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Abstract Background Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.

Abstract Repeated hospitalizations are a characteristic of severe disease courses in patients with affective disorders (PAD). To elucidate how a hospitalization during a nine-year follow-up in PAD affects brain structure, a longitudinal case-control study (mean [SD] follow-up period 8.98 [2.20] years) was conducted using structural neuroimaging. We investigated PAD (N = 38) and healthy controls (N = 37) at two sites (University of Münster, Germany, Trinity College Dublin, Ireland). PAD were divided into two groups based on the experience of in-patient psychiatric treatment during follow-up. Since the Dublin-patients were outpatients at baseline, the re-hospitalization analysis was limited to the Münster site (N = 52). Voxel-based morphometry was employed to examine hippocampus, insula, dorsolateral prefrontal cortex and whole-brain gray matter in two models: (1) group (patients/controls)×time (baseline/follow-up) interaction; (2) group (hospitalized patients/not-hospitalized patients/controls)×time interaction. Patients lost significantly more whole-brain gray matter volume of superior temporal gyrus and temporal pole compared to HC (p FWE = 0.008). Patients hospitalized during follow-up lost significantly more insular volume than healthy controls (p FWE = 0.025) and more volume in their hippocampus compared to not-hospitalized patients (p FWE = 0.023), while patients without re-hospitalization did not differ from controls. These effects of hospitalization remained stable in a smaller sample excluding patients with bipolar disorder. PAD show gray matter volume decline in temporo-limbic regions over nine years. A hospitalization during follow-up comes with intensified gray matter volume decline in the insula and hippocampus. Since hospitalizations are a correlate of severity, this finding corroborates and extends the hypothesis that a severe course of disease has detrimental long-term effects on temporo-limbic brain structure in PAD.

Abstract While it is known that cultural background influences the healthy brain, less is known about how it affects cortical changes in schizophrenia. Here, we tested whether schizophrenia differentially affected the brain in Japanese and German patients. In a sample of 155 patients with a diagnosis of schizophrenia and 191 healthy controls from Japan and Germany, we acquired 3 T-MRI of the brain. We subsequently compared cortical thickness and cortical surface area to identify whether differences between healthy controls and patients might be influenced by ethnicity. Additional analyses were performed to account for effects of duration of illness and medication. We found pronounced interactions between schizophrenia and cultural background in the cortical thickness of several areas, including the left inferior and middle temporal gyrus, as well as the right lateral occipital cortex. Regarding cortical surface area, interaction effects appeared in the insula and the occipital cortex, among others. Some of these brain areas are related to the expression of psychotic symptoms, which are known to differ across cultures. Our results indicate that cultural background impacts cortical structures in different ways, probably resulting in varying clinical manifestations, and call for the inclusion of more diverse samples in schizophrenia research.

Introduction: Studies of brain-damaged patients revealed that amygdala lesions cause deficits in the processing and recognition of emotional faces. Patients with autism spectrum disorders (ASD) have similar deficits also related to dysfunctions of the limbic system including the amygdala.Methods: We investigated a male patient who had been diagnosed with Asperger's syndrome. He also presented with a lesion of the right mesial temporal cortex, including the amygdala. We used functional magnetic resonance imaging (fMRI) to investigate neuronal processing during a passive viewing task of implicit and explicit emotional faces. Clinical assessment included a facial emotion recognition task.Results: There was no amygdala activation on both sides during the presentation of masked emotional faces compared to the no-face control condition. Presentation of unmasked happy and angry faces activated the left amygdala compared to the no-face control condition. There was no amygdala activation in response to unmasked fearful faces on both sides. In the facial emotion recognition task, the patient biased positive and neutral expressions as negative.Conclusions: This case report describes a male patient with right amygdala damage and an ASD. He displayed a non-response of the amygdala to fearful faces and tended to misinterpret fearful expressions. Moreover, a non-reactivity of both amygdalae to emotional facial expressions at an implicit processing level was revealed. It is discussed whether the deficient implicit processing of facial emotional information and abnormalities in fear processing could contribute and aggravate the patient's impairments in social behavior and interaction.

In December 2019, the first case of COVID-19 was reported and since then several groups have already published that the virus can be present in the testis. To study the influence of SARS-CoV-2 which cause a dysregulation of the androgen receptor (AR) level, thereby leading to fertility problems and inducing germ cell testicular changes in patients after the infection. Formalin-Fixed-Paraffin-Embedded (FFPE) testicular samples from patients who died with or as a result of COVID-19 (n = 32) with controls (n = 6), inflammatory changes (n = 9), seminoma with/without metastasis (n = 11) compared with healthy biopsy samples (n = 3) were analyzed and compared via qRT-PCR for the expression of miR-371a-3p. An immunohistochemical analysis (IHC) and ELISA were performed in order to highlight the miR-371a-3p targeting the AR. Serum samples of patients with mild or severe COVID-19 symptoms (n = 34) were analyzed for miR-371a-3p expression. In 70% of the analyzed postmortem testicular tissue samples, a significant upregulation of the miR-371a-3p was detected, and 75% of the samples showed a reduced spermatogenesis. In serum samples, the upregulation of the miR-371a-3p was also detectable. The upregulation of the miR-371a-3p is responsible for the downregulation of the AR in SARS-CoV-2-positive patients, resulting in decreased spermatogenesis. Since the dysregulation of the AR is associated with infertility, further studies have to confirm if the identified dysregulation is regressive after a declining infection.

The remediation of executive function in patients with schizophrenia is important in rehabilitation because these skills affect the patient's capacity to function in the community. There is evidence that instructional techniques can improve deficits in the Wisconsin Card Sorting Test (WCST) in some schizophrenia patients. We used a standard test/training phase/standard test format of the WCST to classify 36 schizophrenia patients as high-achievers, learners or non-retainers. All healthy controls performed as high-achievers. An event-related fMRI design assessed neural activation patterns during post-training WCST performance. Patients showed a linear trend between set-shifting related activation in the anterior cingulate cortex and learning potential, i.e. increased activation in high-achievers, a trend for increased activation in learners, and no activation in non-retainers compared to controls. In addition, activation in the temporoparietal cortex was highest in patients classified as learners, whereas in non-retainers activation was increased in the inferior frontal gyrus compared to controls and high-achieving patients. These results emphasize the relevance of the ACC's neural integrity in learning set-shifting strategies for patients with schizophrenia. Also, our results support the hypothesis that compensatory neural activation in patients with schizophrenia helps them to catch up with healthy controls on cognitive tasks. (Contains 2 tables and 2 figures.)

A high prevalence of deficits in explicit learning has been reported for schizophrenic patients, but it is less clear whether these patients are impaired in implicit learning. Deficits in implicit learning indicative of a fronto-striatal dysfunction have been reported using a serial reaction-time task (SRT), but the impact of typical neuroleptic medication and chronicity remains controversial. The present study compared 37 patients with first-episode schizophrenia treated with atypical neuroleptics and 37 healthy matched control participants on two sequence learning tasks: a modified SRT for implicit sequence learning and a serial generation task (SGT) for explicit sequence learning. The two tasks were designed to be procedurally equivalent, in order to provide better comparability between implicit and explicit performance. Although unaffected in global cognitive functioning, schizophrenic patients were significantly impaired in implicit and explicit sequence learning. Deficient sequence learning in schizophrenic patients was neither related to psychopathology nor to chlorpromazine equivalent daily dosage. As performance was impaired even though patients were exclusively treated with atypical neuroleptics, the present findings concur with converging evidence of a sequence learning deficit inherent in schizophrenia. This deficit would be consistent with a fronto-striatal dysfunction and might constitute a crucial factor for the acquisition of new information.

It has been argued that critical functions of the human amygdala are to modulate the moment-to-moment vigilance level and to enhance the processing and the consolidation of memories of emotionally arousing material. In this functional magnetic resonance study, pictures of human faces bearing fearful, angry, and happy expressions were presented to nine healthy volunteers using a backward masking procedure based on neutral facial expression. Activation of the left and right amygdala in response to the masked fearful faces (compared to neutral faces) was significantly correlated with the number of fearful faces detected. In addition, right but not left amygdala activation in response to the masked angry faces was significantly related to the number of angry faces detected. The present findings underscore the role of the amygdala in the detection and consolidation of memory for marginally perceptible threatening facial expression.

We describe the validation of a serum-based test developed by Rules-Based Medicine which can be used to help confirm the diagnosis of schizophrenia. In preliminary studies using multiplex immunoassay profiling technology, we identified a disease signature comprised of 51 analytes which could distinguish schizophrenia (n = 250) from control (n = 230) subjects. In the next stage, these analytes were developed as a refined 51-plex immunoassay panel for validation using a large independent cohort of schizophrenia (n = 577) and control (n = 229) subjects. The resulting test yielded an overall sensitivity of 83% and specificity of 83% with a receiver operating characteristic area under the curve (ROC-AUC) of 89%. These 51 immunoassays and the associated decision rule delivered a sensitive and specific prediction for the presence of schizophrenia in patients compared to matched healthy controls.