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Nature Neuroscience Jan 2024Panic disorder is characterized by uncontrollable fear accompanied by somatic symptoms that distinguish it from other anxiety disorders. Neural mechanisms underlying...
Panic disorder is characterized by uncontrollable fear accompanied by somatic symptoms that distinguish it from other anxiety disorders. Neural mechanisms underlying these unique symptoms are not completely understood. Here, we report that the pituitary adenylate cyclase-activating polypeptide (PACAP)-expressing neurons in the lateral parabrachial nucleus projecting to the dorsal raphe are crucial for panic-like behavioral and physiological alterations. These neurons are activated by panicogenic stimuli but inhibited in conditioned fear and anxiogenic conditions. Activating these neurons elicits strong defensive behaviors and rapid cardiorespiratory increase without creating aversive memory, whereas inhibiting them attenuates panic-associated symptoms. Chemogenetic or pharmacological inhibition of downstream PACAP receptor-expressing dorsal raphe neurons abolishes panic-like symptoms. The pontomesencephalic PACAPergic pathway is therefore a likely mediator of panicogenesis, and may be a promising therapeutic target for treating panic disorder.
Topics: Mice; Animals; Anxiety; Medically Unexplained Symptoms; Pituitary Adenylate Cyclase-Activating Polypeptide; Fear; Behavior, Animal
PubMed: 38177337
DOI: 10.1038/s41593-023-01504-3 -
Journal of Traumatic Stress Aug 2023Transdiagnostic treatments have been designed to target common processes for clusters of disorders. One such treatment, transdiagnostic behavior therapy (TBT), targets...
Transdiagnostic treatments have been designed to target common processes for clusters of disorders. One such treatment, transdiagnostic behavior therapy (TBT), targets avoidance across emotional disorders, including posttraumatic stress disorder (PTSD), depressive disorders, and anxiety disorders, and has demonstrated efficacy in randomized controlled trials. The current study was designed to examine whether distinct treatment trajectories would emerge in a sample of 112 veterans receiving TBT and whether diagnostic comorbidity, baseline levels of several transdiagnostic risk factors, or treatment engagement influence trajectory membership. Growth mixture modeling revealed three distinct trajectories across depression, ds = 0.55-1.09; PTSD ds = -0.07-1.43; and panic disorder symptoms, ds = -0.13-1.09. Notably, for PTSD and panic disorder symptoms, separate classes for responders and nonresponders emerged among participants with high baseline symptom levels. Findings for the risk factors suggested that PTSD and panic nonresponders evidenced significantly higher behavioral avoidance at baseline and reduced engagement in treatment procedures and homework completion compared to responders. Together, the findings provide additional support for the use of TBT in the treatment of emotional disorders, including PTSD. Potential adaptations are discussed for patients with significantly elevated behavioral avoidance to improve treatment engagement and related outcomes.
Topics: Humans; Stress Disorders, Post-Traumatic; Behavior Therapy; Mood Disorders; Veterans; Anxiety Disorders
PubMed: 37549108
DOI: 10.1002/jts.22963 -
Frontiers in Neuroscience 2024Dopamine is a hormone that is released by the adrenal gland and influences motor control and motivation. Dopamine is known to have 5 receptors which are D1, D2, D3, D4... (Review)
Review
Dopamine is a hormone that is released by the adrenal gland and influences motor control and motivation. Dopamine is known to have 5 receptors which are D1, D2, D3, D4 and D5, which are further categorized into 2 families: D1 family and D2 family. The D1 family is known to play a role in motivation and motor control whereas the D2 family is known to affect attention and sleep. THC, a type of cannabinoid, can lead to feelings of euphoria, anxiety, fear, distrust, or panic. THC is known to affect dopamine in regions such as the anterior cingulate cortex (ACC), and plays a role in fundamental cognitive processes. Although there is a vast amount of research between the relationship of THC on dopamine, there continues to be limited research in relation to THC on dopamine receptors. The D1 receptor plays a role in several essential functions, such as memory, attention, impulse control, regulation of renal function, and locomotion. Accordingly, this review is intended to summarize the relationship between THC and D1 receptors, highlighting key gaps in the literature and avenues for future research.
PubMed: 38419666
DOI: 10.3389/fnins.2024.1360205 -
Naunyn-Schmiedeberg's Archives of... May 2024Mirtazapine (MTZ) is an antidepressant drug with an exceptional pharmacological profile. It also has an excellent safety and tolerability profile. The present review... (Review)
Review
Mirtazapine (MTZ) is an antidepressant drug with an exceptional pharmacological profile. It also has an excellent safety and tolerability profile. The present review provides a pharmacological update on MTZ and summarizes the research findings of MTZ's effects on different diseases. MTZ is hypothesized to have antidepressant effects because of the synergy between noradrenergic and serotonergic actions and is effective in treating major depressive disorder and depression associated with epilepsy, Alzheimer's disease, stroke, cardiovascular disease, and respiratory disease. In cancer patients, MTZ significantly reduced sadness, nausea, sleep disruption, and pain and improved quality of life. Also, it has promising effects on Parkinson's disease, schizophrenia, dysthymia, social anxiety disorder, alcohol dependency, posttraumatic stress disorder, panic disorder, pain syndromes, obsessive-compulsive disorder, and sleep disorders. Additionally, MTZ is potentially therapeutic in different situations associated with depression, such as liver, kidney, cardiovascular, respiratory, infertility, heavy metal-induced neurotoxicity, and pruritus. Potent antioxidative, anti-inflammatory, and anti-apoptotic bioactivities mediate these promising effects. These positive outcomes of the scientific investigations motivate more and more clinical trials for a golden exceptional antidepressant in different conditions.
Topics: Humans; Mirtazapine; Animals; Antidepressive Agents; Antidepressive Agents, Tricyclic
PubMed: 37943296
DOI: 10.1007/s00210-023-02818-6 -
Neurobiology of Disease Sep 2023Benzodiazepine (BZ) drugs treat seizures, anxiety, insomnia, and alcohol withdrawal by potentiating γ2 subunit containing GABA type A receptors (GABARs). BZ clinical...
Benzodiazepine (BZ) drugs treat seizures, anxiety, insomnia, and alcohol withdrawal by potentiating γ2 subunit containing GABA type A receptors (GABARs). BZ clinical use is hampered by tolerance and withdrawal symptoms including heightened seizure susceptibility, panic, and sleep disturbances. Here, we investigated inhibitory GABAergic and excitatory glutamatergic plasticity in mice tolerant to benzodiazepine sedation. Repeated diazepam (DZP) treatment diminished sedative effects and decreased DZP potentiation of GABAR synaptic currents without impacting overall synaptic inhibition. While DZP did not alter γ2-GABAR subunit composition, there was a redistribution of extrasynaptic GABARs to synapses, resulting in higher levels of synaptic BZ-insensitive α4-containing GABARs and a concomitant reduction in tonic inhibition. Conversely, excitatory glutamatergic synaptic transmission was increased, and NMDAR subunits were upregulated at synaptic and total protein levels. Quantitative proteomics further revealed cortex neuroadaptations of key pro-excitatory mediators and synaptic plasticity pathways highlighted by Ca/calmodulin-dependent protein kinase II (CAMKII), MAPK, and PKC signaling. Thus, reduced inhibitory GABAergic tone and elevated glutamatergic neurotransmission contribute to disrupted excitation/inhibition balance and reduced BZ therapeutic power with benzodiazepine tolerance.
Topics: Mice; Animals; Diazepam; Alcoholism; Substance Withdrawal Syndrome; Receptors, GABA-A; Benzodiazepines; Brain; Synapses; gamma-Aminobutyric Acid; Synaptic Transmission
PubMed: 37536384
DOI: 10.1016/j.nbd.2023.106248 -
Frontiers in Psychiatry 2024Panic disorder is a common psychiatric diagnosis characterized by acute, distressing somatic symptoms that mimic medically-relevant symptoms. As a result, individuals... (Review)
Review
Panic disorder is a common psychiatric diagnosis characterized by acute, distressing somatic symptoms that mimic medically-relevant symptoms. As a result, individuals with panic disorder overutilize personal and healthcare resources in an attempt to diagnose and treat physical symptoms that are often medically benign. A biobehavioral perspective on these symptoms is needed that integrates psychological and medical knowledge to avoid costly treatments and prolonged suffering. This narrative review examines six common somatic symptoms of panic attacks (non-cardiac chest pain, palpitations, dyspnea, dizziness, abdominal distress, and paresthesia), identified in the literature as the most severe, prevalent, or critical for differential diagnosis in somatic illness, including long COVID. We review somatic illnesses that are commonly comorbid or produce panic-like symptoms, their relevant risk factors, characteristics that assist in distinguishing them from panic, and treatment approaches that are typical for these conditions. Additionally, this review discusses key factors, including cultural considerations, to assist healthcare professionals in differentiating benign from medically relevant symptoms in panic sufferers.
PubMed: 38779550
DOI: 10.3389/fpsyt.2024.1296569 -
The Korean Journal of Pain Apr 2024Nociplastic pain by the "International Association for the Study of Pain" is defined as pain that arises from altered nociception despite no clear evidence of...
Nociplastic pain by the "International Association for the Study of Pain" is defined as pain that arises from altered nociception despite no clear evidence of nociceptive or neuropathic pain. Augmented central nervous system pain and sensory processing with altered pain modulation are suggested to be the mechanism of nociplastic pain. Clinical criteria for possible nociplastic pain affecting somatic structures include chronic regional pain and evoked pain hypersensitivity including allodynia with after-sensation. In addition to possible nociplastic pain, clinical criteria for probable nociplastic pain are pain hypersensitivity in the region of pain to non-noxious stimuli and presence of comorbidity such as generalized symptoms with sleep disturbance, fatigue, or cognitive problems with hypersensitivity of special senses. Criteria for definitive nociplastic pain is not determined yet. Eight specific disorders related to central sensitization are suggested to be restless leg syndrome, chronic fatigue syndrome, fibromyalgia, temporomandibular disorder, migraine or tension headache, irritable bowel syndrome, multiple chemical sensitivities, and whiplash injury; non-specific emotional disorders related to central sensitization include anxiety or panic attack and depression. These central sensitization pain syndromes are overlapped to previous functional pain syndromes which are unlike organic pain syndromes and have emotional components. Therefore, nociplastic pain can be understood as chronic altered nociception related to central sensitization including both sensory components with nociceptive and/or neuropathic pain and emotional components. Nociplastic pain may be developed to explain unexplained chronic pain beyond tissue damage or pathology regardless of its origin from nociceptive, neuropathic, emotional, or mixed pain components.
PubMed: 38504389
DOI: 10.3344/kjp.23326 -
Heliyon Apr 2024Panic Disorder is a serious anxiety disorder, and one of the severe mental problems that impacts mothers' mental health and fetal health as well. (Review)
Review
BACKGROUND
Panic Disorder is a serious anxiety disorder, and one of the severe mental problems that impacts mothers' mental health and fetal health as well.
AIM
The current scoping review aims to provide a wide overview of the literature regarding panic disorder during pregnancy.
METHODS
Twenty-five eligible articles were selected for full review from SAGE, CINAHL, PubMed, Medline, Research Gate, Science Direct, and Google Scholar literature searches. This review followed the framework suggested by Arksey and O'Malley for a scoping review.
RESULTS
Content analysis of the studies was done, and five categories have been identified: Panic disorder course during pregnancy; prevalence of panic disorder during pregnancy; factors associated with pregnancy panic disorder; impact of panic disorder during pregnancy; and treatment of panic disorder during pregnancy.
CONCLUSION
A significant gap in the literature, and inconsistent and mixed findings regarding prevalence, impact, associated factors, and treatment of PD during pregnancy exist. This scoping review revealed that more studies need to be conducted to further understand and examine PD during pregnancy.
PubMed: 38601643
DOI: 10.1016/j.heliyon.2024.e28999