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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., (© 2023. The Author(s).)

The role of the amygdala in the experience of emotional states and stress is well established. Connections from the amygdala to the hypothalamus activate the hypothalamic-pituitaryadrenal (HPA) axis and the cortisol response. Previous studies have failed to find consistent whole amygdala volume changes in Major Depressive Disorder (MDD), but differences may exist at the smaller substructural level of the amygdala nuclei. High-resolution T1 and T2-weighted-fluid-attenuated inversion recovery MRIs were compared between 80 patients with MDD and 83 healthy controls (HC) using the automated amygdala substructure module in FreeSurfer 6.0. Volumetric assessments were performed for individual nuclei and three anatomico-functional composite groups of nuclei. Salivary cortisol awakening response (CAR), as a measure of HPA responsivity, was measured in a subset of patients. The right medial nucleus volume was larger in MDD compared to HC (p = 0.002). Increased right-left volume ratios were found in MDD for the whole amygdala (p = 0.004), the laterobasal composite (p = 0.009) and in the central (p = 0.003) and medial (p = 0.014) nuclei. The CAR was not significantly different between MDD and HC. Within the MDD group the left corticoamygdaloid transition area was inversely correlated with the CAR, as measured by area under the curve (AUCg) (p ≤ 0.0001). In conclusion, our study found larger right medial nuclei volumes in MDD compared to HC and relatively increased right compared to left whole and substructure volume ratios in MDD. The results suggest that amygdala substructure volumes may be involved in the pathophysiology of depression., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

We present the work towards strengthening the security of DNA-sequencing functionality of future bioinformatics systems against bio-computing attacks. Recent research has shown how using common tools, a perpetrator can synthesize biological material, which upon DNA-analysis opens a cyber-backdoor for the perpetrator to hijack control of a computational resource from the DNA-sequencing pipeline. As DNA analysis finds its way into practical everyday applications, the threat of bio-hacking increases. Our wetlab experiments establish that malicious DNA can be synthesized and inserted into E. coli, a common contaminant. Based on that, we propose a new attack, where a hacker to reach the target hides the DNA with malicious code on common surfaces (e.g., lab coat, bench, rubber glove). We demonstrated that the threat of bio-hacking can be mitigated using dedicated input control techniques similar to those used to counter conventional injection attacks. This article proposes to use genetic similarity of biological samples to identify material that has been generated for bio-hacking. We considered freely available genetic data from 506 mammary, lymphocyte and erythrocyte samples that have a bio-hacking code inserted. During the evaluation we were able to detect up to 95% of malicious DNAs confirming suitability of our method.

The Stria medullaris (SM) Thalami is a discrete white matter tract that directly connects frontolimbic areas to the habenula, allowing the forebrain to influence midbrain monoaminergic output. Habenular dysfunction has been shown in various neuropsychiatric conditions. However, there exists a paucity of research into the habenula's principal afferent tract, the SM. Diffusion-weighted tractography may provide insights into the properties of the SM in vivo , opening up investigation of this tract in conditions of monoamine dysregulation such as depression, schizophrenia, addiction and pain. We present a reliable method for reconstructing the SM using diffusion-weighted imaging, and examine the effects of age and gender on tract diffusion metrics. We also investigate reproducibility of the method through inter-rater comparisons. In consultation with neuroanatomists, a Boolean logic gate protocol was developed for use in ExploreDTI to extract the SM from constrained spherical deconvolution based whole brain tractography. Particular emphasis was placed on the reproducibility of the tract, attention to crossing white matter tract proximity and anatomical consistency of anterior and posterior boundaries. The anterior commissure, pineal gland and mid point of the thalamus were defined as anatomical fixed points used for reconstruction. Fifty subjects were scanned using High Angular Resolution Diffusion Imaging (HARDI; 61 directions, b -value 1500 mm 3 ). Following constrained spherical deconvolution whole brain tractography, two independent raters isolated the SM. Each output was checked, examined and cleaned for extraneous streamlines inconsistent with known anatomy of the tract by the rater and a neuroanatomist. A second neuroanatomist assessed tracts for face validity. The SM was reconstructed with excellent inter-rater reliability for dimensions and diffusion metrics. Gender had no effect on the dimensions or diffusion metrics, however radial diffusivity (RD) showed a positive correlation with age. Reliable identification and quantification of diffusion metrics of the SM invites further exploration of this key habenula linked structure in neuropsychiatric disorders such as depression, anxiety, chronic pain and addiction. The accurate anatomical localization of the SM may also aid preoperative stereotactic localization of the tract for deep brain stimulation (DBS) treatment.

The gene for the glucocorticoid receptor regulator FK506 binding protein 5 (FKBP5) plays a role for risk, response to treatment, and changes in brain areas in major depressive disorder (MDD). Chronic stress is associated with lower methylation of FKBP5. Our aim was to investigate whether methylation of FKBP5 reflected exposure to childhood adversity in MDD and controls and whether it was associated with structure and function of emotional processing regions. FKBP5 intron 7 GR response element region methylation and rs1360780 allelic status were assessed from whole blood in 56 MDD adults and 50 controls. Using magnetic resonance imaging, we assessed gray matter concentration of selected areas and their function during valence recognition of emotional images. Childhood adversity was investigated using the Childhood Trauma Questionnaire. In MDD patients carrying the high-risk T allele of rs1360780, lower methylation of FKBP5 was predicted by childhood adversity (F=4.95, p=0.04). In all participants, lower FKBP5 intron methylation levels were associated with reduced gray matter concentration in the inferior frontal orbital gyrus bilaterally (Wald chi-square=11.93, p FDR <0.01) and, in MDD, with its bilaterally higher activation during valence recognition (Wald chi-square=5.58, p=0.02). Activation of this region, regardless of side, was found to be lower in MDD compared to controls (Wald chi-square=3.88, p=0.049) and to be inversely correlated with depression severity (Wald chi-square=4.65, p=0.03). Our findings support the hypothesis that, in genetically predisposed individuals carrying a high-risk variant of the gene, childhood maltreatment might induce demethylation of FKBP5. This is in turn associated with structural and functional changes in the inferior frontal orbital gyrus, a relevant area for the clinical symptoms of MDD.

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory systems is a consistent finding in patients with Major Depressive Disorder (MDD). Cortisol is often assessed by measurement of the cortisol awakening response (CAR) and/or diurnal cortisol levels. Some methods of cortisol measurement overestimate cortisol concentration due to detection of other glucocorticoids including the relatively inert cortisone, therefore this study aimed to assess the presence of both cortisol and cortisone, and the cortisol-cortisone catalyzing enzyme 11β-hydroxysteroiddehydrogenase type 1 (11β-HSD1), in depressed patients and controls. Because the HPA axis is known to regulate the body's immune system, relationships between measures of cytokines and cortisol were also assessed. Saliva samples were collected from 57 MDD patients and 40 healthy controls at five post-wakening time points (0, +30, +60, +720 and +750 min). Glucocorticoid concentrations were measured by liquid chromatography mass spectrometry. Whole blood mRNA expression of several inflammatory markers was measured by quantitative polymerase chain reaction. This study replicated the common finding of elevated morning cortisol and reduced CAR reactivity in MDD and found no differences in cortisone or 11β-HSD1 mRNA measures. There was a negative association between interleukin 1-β (IL-1β) mRNA and morning cortisol reactivity within the depressed group, indicating that dysregulation of the HPA axis and immune system may be interconnected., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.