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Nature Jan 2024Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as...
Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as post-traumatic stress and panic disorder. Threat-induced behaviours, including freezing and flight, are controlled by neuronal circuits in the central amygdala (CeA); however, the source of neuronal excitation of the CeA that contributes to high-intensity defensive responses is unknown. Here we used a combination of neuroanatomical mapping, in vivo calcium imaging, functional manipulations and electrophysiology to characterize a previously unknown projection from the dorsal peduncular (DP) prefrontal cortex to the CeA. DP-to-CeA neurons are glutamatergic and specifically target the medial CeA, the main amygdalar output nucleus mediating conditioned responses to threat. Using a behavioural paradigm that elicits both conditioned freezing and flight, we found that CeA-projecting DP neurons are activated by high-intensity threats in a context-dependent manner. Functional manipulations revealed that the DP-to-CeA pathway is necessary and sufficient for both avoidance behaviour and flight. Furthermore, we found that DP neurons synapse onto neurons within the medial CeA that project to midbrain flight centres. These results elucidate a non-canonical top-down pathway regulating defensive responses.
Topics: Avoidance Learning; Central Amygdaloid Nucleus; Neurons; Prefrontal Cortex; Excitatory Amino Acid Agents; Glutamic Acid; Neural Pathways; Calcium; Electrophysiology; Pons
PubMed: 38233522
DOI: 10.1038/s41586-023-06912-w -
International Journal of Psychiatry in... Mar 2024
Topics: Humans; Mental Disorders; Stress, Psychological; Hydrocortisone; Resilience, Psychological
PubMed: 38195001
DOI: 10.1177/00912174241227019 -
Journal of Personalized Medicine Oct 2023Mast cell activation syndrome (MCAS) is an immune disease with an estimated prevalence of 17%. Mast cell chemical mediators lead to heterogeneous multisystemic...
Mast cell activation syndrome (MCAS) is an immune disease with an estimated prevalence of 17%. Mast cell chemical mediators lead to heterogeneous multisystemic inflammatory and allergic manifestations. This syndrome is associated with various neurologic and psychiatric disorders, including headache, dysautonomia, depression, generalized anxiety disorder, and many others. Although MCAS is common, it is rarely recognized, and thus, patients can suffer for decades. The syndrome is caused by aberrant mast cell reactivity due to the mutation of the controller gene. A case series is presented herein including eight patients with significant neuropsychiatric disorders that were often refractory to standard medical therapeutics. Five patients had depression, five had generalized anxiety disorder, and four had panic disorder. Other psychiatric disorders included attention-deficit hyperactivity disorder, obsessive compulsive disorder, phobias, and bipolar disorder. All eight patients were subsequently diagnosed with mast cell activation syndrome; six had comorbid autonomic disorders, the most common being postural orthostatic tachycardia syndrome; and four had hypermobile Ehlers-Danlos syndrome. All patients experienced significant improvements regarding neuropsychiatric and multisystemic symptoms after mast-cell-directed therapy. In neuropsychiatric patients who have systemic symptoms and syndromes, it is important to consider the presence of an underlying or comorbid MCAS.
PubMed: 38003876
DOI: 10.3390/jpm13111562 -
Journal of Affective Disorders Dec 2023Brain functional abnormalities have been commonly reported in anxiety disorders, including generalized anxiety disorder, social anxiety disorder, panic disorder,... (Review)
Review
BACKGROUND
Brain functional abnormalities have been commonly reported in anxiety disorders, including generalized anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, and specific phobias. The role of functional abnormalities in the discrimination of these disorders can be tested with machine learning (ML) techniques. Here, we aim to provide a comprehensive overview of ML studies exploring the potential discriminating role of functional brain alterations identified by functional magnetic resonance imaging (fMRI) in anxiety disorders.
METHODS
We conducted a search on PubMed, Web of Science, and Scopus of ML investigations using fMRI as features in patients with anxiety disorders. A total of 12 studies (resting-state fMRI n = 5, task-based fMRI n = 6, resting-state and task-based fMRI n=1) met our inclusion criteria.
RESULTS
Overall, the studies showed that, regardless of the classifiers, alterations in functional connectivity and aberrant neural activation involving the amygdala, anterior cingulate cortex, hippocampus, insula, orbitofrontal cortex, temporal pole, cerebellum, default mode network, dorsal attention network, sensory network, and affective network were able to discriminate patients with anxiety from controls, with accuracies spanning from 36 % to 94 %.
LIMITATIONS
The small sample size, different ML approaches and heterogeneity in the selection of regions included in the multivariate pattern analyses limit the conclusions of the present review.
CONCLUSIONS
ML methods using fMRI as features can distinguish patients with anxiety disorders from healthy controls, indicating that these techniques could be used as a helpful tool for the diagnosis and the development of more targeted treatments for these disorders.
Topics: Humans; Anxiety Disorders; Phobic Disorders; Panic Disorder; Anxiety; Brain; Magnetic Resonance Imaging; Brain Mapping
PubMed: 37683943
DOI: 10.1016/j.jad.2023.09.006 -
Seizure Aug 2023Dissociation is a "disruption of the usually integrated functions of consciousness, memory, identity or perception of the environment" according to DSM-5. It is... (Review)
Review
Dissociation is a "disruption of the usually integrated functions of consciousness, memory, identity or perception of the environment" according to DSM-5. It is commonly seen in psychiatric disorders including primary dissociative disorders, post-traumatic stress disorder, depression, and panic disorder. Dissociative phenomena are also described in the context of substance intoxication, sleep deprivation and medical illnesses including traumatic brain injury, migraines, and epilepsy. Patients with epilepsy have higher rates of dissociative experiences as measured on the Dissociative Experiences Scale compared to healthy controls. Ictal symptoms, especially in focal epilepsy of temporal lobe origin, may include dissociative-like experiences such as déjà vu/jamais vu, depersonalization, derealization and what has been described as a "dreamy state". These descriptions are common in the setting of seizures that originate from mesial temporal lobe epilepsy and may involve the amygdala and hippocampus. Other ictal dissociative phenomena include autoscopy and out of body experiences, which are thought to be due to disruptions in networks responsible for the integration of one's own body and extra-personal space and involve the temporoparietal junction and posterior insula. In this narrative review, we will summarize the updated literature on dissociative experiences in epilepsy, as well as dissociative experiences in functional seizures. Using a case example, we will review the differential diagnosis of dissociative symptoms. We will also review neurobiological underpinnings of dissociative symptoms across different diagnostic entities and discuss how ictal symptoms may shed light on the neurobiology of complex mental processes including the subjective nature of consciousness and self-identity.
Topics: Humans; Seizures; Epilepsy; Epilepsy, Temporal Lobe; Dissociative Disorders; Stress Disorders, Post-Traumatic
PubMed: 37433243
DOI: 10.1016/j.seizure.2023.06.020 -
BMC Medical Genomics Oct 2023Whether the positive associations of blood lipids with psychiatric disorders are causal is uncertain. We conducted this two-sample Mendelian randomization (MR) analysis...
BACKGROUND
Whether the positive associations of blood lipids with psychiatric disorders are causal is uncertain. We conducted this two-sample Mendelian randomization (MR) analysis to comprehensively investigate associations of blood lipids with psychiatric disorders.
METHODS
Univariable and multivariable models were established for MR analyses. Inverse variance-weighted (IVW) MR was employed as the main approach; weighted median and MR-Egger were used as sensitivity analysis methods. The possibility of violating MR assumptions was evaluated utilizing several sensitivity analyses, including heterogeneity statistics, horizontal pleiotropy statistics, single SNP analysis, leave-one-out analysis and MR-PRESSO analysis. As instrumental variables, we screened 362 independent single-nucleotide polymorphisms (SNP) related to blood lipids from a recent genome-wide association study involving 76,627 individuals of European ancestry, with a genome-wide significance level of p < 5 × 10. Summary-level information for the six psychiatric disorders was extracted from Psychiatric Genomics Consortium and Alzheimer Disease Genetics Consortium.
RESULTS
We observed eight significant associations in univariable MR analysis, four of which were corroborated by multivariable MR (MVMR) analysis modified for the other three lipid traits: high-density lipoprotein cholesterol (HDL-C) level with the risk of PTSD (OR = 0.91, 95% CI = 0.85-0.97, p = 0.002) and AD (OR = 0.79, 95% CI = 0.71-0.88, p < 0.001) and triglycerides (TG) level with the risk of MDD (OR = 1.02, 95% CI = 1.003-1.03, p = 0.01) and panic disorder (OR = 0.83, 95% CI = 0.74-0.92, p < 0.001). In addition, four associations were not significant in MVMR analysis after adjustment for three lipid traits: total cholesterol (TC) level with the risk of PTSD, low-density lipoprotein cholesterol (LDL-C) level with the risk of MDD and AD and TG level with the risk of AD.
CONCLUSIONS
Our results show that blood lipids and psychiatric disorders may be related in a causal manner. This shows that abnormal blood lipid levels may act as reliable biomarker of psychiatric disorders and as suitable targets for their prevention and treatment.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Mental Disorders; Cholesterol, LDL; Lipids; Polymorphism, Single Nucleotide
PubMed: 37853421
DOI: 10.1186/s12920-023-01692-8 -
Journal of Affective Disorders Sep 2023It has been suggested that gender differences in anxiety and depressive symptoms characterize panic disorder (PD) in terms of vulnerability to stressful life events,...
BACKGROUND
It has been suggested that gender differences in anxiety and depressive symptoms characterize panic disorder (PD) in terms of vulnerability to stressful life events, anxiety, depressive symptom patterns, and brain structure. However, few studies have investigated the gender differences in PD using a network approach.
METHODS
This study included 619 participants with PD (313 men). The Panic Disorder Severity Scale, Albany Panic and Phobia Questionnaire, and Beck Depression Inventory-II were used to evaluate symptomatology. To investigate the PD-related white matter (WM) neural correlates, tract-based spatial statistics were used. The PD-related clinical scales and WM neural correlates were included in the network analysis to identify associations between variables. To evaluate network differences between genders, network comparison tests were conducted.
RESULTS
Our findings revealed that agoraphobia in men was the strongest central symptom. In addition, loss of pleasure, and not anxiety or panic symptoms, was the strongest central symptom in women with PD. The network comparison test revealed that the bridge strength score was higher in agoraphobia and tiredness in men and in self-criticalness in women. Furthermore, in the network that includes neural correlates of WM, the bridge strength score was higher in the cingulate gyrus WM in men and the cingulum hippocampus in women.
LIMITATIONS
Since this is a cross-sectional network study of PD patients, the causal relationship between interactions in this network analysis for both genders may not be accurately determined.
CONCLUSION
Network structures of anxiety and depressive symptomatology and related WM neural correlates can differ according to gender in PD patients.
Topics: Humans; Female; Male; Panic Disorder; Sex Factors; Cross-Sectional Studies; Anxiety; Anxiety Disorders; Agoraphobia
PubMed: 37247787
DOI: 10.1016/j.jad.2023.05.087 -
Acta Psychiatrica Scandinavica Apr 2024Although not approved for the treatment of anxiety disorders (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics... (Review)
Review
BACKGROUND
Although not approved for the treatment of anxiety disorders (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for anxiety disorders. There have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of which focused on SGAs.
OBJECTIVE
The specific aims of this umbrella review are to: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to traditional antidepressant treatments and other nonantipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects. The review protocol is registered on PROSPERO (CRD42021237436).
METHODS
An initial search was undertaken to identify systematic reviews and meta-analyses from inception until 2020, with an updated search completed August 2021 and January 2023. The searches were conducted in PubMed, MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), and the Cochrane Library through hand searches of references of included articles. Review quality was measured using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) scale.
RESULTS
The original and updated searches yielded 1796 and 3744 articles respectively, of which 45 were eligible. After final review, 25 systematic reviews and meta-analyses were included in the analysis. Most of the systematic reviews and meta-analyses were deemed low-quality through AMSTAR-2 with only one review being deemed high-quality. In evaluating the monotherapies with antipsychotics compared with first-line treatments for anxiety disorder there was insufficient evidence due to flawed study designs (such as problems with randomization) and small sample sizes within studies. There was limited evidence suggesting efficacy of antipsychotic agents in anxiety disorders other than quetiapine in generalized anxiety disorder (GAD).
CONCLUSIONS
This umbrella review indicates a lack of high-quality studies of antipsychotics in anxiety disorders outside of the use of quetiapine in GAD. Although potentially effective for anxiety disorders, FGAs and SGAs may have risks and side effects that outweigh their efficacy, although there were limited data. Further long-term and larger-scale studies of antipsychotics in anxiety disorders are needed.
Topics: Humans; Antipsychotic Agents; Anxiety Disorders; PubMed; Quetiapine Fumarate; Trifluoperazine; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 38382649
DOI: 10.1111/acps.13669 -
Social Work Sep 2023Misophonia is a chronic condition that describes aversion to specific auditory stimuli. Misophonia is characterized by physiological responsivity and negative emotional... (Review)
Review
Misophonia is a chronic condition that describes aversion to specific auditory stimuli. Misophonia is characterized by physiological responsivity and negative emotional reactivity. Specific sounds, commonly referred to as "triggers," are often commonplace and sometimes repetitive. They include chewing, coughing, slurping, keyboard tapping, and pen clicking. Common emotional responses include rage, disgust, anxiety, and panic while physical responses include muscle constriction and increased heart rate. This literature review identifies research priorities, limitations, and new directions, examining the implications of misophonia for the social work profession. Misophonia is largely absent from the social work literature. However, the profession is uniquely equipped to understand, screen for, and effectively treat misophonia in direct practice or within interprofessional treatment teams. By conceptualizing misophonia as idiosyncratic and contextual, social workers would enhance the existing body of research by applying an ecological perspective which captures the interaction of individuals and environments in producing human experience. Such an approach would assist clients and clinicians in developing treatment plans that consider the roles of social and physical environments in the development and course of misophonia. A discussion of current limitations within the misophonia literature further emphasizes the need for new perspectives.
Topics: Humans; Social Work; Emotions; Hearing Disorders; Anxiety Disorders
PubMed: 37463856
DOI: 10.1093/sw/swad029 -
Gastroenterology Clinics of North... Dec 2023Because the scientific understanding of obesity has grown, explicit expressions of weight bias have steadily become less acceptable. However, implicit weight bias and... (Review)
Review
Because the scientific understanding of obesity has grown, explicit expressions of weight bias have steadily become less acceptable. However, implicit weight bias and stigma remain common impediments to health. Language frames the public perception of obesity. It is problematic when public discourse or scientific publications reflect misinformation or bias against people with obesity because this can promote stigma and barriers to health. Examples of stigmatizing language include descriptions of obesity as an identity rather than a disease, language that describes obesity as a crisis or a cause for panic, and excessive focus on weight or appearance rather than health outcomes.
Topics: Humans; Language; Obesity; Social Stigma; Health Communication; Bias, Implicit
PubMed: 37919026
DOI: 10.1016/j.gtc.2023.09.002