Current neurobiological models of post-traumatic stress disorder (PTSD) assume excessive medial frontal activation and hypoactivation of cortico-limbic regions as neural markers of post-traumatic dissociation. Script-driven imagery is an established experimental paradigm that is used to study acute dissociative reactions during trauma exposure. However, there is a scarcity of experimental research investigating neural markers of dissociation; findings from existing script-driven neuroimaging studies are inconsistent and based on small sample sizes.

The current aim was to identify the neural correlates of acute post-traumatic dissociation by employing the script-driven imagery paradigm in combination with functional magnetic resonance imaging.

Functional neuroimaging data was acquired in 51 female patients with PTSD with a history of interpersonal childhood trauma. Blood-oxygen-level-dependent response during the traumatic (versus neutral) autobiographical memory recall was analysed, and the derived activation clusters were correlated with dissociation measures.

During trauma recall, enhanced activation in the cerebellum, occipital gyri, supramarginal gyrus and amygdala was identified. None of the derived clusters correlated significantly with dissociative symptoms, although patients reported increased levels of acute dissociation following the paradigm.

The present study is one of the largest functional magnetic resonance imaging investigations of dissociative neural biomarkers in patients with PTSD undergoing experimentally induced trauma confrontation to elicit symptom-specific brain reactivity. In light of the current reproducibility crisis prominent in neuroimaging research owing to costly and time-consuming data acquisition, the current (null) findings highlight the difficulty of extracting reliable neurobiological biomarkers for complex subjective experiences such as dissociation.

The multiplicity and complexity of the neuronal connections in the central nervous system make it difficult to disentangle circuits that play an essential role in the development or treatment of (neuro)psychiatric disorders. By choosing the evolutionary development of the forebrain as a starting point, a certain order in the connections can be created. The dorsal diencephalic connection (DDC) system can be applied for the development of biomarkers that can predict treatment response.

After providing a brief introduction to the theory, we examined neuroanatomical publications on the connectivity of the DDC system. We then searched for neurochemical components that are specific for the habenula.

The best strategy to find biomarkers that reflect the function of the habenular connection is to use genetic variants of receptors, transporters or enzymes specific to this complex. By activating these with probes and measuring the response in people with different functional genotypes, the usefulness of biomarkers can be assessed.

The most promising biomarkers in this respect are those linked to activation or inhibition of the nicotine receptor, dopamine D4 receptor, μ-opioid receptor and also those of the functioning of habenular glia cells (astrocytes and microglia).

Higher inflammation has been linked to poor physical and mental health outcomes, and mortality, but few studies have rigorously examined whether changes in perceived stress and depressive symptoms are associated with increased inflammation within family caregivers and non-caregivers in a longitudinal design.

Longitudinal Study.

REasons for Geographic And Racial Differences in Stroke cohort study.

Participants included 239 individuals who were not caregivers at baseline but transitioned to providing substantial and sustained caregiving over time. They were initially matched to 241 non-caregiver comparisons on age, sex, race, education, marital status, self-rated health, and history of cardiovascular disease. Blood was drawn at baseline and approximately 9.3 years at follow-up for both groups.

Perceived Stress Scale, Center for Epidemiological Studies-Depression, inflammatory biomarkers, including high-sensitivity C-reactive protein, D dimer, tumor necrosis factor alpha receptor 1, interleukin (IL)-2, IL-6, and IL-10 taken at baseline and follow-up.

Although at follow-up, caregivers showed significantly greater worsening in perceived stress and depressive symptoms compared to non-caregivers, there were few significant associations between depressive symptoms or perceived stress on inflammation for either group. Inflammation, however, was associated with multiple demographic and health variables, including age, race, obesity, and use of medications for hypertension and diabetes for caregivers and non-caregivers.

These findings illustrate the complexity of studying the associations between stress, depressive symptoms, and inflammation in older adults, where these associations may depend on demographic, disease, and medication effects. Future studies should examine whether resilience factors may prevent increased inflammation in older caregivers.

This study seeks to identify Alzheimer’s and related dementias (ADRD) biomarkers associated with postoperative delirium (POD) via meta-analysis.

A comprehensive search was conducted. Studies met the following inclusion criteria: >18 years of age, identified POD with standardized assessment, and biomarker measured in the AT(N)-X (A = amyloid, T = tau, (N)=neurodegeneration, X-Other) framework. Exclusion criteria: focus on prediction of delirium, delirium superimposed on dementia, other neurologic or psychiatric disorders, or terminal delirium. Reviewers extracted and synthesized data for the meta-analysis.

Meta-analysis.

Patients with POD.

Primary outcome: association between POD and ATN-X biomarkers. Secondary outcomes involved sample heterogeneity.

28 studies were included in this meta-analysis. Studies focused on inflammatory and neuronal injury biomarkers; there were an insufficient number of studies for amyloid and tau biomarker analysis. Two inflammatory biomarkers (IL-6, and CRP) showed a significant relationship with POD (IL-6 n = 10, standardized mean difference (SMD): 0.53, 95% CI: 0.36–0.70; CRP n = 14, SMD: 0.53, 95% CI: 0.33–0.74). Two neuronal injury biomarkers (blood-based S100B and NfL) were positively associated with POD (S100B n = 5, SMD: 0.40, 95% CI: 0.11–0.69; NFL n = 2, SMD: 0.93, 95% CI: 0.28–1.57). Of note, many analyses were impacted by significant study heterogeneity.

This meta-analysis identified an association between certain inflammatory and neuronal injury biomarkers and POD. Future studies will need to corroborate these relationships and include amyloid and tau biomarkers in order to better understand the relationship between POD and ADRD.

Major depressive disorder (MDD) is the main cause of disability worldwide, its outcome is poor, and its underlying mechanisms deserve a better understanding. Recently, peripheral acetyl-l-carnitine (ALC) has been shown to be lower in patients with major depressive episodes (MDEs) than in controls. l-Carnitine is involved in mitochondrial function and ALC is its short-chain acetyl-ester. Our first aim was to compare the plasma levels of l-carnitine and ALC, and the l-carnitine/ALC ratio in patients with a current MDE and healthy controls (HCs). Our second aim was to assess their changes after antidepressant treatment.

l-Carnitine and ALC levels and the carnitine/ALC ratio were measured in 460 patients with an MDE in a context of MDD and in 893 HCs. Depressed patients were re-assessed after 3 and 6 months of antidepressant treatment for biology and clinical outcome.

As compared to HC, depressed patients had lower ALC levels (p < 0.00001), higher l-carnitine levels (p < 0.00001) and higher l-carnitine/ALC ratios (p < 0.00001). ALC levels increased [coefficient: 0.18; 95% confidence interval (CI) 0.12–0.24; p < 0.00001], and l-carnitine levels (coefficient: −0.58; 95% CI −0.75 to −0.41; p < 0.00001) and l-carnitine/ALC ratios (coefficient: −0.41; 95% CI −0.47 to −0.34; p < 0.00001), decreased after treatment. These parameters were completely restored after 6 months of antidepressant. Moreover, the baseline l-carnitine/ALC ratio predicted remission after 3 months of treatment (odds ratio = 1.14; 95% CI 1.03–1.27; p = 0.015).

Our data suggest a decreased mitochondrial metabolism of l-carnitine into ALC during MDE. This decreased mitochondrial metabolism is restored after a 6-month antidepressant treatment. Moreover, the magnitude of mitochondrial dysfunction may predict remission after 3 months of antidepressant treatment. New strategies targeting mitochondria should be explored to improve treatments of MDD.

The identification of potential biomarkers is crucial to improve the management and treatment of mood disorders. Glycogen synthase kinase-3 (GSK-3) is a multifunctional enzyme with an important role in the etiology of mood disorders. Recent findings suggested GSK-3 as a putative biomarker in mood disorders.

The aims of the study are: - to evaluate GSK3 as potential biomarker for differential diagnosis (MDD and BD); - to analyze the regulation of GSK3 by psychopharmacological treatments.

Patients included fulfill the following criteria: (a) principal diagnosis of MDD or BD (DSM-5); (b) age ≥ 18 years; (c) drug-free for at least 4 weeks before the inclusion. For each patient included a healthy control is enrolled, matched by gender and age. All included subjects at the study entry point (t0) are assessed through: - semistructured clinical interview and clinical rating scales (Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale; Young Mania Rating Scale, Clinical Global Impression) - blood draw, to measure GSK-3 levels Patients with MDD or BD are assessed again after 1 week (T1) and after 2 month (T2) of specific pharmacological treatment.

So far, we enrolled 16 patients and 16 healthy controls. The enrollment is still ongoing.

We expect to find GSK-3 levels differently expressed between healthy controls, patients with DDM and patients with BD. This finding would be crucial as it could contribute to the improvement of differential diagnosis. Moreover, we expect to observe a change in GSK-3 levels after psychopharmacological treatments.

Depression or Major Depressive Disorder (MDD) is the most prevalent psychiatric disorder and a leading cause of disability worldwide. Currently affecting around 300 million people worldwide, depression is a major clinical, emotional, and socioeconomic strain for society. There is a growing interest in the biological underpinnings of depression, which are reflected by altered levels of biomarkers.

The aim of the study was to present an up-to-date review of potential MDD biomarkers.

PubMed, Scopus, and Web of Science databases were searched.

Enhanced inflammation has been reported in MDD, as reflected by increased concentrations of inflammatory markers – interleukin-6, C-reactive protein, tumor necrosis factor-α, and soluble interleukin-2 receptor. Dysregulation of the hypothalamus-pituitary-adrenals axis, along with increased cortisol levels, have also been reported in MDD. Oxidative and nitrosative stress also plays an important role in the pathophysiology of MDD. Notably, increased levels of lipid peroxidation markers are characteristic of MDD. Kynurenine metabolites, increased glutamate and decreased total cholesterol are also features of MDD. Finally, alterations in growth factors, with a significant decrease in brain-derived neurotrophic factor and an increase in fibroblast growth factor-2 and insulin-like growth factor-1 concentrations have also been found in MDD.

A group of substances holds promise as reliable biomarkers for MDD. However, biomarker research in depression faces many difficulties, such as insufficient understanding of MDD etiopathogenesis, substantial heterogeneity of the disorder and low specificity of biomarkers. The construction of biomarker panels and their evaluation with use of new technologies may have the potential to overcome the above mentioned obstacles.

No significant relationships.

There is growing evidence that generalised joint hypermobility (GJH) is associated with several psychiatric conditions. There are no previous studies on adult ADHD.

To evaluate, in a large Swedish sample, if generalised joint hypermobility and adult ADHD are associated.

431 adults with ADHD and 417 controls were included. GJH was assessed by the Beighton Score, a physical examination, and the 5PQ, a self-report screening tool. Exploratively, reported musculoskeletal symptoms and abnormal skin manifestations suggestive of symptomatic GJH (e.g. Ehlers-Danlos syndrome), were assessed to differentiate this group from the general GJH group. Logistic regressions determined the influence of an ADHD diagnosis and known covariates (age, sex and ethnicity) on GJH and symptomatic GJH respectively.

ADHD was associated to GJH, as defined by the Beighton Score and the 5PQ, with adjusted odds ratios of 4.65 (CI 95% 3.01-7.18, p<.005) and 1.86 (CI 95% 1.39-2.48, p<.005), respectively. Likewise, ADHD and symptomatic GJH were associated with adjusted odds ratios of 6.94 (CI 95% 4.05-11.89, p<.005) and 2.66 (CI 95% 1.94-3.66, p<.005).

GJH and adult ADHD are associated conditions. Symptomatic GJH, defined as additional symptoms of pain and/or skin manifestations, has a considerably stronger link to adult ADHD than unspecific GJH has. GJH may represent a marker of an underlying systemic disorder with physical manifestations in connective tissue as well as behavioural manifestations including hyperactivity, impulsiveness and inattentiveness. Future studies should investigate if this represents a novel subtype of ADHD and if symptomatic GJH affects the ADHD management.

No significant relationships.