Female Panic Disorder Patients Research Articles

Panik bozukluk hastalarında cinsel işlev bozukluğu sıklığının cinsiyet açısından karşılaştırması

Purpose: The aim of this study is to evaluate the frequency of sexual dysfunction in male and female panic disorder (PD) patients and to make a comparison between genders.
 Materials and Methods: A total of 57 cases, including 33 females aged 36±6 years and 24 males aged 35±7 years, who were sexually active, did not use psychotropic drugs, with primary diagnosis of PD according to DSM-5, were included in the study. Individual information collection forms and the Arizona Sexual Experiences Scale (ASEX) were applied to all cases, and sexual dysfunctions (SD) were questioned.
 Results: According to the suggested cut-off score of the Turkish version of the Arizona Sexual Experiences Scale, 77.2% of all participants had SD. SD was detected in 81.8% of women and 70.8% of men. There was a significant difference between men and women in terms of ASEX total scores. There was no significant difference between men and women in terms of sexual desire and orgasm satisfaction. Sub-dimension scores of arousal, lubrication/erection, and reaching orgasm were significantly higher in females. Sexual reluctance was the most common in both genders, with 30.4% of women and 36.5% of men.
 Conclusion: Sexual dysfunction is common among PD patients. Sexual reluctance is the most common in male and female patients with PD. Arousal and orgasm problems are more common in female PD patients than in male PD patients.

Association between Uncinate Fasciculus Integrity and Agoraphobia Symptoms in Female Patients with Panic Disorder.

ObjectiveAlthough neural correlates of sub-clinical agoraphobia (AG) symptoms have been previously suggested, only a few studies evaluating structural changes of the brain have been conducted in agoraphobic patients with panic disorder (PD). We investigated and compared white matter (WM) micro-structural alterations between PD patients with AG (PD ＋ AG) and those without AG (PD − AG).MethodsOur study included 56 female PD patients, of which 25 were diagnosed with AG and 31 were diagnosed without AG. Diffusion tensor imaging was performed to investigate micro-structural changes in the WM tracts related to fronto-temporo-occipital areas (uncinate fasciculus, cingulum bundle, inferior longitudinal/fronto-occipital fasciculus, fornix column and body, and fornix/stria terminalis). All participants were subjected to the Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Depression Inventory-II (BDI-II), and Albany Panic and Phobia questionnaires.ResultsThe fractional anisotropy values of the right uncinate fasciculus in PD ＋ AG were significantly lower than that of PD − AG and showed significant correlations with BDI-II and ASI-R total scores. Mean diffusivity and radial diffusivity values of the right uncinate fasciculus were significantly higher in PD ＋ AG as compared to PD − AG.ConclusionOur findings suggest that the uncinate fasciculus may be associated with AG symptoms in PD, possibly through demyelination. Our findings may contribute to the neurobiological evidence regarding the association between AG and WM structural changes in PD.

Clinical Characteristics of Female Panic Disorder Patients with Abortion History

Clinical Characteristics of Female Panic Disorder Patients with Abortion History

\u201cDNA Methylation signatures in panic disorder\u201d

Panic disorder (PD) affects about four million Europeans, with women affected twice as likely as men, causing substantial suffering and high economic costs. The etiopathogenesis of PD remains largely unknown, but both genetic and environmental factors contribute to risk. An epigenome-wide association study (EWAS) was conducted to compare medication-free PD patients (n = 89) with healthy controls (n = 76) stratified by gender. Replication was sought in an independent sample (131 cases, 169 controls) and functional analyses were conducted in a third sample (N = 71). DNA methylation was assessed in whole blood using the Infinium HumanMethylation450 BeadChip. One genome-wide association surviving FDR of 5% (cg07308824, P = 1.094 × 10-7, P-adj = 0.046) was identified in female PD patients (N = 49) compared to controls (N = 48). The same locus, located in an enhancer region of the HECA gene, was also hypermethylated in female PD patients in the replication sample (P = 0.035) and the significance of the association improved in the meta-analysis (P-adj = 0.004). Methylation at this CpG site was associated with HECA mRNA expression in another independent female sample (N = 71) both at baseline (P = 0.046) and after induction by dexamethasone (P = 0.029). Of 15 candidates, 5 previously reported as associated with PD or anxiety traits also showed differences in DNA methylation after gene-wise correction and included SGK1, FHIT, ADCYAP1, HTR1A, HTR2A. Our study examines epigenome-wide differences in peripheral blood for PD patients. Our results point to possible sex-specific methylation changes in the HECA gene for PD but overall highlight that this disorder is not associated with extensive changes in DNA methylation in peripheral blood.

T24 - Sex-Specific Dna Methylation Signatures In Panic Disorder

Background Panic disorder (PD) is characterized by sudden episodes of acute anxiety occurring without any apparent reason. PD is the most disabling anxiety disorder and it affects twice as many women as men. The heritability of PD is estimated to be up to 48% and epidemiological studies show that both cumulative and specific life events are risk factors for the development of PD. Therefore, the investigation of genetic factors and gene-environment interaction is of high importance for understanding the pathophysiology of PD. As such, examining epigenetic differences in PD patients is of great interest given that environmental factors, in combination with genetic variation, can influence DNA methylation. Methods We conducted an Epigenome-Wide Association Study (EWAS) comparing non-medicated PD patients (49 females, 40 males) with healthy controls (48 females, 28 males). Replication was sought in an independent sample (131 cases, 190 controls) and further confirmed with a meta-analysis across both samples (220 cases, 266 controls). DNA methylation levels were assessed in whole blood using the Infinium HumanMethylation450 BeadChip. Failed probes were excluded based on a detection p-value larger than 0.01 in >50% of the samples. X chromosome, Y chromosome and non-specific binding probes were removed. The data were normalized with functional normalization in Minfi and batch-corrected using ComBat. Regression analyses accounting for cellular heterogeneity, sex and age were performed to test for associations between PD status and DNA methylation. To further assess functionality of the significant CpG, gene expression profiles (Illumina HumanHT-12 v3.0 array) in peripheral blood before and after exposure to the glucocorticoid receptor agonist dexamethasone were tested for association with DNA methylation in another independent female sample (N=71). Results No genome-wide associations were observed in PD patients compared to controls in the whole sample. Interestingly when stratified by sex, only the comparison of female PD patients with controls yielded one genome-wide association surviving FDR of 5% (P= 1.094 x 10-7 , P-adj=0.046). Specifically, cg07308824, located in the promoter of the HECA gene, was hypermethylated in female PD patients (N=49) compared to controls (N=48). The same CpG was also hypermethylated in female PD patients in the replication sample (P=0.035) and the genome-wide significant association was confirmed in the meta-analysis (P-adj=0.007). Methylation at this CpG site was associated with mRNA expression of HECA both at baseline (P= 0.046) and after induction by dexamethasone (P= 0.029). Pathway analyses using Web Gestalt investigating the top 50 associated CpG sites showed enrichment in female-specific pathways, e.g. female infertility pathways. Discussion Our study is the first to examine epigenome wide differences in peripheral blood for PD patients. Interestingly, our results point to possible sex-specific and functional methylation changes in PD. Further studies are needed to examine a possible contribution of the HECA gene methylation to female specific factors in PD.

Clinical Characteristics of Female Panic Disorder with Early Sexual Abuse History

Objective: Research has accumulated over the past several years demonstrating a relationship between childhood trauma such as sexual abuse and female panic disorder (PD). Most of studies have generally suffered from methodological limitations, including small sample size and not controlling for psychiatric comorbidity and suicidality which can influence the clinical characteristics. This study aimed to investigate differences of demographic and clinical characteristics between female PD patients with (PD+S) and without early sexual abuse history (PD-S). Design and Method: We examined data from 101 patients diagnosed with PD. We divided the patients with PD into PD-S (69 patients) and PD+S (32 patients) to compare demographic (age, marriage, education, suicidality history, comorbidity) and clinical characteristics [coping strategies, Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Panic disorder severity (PDSS), Anxiety Sensitivity Index (ASI), Albany Panic and Phobia Questionnaire (APPQ) - agoraphobia subscale, NEO-neuroticism (NEO-N)]. IBM SPSS version 21.0 was used for statistical analysis. Results: There were no differences between PD+S group and PD–S group with respect to demographics and coping strategies, BAI, BDI, PDSS and ASI. Compared to the PD-S, PD+S group showed higher levels of neuroticism (p=0.00) and agoraphobia (p=0.04). Conclusions: The current study suggests that female PD+S patients can be associated with neuroticism and agoraphobia. Therefore it may be needed to pay attention to the sexual abuse history in female patients with PD.

MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy.

Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28% P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.

한의학 칠정(七情)에 기반을 둔 핵심감정평가척도를 이용한 공황장애 환자의 특성 연구

Objectives: The purpose was to conduct a characteristic study on panic disorder patients through The Core Emotional Assessmental Questionnaire (CEAQ), followed by a correlation analysis with STAI, STAXI and BDI.Methods: We analyzed medical records of 62 patients who had visited ○○ University hospital, ori-ental neuropsychiatric department and completed the The Core Emotional Assessmental Questionnaire (CEAQ), STAI, STAXI, and BDI. Finally, 20 patients who were diagnosed as Panic Disorder according to DSM- Ⅴ (2013) were included in the study. Patient data was analyzed by Chi-Square test, frequency analysis, independent t-test, one-sample t-test, and correlation analysis using the SPSS (Statistical Package for the Social S 21.0 Version).Results: 1. Panic disorder patients experienced less Hui, and more Sa ( 思), Gong ( 恐), Kyeong ( 驚), and Bi (悲). 2. Female Panic disorder patients experienced more Hui (喜), as compared to male patients; whereas, male patients experienced more No ( 怒). 3. U ( 憂), Bi ( 悲), Sa ( 思), Gong ( 恐), and Kyeong ( 驚) emotions of Panic disorder patients were correlated to STAI-S, STAI-T, and BDI.Key Words: Panic Disorder, Seven Emotions, The Core Emotional Assessmental Questionnaire (CEAQ), STAI, STAXI, BDI, Characteristic study, Correlation.

Gender-Specific Association between the COMT Val158Met Polymorphism and Openness to Experience in Panic Disorder Patients

Background: Because major depression and panic disorder are both more prevalent among females and since several lines of evidence suggest that genetic factors might influence an individual's vulnerability to panic disorder, gene-gender interactions are being examined in such psychiatric disorders and mental traits. A number of studies have suggested that specific genes, e.g. catechol-O-methyltransferase (COMT), might lead to distinct clinical characteristics of panic disorder. Method: We compared gender-specific personality-related psychological factors of 470 individuals with panic disorder and 458 healthy controls in terms of their COMT Val158Met polymorphism and their scores on the Revised NEO Personality Inventory (NEO PI-R) and State-Trait Anxiety Inventory (STAI) with a 1-way analysis of covariance. Results: In the male panic disorder patients, the NEO PI-R score for openness to experience was significantly lower in the Met/Met carrier group, whereas there was no such association among the female panic disorder patients or the male or female control groups. Conclusion: The gender-specific effect of the COMT genotype suggests that the COMT Val/Met genotype may influence a personality trait, openness to experience, in males with panic disorder.

Dopamine transporter binding in females with panic disorder may vary with clinical status

Background To date the involvement of dopamine system in neurobiology of panic disorder (PD) has been not investigated by imaging studies in humans. In this study, we evaluated the binding potential of dopamine transporter (DAT) in striatum of patients with PD. Methods Subjects comprised seven female patients with current PD, seven female PD patients in remission and seven female healthy controls, matched by age. Striatal DAT binding was evaluated using single-photon emission computed tomography and [ 123I]nor-β-CIT tracer. Results Significantly higher DAT binding in striatum was detected in remitted PD females as compared with both currently ill PD and control females. The females with current PD demonstrated non-significant lowering in striatal DAT binding as compared with healthy controls. The correlation analysis in total sample of female patients showed significant and inverse relationship between striatal DAT binding characteristics and severity of panic symptoms. Conclusions This is first report showing that DAT binding in striatum may depend on the clinical status in females with PD. Our data suggest that increased level of DAT may contribute to stability of remission; however, the exact involvement of dopamine system in PD pathogenesis requires further investigations. The preliminary results of current study should be confirmed by other independent studies and should also be extended to include male patients.

Associations between serotonin-related gene polymorphisms and panic disorder

Studies suggest that vulnerability to panic attacks and panic disorder (PD) may be related to a deficient serotonin (5-HT) neurotransmission. In the present case-control study we investigated possible associations between PD phenotype and five candidate polymorphisms including 5-HT transporter (5-HTTLPR and VNTR), monoamine oxidase A (MAOA promoter region), tryptophan hydroxylase 1 (TPH1 218A/C) and 5-HT1B receptor (5-HT1BR 861G/C) genes. The study sample consisted of 158 patients with PD and 215 healthy control subjects. The analysis showed higher frequencies of LL genotype (p = 0.016) and L allele variant (p = 0.007) of 5-HTTLPR in the patients. No significant associations were observed between PD and other candidate gene polymorphisms. However, a higher frequency of longer allele genotypes of the MAOA promoter region was observed in female PD patients with agoraphobia than in female controls (p = 0.016). These findings indicate that genetic variants conceivably related to lower 5-HT neurotransmission may be involved in the development of PD.

The N200 abnormalities of auditory event-related potentials in patients with panic disorder

Cognitive impairment in patients with panic disorder (PD) has been studied using event-related potentials (ERPs). However, previous studies obtained ERP data only at a few scalp sites, and seldom investigated N200 measurements from the difference waveforms. In the present study, auditory ERPs were recorded at 16 scalp sites during an active discrimination task of oddball paradigm. Fourteen PD patients (8 with agoraphobia; 6 without agoraphobia) were compared with 14 sex- and age-matched control subjects. For the nontarget waveforms, P2 amplitude was reduced in PD patients. For the target waveforms, a topographical difference between female PD patients and female controls was found for N200 amplitude, which attenuated in female PD patients over the parietal area. Two subcomponents of N200, N2a and N2b, were measured from the difference waveforms. A significant group difference was found for N2b amplitude, which reduced in PD patients compared with unaffected control subjects. It is suggested that N2b reduction reflects an abnormally controlled processing of stimulus information in PD.

Effect of ethinyl estradiol on the panic response to the panicogenic agent pentagastrin

Background: Panic disorder (PD) symptomatology has been reported to be altered by hormonal events or treatments which affect estrogen levels. Coryell et al. [Arch. Gen. Psychiatry, 39 (1982) 701–703; Am. J. Psychiatry, 143 (1986) 508–510] have suggested that the increased cardiovascular risk associated with PD is significantly greater in males, alluding to a potential cardioprotective effect of female hormones in the context of panic attacks. In the present study, we were, therefore, interested in elucidating the role of estrogen in modulating the behavioural and cardiovascular responses induced by the panicogenic agent pentagastrin, a cholecystokinin-B (CCK B) receptor agonist. Methods: A double-blind cross-over placebo-controlled design with randomization of the order of a 3-day pretreatment of ethinyl estradiol (EE) (50 μg/day) or placebo was used to assess the effect of a 30-μg i.v. bolus injection of pentagastrin on panic symptom intensity and on increases in heart rate (ΔHR), systolic (ΔSBP) and diastolic (ΔDBP) blood pressure following each pretreatment. Subjects were 9 male healthy controls and 11 male PD patients. Results: EE pretreatment did not significantly reduce the pentagastrin-induced panic symptom scale (PSS) scores and had no effect on ΔDBP or ΔSBP. EE did, however, attenuate the pentagastrin-induced increase in HR in both PD patients and healthy controls. Limitations: Only male subjects were included in the present study, however, we are currently investigating the influence of female gonadal hormones on the panic response to pentagastrin in female PD patients and healthy controls. Conclusion: Our results suggest that estrogens may display cardioprotective effects in the context of panic attacks.

Gender-related distribution of personality disorders in a sample of patients with panic disorder

Objective. We examined gender differences in the frequency of DSM-IV personality disorder diagnoses in a sample of patients with a diagnosis of panic disorder (PD). Method. One hundred and eighty-four outpatients with a principal diagnosis of PD (DSM-IV) were enrolled. All patients were evaluated with a semi-structured interview to collect demographic and clinical data and to generate Axis I and Axis II diagnoses in accordance with DSM-IV criteria. Results. Males were significantly more likely than females to meet diagnoses for schizoid and borderline personality disorder. Compared to males, females predominated in histrionic and cluster C diagnoses, particularly dependent personality disorder diagnoses. A significant interaction was found between female sex and agoraphobia on personality disorder (PD) distribution. Conclusions. Male PD patients seem to be characterized by more severe personality disorders, while female PD patients, particularly with co-morbid agoraphobia, have higher co-morbidity rates with personality disorders belonging to the ‘anxious-fearful cluster’.

Brief research report: Somatization in young versus older female panic disorder patients

Background and rationale. Studies in younger patients with panic disorder suggest greater somatization compared to similarly aged normal controls. Thus, we compared the degree of somatization in young versus older female patients with panic disorder to ascertain whether similarly high levels of somatization exist in older panic disorder patients. Method. Community-dwelling subjects were recruited for clinical trials for panic disorder and met Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria for panic disorder as a primary diagnosis. Our sample (N=64) contained 42 younger females (&ltno;55 years of age; age range 21–54, mean age 34·6) who were compared to 22 older females (&geqno;55 years of age; age range 55–73, mean age 60·8). Subjects were evaluated at baseline using the Self-Report Inventory for Somatic Symptoms (SISS). Statistical analysis of total somatization disorder scores (TSDS) was accomplished by t-tests for independent groups. Results. Older patients showed statistically significantly higher total somatization disorder scores (TSDS) (X=11·54, SD=7·45) than did younger patients (X=8·07, SD=4·77; t(62)=2·27, p=<0·05). Conclusion. Our results are suggestive of a higher degree of somatization in older compared to younger female panic disorder patients. © 1998 John Wiley & Sons, Ltd.

Somatization in young versus older female panic disorder patients.

Studies in younger patients with panic disorder suggest greater somatization compared to similarly aged normal controls. Thus, we compared the degree of somatization in young versus older female patients with panic disorder to ascertain whether similarly high levels of somatization exist in older panic disorder patients. Community-dwelling subjects were recruited for clinical trials for panic disorder and met Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria for panic disorder as a primary diagnosis. Our sample (N = 64) contained 42 younger females (< 55 years of age; age range 21-54, mean age 34.6) who were compared to 22 older females (> or = 55 years of age; age range 55-73, mean age 60.8). Subjects were evaluated at baseline using the Self-Report Inventory for Somatic Symptoms (SISS). Statistical analysis of total somatization disorder scores (TSDS) was accomplished by t-tests for independent groups. Older patients showed statistically significantly higher total somatization disorder scores (TSDS) (X = 11.54, SD = 7.45) than did younger patients (X = 8.07, SD = 4.77; t(62) = 2.27, p = < 0.05). Our results are suggestive of a higher degree of somatization in older compared to younger female panic disorder patients.

Response to meta-chlorophenylpiperazine in panic disorder patients and healthy subjects: Influence of reduction in intravenous dosage

As a further test of the hypothesis of serotonin hypersensitivity in panic disorder (PD), the serotonin agonist meta-chlorophenylpiperazine (MCPP) was administered intravenously in a dose of 0.05 mg/kg to 27 PD patients and 22 normal control subjects. This is one-half the dose used in our previous study of PD patients, where the dose may have been too high to provide evidence of hypersensitivity to the agent. Responses of anxiety and nervousness were statistically indistinguishable by analysis of variance in the two groups, replicating our previous findings. Panic attack symptom score (PASS) ratings were significantly higher in the PD group, compared with a trend toward higher PASS ratings in the 0.1 mg/kg study. Cortisol, human growth hormone, and male prolactin responses showed no significant differences in the two groups by analysis of variance. Prolactin responses were significantly blunted in the female patients. The unexpected blunted prolactin response to MCPP in female PD patients may reflect a nonspecific blunting of prolactin response to stress. The PASS data provide some evidence of serotonergic hypersensitivity in PD.

Pituitary hormone responses to meta-chlorophenylpiperazine in panic disorder and healthy control subjects

The present study reports adrenocorticotropic hormone (ACTH) and prolactin responses after oral administration of 0.25 mg/kg of the serotonin agonist, meta-chlorophenylpiperazine (MCPP), in patients with panic disorder (PD) and in healthy subjects. MCPP blood levels were similar for the two groups, but almost twice as high in males as in females. Female patients had augmented ACTH and prolactin release as compared to healthy females, while ACTH and prolactin release in male patients was similar to that of male controls. These results suggest that female PD patients have hypersensitive serotonin receptors. Moreover, they indicate that pharmacokinetic gender differences may affect challenge studies, and that different doses may be required to study neuroendocrine responses in males and females.

Risk Factors for Cardiovascular Illness in Panic Disorder Patients

Supine and standing heart rate (HR) and blood pressure measures were compared among 19 nonsmoking normal controls, 29 smoking patients and 36 nonsmoking patients with panic disorder. The smoking patients had a significantly higher supine HR, standing diastolic blood pressure, standing mean blood pressure and supine and standing cardiac load measures compared to both patient nonsmokers and controls. There was no significant difference between controls and nonsmoking patients for any of the above measures except for the higher standing HR and the ▵ increase in HR upon standing in female panic disorder patients which suggests increased adrenergic activity. When lipid values of panic disorder patients (n = 92) were compared to National Reference Values for their sex and age for an increased risk of cardiovascular illness, there was no significant risk with regard to plasma levels of total cholesterol, high-density lipoprotein cholesterol or low-density lipoprotein cholesterol.