Marker Of Panic Disorder Research Articles

Increased functional connectivity of amygdala subregions in patients with drug-naïve panic disorder and without comorbidities.

Amygdala plays an important role in the neurobiological basis of panic disorder (PD), and the amygdala contains different subregions, which may play different roles in PD. The aim of the present study was to examine whether there are common or distinct patterns of functional connectivity of the amygdala subregions in PD using resting-state functional magnetic resonance imaging and to explore the relationship between the abnormal spontaneous functional connectivity patterns of the regions of interest (ROIs) and the clinical symptoms of PD patients. Fifty-three drug-naïve, non-comorbid PD patients and 70 healthy controls (HCs) were recruited. Seed-based resting-state functional connectivity (rsFC) analyses were conducted using the bilateral amygdalae and its subregions as the ROI seed. Two samples t test was performed for the seed-based Fisher's z -transformed correlation maps. The relationship between the abnormal spontaneous functional connectivity patterns of the ROIs and the clinical symptoms of PD patients was investigated by Pearson correlation analysis. PD patients showed increased rsFC of the bilateral amygdalae and almost all the amygdala subregions with the precuneus/posterior cingulate gyrus compared with the HC group (left amygdala [lAMY]: t = 4.84, P <0.001; right amygdala [rAMY]: t = 4.55, P <0.001; left centromedial amygdala [lCMA]: t = 3.87, P <0.001; right centromedial amygdala [rCMA]: t = 3.82, P = 0.002; left laterobasal amygdala [lBLA]: t = 4.33, P <0.001; right laterobasal amygdala [rBLA]: t = 4.97, P <0.001; left superficial amygdala [lSFA]: t = 3.26, P = 0.006). The rsFC of the lBLA with the left angular gyrus/inferior parietal lobule remarkably increased in the PD group ( t = 3.70, P = 0.003). And most of the altered rsFCs were located in the default mode network (DMN). A significant positive correlation was observed between the severity of anxiety and the rsFC between the lSFA and the left precuneus in PD patients ( r = 0.285, P = 0.039). Our research suggested that the increased rsFC of amygdala subregions with DMN plays an important role in the pathogenesis of PD. Future studies may further explore whether the rsFC of amygdala subregions, especially with the regions in DMN, can be used as a biological marker of PD.

Biological and Clinical Markers in Panic Disorder.

ObjectiveClassifying mental disorders on the basis of objective makers might clarify their aetiology, help in making the diagnosis, identify “at risk” individuals, determine the severity of mental illness, and predict the course of the disorder. This study aims to review biological and clinical markers of panic disorder (PD). MethodsA computerized search was carried out in PubMed and Science Direct using the key words: “marker/biomarker/clinical marker/neurobiology/staging” combined using Boolean AND operator with “panic.” In addition, the reference lists from existing reviews and from the articles retrieved were inspected. Only English language papers published in peer-reviewed journals were included. ResultsStructural changes in the amygdala, hippocampus, cerebral blood level in the left occipital cortex, serotonin 5-TH and noradrenergic systems activation, aberrant respiratory regulation, hearth rate variability, blood cells and peripheral blood stem cells, hypothalamic–pituitary–adrenal axis dysregulation were identified as potential candidate biomarkers of PD. Staging was identified as clinical marker of PD. According to the staging model, PD is described as follows: prodromal phase (stage 1); acute phase (stage 2); panic attacks (stage 3); chronic phase (stage 4). ConclusionThe clinical utility, sensitivity, specificity, and the predictive value of biomarkers for PD is still questionable. The staging model of PD might be a valid susceptibility, diagnostic, prognostic, and predictive marker of PD. A possible longitudinal model of biological and clinical markers of PD is proposed.

Mean platelet volume and red cell distribution width levels in initial evaluation of panic disorder.

BackgroundAs the relationship between psychological stress and platelet activation has been widely studied in recent years, activated platelets lead to certain biochemical changes, which occur in the brain in patients with mental disorders. However, data relating to the mean platelet volume (MPV) in patients with panic disorder (PD) are both limited and controversial. Herein, we aimed to evaluate, for the first time, the red cell distribution width (RDW) levels combined with MPV levels in patients with PD.Patients and methodsBetween January 2012 and June 2015, data of 30 treatment-naïve patients (16 females, 14 males; mean age: 37±10 years; range: 18–59 years) who were diagnosed with PD and 25 age- and sex-matched healthy volunteers (10 females, 15 males; mean age: 36±13 years; range: 18–59 years) (control group) were retrospectively analyzed. The white blood cell count (WBC), MPV, and RDW levels were measured in both groups.ResultsThe mean WBC, MPV, and RDW levels were 9,173.03±2,400.31/mm3, 8.19±1.13 fl, and 12.47±1.14%, respectively, in the PD group. These values were found to be 7,090.24±1,032.61, 6.85±0.67, and 11.63±0.85, respectively, in the healthy controls. The WBC, MPV, and RDW levels were significantly higher in the patients with PD compared to the healthy controls (P=0.001, P=0.001, and P=0.003, respectively). However, there was no significant difference in the platelet number between the patients with PD and healthy controls (P>0.05).ConclusionOur study results are the first to demonstrate that the RDW levels combined with MPV levels significantly increase among patients with PD. We believe that increased RDW and MPV levels can be used as a novel marker for PD.

Respiratory patterns in panic disorder reviewed: a focus on biological challenge tests

To provide a systematic review of studies investigating respiration in PD and comments on relative inconsistencies. A Medline search of controlled studies focusing on pCO(2), respiratory rate, tidal volume, and minute volume in PD patients was conducted for baseline/resting condition, challenge, and recovery phase. Respiratory variability and comparisons between panickers and non-panickers were also examined. Lower pCO(2) levels in PD subjects are a consistent finding during the baseline/resting condition, the challenge, and recovery phases. Tidal volume and minute volume are increased in PD subjects relative to controls during the baseline/resting condition. However, the most robust finding is a higher than normal respiratory variability, which appears to be a promising factor for the identification of respiratory etiopathological pathways in PD. Respiratory variability might be a candidate for a biological marker of PD: an abnormal breathing pattern as found in panic disorder (PD) patients compared with controls might indicate instability of the respiratory homeostasis.

Physiological markers for anxiety: Panic disorder and phobias

Physiological activation is a cardinal symptom of anxiety, although physiological measurement is still not used for psychiatric diagnosis. An ambulatory study of phobics who were afraid of highway driving showed a concordance between self-reported anxiety during driving, autonomic activation, hypocapnia, and sighing respiration. Patients with panic attacks do not exhibit autonomic activation when they are quietly sitting and not having panic attacks, but do have the same respiratory abnormalities as driving phobics, suggesting that these abnormalities could be a marker for panic disorder. Such abnormalities are compatible with both the false suffocation alarm (D. Klein) and hyperventilation (R. Ley) theories of panic. Hypocapnia, however, is often absent during full-blown panic attacks. Since activation functions as preparation for physical activity, it may not occur when a patient has learned that avoidance of fear by flight or fight is futile. We developed a capnometry feedback assisted breathing training therapy for panic disorder designed to reduce hyperventilation and making breathing regular. Without feedback, conventional therapeutic breathing instructions may actually increase hyperventilation by increasing dyspnea. Five weekly therapy sessions accompanied by daily home practice with a capnometer produced marked clinical improvement compared to changes in an untreated group. Improvement was sustained over a 12-month follow-up period. The therapist avoided any statements or procedures designed to alter cognitions. Improvement occurred regardless of whether patients initially reported mostly respiratory or non-respiratory symptoms during their attacks. There is evidence that modifying any of the three systems comprising a fear network can be therapeutic, as exemplified by cognitive therapy modifying thoughts, exposure therapy modifying avoidance, and breathing training procedures modifying pCO 2.

Response to 5% Carbon Dioxide in Children and Adolescents

Carbon dioxide (CO(2)) sensitivity is postulated to be a familial risk marker of panic disorder (PD). Exaggerated responses to CO(2) inhalation have been reported in adults with PD and their unaffected adult relatives, as well as in clinic-referred children with anxiety disorders. To test in a family-based design whether CO(2) hypersensitivity is a familial risk marker for PD and associated with current anxiety disorders in children and adolescents. One hundred forty-two offspring (aged 9-19 years) of parents with PD, major depressive disorder, or no disorder. Forty-five (32%) had a current anxiety disorder, excluding specific phobia. Parents and offspring received diagnostic assessments. Offspring underwent 5% CO(2) inhalation at home. Panic symptoms and panic attacks were rated with the Acute Panic Inventory at baseline, while anticipating CO(2) delivery ("threat"), and during CO(2) inhalation. Respiratory rate and volume were measured with spirometry. No group differences were found in Acute Panic Inventory ratings at baseline or in respiratory measures during threat. Risk for PD was not associated with CO(2) sensitivity (panic symptoms and respiratory physiologic response). During CO(2) inhalation, offspring with anxiety disorders, relative to offspring without anxiety disorders, experienced significantly more panic symptoms and panic attacks, as well as elevated respiratory rates. During threat, panic symptoms were significantly and independently associated with both parental PD and offspring anxiety disorders. No support was obtained for CO(2) hypersensitivity as a familial risk marker for PD in children and adolescents. Links between childhood anxiety disorders and CO(2) sensitivity were replicated. Familial risk for PD in children and adolescents may be associated with vulnerability to anticipatory anxiety.

Trait anxiety, coping with stress, and norharman.

Plasma levels of the beta-carboline norharman, concentration of platelet 5-HT, trait measures of anxiety, and measures of coping and defense mechanisms were compared for 15 patients with panic disorder and 24 healthy volunteers. Patients indicated that they made less use of the defense mechanism of principalization than control subjects. No other differences between patients and controls were significant. Platelet 5-HT concentration was positively correlated with the subjectively reported anxiety. Plasma norharman concentration was negatively correlated with the defense mechanisms of principalization and repression and positively correlated with coping strategies involving palliation. The positive correlations of norharman levels with projection and self-comforting fell short of significance and existed in the patient group only. No correlation was apparent between levels of plasma norharman and scores on anxiety. It was concluded that norharman is not a marker for panic disorder or trait anxiety, but that it might reflect intrapsychic and coping processes.

TRAIT ANXIETY, COPING WITH STRESS, AND NORHARMAN

Plasma levels of the β-carboline norharman, concentration of platelet 5-HT, trait measures of anxiety, and measures of coping and defense mechanisms were compared for 15 patients with panic disorder and 24 healthy volunteers. Patients indicated that they made less use of the defense mechanism of principalization than control subjects. No other differences between patients and controls were significant. Platelet 5-HT concentration was positively correlated with the subjectively reported anxiety. Plasma norharman concentration was negatively correlated with the defense mechanisms of principalization and repression and positively correlated with coping strategies involving palliation. The positive correlations of norharman levels with projection and self-comforting fell short of significance and existed in the patient group only. No correlation was apparent between levels of plasma norharman and scores on anxiety. It was concluded that norharman is not a marker for panic disorder or trait anxiety, but that it might reflect intrapsychic and coping processes.

Is CO2 inhalation a specific marker for panic disorder? An experimental panic model.

Patients with panic disorder (PD) report a transient feeling of anxiety upon inhalation of CO2 enriched air. They rate this experience as similar to symptoms of a panic attack. This hypersensitivity has been proposed as an experimental disease model. This paper examines the validity of single breath inhalation of 35% CO2 as a model for PD.

232. - Stress — Restress: An animal model of HPA abnormalities in PTSD

s mOL PSYCIIIATRY 1996;39;500-666 567 binding. Theantisense treatment withCRH.-R AS-DON when :Jpplicll to clonal mouse pituitary cells reduced CRH·clicitcd ACTH release. Moreover, chronic infusion of CRH1R AS·DON into the central nucleus of the amygdala reduced anxiety-related behavior. This effect. however. wasnotassociated with reductions ofCRH1·R mRNA and CRH binding in this particular bruin area, Similar Investigations using AS-OON targeted against theCRH2R mRNA failed to induceanxiolytic effects in rats thal were rendered anxious by exposure to social defeat. These findings support the idea that the CRH, receptor plays it key role in mcdlating CRH·etici{ed anxiety and thus is II prime target for anxiolytlc drugs. 232. STRESS RESTRESS: AN ANIMAL MODEL OF HPA ABNORMALITIES IN PTSD I. Liberzon, M, Krstov, & E.A. Young MHRI, University of Michigan. Ann Arbor, MI 48104 While ACTH andcorticosterone responses have been extensively studied in normal or chronically stressed animals, little is known regarding the longer lasting effects of a single severe stressoron this system. This is pilrticularly important since II single stressful event can result in post traumatic stress disorder in humans. Specific HPA axis abnorrnalltiesr low 24h glucocorticoid secretion and hypersensitive negative feedback were reported in this disorder. In the current study we examined the effects of delayed stress on corticosterone and ACTH responses to restrcss and on ghicocerticold negative feedback sensitivity in rats, Sprague-Dawley male rots (250 g) were studied in II stress restress paradigm in two experiments. with and without pretreatment with cortisol. After single severe stress (2 hours restrain + swim + ether), anima/ 6.0 under the dominant genetic model) have been genotyped with an ordered set of markers encompassing ::111 {he autosomes at an average marker density of 14 eM. Over 110.000 genotypes have been generated on the whole set of families (as of November 1995)and the data have been analyzed under both dominant and a recessive models. No 100 scores exceed 2.0 foreithermodel. Two markers give lod scoresover 1.0 under dominant model, and live under the recessive model. Under the homogeneous dominant genetic model wehave 100 scoresbelow-2.0 for greaterthan85% of the genetic length of the autosomes, This collection of pedigrees is lessinformative under therecessive model. Consequently, less than 50% of 'he genetic length of the autosomes have lod scores below -2.0 with the homogeneous recessive model. Given the lack of significant positive lad scores and the presence of lod scoresbelow ·2.0 for almost all of the autosomes, we conclude' that panic disorder is unlikely to be caused by a single dominant genetic locus. A single recessive locus. dominant or recessive loci with genetic heterogeneity, ami multiple additive genetic loci can not be excluded from our results. 234. A TRAIT MARKER FOR PANIC DISORDER

Plasma interleukin-1 beta concentrations in panic disorder

Plasma interleukin-1β (IL-1β) concentrations were measured in 10 outpatients with panic disorder before and on days 30 and 32 of treatment with alprazolam (2–2.5 mg/day). IL-1β concentrations were found to be significantly higher in patients than in control subjects both before and during therapy. Thus, IL-1β levels may be a marker of panic disorder that is not related to the current level of symptomatology.

Five percent carbon dioxide challenge: Valid analogue and marker of panic disorder?

The administration of 5% carbon dioxide (CO 2) to patients with panic disorder (PD) induces a behavioral response similar to a naturally occurring panic attack. This article reviews the literature on the nature and incidence of this response. We conclude that the 5% CO 2 challenge test is a valid and useful laboratory analogue of naturally occurring panic attacks, and shows promise as a marker to identify a subset of PD patients. Though further research on reliability, validity, and dose-response effects must be conducted, the CO 2 challenge test provides important information regarding the phenomenology of panic states.