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Twenty panic disorder patients with mitral valve prolapse showed amelioration of prolapse on repeat echocardiogram after treatment for panic disorder. This effect was significant when compared to repeat echocardiograms in eight psychiatrically normal control subjects with mitral valve prolapse.

Objective: To further the understanding of lactate-induced panic in patients with panic disorder, the authors examined cisternal lactate and carbon dioxide levels in nonhuman primates after infusions of sodium lactate comparable to those used in studies of human beings., Method: CSF and venous blood lactate, pH, PCO2, PO2, and bicarbonate were measured in five ketamine-anesthetized nonhuman primates, without mechanical ventilation, before and after they underwent infusions of sodium lactate. In addition, the same measurements were made for three of the five subjects who were given saline infusions., Results: Despite the development of the characteristic peripheral biochemical effects of infused sodium lactate--increased lactate and bicarbonate levels and metabolic alkalosis--no increases in central lactate or carbon dioxide levels were observed. Saline infusions produced no biochemical effects on venous and cisternal measures., Conclusions: The results of this study are in keeping with previous findings of nonpermeability of the blood-brain barrier to anionic compounds such as lactate. They therefore support theories of lactate panic based on cognitive and/or brainstem misevaluation of peripheral somatic sensations.

The antipanic utility of imipramine and monoamine oxidase inhibitors has led to hypotheses of noradrenergic and/or serotonin (5-HT)-related abnormalities underlying panic disorder (PD) and its agoraphobic complications. Further data support significant antipanic effects for agents with acute 5-HT reuptake blockade effects. It is unlikely that ameliorative effects observed following chronic administration of 5-HT drugs remain 5-HT specific. Despite a range of recently discovered 5-HT receptor subtypes, evidence for a specific receptor abnormality in PD is lacking. Preclinical studies suggest an important role for 5-HT effects in several animal models of anxiety, including separation-induced infant protest responses and respiratory modulation. Induction of anxiety with putative 5-HT agents such as meth-chloro-phenylpiperazine and fenfluramine lend further support to 5-HT involvement in anxiety states. Critical behavioral, physiologic, and neuroendocrine differences between putative 5-HT anxiogens and "classic" panicogens, such as lactate and carbon dioxide are discussed. We propose that 5-HT agents mediate antipanic effects through amelioration of a deranged internal evaluative mechanism along cybernetic lines, rather than simple augmentation or reduction of 5-HT function.

To assess the role of noradrenergic stimulation during lactate-induced panic, ten patients with panic disorder who panicked during a standard sodium-lactate infusion underwent a repeat infusion following intravenous clonidine pretreatment. Although clonidine significantly lowered prelactate systolic blood pressure, the drug did not significantly lower prelactate anxiety levels, as reflected by the Acute Panic Inventory (API). Clonidine blocked lactate-induced panic in four of ten subjects, a significant effect. Clonidine treatment also significantly attenuated lactate-panic symptoms, as reflected by time to panic and API comparison between trials. Nevertheless, over half the subjects still panicked in response to lactate despite clonidine. This preliminary study suggests that reduction of central noradrenergic activity by clonidine, at least at the dosage levels employed in the current study, only partially attenuates panic response to lactate. Noradrenergic theories of panic may not therefore fully account for lactate panicogenesis.

Eight unrestrained macaques were observed for 2 hours following either two oral doses of yohimbine (0.2 mg/kg and 2.0 mg/kg) or placebo administration. Four of the subjects were normally reared and four subjects had early maternal and social deprivation. In the normal subjects, yohimbine, at both doses, produced increased tension and enervation and decreased species-typical "normal" behaviors. In deprivation-reared subjects, low-dose yohimbine produced reductions in tension and enervation, and increases in "normal" behaviors. High doses of yohimbine diminished behavioral score differences between groups. The prominent increases in enervation observed in normally reared subjects suggests that yohimbine is not unequivocally anxiogenic. Moreover, early social deprivation may alter the pattern of response to yohimbine, perhaps as a result of aberrant neurodevelopment. This study reflects the role of experiential factors in determining patterns of affective response to putative anxiogenic agents.

Six unrestrained bonnet macaques were each observed after oral administration of four dosages of yohimbine hydrochloride (0.10, 0.25, 0.50, and 0.75 mg/kg) and a placebo. Yohimbine significantly increased episodes of motoric activation and affective response interspersed with intervals of behavioral enervation. Yohimbine scores correlated closely with baseline levels; there was no dose-response relationship. Response to oral yohimbine differed in several ways from subcutaneous and intravenous sodium lactate infusions, including prominent enervative symptoms and the appearance of sexual arousal. In light of the appearance of cyclic enervative episodes, this study suggests limitations to primate models of panic disorder utilizing oral yohimbine.

Panic disorder is a psychiatric disorder characterized by recurrent panic attacks, with a prevalence of ~ 4% in the general population, causing heavy personal and socioeconomic burdens. The similarities of animal defense responses to clinical panic attack symptoms in humans make it possible to translate neuroanatomical pathways identified in animal studies to panic disorder in humans. Therefore, in this review we first present a basic overview of panic disorder in humans including the main subtypes, models commonly used to trigger panic attacks, related hypotheses, the neurotransmitter systems that may be involved, and the current clinical treatments to give the reader a comprehensive understanding of panic disorder. The animal section introduces the models that trigger panic-like behavior in animals and the brain regions that may be involved, providing insights for future elucidation of the neural circuit mechanisms behind panic attacks. [ABSTRACT FROM AUTHOR]

Purpose: Anxious depression (AD) is a common, distinct depression subtype. This exploratory subgroup analysis aimed to explore the effects of acupuncture as an add-on therapy of selective serotonin reuptake inhibitors (SSRIs) for patients with AD or non-anxious depression (NAD). Patients and Methods: Four hundred and sixty-five patients with moderate-to-severe depression from the AcuSDep pragmatic trial were included in analysis. Patients were randomly assigned to receive MA+SSRIs, EA+SSRIs, or SSRIs alone (1:1:1) for six weeks. AD was defined by using dimensional criteria. The measurement instruments included 17-items Hamilton Depression Scale (HAMD-17), Self-Rating Depression Scale (SDS), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS), and WHO Quality of Life-BREF (WHOQOL-BREF). Comparison between AD and NAD subgroups and comparisons between groups within either AD or NAD subgroups were conducted. Results: Eighty percent of the patients met the criteria for AD. The AD subgroup had poorer clinical manifestations and treatment outcomes compared to those of the NAD subgroup. For AD patients, the HAMD response rate, remission rate, early onset rate, and the score changes on each scale at most measurement points on the two acupuncture groups were significantly better than the SSRIs group. For NAD patients, the HAMD early onset rates of the two acupuncture groups were significantly better than the SSRIs group. Conclusion: For AD subtype patients, either MA or EA add-on SSRIs showed comprehensive improvements, with small-to-medium effect sizes. For NAD subtype patients, both the add-on acupuncture could accelerate the response to SSRIs treatment. The study contributed to the existing literature by providing insights into the potential benefits of acupuncture in combination with SSRIs, especially for patients with AD subtypes. Due to its limited nature as a post hoc subgroup analysis, prospectively designed, high-quality trials are warranted. Clinical Trials Registration: ChiCTR-TRC-08000297. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with anxiety and depression. Few studies have addressed interventions for symptoms of anxiety and depression in this population. To determine the efficacy of interventions for anxiety and depression in patients with AD. PubMed, MEDLINE, EMBASE, and PsycINFO were searched from inception to November 2023. English-language studies published in peer-reviewed journals evaluating the effect of interventions on anxiety and/or depression using validated assessment tools on patients with AD were included. Titles, abstracts, and articles were screened by at least two independent reviewers. Of 1410 references that resulted in the initial search, 17 studies were included. Fourteen of these studies are randomized controlled trials, while the other 3 studies are prospective controlled trials with pre and post-test designs. Data were extracted using a standardized extraction form, and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. To accommodate trials with multiple interventions (each compared to a control group), we conducted a mixed-effects meta-analysis with the trial as a random effect. Prespecified outcomes were changes in symptoms of anxiety and depression in patients with AD as evaluated using standardized assessment tools. Of the 17 studies included in this systematic review, 7 pharmacological intervention studies with 4723 participants examining 5 different medications were included in a meta-analysis. Of these studies, only 1 study evaluated medications prescribed to treat anxiety and/or depression; the rest evaluated medications prescribed to treat AD. Meta-analysis of all the pharmacological interventions resulted in significant improvement in anxiety, depression, and combined anxiety-depression scale scores (standardized mean difference [95% CI]: − 0.29 [− 0.49 to − 0.09], − 0.27 [− 0.45 to − 0.08], − 0.27 [− 0.45 to − 0.08]) respectively. The 10 non-pharmacological studies with 2058 participants showed general improvement in anxiety but not depression. A meta-analysis of the non-pharmacological interventions was not conducted due to variable approaches and limited data. Pharmacological interventions designed to improve AD were found to improve anxiety and depression in patients with moderate-severe disease. More comprehensive studies on non-pharmacological and pharmacological interventions that primarily target anxiety and depression are needed. [ABSTRACT FROM AUTHOR]

Introduction: Treatment-resistant depression (TRD) is commonly defined as the failure of at least two trials with antidepressant drugs, given at the right dose and for an appropriate duration. TRD is associated with increased mortality, compared to patients with a simple major depressive episode. This increased rate was mainly attributed to death from external causes, including suicide and accidents. The aim of our study is to identify socio-demographic and psychopathological variables associated with suicidal attempts in a sample of outpatients with TRD. Material and methods: We performed a monocentric observational study with a retrospective design including a sample of 63 subjects with TRD referred to an Italian outpatient mental health centre. We collected socio-demographic and psychopathological data from interviews and clinical records. Results: 77.8% of the sample (N=49) were females, the mean age was 49.2 (15.9). 33.3% (N=21) of patients had attempted suicide. 54% (N=34) of patients had a psychiatric comorbidity. Among the collected variables, substance use (p=0.031), psychiatric comorbidities (p=0.049) and high scores of HAM-D (p=0.011) were associated with the occurrence of suicide attempts. In the regression model, substance use (OR 6.779), psychiatric comorbidities (OR 3.788) and HAM-D scores (OR 1.057) were predictive of suicide attempts. When controlling for gender, only substance use (OR 6.114) and HAM-D scores (OR 1.057) maintained association with suicide attempts. Conclusion: The integrated treatment of comorbidities and substance abuse, which involves different mental health services, is fundamental in achieving the recovery of these patients. Our study supports the importance of performing a careful clinical evaluation of patients with TRD in order to identify factors associated with increased risk of suicide attempts. [ABSTRACT FROM AUTHOR]

Symptoms compatible with a diagnosis of anxiety disorder frequently complicate the course of affective illness. Patients with depression may have panic attacks, phobias, severe social anxiety, obsessions, compulsions, and generalized anxiety. If the affective disorder is the primary condition, its treatment should be sufficient in most instances to relieve the concomitant anxiety symptoms. Thus, judicious choice of antidepressant therapy for treatment of major and atypical depression will usually resolve associated panic attacks, generalized anxiety, phobias, and compulsions. It must be recalled, however, that antidepressant therapy usually takes between 4 and 6 weeks to have full clinical effect; in the interim, anxiety symptoms may be the most troubling and disabling aspect of the illness. Therefore, using antianxiety agents in treating depressed patients who also have anxiety symptoms is often recommended while waiting for the antidepressant to work. Benzodiazepines are extremely useful for short-term treatment of most anxiety symptoms in depressed patients. The dose should be kept to the lowest possible to relieve symptoms, and the medication should be tapered and then discontinued once the underlying affective disturbance is relieved. Buspirone is also very effective in treating generalized anxiety disorder and may be used in conjunction with antidepressants of most classes. A wide range of behavioral and cognitive techniques may also help relieve anxiety symptoms in the depressed patient.

Early life adversity (ELA) is a major risk factor for mental illness, but the neurobiological mechanisms by which ELA increases the risk for future psychopathology are still poorly understood. Brain development is particularly malleable during prenatal and early postnatal life, when complex neural circuits are being formed and refined through an interplay of excitatory and inhibitory neural input, synaptogenesis, synaptic pruning, myelination, and neurogenesis. Adversity that influences these processes during sensitive periods of development can thus have long-lasting and pervasive effects on neural circuit maturation. In this review, we will discuss clinical and preclinical evidence for the impact of ELA on neural circuit formation with a focus on the early postnatal period, and how long-lasting impairments in these circuits can affect future behavior. We provide converging evidence from human and animal studies on how ELA alters the functional development of brain regions, neural circuits, and neurotransmitter systems that are crucial for cognition and affective behavior, including the hippocampus, the hypothalamus-pituitary-adrenal (HPA) axis, neural networks of fear responses and cognition, and the serotonin (5-HT) system. We also discuss how gene-by-environment (GxE) interactions can determine individual differences in susceptibility and resilience to ELA, as well as molecular pathways by which ELA regulates neural circuit development, for which we emphasize epigenetic mechanisms. Understanding the molecular and neurobiological mechanisms underlying ELA effects on brain function and psychopathology during early postnatal sensitive periods may have great potential to advance strategies to better treat or prevent psychiatric disorders that have their origin early in life., (© 2022. The Author(s).)

Neuron-specific enolase (NSE) is a biomarker indicative of neuronal cell damage. The aim of this study is to assess the NSE levels in patients diagnosed with post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). Blood samples were collected from 43 individuals with PTSD (age range 11-17), 43 individuals with MDD (age range 10-17), and 40 age- and gender-matched healthy controls. The NSE levels were analyzed, and participants completed the Post-traumatic Stress Reaction Index, the Children's Depression Inventory, and the Screen for Child Anxiety Related Disorders. Additionally, the Clinical Global Impressions Scale was filled out by the researcher. Results indicated that the NSE levels in the PTSD group were significantly higher than those in both the MDD group and the healthy control group. No significant difference in NSE levels was observed between the MDD group and the healthy control group., Conclusions: The findings suggest that elevated NSE levels in PTSD may be indicative of stress-related neuronal damage, distinguishing PTSD from MDD and healthy controls. These results underline the need for further research to explore the potential of NSE as a biomarker for PTSD and its implications for diagnosis and intervention strategies., What Is Known: • Neuron-specific enolase (NSE) is a biomarker indicative of neuronal cell damage. • Elevated NSE levels have been observed in certain neuropsychiatric and neurological conditions, reflecting neuronal damage or stress., What Is New: • NSE levels in adolescents with PTSD are significantly higher than those in both MDD patients and healthy controls, suggesting a specific association with trauma-related neuronal damage. • No significant difference in NSE levels was observed between MDD patients and healthy controls, highlighting the distinct neurobiological impact of trauma compared to depressive disorders., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Panic disorder (PD) may cause serious cardiac arrhythmias by causing electrical abnormalities. Abnormal P-wave axis (aPwa), presence of fragmented QRS (fQRS), wide frontal QRS-T angle (fQRSTa), QRS duration corrected (QRSdc) and log/ logQRS duration/RR interval (log/logQRS/RR) have been correlated with increased risk of serious supraventricular and ventricular cardiac arrhythmias in a general population. The purpose of this study was to compare these newly explored atrial and ventricular arrhythmia indicators in patients with PD and in healthy subjects. Method: A total of 169 newly diagnosed PD patients and 128 healthy subjects were included in the study. The Panic and Agoraphobia Scale (PAS) was administered, and 12-lead electrocardiography (ECG) measurements were obtained. Electrocardiographic parameters including aPwa, fQRSTa, presence of fQRS, QRS duration corrected (QRSdc), and log/logQRS duration/RR distance (log/logQRS/RR) were compared between the two groups. Results: aPwa and fQRS, in addition to fQRSTa, QRSdc, and log/ logQRS/RR ratio values, were significantly increased in the PD group compared to healthy controls. Correlation analyses revealed that wider fQRSTa, number of fQRS derivation, number of total fQRS, wider QRSdc, and log/logQRS/RR ratio significantly correlated with PAS score. Logistic regression analysis demonstrated that fQRSTa and the number of total fQRS were independently associated with PD. Conclusion: PD is associated with wider fQRSTa, QRSdc, and log/logQRS/RR in addition to the increased abnormal aPwa and presence of fQRS. These findings suggest that untreated PD patients may be susceptible to supraventricular and ventricular arrhythmia, indicating that ECG should be routinely obtained in the management of PD patients. [ABSTRACT FROM AUTHOR]

Consistent individual preferences for specific reinforcers and adherence to specific regulators could be observed in behaviour from a very early age. The neurochemical framework Functional Ensemble of Temperament (FET) identified neurochemical biomarkers for these consistent patterns in behavioural orientation as specific temperament traits. The FET uses the activity-specific approach: this approach differentiates between the traits related to physical, social and mental (probabilistic) aspects of behaviour. This study investigated the validity of such activity-specific differentiation, the discriminant and concurrent validity of the orientation-related scales (Sensation Seeking, Empathy, Probabilistic Processing, Neuroticism, dispositional Satisfaction) of the Structure of Temperament Questionnaire (STQ-77) that uses the FET structure. Using a healthy adult sample (N = 296, M/F = 152/144) the study examined the association of the twelve STQ-77 scales with 34 other scales representing the Sensation Seeking Scales, Questionnaire of Cognitive & Affective Empathy, Locus of Control, Big Five Inventory, Polymathic Orientation Scale, Interest in Games, Grit scale, and Schutte's Emotional Intelligence Scale. The results showed that the pattern of correlations supports the activity-specific approach and the divergent and concurrent validity of the STQ-77 scales. [ABSTRACT FROM AUTHOR]

Cortisol awakening response (CAR) refers to the dynamic change of cortisol concentration within 1 h after awakening. Trait anxiety is a general risk marker of anxiety disorders. The present study aimed to investigate the effect of trait anxiety on CAR using R30 (change in cortisol level at 30 min after awakening) and AUCi (the area under the curve with respect to the increase) as indicators. 133 college students were divided into high trait anxiety (HTA) and low trait anxiety (LTA) group according to the median score of the trait version of State-Trait Anxiety Inventory. Saliva samples were collected immediately upon awakening, 30 min, 45 and 60 min on two consecutive mornings. The results showed that, (1) decreased CAR was found for the male than female participants. (2) Compared to the LTA group, the HTA group showed decreased R30 and AUCi. (3) Both R30 and AUCi were negatively correlated with trait anxiety scores. These results demonstrated that trait anxiety might weaken the CAR, and both R30 and AUCi can be used as CAR indicators in detecting trait anxiety. Future research on CAR should consider the moderating effect of trait anxiety. [ABSTRACT FROM AUTHOR]

The human brain undergoes metabolic adaptations in obesity, but the underlying mechanisms have remained largely unknown. We compared concentrations of often reported brain metabolites measured with magnetic resonance spectroscopy (1H-MRS, 3 T MRI) in the occipital lobe in subjects with obesity and lean controls under different metabolic conditions (fasting, insulin clamp, following weight loss). Brain glucose uptake (BGU) quantified with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)) was also performed in a subset of subjects during clamp. In dataset A, 48 participants were studied during fasting with brain 1H-MRS, while in dataset B 21 participants underwent paired brain 1H-MRS acquisitions under fasting and clamp conditions. In dataset C 16 subjects underwent brain 18F-FDG-PET and 1H-MRS during clamp. In the fasting state, total N-acetylaspartate was lower in subjects with obesity, while brain myo-inositol increased in response to hyperinsulinemia similarly in both lean participants and subjects with obesity. During clamp, BGU correlated positively with brain glutamine/glutamate, total choline, and total creatine levels. Following weight loss, brain creatine levels were increased, whereas increases in other metabolites remained not significant. To conclude, insulin signaling and glucose metabolism are significantly coupled with several of the changes in brain metabolites that occur in obesity. [ABSTRACT FROM AUTHOR]

Anxiety disorders (AD) are associated with altered connectivity in large-scale intrinsic brain networks. It remains uncertain how much these signatures overlap across different phenotypes due to a lack of well-powered cross-disorder comparisons. We used resting-state functional magnetic resonance imaging (rsfMRI) to investigate differences in functional connectivity (FC) in a cross-disorder sample of AD patients and healthy controls (HC). Before treatment, 439 patients from two German multicenter clinical trials at eight different sites fulfilling a primary diagnosis of panic disorder and/or agoraphobia (PD/AG, N = 154), social anxiety disorder (SAD, N = 95), or specific phobia (SP, N = 190) and 105 HC underwent an 8 min rsfMRI assessment. We performed categorical and dimensional regions of interest (ROI)-to-ROI analyses focusing on connectivity between regions of the defensive system and prefrontal regulation areas. AD patients showed increased connectivity between the insula and the thalamus compared to controls. This was mainly driven by PD/AG patients who showed increased (insula/hippocampus/amygdala-thalamus) and decreased (dorsomedial prefrontal cortex/periaqueductal gray-anterior cingulate cortex) positive connectivity between subcortical and cortical areas. In contrast, SAD patients showed decreased negative connectivity exclusively in cortical areas (insula-orbitofrontal cortex), whereas no differences were found in SP patients. State anxiety associated with the scanner environment did not explain the FC between these regions. Only PD/AG patients showed pronounced connectivity changes along a widespread subcortical-cortical network, including the midbrain. Dimensional analyses yielded no significant results. The results highlighting categorical differences between ADs at a systems neuroscience level are discussed within the context of personalized neuroscience-informed treatments. PROTECT-AD's registration at NIMH Protocol Registration System: 01EE1402A and German Register of Clinical Studies: DRKS00008743. SpiderVR's registration at ClinicalTrials.gov: NCT03208400., (© 2024. The Author(s).)

Abstract: Understanding the development of chronic pain (CP) is challenging due to its multifactorial etiology. Child maltreatment (CM), encompassing various types of neglect and abuse affecting more than one-third of the population, is a critical aspect of early-life adversity with long-lasting impacts. It is increasingly recognized for its role in altering biopsychosocial processes, potentially increasing vulnerability to CP. However, the exact path connecting CM to CP is not fully elucidated, primarily attributable to limitations in prior research, including insufficient sample sizes, inadequate consideration of comprehensive mediative variables, and a lack of longitudinal data. To address these gaps, our study utilizes a large-scale dataset (n = 150,989) comprising both cross-sectional and longitudinal data, along with an extensive range of biopsychosocial variables. Our findings reveal that all types of CMs, except physical neglect, significantly increase the risk of CP, and all types of CPs, except headache, were affected by CM. Furthermore, we demonstrate that individuals with CM histories are more predisposed to comorbid CP conditions. Importantly, biopsychosocial factors are found to explain over 60% of the association between CM and CP, with psychological factors playing a key role. This study not only characterizes the relationship between CM and CP but also underscores the influence of psychosocial elements in this dynamic interplay. These findings offer important insights into the long-term impacts of CM and provide a foundation for developing targeted therapeutic and preventive strategies for CP., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: Transcranial magnetic stimulation (TMS) is a promising intervention for treatment-resistant psychiatric disorders. However, conventional TMS typically utilises a one-size-fits-all approach when determining stimulation targets. Recent retrospective brain circuit-based analyses using lesion network mapping have suggested that a left dorsal lateral prefrontal cortex target has a higher efficacy for alleviating depression symptoms, a dorsomedial prefrontal cortex target is more effective for anxiety symptoms, and a rostromedial prefrontal cortex target is effective for schizophrenia-associated psychiatric symptoms. Nonetheless, symptom-specific brain circuit targeting has not been tested prospectively. We conducted a narrative review of selected literature to investigate individualised targeting for TMS and discuss potential future directions to elucidate the efficacy of this approach., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

Trait social anxiety may predict differences in the cognitive control of emotional distraction when emotional face discrimination is required. This effect can be investigated using an emotional face flanker task. This study addresses an important research gap, as previous studies did not separate the effects of trait social interaction anxiety from the effects of trait social phobia upon emotional face flanker task performance. In this laboratory based behavioural experiment, the 87 participants (mean age 24.3) were university students or staff recruited via departmental adverts. We used an emotional (happy versus fearful) face flanker task, and assessed sub-clinical social anxiety with the SIAS/SPS. Elevated trait social phobia was related to an increased reaction time (RT) congruency effect, whereas trait social interaction anxiety was not. Elevated trait social interaction anxiety was related to a decreased happy face RT advantage for central target faces, but the effect of trait social phobia was very weak. Trait social interaction anxiety and trait social phobia may predict subtle differences when the cognitive control of reactions to emotional facial expressions is required. [ABSTRACT FROM AUTHOR]

Introduction: This paper aims to examine the frequency and significance of diagnostic comorbidity of psychiatric disorders and somatic diseases in a sample of patients with depression as well as present current psychopharmacological treatment of the patients in the sample. Methods: The subjects in this study sample were 489 patients from the four Western Balkan countries with current primary diagnosis of major depression according to ICD 10. Comorbid psychiatric disorders and non-psychiatric illnesses were noted according to ICD 10 criteria during the diagnostic interview and analysed later. Additionally, the pharmacological treatment (existing and newly introduced) for each patient was noted and analysed later. Results: At least one comorbid psychiatric disorder was present in 72.5% of patients. The most frequent were anxiety disorders (53.6%), specifically generalized anxiety disorder (20.2%); non-organic sleep disorders (50.7%), specifically insomnia (48.4%); and sexual dysfunctions (21.4%), specifically lack of sexual desire (20.2%). Comorbidity with any non-psychiatric illness was present in 80.3% of patients. The most frequent were circulatory system diseases (55.9%), specifically hypertension (45.9%); endocrine, nutritional and metabolic disorders (51.3%), specifically hyperlipidaemia (24.0%); and other non-psychiatric disorders (60.7%), specifically low back pain (22.7%). All patients received pharmacological treatment with different medications. Most patients received monotherapy or combination therapy of antidepressants, anxiolytics, antipsychotics and antiepileptics. The most frequently used antidepressants were escitalopram, sertraline, and duloxetine. The most frequently used anxiolytics were alprazolam and diazepam, the most used antiepileptic was pregabalin, and the most used antipsychotics were olanzapine, quetiapine, and aripiprazole. Conclusion: The results of the study confirm the results of previous research studies about the high prevalence of psychiatric and non-psychiatric comorbidities in patients with depression that were conducted in the past. It would be important if future studies could prove the importance of those comorbidities on clinical severity, choice of treatment, and its outcome in patients with depression. [ABSTRACT FROM AUTHOR]

Subcortical brain regions play essential roles in the pathology of social anxiety disorder (SAD). While adolescence is the peak period of SAD, the relationships between altered development of the subcortical regions during this period and SAD are still unclear. This study investigated the age-dependent alterations in structural co-variance among subcortical regions and between subcortical and cortical regions, aiming to reflect aberrant coordination during development in the adolescent with SAD. High-resolution T1-weighted images were obtained from 76 adolescents with SAD and 67 healthy controls (HC), ranging from 11 to 17.9 years. Symptom severity was evaluated with the Social Anxiety Scale for Children (SASC) and the Depression Self Rating Scale for Children (DSRS-C). Structural co-variance and sliding age-window analyses were used to detect age-dependent group differences in inter-regional coordination patterns among subcortical regions and between subcortical and cortical regions. The volume of the striatum significantly correlated with SAD symptom severity. The SAD group exhibited significantly enhanced structural co-variance among key regions of the striatum (putamen and caudate). While the co-variance decreased with age in healthy adolescents, the co-variance in SAD adolescents stayed high, leading to more apparent group differences in middle adolescence. Moreover, the striatum's mean structural co-variance with cortical regions decreased with age in HC but increased with age in SAD. Adolescents with SAD suffer aberrant developmental coordination among the key regions of the striatum and between the striatum and cortical regions. The degree of incoordination is age-dependent, which may represent a neurodevelopmental trait of SAD. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to evaluate the efficacy of Passiflora incarnata L for the control of anxiety during third mandibular molar extraction and compare it to midazolam, the most used benzodiazepine in dentistry. Method and materials: The investigators implemented a prospective, randomized, double-blind, split-mouth study. The degree of anxiety of the patients was assessed before the surgical procedure. The surgeries took place in two sessions: one on each side of the hemi-mandible and, on each of them, the patient received one of the drugs, crosswise. Anxiety control was measured through physical parameters, at the following periods during the surgery: (1) immediately administration of anxiolytic medication, (2) 30minutes after anxiolytic medication, (3) after extraoral antisepsis, (4) after local anesthesia, (5) during incision, (6) during osteotomy, (7) between osteotomy and odontosection, (8) during odontosection, (9) during surgical store curettage, (10) during suture, and (11) immediately after postoperative care guidelines. Lastly, the volunteers received a self-assessment form in order to report their experience. Statistical analysis was performed using the Wilcoxon test. Results: The final sample was composed of 20 patients, with a mean age of 22.5 years. The results of the physical parameters showed statistically significant differences (P < .05) for certain times and physical parameters, especially heart rate (P = .036), which showed the highest control for Passiflora at time point (3). The undesirable effects reported by patients such as drowsiness, muscle relaxation, and dizziness were greater with benzodiazepine. Conclusion: The results of this study suggest that Passiflora may be considered as an alternative to midazolam in controlling anxiety in dentistry. Future studies will focus on other benzodiazepines and herbal medicines. [ABSTRACT FROM AUTHOR]

Rationale: Chronic fatigue syndrome (CFS) is a common and burdensome illness with a poorly understood pathophysiology, though many of the characteristic symptoms are likely to be of brain origin. The use of high-field proton magnetic resonance spectroscopy (MRS) enables the detection of a range of brain neurochemicals relevant to aetiological processes that have been linked to CFS, for example, oxidative stress and mitochondrial dysfunction., Methods: We studied 22 CFS patients and 13 healthy controls who underwent MRS scanning at 7 T with a voxel placed in the anterior cingulate cortex. Neurometabolite concentrations were calculated using the unsuppressed water signal as a reference., Results: Compared to controls, CFS patients had lowered levels of glutathione, total creatine and myo-inositol in anterior cingulate cortex. However, when using N-acetylaspartate as a reference metabolite, only myo-inositol levels continued to be significantly lower in CFS participants., Conclusions: The changes in glutathione and creatine are consistent with the presence of oxidative and energetic stress in CFS patients and are potentially remediable by nutritional intervention. A reduction in myo-inositol would be consistent with glial dysfunction. However, the relationship of the neurochemical abnormalities to the causation of CFS remains to be established, and the current findings require prospective replication in a larger sample., (© 2021. The Author(s).)

Background: Anxiety and depression are psychopathological states frequently co‐occurring with severe alcohol use disorder (SAUD). These symptoms generally disappear with abstinence but may persist in some patients, increasing the relapse risk. Methods: The cerebral cortex thickness of 94 male patients with SAUD was correlated with symptoms of depression and anxiety, both measured at the end (2–3 weeks) of the detoxification treatment. Cortical measures were obtained using surface‐based morphometry implemented with Freesurfer. Results: Depressive symptoms were associated with reduced cortical thickness in the superior temporal gyrus of the right hemisphere. Anxiety level was correlated with lower cortical thickness in the rostral middle frontal region, inferior temporal region, and supramarginal, postcentral, superior temporal, and transverse temporal regions of the left hemisphere, as well as with a large cluster in the middle temporal region of the right hemisphere. Conclusions: At the end of the detoxification stage, the intensity of depressive and anxiety symptoms is inversely associated with the cortical thickness of regions involved in emotions‐related processes, and the persistence of the symptoms could be explained by these brain deficits. [ABSTRACT FROM AUTHOR]

Introduction: Pain is frequently accompanied by enhanced arousal and hypervigilance to painful sensations. Here, we describe our findings in an experimental vigilance task requiring healthy participants to indicate when randomly timed moderately painful stimuli occur in a long train of mildly painful stimuli.Methods: During a continuous performance task with painful laser stimuli (CPTpain), 18 participants rated pain intensity, unpleasantness, and salience. We tested for a vigilance decrement over time using classical metrics including correct targets (hits), incorrectly identified non-targets (false alarms), hit reaction time, and false alarm reaction time. We measured state anxiety and tense arousal before and after the task.Results: We found a vigilance decrement across four 12.5-minute blocks of painful laser stimuli in hits [F3,51=2.91; p=0.043; time block 1>block 4 (t=2.77; p=0.035)]. Both self-report state anxiety (tpaired,17=3.34; p=0.0039) and tense arousal (tpaired,17=3.20; p=0.0053) increased after the task. We found a vigilance decrement during our laser pain vigilance task consistent with vigilance decrements found in other stimulus modalities. Furthermore, state anxiety positively correlated with tense arousal.Discussion: CPTpain acutely increased tense arousal and state anxiety, consistent with previous results implicating the reciprocal interaction of state anxiety and acute painful sensations and the role of pain in augmenting tense arousal. These results may indicate a psychological process which predisposes the hypervigilant to developing greater acute pain, resulting in positive feedback, greater pain and anxiety. [ABSTRACT FROM AUTHOR]

The aim: was to assess the level of subjective control of emotional states among patients treated for dermatological and gastrointestinal somatic diseases compared to those with depressive and anxiety disorders. The results were related to the analyzed dimensions of emotion regulation in healthy subjects. Materials and methods: The reports of the conducted studies were compiled for a total of 310 people, including 120 patients diagnosed with a somatic disease (psoriasis, rosacea, irritable bowel syndrome, and gastroesophageal reflux), as well as 96 patients diagnosed with depressive disorders and 30 patients with anxiety disorders. The control group consisted of healthy subjects (64 individuals). To assess the psychological variables analyzed, the subjects completed the Emotion Regulation Questionnaire developed by J. Brzeziński. Results: The study showed that the patients suffering from a chronic somatic symptom disorder, similarly to those treated for depression and anxiety disorders, differed from the healthy individuals in most aspects of emotional control. The patients with dermatological and gastrointestinal diseases differed statistically significantly from the patients with depression and the patients with anxiety disorders in relation to three dimensions of emotional control. Patients with a somatic disease are characterized by higher emotional and rational motivation, lower emotional resilience and lower emotional arousal. Conclusions: A chronic disease co-occurs with the emotional sphere of a person's daily functioning. Regardless of the diagnosis in terms of somatic disorders and mental illnesses, the way in which emotional states are controlled can be an important factor in the onset of the disease, coping with it as well as the treatment process. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation (DBS) is still an experimental treatment modality for psychiatric disorders including treatment-resistant depression (TRD). There is preliminary evidence that stimulation of brain reward circuit structures including the ventral striatum (VS) may exert an antidepressant effect. The main nucleus of the reward circuit is the nucleus accumbens (NAc). The NAc is a major structure of VS that plays a critical role in reward-seeking behavior, motivation, and addiction. Aims: This study aimed to review the current studies including randomized clinical trials, open-label trials, and case reports of NAc/VS and VC DBS for TRD in humans. Method: The literature was reviewed using a medical database--Medical Literature, Analysis, and Retrieval System Online (MEDLINE) on NAc/VS or VC DBS in TRD. The identified studies were assessed based on the patient's characteristics, clinical outcomes, and adverse events related to DBS as well as the stereotactic technique used to guide the implantation of DBS electrodes. The inclusion and exclusion criteria of DBS for TRD were presented and discussed. Results: The searched literature revealed one case report, three open-label studies (OLS), one multicenter open-label study (mOLS), and two randomized clinical trials (RCTs). There were three additional studies reporting the clinical outcomes in the long term in TRD patients included in the two mentioned RCTs. The total number of patients with TRD treated by NAc/VS or VC is estimated to be 85 individuals worldwide. The response rate to DBS defined as a 50% reduction of postoperative Montgomery-Asberg Depression Rating Scale (MADRS) scores was achieved in 39.8% of the operated patients (range, 23-53%). The remission defined as MADRS scores of < 10 was found in 17.8% after DBS (range, 0-40%). The mean follow-up was 19.7 months (range 3.7-24 months). Conclusion: The current results of NAc/VS and VC DBS are still limited by a relatively small number of patients treated worldwide. Nevertheless, the results suggest that NAc/VS and VC can be regarded as promising and efficacious targets for DBS, taking into account the response and remission rates among TRD patients with no other treatment option. The adverse events of NAc/VS and VC DBS are reversible due to the adjustment of stimulation parameters. The most common adverse events were hypomanic/manic states, suicidal thoughts/attempts, and suicides. Patients with TRD after NAc/VS and VC DBS should be strictly followed to prevent or diminish these stimulation-induced adverse events. [ABSTRACT FROM AUTHOR]

Neurogenesis, the process of generating neurons from neural stem cells, occurs during both embryonic and adult stages, with each stage possessing distinct characteristics. Dysfunction in either stage can disrupt normal neural development, impair cognitive functions, and lead to various neurological disorders. Recent technological advancements in single-cell multiomics and gene-editing have facilitated investigations into primate neurogenesis. Here, we provide a comprehensive overview of neurogenesis across rodents, non-human primates, and humans, covering embryonic development to adulthood and focusing on the conservation and diversity among species. While non-human primates, especially monkeys, serve as valuable models with closer neural resemblance to humans, we highlight the potential impacts and limitations of non-human primate models on both physiological and pathological neurogenesis research. [ABSTRACT FROM AUTHOR]

Introduction: The high level of emotional problems in youths placed in foster care contrasts with the limited use of evidence-based treatments. This study aims to better characterize the clinical features and therapeutic outcomes of foster care youths with mood disorders. Methods: A secondary analysis of data collected in the context of a French-Canadian clinical research network on pediatric mood disorders in four sites was conducted to compare three groups of patients with depressive or bipolar disorder: those without exposure to child welfare intervention (WCWI, n = 181), those who received non-placement psychosocial intervention (NPI, n = 62), and those in placement interventions (PI, n = 41). Results: We observed a very high rate of academic problems in patients in the groups NPI/PI compared to those in the WCWI group. Patients in the PI group had more disruptive behavioral disorders (OR = 6.87, 95% CI [3.25-14.52]), traumarelated disorders (OR = 3.78, 95% CI [1.6-8.94]), and any neurodevelopmental disorders (OR = 2.73, 95% CI [1.36-5.49]) compared to the other groups (NPI/WCWI). Among inpatients, the Clinical Global Impression-Improvement scale and the change in the Children Global Assessment Scale during the hospital stay did not differ across the three groups. We observed a higher prescription rate of antipsychotics in the PI group compared to the NPI/WCWI groups, but no significant difference for antidepressants and mood stabilizers. Discussion: These findings support the view that, when provided with dedicated support, fostered inpatient youths can improve in a range comparable to other inpatients. Undetected neurodevelopmental disorders and academic problems are likely important contributors of the burden of mood disorders in these youths. [ABSTRACT FROM AUTHOR]

Early life stress (ELS), characterized as abuse, neglect, and abandonment, can cause several adverse consequences in the lives of affected individuals. ELS experiences can affect an individual's development in variable ways, persisting in the long term and promoting lasting impacts, considering that early exposure to stressors can be biologically incorporated, as prolonged stimulation of stress response systems affects the development of the brain structure and other body systems, increasing the risk of diseases associated with stress and cognitive impairment. This type of stress increases the risk of developing major depressive disorder (MDD) in a severe form that does not respond adequately to traditional antidepressant treatments. Several alterations are studied as mechanisms that relate ELS with MDD, such as epigenetic alterations, neurotransmitters, and neuronal signaling. This review discusses research that brings evidence about the ELS mechanisms involved in synaptic impairments and MDD. The processes involved in epigenetic changes and the HPA axis are highlighted, as well as changes in neurotransmitters and neuronal signaling mechanisms., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The amygdala joins the model of fear neurocircuitry for its subregional roles in processing and mediating panic. This study aims to explore the underlying neuromechanisms of temporal lobe epilepsy (TLE) patients with ictal panic (IP) by investigating the amygdala subregions functional connectivity (FC) alteration., Methods: 18 TLE patients with IP (TLE-IP group), 23 TLE patients without IP (TLE-none-IP group) and 22 age- and sex- matched healthy controls (HC) were enrolled and required to take resting-state functional magnetic resonance imaging (rs-fMRI) scanning. The basolateral (BLA), centromedial (CMA), and superficial (SFA) amygdala subregions were extracted from Juelich histological atlas. The amygdala subregions-based FC was computed and compared among three groups., Results: The TLE-IP group demonstrated stronger FC between the left BLA and right middle frontal gyrus (MFG) than the TLE-none-IP group and HC. Compared with the TLE-none-IP group and HC, the TLE-IP group showed increased FC between the right BLA and right postcentral gyrus. The FC between the left BLA/SFA and the orbital part of right MFG increased in the TLE-IP group. Furthermore, the TLE-IP group exhibited decreased FC between the left CMA and pons. Further analysis indicated altered FC between the amygdala subregions and the pons, precuneus and thalamus in the left-sided TLE-IP group, but the MFG, inferior parietal gyrus, supplementary motor area and cerebellum in the right-sided TLE-IP group., Conclusions: The present study revealed aberrant amygdala subregions-based FC in TLE patients with IP. These findings offer unique insights into the understanding of fear neurocircuitry in TLE patients with IP., (© 2024. Fondazione Società Italiana di Neurologia.)

Obesity is among the most common chronic disorders, worldwide. It is a complex disease that reflects the interactions between environmental influences, multiple genetic allelic variants, and behavioral factors. Recent developments have also shown that biological conditions in utero play an important role in the programming of energy homeostasis systems and might have an impact on obesity and metabolic disease risk. The corticotropin-releasing hormone (CRH) family of neuropeptides, as a central element of energy homeostasis, has been evaluated for its role in the pathophysiology of obesity. This review aims to summarize the relevance and effects of the CRH family of peptides in the pathophysiology of obesity spanning from fetal life to adulthood., (© 2024 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Aim: Previous behavioral pharmacology studies involving rodents suggested riluzole had potential to be an ideal psychotropic drug for psychiatric disorders with anxiety or fear as primary symptoms. Several clinical studies have recently been conducted. The purpose of this study was to gather information about the efficacy and tolerability of riluzole for patients with those symptoms. Methods: We searched PubMed, PsycINFO, CINAHL, EMBASE, and the Cochrane database from inception until April 2021, and performed manual searches for additional relevant articles. This review included: (1) studies involving participants that were patients with generalized anxiety disorder (GAD), social anxiety disorder, panic disorder, obsessive‐compulsive disorder (OCD), posttraumatic stress disorder (PTSD), acute stress disorder, or phobias; and (2) randomized controlled trials (RCTs) or intervention studies (e.g., single arm trials) examining the effects and safety of riluzole. Results: Of the 795 identified articles, four RCTs, one RCT subgroup‐analysis, and three open‐label trials without control groups met the inclusion criteria. Most trials evaluated the efficacy of riluzole as an augmentation therapy with selective serotonin reuptake inhibitors and other antidepressants for PTSD, OCD, or GAD. However, there was insufficient evidence to confirm the effects of riluzole for patients with these psychiatric disorders. Most trials demonstrated adequate study quality. Conclusions: This review found insufficient evidence to confirm the effects of riluzole for psychiatric disorders with anxiety or fear as primary symptoms. It would be worthwhile to conduct studies that incorporate novel perspectives, such as examining the efficacy of riluzole as a concomitant medication for psychotherapy. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Some of the most debilitating aspects of schizophrenia and other serious mental illnesses (SMI) are the impairments in social perception, motivation, and behavior that frequently accompany these conditions. These impairments may ultimately lead to chronic social disconnection (ie, social withdrawal, objective isolation, and perceived social isolation or loneliness), which may contribute to the poor cardiometabolic health and early mortality commonly observed in SMI. However, the psychological and neurobiological mechanisms underlying relationships between impairments in social perception and motivation and social isolation and loneliness in SMI remain incompletely understood. Study Design A narrative, selective review of studies on social withdrawal, isolation, loneliness, and health in SMI. Study Results We describe some of what is known and hypothesized about the psychological and neurobiological mechanisms of social disconnection in the general population, and how these mechanisms may contribute to social isolation and loneliness, and their consequences, in individuals with SMI. Conclusions A synthesis of evolutionary and cognitive theories with the "social homeostasis" model of social isolation and loneliness represents one testable framework for understanding the dynamic cognitive and biological correlates, as well as the health consequences, of social disconnection in SMI. The development of such an understanding may provide the basis for novel approaches for preventing or treating both functional disability and poor physical health that diminish the quality and length of life for many individuals with these conditions. [ABSTRACT FROM AUTHOR]

In the central nervous system, nitric oxide (NO), a free gas with multitudinous bioactivities, is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase (nNOS). In the past 20 years, the studies in our group and other laboratories have suggested a significant involvement of nNOS in a variety of neurological and neuropsychiatric disorders. In particular, the interactions between the PDZ domain of nNOS and its adaptor proteins, including post-synaptic density 95, the carboxy-terminal PDZ ligand of nNOS, and the serotonin transporter, significantly influence the subcellular localization and functions of nNOS in the brain. The nNOS-mediated protein-protein interactions provide new attractive targets and guide the discovery of therapeutic drugs for neurological and neuropsychiatric disorders. Here, we summarize the work on the roles of nNOS and its association with multiple adaptor proteins on neurological and neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Depression is estimated to be a leading contributor to the global mental healthrelated burden. The determinants of this huge prevalence lie in the fact that depressive symptoms may be comorbid in a wide variety of disorders, thus complicating and exacerbating their clinical framework. This makes the treatment of depressive symptoms difficult, since many pharmacological interactions should be considered by physicians planning therapy. Hence, depression still represents a challenge for both psychiatrists and other clinicians, in terms of its high rates of relapse and resistance despite well-established protocols. It is also complicated by the well-known latency in its complete response to current antidepressant treatments. In this context, the search for new strategies regarding antidepressant treatment is mandatory. Revising the use of “old” pharmacotherapies by considering their specific features may help to perfecting the treatment of depression, both in its standalone psychiatric manifestation and in the framework of other clinical conditions. Using a nominal group technique approach, the results of a consensus of expert physicians regarding the possible use of trazodone as a valuable strategy for addressing the “real world” unmet needs of depression treatment in different fields (psychiatry, primary care, neurology and geriatrics) is herein provided. This idea is based on the unique characteristics of this drug which delivers a more rapid antidepressant action as compared to other selective serotonin reuptake inhibitors. It also has pharmacodynamic malleability (i.e., the possibility of exerting different effects on depressive symptoms at different dosages) and pharmacokinetic tolerability (i.e., the possibility of being used as an add-on to other antidepressants with scarce interaction and achieving complimentary effects) when used in the milieu of other drugs in treating comorbid depressive symptoms. Moreover, the large number of formulations available permits finite dosage adjustments, and the use of trazodone for specific pathologies, such as dysphagia. Therefore, although additional studies exploring the real-world conditions of antidepressant treatment are warranted, experts agree on the idea that depressive disorder, in both its standalone and its comorbid manifestations, may surely take advantage of the particular characteristics of trazodone, thus attempting to reach the greatest effectiveness in different contexts. [ABSTRACT FROM AUTHOR]

Neurotrophins and neuropeptides are the essential regulators of peripheral nociceptive nerves that help to induce, sensitize, and maintain pain. Neuropeptide has a neuroprotective impact as it increases trophic support, regulates calcium homeostasis, and reduces excitotoxicity and neuroinflammation. In contrast, neurotrophins target neurons afflicted by ischemia, epilepsy, depression, and eating disorders, among other neuropsychiatric conditions. Neurotrophins are reported to inhibit neuronal death. Strategies maintained for "brain-derived neurotrophic factor (BDNF) therapies" are to upregulate BDNF levels using the delivery of protein and genes or compounds that target BDNF production and boosting BDNF signals by expanding with BDNF mimetics. This review discusses the mechanisms of neurotrophins and neuropeptides against acute neural damage as well as highlighting neuropeptides as a potential therapeutic agent against Parkinson's disease (PD), Huntington's disease (HD), Alzheimer's disease (AD), and Machado–Joseph disease (MJD), the signaling pathways affected by neurotrophins and their receptors in both standard and diseased CNS systems, and future perspectives that can lead to the potent application of neurotrophins and neuropeptides in neurodegenerative diseases (NDs). [ABSTRACT FROM AUTHOR]