Consistent evidence that brain serotonin 2A receptor binding is positively associated with personality-based risk markers of depression.

Background: Using [F]altanserin, a serotonin 2A receptor (5-HTR) antagonist Positron Emission Tomography (PET) tracer, a positive association between cortical 5-HTR binding and the inward-directed facets of neuroticism has been demonstrated in healthy individuals. Psilocybin, a 5-HTR agonist, shows promise for the treatment of depression, reducing neuroticism and mood symptoms potentially via hypothalamic-pituitary-adrenal (HPA) modulation. 5-HTR and neuroticism are both modulated by HPA axis function.

DNA methylation of serotonin genes as predictive biomarkers of antidepressant treatment response.

Selective serotonin reuptake inhibitors (SSRI) are frequently ineffective in treating depressive episodes and biomarkers are needed to optimize antidepressant treatment outcomes. DNA methylation levels of serotonin transporter (SLC6A4) and tryptophan hydroxylase 2 genes (TPH2) have been suggested to predict antidepressant clinical outcomes but their applicability remains uncertain. In this study, we: 1) evaluated SLC6A4/TPH2 methylation biomarker potential for predicting clinical outcomes after escitalopram treatment; 2) evaluated whether changes in SLC6A4/TPH2 methylation are informative of treatment mechanisms.

Whole-brain turbulent dynamics predict responsiveness to pharmacological treatment in major depressive disorder.

Depression is a multifactorial clinical syndrome with a low pharmacological treatment response rate. Therefore, identifying predictors of treatment response capable of providing the basis for future developments of individualized therapies is crucial. Here, we applied model-free and model-based measures of whole-brain turbulent dynamics in resting-state functional magnetic resonance imaging (fMRI) in healthy controls and unmedicated depressed patients.

Effect of Antidepressant Treatment on 5-HT Receptor Binding and Associations With Clinical Outcomes and Verbal Memory in Major Depressive Disorder.

Background: Brain serotonin 4 receptor (5-HTR) levels are lower in untreated patients with major depressive disorder (MDD) and are linked to verbal memory. Here, we investigated the relationship between 5-HTR levels, clinical outcomes, and cognitive function in patients with MDD who initiated selective serotonin reuptake inhibitor drug treatment.

Methods: Ninety patients with moderate to severe depression underwent molecular brain imaging to measure 5-HTR binding prior to antidepressant treatment with escitalopram.

The effect of antidepressant treatment on blood BDNF levels in depressed patients: A review and methodological recommendations for assessment of BDNF in blood.

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder and a leading cause of disability worldwide. Brain-derived neurotrophic factor (BDNF), a signaling protein responsible for promoting neuroplasticity, is highly expressed in the central nervous system but can also be found in the blood. Since impaired brain plasticity is considered a cornerstone in the pathophysiology of MDD, measurement of BDNF in blood has been proposed as a potential biomarker in MDD.

Brain network changes and cognitive function after cardiac arrest.

Survival rates after out-of-hospital cardiac arrest have improved over the past two decades. Despite this progress, long-term cognitive impairment remains prevalent even in those with early recovery of consciousness after out-of-hospital cardiac arrest; however, little is known about the determinants and underlying mechanisms. We utilized the REcovery after cardiac arrest surVIVAL cohort of out-of-hospital cardiac arrest survivors who fully regained consciousness to correlate cognition measurements with brain network changes using resting-state functional MRI and the Montreal Cognitive Assessment at hospital discharge and a comprehensive neuropsychological assessment at three-month follow-up.

An In Vivo High-Resolution Human Brain Atlas of Synaptic Density.

Synapses are fundamental to the function of the central nervous system and are implicated in a number of brain disorders. Despite their pivotal role, a comprehensive imaging resource detailing the distribution of synapses in the human brain has been lacking until now. Here, we employ high-resolution PET neuroimaging in healthy humans (17F/16M) to create a 3D atlas of the synaptic marker Synaptic Vesicle glycoprotein 2A (SV2A).

Development of Peptide-Based Probes for Molecular Imaging of the Postsynaptic Density in the Brain.

The postsynaptic density (PSD) comprises numerous scaffolding proteins, receptors, and signaling molecules that coordinate synaptic transmission in the brain. Postsynaptic density protein 95 (PSD-95) is a master scaffold protein within the PSD and one of its most abundant proteins and therefore constitutes a very attractive biomarker of PSD function and its pathological changes. Here, we exploit a high-affinity inhibitor of PSD-95, AVLX-144, as a template for developing probes for molecular imaging of the PSD.

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo.

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( = 1,384) of medication-free individuals with first-episode and recurrent MDD ( = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( = 699).

Arterial Spin Labeling Magnetic Resonance Imaging for Acute Disorders of Consciousness in the Intensive Care Unit.

Background: To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission tomography. However, this is not feasible in the intensive care unit (ICU). Cerebral blood flow (CBF) assessed by arterial spin labeling magnetic resonance imaging (ASL-MRI) could serve as a proxy for brain metabolism and reflect consciousness levels in acute DoC.

Rumination in patients with major depressive disorder before and after antidepressant treatment.

Background: Rumination is a maladaptive response to distress characteristic of Major Depressive Disorder (MDD). It is unclear to what degree rumination is associated with depression severity prior to treatment and how it responds to antidepressant treatment. Therefore, we evaluated the association between rumination and depression severity in 92 untreated patients with MDD and explored the changes in rumination after initiation of antidepressant medication.

Stable neural underpinnings of emotional cognition subgroups in patients newly diagnosed with bipolar disorder: A prospective fMRI study.

Objectives: This study aimed to investigate the neural underpinnings of emotional cognition subgroups in recently diagnosed patients with bipolar disorder (BD) and change over time over a 15-month follow-up period.

Methods: Patients and healthy controls (HC) underwent emotional and nonemotional cognitive assessments and functional magnetic resonance imaging (fMRI) at the baseline (BD n = 87; HC n = 65) and at 15-month follow-up (BD n = 44; HC n = 38). Neural activity during emotion reactivity and regulation in response to aversive pictures was assessed during fMRI.

Perivascular space diffusivity and brain microstructural measures are associated with circadian time and sleep quality.

The glymphatic system is centred around brain cerebrospinal fluid flow and is enhanced during sleep, and the synaptic homeostasis hypothesis proposes that sleep acts on brain microstructure by selective synaptic downscaling. While so far primarily studied in animals, we here examine in humans if brain diffusivity and microstructure is related to time of day, sleep quality and cognitive performance. We use diffusion weighted images from 916 young healthy individuals, aged between 22 and 37 years, collected as part of the Human Connectome Project to assess diffusion tensor image analysis along the perivascular space index, white matter fractional anisotropy, intra-neurite volume fraction and extra-neurite mean diffusivity.

Multimodal brain age prediction using machine learning: combining structural MRI and 5-HT2AR PET-derived features.

To better assess the pathology of neurodegenerative disorders and the efficacy of neuroprotective interventions, it is necessary to develop biomarkers that can accurately capture age-related biological changes in the human brain. Brain serotonin 2A receptors (5-HT2AR) show a particularly profound age-related decline and are also reduced in neurodegenerative disorders, such as Alzheimer's disease. This study investigates whether the decline in 5-HT2AR binding, measured in vivo using positron emission tomography (PET), can be used as a biomarker for brain aging.

Longitudinal changes in resting-state functional connectivity as markers of vulnerability or resilience in first-degree relatives of patients with bipolar disorder.

Background: There is a significant contribution of genetic factors to the etiology of bipolar disorder (BD). Unaffected first-degree relatives of patients (UR) with BD are at increased risk of developing mental disorders and may manifest cognitive impairments and alterations in brain functional and connective dynamics, akin to their affected relatives.

Methods: In this prospective longitudinal study, resting-state functional connectivity was used to explore stable and progressive markers of vulnerability i.

Characterizing the binding of TC-5619 and encenicline on the alpha7 nicotinic acetylcholine receptor using PET imaging in the pig.

The alpha7 nicotinic acetylcholine receptor (α7-nAChR) has has long been considered a promising therapeutic target for addressing cognitive impairments associated with a spectrum of neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, despite this potential, clinical trials employing α7-nAChR (partial) agonists such as TC-5619 and encenicline (EVP-6124) have fallen short in demonstrating sufficient efficacy. We here investigate the target engagement of TC-5619 and encenicline in the pig brain by use of the α7-nAChR radioligand C-NS14492 to characterize binding both with autoradiography and occupancy using positron emission tomography (PET).

Comorbid physical health burden of serious mental health disorders in 32 European countries.

Background: Mental health disorders (MHDs) are associated with physical health disparities, but underlying excess risk and health burden have not yet been comprehensively assessed.

Objective: To assess the burden of comorbid physical health conditions (PHCs) across serious MHDs in Europe.

Methods: We estimated the relative prevalence risk of PHCs associated with alcohol use disorders (AUD), bipolar disorder (BD), depressive disorders (DD) and schizophrenia (SZ) across working-age populations of 32 European countries in 2019 based on a targeted literature review.

Effects of erythropoietin on cognitive impairment and prefrontal cortex activity across affective disorders: A randomized, double-blinded, placebo-controlled trial.

Background: Persistent cognitive impairment is frequent across bipolar disorder (BD) and major depressive disorder (MDD), highlighting an urgent need for pro-cognitive treatments.

Aim: This study investigated effects of erythropoietin (EPO) on cognitive impairment and dorsal prefrontal cortex (dPFC) activity in affective disorders.

Methods: In this randomized, double-blinded, placebo-controlled trial, cognitively impaired patients with remitted BD or MDD received 1 weekly recombinant human EPO (40,000 IU/mL) or saline infusion for a 12-week period.

Functional brain responses to emotional faces after three to five weeks of intake of escitalopram in healthy individuals: a double-blind, placebo-controlled randomised study.

Short-term intake of selective serotonin reuptake inhibitors (SSRIs) modulates threat-related amygdala responses in healthy individuals. However, how SSRI intake over a clinically relevant time period modulates threat-related amygdala responses is less clear. In a semi-randomised, double-blind, placebo-controlled study of 64 healthy individuals (SSRI n = 32, placebo n = 32), we examined the effect of 3-5 weeks of SSRI escitalopram (20 mg daily) on brain response to angry, fearful and neutral faces using BOLD fMRI.