic, and legal settings.
Following the PRISMA guidelines and literature searches until January 2018, we found 21 original studies that fulfilled the inclusion criteria: (1) Studies of persons with schizophrenia, (2) a history of violence or aggressive behavior, (3) the use of one or more MRI-modalities (sMRI, DTI, fMRI).
The most consistent findings from the structural studies were reduced volumes of the hippocampus and the frontal lobe (in particular the orbitofrontal and anterior cingulate cortex) in schizophrenia patients with a history of violence or higher aggression scores. The functional studies mainly showed differences and aggression correlates in the frontal lobe and amygdala. However, the studies were methodologically heterogeneous, with four particular areas of concern: different definitions of violence, region of interest vs. whole-brain studies, small subject samples, and group comparisons in a heterogeneous diagnostic category (schizophrenia).
The literature reports subtle, but inconsistent group level differences in brain structure and function associated with violence and aggression with schizophrenia, in particular in areas involved in the formation of psychosis symptoms and affective regulation. Due to methodological challenges the results should be interpreted with caution. In order to come closer to the neurobiological underpinnings of violence in schizophrenia future studies could: (1) address the neurobiological differences of premeditated and reactive violence, (2) use RDoC criteria, for example, or other symptom-based systems to categorize psychosis patients, (3) increase subject cohorts and apply new data driven methods. In this perspective, MRI-studies of violence in schizophrenia have the potential to inform clinical violence prediction and legal evaluations
.
Reduced social cognition has been reported in individuals who have committed interpersonal violence. It is unclear if individuals with schizophrenia and a history of violence have larger impairments ...than violent individuals without psychosis and non-violent individuals with schizophrenia. We examined social cognition in two groups with violent offenses, comparing their performance to non-violent individuals with schizophrenia and healthy controls.
Two social cognitive domains were assessed in four groups: men with a schizophrenia spectrum disorder with (SSD-V, n = 27) or without (SSD-NV, n = 42) a history of violence, incarcerated men serving preventive detention sentences (V, n = 22), and healthy male controls (HC, n = 76). Theory of mind (ToM) was measured with the Movie for the Assessment of Social Cognition (MASC), body emotion perception with Emotion in Biological Motion (EmoBio) test.
Kruskal-Wallis H-tests revealed overall group differences for social cognition. SSD-V had a global and clinically significant social cognitive impairment. V had a specific impairment, for ToM. Binary logistic regressions predicting violence category membership from social cognition and psychosis (SSD status) were conducted. The model with best fit, explaining 18%-25% of the variance, had ToM as the only predictor.
Social cognitive impairment was present in individuals with a history of violence, with larger and more widespread impairment seen in schizophrenia. ToM predicted violence category membership, psychosis did not. The results suggest a role for social cognition in understanding interpersonal violence.
Background Schizophrenia and bipolar disorder are severe psychiatric diseases with overlapping symptomatology. Widespread brain morphologic abnormalities, including cortical thinning and subcortical ...volume reductions, have been demonstrated in schizophrenia but it is unclear whether similar abnormalities are present in bipolar disorder. The purpose of this study was to compare cortical thickness and subcortical volumes in schizophrenia and bipolar disorder, to assess differences and similarities in cortical and subcortical brain structure. Methods We analyzed magnetic resonance images from a sample of 173 patients with schizophrenia spectrum disorder, 139 patients with bipolar disorder, and 207 healthy control subjects. Cortical thickness was compared between the groups in multiple locations across the continuous cortical surface. Subcortical volumes were compared on a structure-by-structure basis. Results There was widespread cortical thinning in schizophrenia compared with control subjects, in frontal, temporal, occipital, and smaller parietal regions. There was no cortical thinning in bipolar disorder compared with control subjects or in schizophrenia compared with bipolar disorder. However, the subgroup of patients with bipolar disorder Type 1 showed cortical thinning, primarily in the frontal lobes and superior temporal and temporoparietal regions. Both patient groups showed substantial subcortical volume reductions bilaterally in the hippocampus, the left thalamus, the right nucleus accumbens, the left cerebellar cortex, and the brainstem, along with substantial ventricular enlargements. Conclusions We found substantial overlap in the underlying brain morphologic abnormalities in schizophrenia and bipolar disorder in subcortical structures, and between schizophrenia and bipolar disorder Type 1 in the cerebral cortex.
Oxytocin plays a vital role in social behavior and homeostatic processes, with animal models indicating that oxytocin receptor (OXTR) expression patterns in the brain influence behavior and ...physiology. However, the developmental trajectory of OXTR gene expression is unclear. By analyzing gene expression data in human post-mortem brain samples, from the prenatal period to late adulthood, we demonstrate distinct patterns of OXTR gene expression in the developing brain, with increasing OXTR expression along the course of the prenatal period culminating in a peak during early childhood. This early life OXTR expression peak pattern appears slightly earlier in a comparative macaque sample, which is consistent with the relative immaturity of the human brain during early life compared to macaques. We also show that a network of genes with strong spatiotemporal couplings with OXTR is enriched in several psychiatric illness and body composition phenotypes. Taken together, these results demonstrate that oxytocin signaling plays an important role in a diverse set of psychological and somatic processes across the lifespan.
Abstract
Objectives
Cytomegalovirus (CMV) congenital infection and in immunodeficiency can have deleterious effects on human cortex. In immunocompetent adults, the putative association between CMV ...infection and cortical measures has not been explored. We hypothesized that CMV exposure is associated with smaller cortical surface area or cortical thinning mainly in patients with schizophrenia spectrum disorders.
Study Design
We included 67 adult patients with schizophrenia spectrum disorders and 262 adult healthy controls. We measured circulating CMV IgG antibody concentrations with solid-phase immunoassay techniques. We measured the total cortical surface area, regional cortical surface areas and the overall mean cortical thickness based on T1-weighted MRI scans processed in FreeSurfer v6.0.
Study Results
In the whole sample analysis, we found a significant diagnostic group-by-CMV status interaction on the total surface area (P = .020). Among patients, CMV antibody positivity was significantly associated with smaller total surface area (P = .002, partial eta2 = 0.138) whereas no such association was found in healthy controls (P = .059). Post hoc analysis among patients showed that higher CMV antibody concentrations were also significantly associated with smaller total surface area (P = .038), and that CMV antibody positivity was significantly inversely associated with 14 left and 16 right regional surface areas mainly in the frontal and temporal lobes. CMV infection was not associated with the overall mean cortical thickness.
Conclusions
The results are indicative of a cortical surface area vulnerability to CMV infection in patients with schizophrenia spectrum disorders but not in healthy controls. CMV infection may contribute to the established cortical surface area aberrations in schizophrenia.
Abstract
Background and Hypothesis
The hippocampus is a heterogenous brain structure that differs between the sexes and has been implicated in the pathophysiology of psychiatric illnesses. Here, we ...explored sex and diagnostic group differences in hippocampal subfield volumes, in individuals with schizophrenia spectrum disorder (SZ), bipolar disorders (BD), and healthy controls (CTL).
Study Design
One thousand and five hundred and twenty-one participants underwent T1-weighted magnetic resonance imaging (SZ, n = 452, mean age 30.7 ± 9.2 SD years, males 59.1%; BD, n = 316, 33.7 ± 11.4, 41.5%; CTL, n = 753, 34.1 ± 9.1, 55.6%). Total hippocampal, subfield, and intracranial volumes were estimated with Freesurfer (v6.0.0). Analysis of covariance and multiple regression models were fitted to examine sex-by-diagnostic (sub)group interactions in volume. In SZ and BD, separately, associations between volumes and clinical as well as cognitive measures were examined between the sexes using regression models.
Study Results
Significant sex-by-group interactions were found for the total hippocampus, dentate gyrus, molecular layer, presubiculum, fimbria, hippocampal-amygdaloid transition area, and CA4, indicating a larger volumetric deficit in male patients relative to female patients when compared with same-sex CTL. Subgroup analyses revealed that this interaction was driven by males with schizophrenia. Effect sizes were overall small (partial η < 0.02). We found no significant sex differences in the associations between hippocampal volumes and clinical or cognitive measures in SZ and BD.
Conclusions
Using a well-powered sample, our findings indicate that the pattern of morphological sex differences in hippocampal subfields is altered in individuals with schizophrenia relative to CTL, due to higher volumetric deficits in males.
Abstract
Schizophrenia and bipolar disorder are severe mental illnesses (SMI) linked to both genetic and environmental factors. Herpes simplex virus 1 (HSV1) is a common neurotropic pathogen which ...after the primary infection establishes latency with periodic reactivations. We hypothesized that the latent HSV1 infection is associated with brain structural abnormalities and cognitive impairment, especially in SMI. We included 420 adult patients with SMI (schizophrenia or bipolar spectrum) and 481 healthy controls. Circulating HSV1 immunoglobulin G concentrations were measured with immunoassays. We measured the total grey matter volume (TGMV), cortical, subcortical, cerebellar and regional cortical volumes based on T1-weighted MRI scans processed in FreeSurfer v6.0.0. Intelligence quotient (IQ) was assessed with the Wechsler Abbreviated Scale of Intelligence. Seropositive patients had significantly smaller TGMV than seronegative patients (642 cm
3
and 654 cm
3
, respectively;
p
= 0.019) and lower IQ (104 and 107, respectively;
p
= 0.018). No TGMV or IQ differences were found between seropositive and seronegative healthy controls. Post-hoc analysis showed that (a) in both schizophrenia and bipolar spectrum, seropositive patients had similarly smaller TGMV than seronegative patients, whereas the HSV1-IQ association was driven by the schizophrenia spectrum group, and (b) among all patients, seropositivity was associated with smaller total cortical (
p
= 0.016), but not subcortical or cerebellar grey matter volumes, and with smaller left caudal middle frontal, precentral, lingual, middle temporal and banks of superior temporal sulcus regional cortical grey matter volumes. The results of this cross-sectional study indicate that HSV1 may be an environmental factor associated with brain structural abnormalities and cognitive impairment in SMI.
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