Amygdala structural and functional reorganization as an indicator of affective dysfunction in patients with tinnitus.

The aim of this study was to systematically investigate structural and functional alterations in amygdala subregions using multimodal magnetic resonance imaging (MRI) in patients with tinnitus with or without affective dysfunction. Sixty patients with persistent tinnitus and 40 healthy controls (HCs) were recruited. Based on a questionnaire assessment, 26 and 34 patients were categorized into the tinnitus patients with affective dysfunction (TPAD) and tinnitus patients without affective dysfunction (TPWAD) groups, respectively. MRI-based measurements of gray matter volume, fractional anisotropy (FA), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC) were conducted within 14 amygdala subregions for intergroup comparisons. Associations between the MRI properties and clinical characteristics were estimated via partial correlation analyses. Compared with that of the HCs, the TPAD and TPWAD groups exhibited significant structural and functional changes, including white matter integrity (WMI), fALFF, ReHo, DC, and FC alterations, with more pronounced WMI changes in the TPAD group, predominantly within the left auxiliary basal or basomedial nucleus (AB/BM), right central nucleus, right lateral nuclei (dorsal portion), and left lateral nuclei (ventral portion containing basolateral portions). Moreover, the TPAD group exhibited decreased FC between the left AB/BM and left middle occipital gyrus and right superior frontal gyrus (SFG), left basal nucleus and right SFG, and right lateral nuclei (intermediate portion) and right SFG. In combination, these amygdalar alterations exhibited a sensitivity of 65.4% and specificity of 96.9% in predicting affective dysfunction in patients with tinnitus. Although similar structural and functional amygdala remodeling were observed in the TPAD and TPWAD groups, the changes were more pronounced in the TPAD group. These changes mainly involved alterations in functionality and white matter microstructure in various amygdala subregions; in combination, these changes could serve as an imaging-based predictor of emotional disorders in patients with tinnitus.

Neurobiological correlates of religious coping among older adults with and without mood disorders: An exploratory study.

In this study, 32 older adults with and without mood disorders completed resting-state functional Magnetic Resonance Imaging and measures of demographics, spirituality/religion, positive and negative religious coping, and depression. Group Independent Component Analysis identified and selected three a priori resting state networks [cingulo-opercular salience (cSN), central executive (CEN) and Default Mode Networks (DMN)] within the Triple Network Mode. We investigated associations of religious coping with within- and between-network connectivity, controlling for age. Insular connectivity within the cSN was associated with negative religious coping. Religious coping was associated with anti-correlation between the DMN and CEN even when controlling for depression.

Neuropathic pain, mood, and stress-related disorders: A literature review of comorbidity and co-pathogenesis.

Neuropathic pain can be caused by multiple factors, and its prevalence can reach 10% of the global population. It is becoming increasingly evident that limited or short-lasting response to treatments for neuropathic pain is associated with psychological factors, which include psychiatric comorbidities known to affect quality of life. It is estimated that 60% of patients with neuropathic pain also experience depression, anxiety, and stress symptoms. Altered mood, including stress, can be a consequence of several painful conditions but can also favor pain chronicization when preexisting. Despite the apparent tight connection between clinical pain and mood/stress disorders, the exact physiological mechanisms remain unclear. This review aims to provide an overview of state-of-the-art research on the mechanisms of pain related to the pathophysiology of depression, anxiety, and stress disorders.

The VLPFC-Engaged Voluntary Emotion Regulation: Combined TMS-fMRI Evidence for the Neural Circuit of Cognitive Reappraisal.

A clear understanding of the neural circuit underlying emotion regulation (ER) is important for both basic and translational research. However, a lack of evidence based on combined neuroimaging and neuromodulation techniques calls into question (1) whether the change of prefrontal-subcortical activity intrinsically and causally contributes to the ER effect; and (2) whether the prefrontal control system directly modulates the subcortical affective system. Accordingly, we combined fMRI recordings with transcranial magnetic stimulation (TMS) to map the causal connections between the PFC and subcortical affective structures (amygdala and insula). A total of 117 human adult participants (57 males and 60 females) were included in the study. The results revealed that TMS-induced ventrolateral PFC (VLPFC) facilitation led to enhanced activity in the VLPFC and ventromedial PFC (VMPFC) as well as attenuated activity in the amygdala and insula during reappraisal but not during nonreappraisal (i.e., baseline). Moreover, the activated VLPFC intensified the prefrontal-subcortical couplings via the VMPFC during reappraisal only. This study provides combined TMS-fMRI evidence that downregulating negative emotion involves the prefrontal control system suppressing the subcortical affective system, with the VMPFC serving as a crucial hub within the VLPFC-subcortical network, suggesting an indirect pathway model of the ER circuit. Our findings outline potential protocols for improving ER ability by intensifying the VLPFC-VMPFC coupling in patients with mood and anxiety disorders.SIGNIFICANCE STATEMENT Using fMRI to examine the TMS effect, we uncovered that the opposite neural changes in prefrontal (enhanced) and subcortical (attenuated) regions are not a byproduct of emotion regulation (ER); instead, this prefrontal-subcortical activity per se causally contributes to the ER effect. Furthermore, using TMS to amplify the neural changes within the ER circuit, the "bridge" role of the VMPFC is highlighted under the reappraisal versus nonreappraisal contrast. This "perturb-and-measure" approach overcomes the correlational nature of fMRI data, helping us to identify brain regions that causally support reappraisal (the VLPFC and VMPFC) and those that are modulated by reappraisal (the amygdala and insula). The uncovered ER circuit is important for understanding the neural systems underlying reappraisal and valuable for translational research.

Role of Nociceptin/Orphanin FQ-NOP Receptor System in the Regulation of Stress-Related Disorders.

Nociceptin/orphanin FQ (N/OFQ) is a 17-residue neuropeptide that binds the nociceptin opioid-like receptor (NOP). N/OFQ exhibits nucleotidic and aminoacidics sequence homology with the precursors of other opioid neuropeptides but it does not activate either MOP, KOP or DOP receptors. Furthermore, opioid neuropeptides do not activate the NOP receptor. Generally, activation of N/OFQ system exerts anti-opioids effects, for instance toward opioid-induced reward and analgesia. The NOP receptor is widely expressed throughout the brain, whereas N/OFQ localization is confined to brain nuclei that are involved in stress response such as amygdala, BNST and hypothalamus. Decades of studies have delineated the biological role of this system demonstrating its involvement in significant physiological processes such as pain, learning and memory, anxiety, depression, feeding, drug and alcohol dependence. This review discusses the role of this peptidergic system in the modulation of stress and stress-associated psychiatric disorders in particular drug addiction, mood, anxiety and food-related associated-disorders. Emerging preclinical evidence suggests that both NOP agonists and antagonists may represent a effective therapeutic approaches for substances use disorder. Moreover, the current literature suggests that NOP antagonists can be useful to treat depression and feeding-related diseases, such as obesity and binge eating behavior, whereas the activation of NOP receptor by agonists could be a promising tool for anxiety.

Convergence, preliminary findings and future directions across the four human connectome projects investigating mood and anxiety disorders.

In this paper we provide an overview of the rationale, methods, and preliminary results of the four Connectome Studies Related to Human Disease investigating mood and anxiety disorders. The first study, "Dimensional connectomics of anxious misery" (HCP-DAM), characterizes brain-symptom relations of a transdiagnostic sample of anxious misery disorders. The second study, "Human connectome Project for disordered emotional states" (HCP-DES), tests a hypothesis-driven model of brain circuit dysfunction in a sample of untreated young adults with symptoms of depression and anxiety. The third study, "Perturbation of the treatment resistant depression connectome by fast-acting therapies" (HCP-MDD), quantifies alterations of the structural and functional connectome as a result of three fast-acting interventions: electroconvulsive therapy, serial ketamine therapy, and total sleep deprivation. Finally, the fourth study, "Connectomes related to anxiety and depression in adolescents" (HCP-ADA), investigates developmental trajectories of subtypes of anxiety and depression in adolescence. The four projects use comparable and standardized Human Connectome Project magnetic resonance imaging (MRI) protocols, including structural MRI, diffusion-weighted MRI, and both task and resting state functional MRI. All four projects also conducted comprehensive and convergent clinical and neuropsychological assessments, including (but not limited to) demographic information, clinical diagnoses, symptoms of mood and anxiety disorders, negative and positive affect, cognitive function, and exposure to early life stress. The first round of analyses conducted in the four projects offered novel methods to investigate relations between functional connectomes and self-reports in large datasets, identified new functional correlates of symptoms of mood and anxiety disorders, characterized the trajectory of connectome-symptom profiles over time, and quantified the impact of novel treatments on aberrant connectivity. Taken together, the data obtained and reported by the four Connectome Studies Related to Human Disease investigating mood and anxiety disorders describe a rich constellation of convergent biological, clinical, and behavioral phenotypes that span the peak ages for the onset of emotional disorders. These data are being prepared for open sharing with the scientific community following screens for quality by the Connectome Coordinating Facility (CCF). The CCF also plans to release data from all projects that have been pre-processed using identical state-of-the-art pipelines. The resultant dataset will give researchers the opportunity to pool complementary data across the four projects to study circuit dysfunctions that may underlie mood and anxiety disorders, to map cohesive relations among circuits and symptoms, and to probe how these relations change as a function of age and acute interventions. This large and combined dataset may also be ideal for using data-driven analytic approaches to inform neurobiological targets for future clinical trials and interventions focused on clinical or behavioral outcomes.

The Translational Potential of Non-coding RNAs and Multimodal MRI Data Sets as Diagnostic and Differential Diagnostic Biomarkers for Mood Disorders.

Major Depressive Disorder (MDD) and Bipolar Disorder (BD) have a high prevalence and detrimental socio-economic consequences for the patients and the community. Furthermore, the depressive symptomatology of both disorders is essentially identical, thus rendering the clinical differential diagnosis between the two significantly more difficult considering the concomitant lack of objective biomarkers. Mood disorders are multifactorial disorders the pathophysiology of which includes genetic, epigenetic, neurobiological, neuroimmunological, structural and functional brain alterations, etc. Aberrant genetic variants as well as changed differential expression of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been implicated in the pathophysiology of MDD and BD. MiRNAs as well as lncRNAs have regulatory and modulating functions on protein-- coding gene expression thus influencing the remodeling of the architecture, neurotransmission, immunomodulation, etc. in the Central Nervous System (CNS) which are essential in the development of psychiatric disorders including MDD and BD. Moreover, both shared and distinct structural, connectivity, task-related and metabolic features have been observed via functional magnetic resonance imaging and magnetic resonance spectroscopy, suggesting the possibility of a dimensional continuum between the two disorders instead of a categorical differentiation. Aberrant connectivity within and between the Default Mode Network, the Salience Network, Executive Network, etc. as well as dysfunctional emotion, cognitive and executive processing have been associated with mood disorders. Therefore, the aim of this review is to explore a more multidimensional framework in the scientific research of mood disorders, including epigenetic and neuroimaging data in order to shape an outline for their translational capacity in clinical practice.

Verification of a multi-function closed maze for the detection of affective disorder and spatial cognitive impairment in post-weaning socially isolated rats.

OBJECTIVE: To verify a behavioral device for the detection of learning, memory, and affective disorders in post-weaning socially isolated rats. METHODS: We tested the behavioral changes in post-weaning socially isolated rats using a multi-function closed maze, a self-developed behavioral device, against the classical mood disorder detection method, the IntelliCage system and Morris water maze. RESULTS: In the multifunctional closed maze experiment, the spatial learning and memory ability of post-weaning socially isolated rats decreased, which was consistent with the results of the water maze and IntelliCage system. Furthermore, the behavioral changes in the post-weaning socially isolated rats in the multi-function closed maze test were the same as those of the forced swimming and open field tests, indicating that the rats had depression- and anxiety-like behaviors. CONCLUSION: A multi-function closed maze can detect emotional changes, spatial learning ability, and memory ability.

Hippocampal and rostral anterior cingulate blood flow is associated with affective symptoms in chronic traumatic brain injury.

OBJECTIVE: The purpose of this study was to assess cerebral blood flow (CBF) and its association with self-reported symptoms in chronic traumatic brain injury (TBI). PARTICIPANTS: Sixteen participants with mild to severe TBI and persistent self-reported neurological symptoms, 6 to 72 months post-injury were included. For comparison, 16 age- and gender-matched healthy normal control participants were also included. MAIN MEASURES: Regional CBF and brain volume were assessed using pseudo-continuous Arterial Spin Labeling (PCASL) and T1-weighted data respectively. Cognitive function and self-reported symptoms were assessed in TBI participants using the national institutes of health (NIH) Toolbox Cognition Battery and Patient-Reported Outcome Measurement Information System respectively. Associations between CBF and cognitive function, symptoms were assessed. RESULTS: Global CBF and regional brain volumes were similar between groups, but region of interest (ROI) analysis revealed lower CBF bilaterally in the thalamus, hippocampus, left caudate, and left amygdala in the TBI group. Voxel-wise analysis revealed that CBF in the hippocampus, parahippocampus, rostral anterior cingulate, inferior frontal gyrus, and other temporal regions were negatively associated with self-reported anger, anxiety, and depression symptoms. Furthermore, region of interest (ROI) analysis revealed that hippocampal and rostral anterior cingulate CBF were negatively associated with symptoms of fatigue, anxiety, depression, and sleep issues. CONCLUSION: Regional CBF deficit was observed in the group with chronic TBI compared to the normal control (NC) group despite similar volume of cerebral structures. The observed negative correlation between regional CBF and affective symptoms suggests that CBF-targeted intervention may potentially improve affective symptoms and quality of life after TBI, which needs to be assessed in future studies.

Impact of Confinement in Patients under Long-Term Noninvasive Ventilation during the First Wave of the SARS-CoV-2 Pandemic: A Remarkable Resilience.

BACKGROUND: During the first wave of the SARS-CoV-2 pandemic in Switzerland, confinement was imposed to limit transmission and protect vulnerable persons. These measures may have had a negative impact on perceived quality of care and symptoms in patients with chronic disorders. OBJECTIVES: To determine whether patients under long-term home noninvasive ventilation (LTHNIV) for chronic respiratory failure (CRF) were negatively affected by the 56-day confinement (March-April 2020). METHODS: A questionnaire-based survey exploring mood disturbances (HAD), symptom scores related to NIV (S3-NIV), and perception of health-care providers during confinement was sent to all patients under LTHNIV followed up by our center. Symptom scores and data obtained by ventilator software were compared between confinement and the 56 days prior to confinement. RESULTS: Of a total of 100 eligible patients, 66 were included (median age: 66 years [IQR: 53-74]): 35 (53%) with restrictive lung disorders, 20 (30%) with OHS or SRBD, and 11 (17%) with COPD or overlap syndrome. Prevalence of anxiety (n = 7; 11%) and depressive (n = 2; 3%) disorders was remarkably low. Symptom scores were slightly higher during confinement although this difference was not clinically relevant. Technical data regarding ventilation, including compliance, did not change. Patients complained of isolation and lack of social contact. They felt supported by their relatives and caregivers but complained of the lack of regular contact and information by health-care professionals. CONCLUSIONS: Patients under LTHNIV for CRF showed a remarkable resilience during the SARS-CoV-2 confinement period. Comments provided may be helpful for managing similar future health-care crises.

Clinical Phenotypes of Behavioral Variant Frontotemporal Dementia by Age at Onset.

BACKGROUND: Behavioral variant frontotemporal dementia (bvFTD) is generally considered a young-onset dementia, although age at onset is highly variable. While several studies indicate clinical differences regarding age at onset, no biomarker validated cohort studies with updated clinical criteria have been performed. OBJECTIVE: We aimed to examine behavior, cognition, and mortality over the full age spectrum in a cohort of bvFTD patients with neuroimaging, genetic, or histopathological confirmation and exclusion of positive Alzheimer's disease biomarkers or severe cerebrovascular damage. METHODS: In total, 315 patients with a clinical diagnosis of probable or definite bvFTD were included from the Amsterdam Dementia Cohort and grouped into quartiles by age-at-diagnosis. Neuropsychiatric symptoms and cognitive functioning were assessed with the neuropsychiatric inventory, the geriatric depression scale and a neuropsychological test battery. Data on mortality was obtained from the Dutch municipal register. Associations between age-at-diagnosis and clinical features and mortality risk were examined. RESULTS: Age-at-diagnosis ranged from 26 to 85 years and established quartiles with mean ages of 52±6, 61±2, 66±2, and 74±3 years. In the total sample, 44.4%exceeded an age of 65 years at time of diagnosis. Earlier age-at-diagnosis was associated with more severe behavioral symptoms, while later age-at-diagnosis was associated with more severe memory impairment. Unexpectedly, mortality risk was not associated with age-at-diagnosis. CONCLUSION: In bvFTD, symptom profile is associated with age-at-diagnosis. This should be taken into account with regard to diagnostics, patient management, and trial design. Additionally, based on our sample, the prevalence of late-onset bvFTD is higher than generally thought.

RNA therapeutics for mood disorders: current evidence toward clinical trials.

INTRODUCTION: Mood disorders are severe yet frequent psychiatric disorders worldwide, comprising major depressive disorder (MDD) and bipolar disorders (BD). Their treatment remains poorly effective. Recently, growing evidence for epigenetic mechanisms has emerged. Consequently, a great interest in a novel pharmacological class arose: RNA therapeutics. AREAS COVERED: We conducted a systematic review of RNA therapeutics -antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), short hairpin RNAs (shRNAs), and micro-RNA (miRNA) therapeutics- for the treatment of mood disorders studied in pre-clinical animal models listed in PubMed, in clinical trials registered in ClinicalTrials.gov and available on the market by combining literature search and Food and Drug Administration and European Medicine Agency online databases. Eighteen pre-clinical studies investigated the antidepressant effects of RNA therapeutics. However, even though there is an increasing number of marketing authorizations and clinical trials for the past twenty years, no RNA therapeutic has reached the clinical development pipeline for the treatment of psychiatric disorders yet. EXPERT OPINION: Several promising RNA therapeutics have been tested in pre-clinical studies for MDD, whereas no molecule has been developed for BD. There are several issues to address before reaching clinical development and new challenges include stratifying patient population and predicting therapeutic response.

Irritability in Mood Disorders: Neurobiological Underpinnings and Implications for Pharmacological Intervention.

Feeling irritable is a common experience, both in health and disease. In the context of psychiatric illnesses, it is a transdiagnostic phenomenon that features across all ages, and often causes significant distress and impairment. In mood disorders, irritability is near ubiquitous and plays a central role in diagnosis and yet, despite its prevalence, it remains poorly understood. A neurobiological model of irritability posits that, in children and adolescents, it is consequent upon deficits in reward and threat processing, involving regions such as the amygdala and frontal cortices. In comparison, in adults with mood disorders, the few studies that have been conducted implicate the amygdala, orbitofrontal cortices, and hypothalamus; however, the patterns of activity in these areas are at variance with the findings in youth. These age-related differences seem to extend to the neurochemistry of irritability, with links between increased monoamine transmission and irritability evident in adults, but aberrant levels of, and responses to, dopamine in youth. Presently, there are no specific treatments that have significant efficacy in reducing irritability in mood disorders. However, treatments that hold some potential and warrant further exploration include agents that act on serotonergic and dopaminergic systems, especially as irritability may serve as a prognostic indicator for overall clinical responsiveness to specific medications. Therefore, for understanding and treatment of irritability to advance meaningfully, it is imperative that an accurate definition and means of measuring irritability are developed. To achieve this, it is necessary that the subjective experience of irritability, both in health and illness, is better understood. These insights will inform an accurate, comprehensive, and valid interrogation of the qualities of irritability in health and illness, and allow not only a clinical appreciation of the phenomenon, but also a deeper understanding of its important role within the development and manifestation of mood disorders.

Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status.

The efficacy of standard antidepressants is limited for many patients with mood disorders such as major depressive disorder (MDD) and bipolar depression, underscoring the urgent need to develop novel therapeutics. Both clinical and preclinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders. In particular, rapid reductions in depressive symptoms have been observed in response to subanesthetic doses of the glutamatergic modulator racemic (R,S)-ketamine in individuals with mood disorders. These results have prompted investigation into other glutamatergic modulators for depression, both as monotherapy and adjunctively. Several glutamate receptor-modulating agents have been tested in proof-of-concept studies for mood disorders. This manuscript gives a brief overview of the glutamate system and its relevance to rapid antidepressant response and discusses the existing clinical evidence for glutamate receptor-modulating agents, including (1) broad glutamatergic modulators ((R,S)-ketamine, esketamine, (R)-ketamine, (2R,6R)-hydroxynorketamine [HNK], dextromethorphan, Nuedexta [a combination of dextromethorphan and quinidine], deudextromethorphan [AVP-786], axsome [AXS-05], dextromethadone [REL-1017], nitrous oxide, AZD6765, CLE100, AGN-241751); (2) glycine site modulators (D-cycloserine [DCS], NRX-101, rapastinel [GLYX-13], apimostinel [NRX-1074], sarcosine, 4-chlorokynurenine [4-Cl-KYN/AV-101]); (3) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists (eliprodil [EVT-101], traxoprodil [CP-101,606], rislenemdaz [MK-0657/CERC-301]); (4) metabotropic glutamate receptor (mGluR) modulators (basimglurant, AZD2066, RG1578, TS-161); and (5) mammalian target of rapamycin complex 1 (mTORC1) activators (NV-5138). Many of these agents are still in the preliminary stages of development. Furthermore, to date, most have demonstrated relatively modest effects compared with (R,S)-ketamine and esketamine, though some have shown more favorable characteristics. Of these novel agents, the most promising, and the ones for which the most evidence exists, appear to be those targeting ionotropic glutamate receptors.

Thyroid Function and Mood Disorders: A Mendelian Randomization Study.

Background: Observational studies suggest that even minor variations in thyroid function are associated with the risk of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). However, it is unknown whether these associations are causal or not. We used a Mendelian randomization (MR) approach to investigate causal effects of minor variations in thyrotropin (TSH) and free thyroxine (fT4) levels on MDD and BD risk. Materials and Methods: We performed two-sample MR analyses using data from the largest publicly available genome-wide association studies on normal-range TSH (n = 54,288) and fT4 (n = 49,269) levels, MDD (170,756 cases, 329,443 controls) and BD (20,352 cases, 31,358 controls). Secondary MR analyses investigated the effects of TSH and fT4 levels on specific MDD and BD subtypes. Reverse MR was also performed to assess the effects of MDD and BD on TSH and fT4 levels. Results: There were no associations between genetically predicted TSH and fT4 levels and MDD risk, nor MDD subtypes and minor depressive symptoms. A one standard deviation increase in fT4 levels was nominally associated with an 11% decrease in the overall BD risk (odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.80-0.98, p = 0.022) and a 13% decrease in the BD type 1 risk (OR = 0.87, CI = 0.75-1.00, p = 0.047). In the reverse direction, genetic predisposition to MDD and BD was not associated with TSH nor fT4 levels. Conclusions: Variations in normal-range TSH and fT4 levels have no effects on the risk of MDD and its subtypes, and neither on minor depressive symptoms. This indicates that depressive symptoms should not be attributed to minor variations in thyroid function. Borderline associations with BD and BD type 1 risks suggest that further clinical studies should investigate the effect of thyroid hormone treatment in BD.

The Role of Hypothalamic Inflammation in Diet-Induced Obesity and Its Association with Cognitive and Mood Disorders.

Obesity is often associated with cognitive and mood disorders. Recent evidence suggests that obesity may cause hypothalamic inflammation. Our aim was to investigate the hypothesis that there is a causal link between obesity-induced hypothalamic inflammation and cognitive and mood disorders. Inflammation may influence hypothalamic inter-connections with regions important for cognition and mood, while it may cause dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and influence monoaminergic systems. Exercise, healthy diet, and glucagon-like peptide receptor agonists, which can reduce hypothalamic inflammation in obese models, could improve the deleterious effects on cognition and mood.

Gender-specific approach in psychiatric diseases: Because sex matters.

In both animals and human beings, males and females differ in their genetic background and hormonally driven behaviour and show sex-related differences in brain activity and response to internal and external stimuli. Gender-specific medicine has been a neglected dimension of medicine for long time, and only in the last three decades it is receiving the due scientific and clinical attention. Research has recently begun to identify factors that could provide a neurobiological basis for gender-based differences in health and disease and to point to gonadal hormones as important determinants of male-female differences. Animal studies have been of great help in understanding factors contributing to sex-dependent differences and sex hormones action. Here we review and discuss evidence provided by clinical and animal studies in the last two decades showing gender (in humans) and sex (in animals) differences in selected psychiatric disorders, namely eating disorders (anorexia nervosa, bulimia nervosa, binge eating disorder), schizophrenia, mood disorders (anxiety, depression, obsessive-compulsive disorder) and neurodevelopmental disorders (autism spectrum disorders, attention-deficit/hyperactivity disorder).

Quantitative MRI adds to neuropsychiatric lupus diagnostics.

OBJECTIVE: Attributing neuropsychiatric manifestations to SLE is often challenging. Brain white matter lesions are frequent in SLE at MRI, but their diagnostic role is unclear. Here, we assessed whether white matter lesions count, volume and distribution measurement can help in the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Brain dual-echo and 3D T1-weighted sequences were acquired from 32 patients with SLE and 32 healthy controls with a 3 T-scanner and employed to derive T2-hyperintense lesion volume (T2LV), number (T2LN) and probability maps (LPM) using a semi-automatic local thresholding segmentation technique. NPSLE was classified as per the ACR nomenclature, the Italian Society for Rheumatology algorithm and by clinical impression. Clinical descriptors including the SLE International Collaborating Clinics/ACR damage index (SDI) were also recorded. RESULTS: Higher T2LV were observed in SLE vs healthy controls (P < 0.001) and in NPSLE vs other SLE (P =0.006). Patients with NPSLE also had higher T2LN (P =0.003) compared with other SLE. In SLE, T2LPM revealed a high prevalence of lesions in the splenium of the corpus callosum, right superior longitudinal fasciculus and right corona radiata. T2LV and T2LN correlated with SLE duration (rho = 0.606; P <0.001 and rho = 0.483; P =0.005, respectively) and age (rho = 0.478; P =0.006 and rho = 0.362; P = 0.042, respectively). T2LV also correlated with SDI (rho = 0.352; P =0.048). SLE patients with fatigue had lower T2LN (P =0.038) compared with patients without fatigue. Thresholds of T2LV ≥ 0.423 cm3 or of T2LN ≥ 12 were associated with definite NPSLE and improved the classification of patients with possible NPSLE per clinical impression. CONCLUSION: Brain white matter lesions (WML) quantitation adds to NPSLE diagnostics.

Induced affective states do not modulate effort avoidance.

Recent research reveals that when faced with alternative lines of action, humans tend to choose the less cognitively demanding one, suggesting that cognitive control is intrinsically registered as costly. This idea is further supported by studies showing that the exertion of cognitive control evokes negative affective states. Despite extensive evidence for mood-induced modulations on control abilities, the impact of affective states on the avoidance of cognitive demand is still unknown. Across two well-powered experiments, we tested the hypothesis that negative affective states would increase the avoidance of cognitively demanding tasks. Contrary to our expectations, induced affective states did not modulate the avoidance of demand, despite having an effect on task performance and subjective experience. Altogether, our results indicate that there are limits to the effect of affective signals on cognitive control and that such interaction might depend on specific affective and control settings.