Alterations of oral microbiota in patients with panic disorder.

The main characteristics of panic disorder (PD) include recurrent panic attacks and persistent worry, accompanied by other physical and cognitive symptoms. While recent studies have revealed that gut bacteria play an important role in anxiety and depression, little is known about the relationship between oral microbiota and PD. Therefore, the objective of this study was to explore a possible correlation between oral microbiota and PD. We conducted 16S rRNA sequencing to compare differences in the oral microbiota of patients with PD (n = 26) and healthy controls (n = 40). Patients with PD exhibited higher alpha diversity (abundance and evenness) in their oral microbiota than healthy controls, while analysis of beta diversity revealed that the two groups differed in microbial community composition. Moreover, the relative abundance of 61 genera differed between them. Overall, PD resulted in distinct oral microbial profiles that could be potential diagnostic markers and therapeutic targets.

Lasting effects of ketamine and isoflurane administration on anxiety- and panic-like behavioral responses in Wistar rats.

In clinical and laboratory practice, the use of anesthetics is essential in order to perform surgeries. Anesthetics, besides causing sedation and muscle relaxation, promote several physiological outcomes, such as psychotomimetic alterations, increased heart rate, and blood pressure. However, studies depicting the behavioral effect induced by ketamine and isoflurane are conflicting. In the present study, we assessed the behavioral effects precipitated by ketamine and isoflurane administration. We have also evaluated the ketamine effect on cell cytotoxicity and viability in an amygdalar neuronal primary cell culture. Ketamine (80 mg/kg) caused an anxiogenic effect in rats exposed to the elevated T-maze test (ETM) 2 and 7 days after ketamine administration. Ketamine (40 and 80 mg/kg) administration also decreased panic-like behavior in the ETM. In the light/dark test, ketamine had an anxiogenic effect. Isoflurane did not change animal behavior on the ETM. Neither ketamine nor isoflurane changed the spontaneous locomotor activity in the open field test. However, isoflurane-treated animals explored less frequently the OF central area seven days after treatment. Neither anesthetic caused oxidative damage in the liver. Ketamine also reduced cellular metabolism and led to neuronal death in amygdalar primary cell cultures. Thus, our work provides evidence that ketamine and isoflurane induce pronounced long lasting anxiety-related behaviors in male rats.

The Mediating Effect of Insomnia on the Relationship between Panic Symptoms and Depression in Patients with Panic Disorder.

BACKGROUND: This study aimed to determine if sleep disturbances may mediate the relationship between panic symptoms and depression in patients with panic disorder (PD). METHODS: Electronic medical records were retrospectively reviewed for 110 consecutive patients with diagnosed PD in an outpatient clinic between October 2018 and December 2019. Measurements include the PD Severity Scale, Beck Depression Inventory-II (BDI-II) and Insomnia Severity Index (ISI). Statistical analyses were performed to assess any potential relationship between PD, insomnia and depression. RESULTS: Of the PD patients, 88 (80%) and 89 (80.9%) had comorbid depression (BDI-II ≥ 14) and insomnia (Korean version of the ISI ≥ 8), respectively. In a mediation model using insomnia as the mediating variable, the total effect of panic symptom severity on depression was significant (t = 7.23, P < 0.001). There were significant effects of panic symptoms on insomnia (t = 4.62, P < 0.001) and of insomnia on depression (t = 6.69, P < 0.001). The main effect of panic symptom severity on depression was also significant, after controlling for the effect of insomnia (t = 5.10, P < 0.001), suggesting partial mediation. CONCLUSION: Both depressive symptoms and insomnia are common in patients with PD and depression was partially mediated by insomnia in these patients. These results suggest that an intervention for insomnia in patients with PD might help prevent the development of depression.

The modulating impact of cigarette smoking on brain structure in panic disorder: a voxel-based morphometry study.

Cigarette smoking increases the likelihood of developing anxiety disorders, among them panic disorder (PD). While brain structures altered by smoking partly overlap with morphological changes identified in PD, the modulating impact of smoking as a potential confounder on structural alterations in PD has not yet been addressed. In total, 143 PD patients (71 smokers) and 178 healthy controls (62 smokers) participated in a multicenter magnetic resonance imaging (MRI) study. T1-weighted images were used to examine brain structural alterations using voxel-based morphometry in a priori defined regions of the defensive system network. PD was associated with gray matter volume reductions in the amygdala and hippocampus. This difference was driven by non-smokers and absent in smoking subjects. Bilateral amygdala volumes were reduced with increasing health burden (neither PD nor smoking > either PD or smoking > both PD and smoking). As smoking can narrow or diminish commonly observed structural abnormalities in PD, the effect of smoking should be considered in MRI studies focusing on patients with pathological forms of fear and anxiety. Future studies are needed to determine if smoking may increase the risk for subsequent psychopathology via brain functional or structural alterations.

Anterior hippocampal volume predicts affect-focused psychotherapy outcome.

BACKGROUND: The hippocampus plays an important role in psychopathology and treatment outcome. While posterior hippocampus (PH) may be crucial for the learning process that exposure-based treatments require, affect-focused treatments might preferentially engage anterior hippocampus (AH). Previous studies have distinguished the different functions of these hippocampal sub-regions in memory, learning, and emotional processes, but not in treatment outcome. Examining two independent clinical trials, we hypothesized that anterior hippocampal volume would predict outcome of affect-focused treatment outcome [Interpersonal Psychotherapy (IPT); Panic-Focused Psychodynamic Psychotherapy (PFPP)], whereas posterior hippocampal volume would predict exposure-based treatment outcome [Prolonged Exposure (PE); Cognitive Behavioral Therapy (CBT); Applied Relaxation Training (ART)]. METHODS: Thirty-five patients with posttraumatic stress disorder (PTSD) and 24 with panic disorder (PD) underwent structural magnetic resonance imaging (MRI) before randomization to affect-focused (IPT for PTSD; PFPP for PD) or exposure-based treatments (PE for PTSD; CBT or ART for PD). AH and PH volume were regressed with clinical outcome changes. RESULTS: Baseline whole hippocampal volume did not predict post-treatment clinical severity scores in any treatment. For affect-focused treatments, but not exposure-based treatments, anterior hippocampal volume predicted clinical improvement. Smaller AH correlated with greater affect-focused treatment improvement. Posterior hippocampal volume did not predict treatment outcome. CONCLUSIONS: This is the first study to explore associations between hippocampal volume sub-regions and treatment outcome in PTSD and PD. Convergent results suggest that affect-focused treatment may influence the clinical outcome through the 'limbic' AH, whereas exposure-based treatments do not. These preliminary, theory-congruent, therapeutic findings require replication in a larger clinical trial.

White matter connectivity differences between treatment responders and non-responders in patients with panic disorder.

BACKGROUND: Panic disorder (PD) is a prevalent and highly disabling mental condition. However, less is known about relationships between biomarkers that may together predict a better response to pharmacological treatment. The objective of the present study was to compare the brain white matter (WM) connectivity between treatment-responsive patients with panic disorder (RPD) and non-responsive patients with panic disorder (NRPD) after 12 weeks of pharmacotherapy. METHODS: Sixty-four patients with PD were enrolled in this study (RPD, n = 37; NRPD, n = 27). All patients were examined by using magnetic resonance imaging at 3 Tesla. The Panic Disorder Severity Scale (PDSS), Albany Panic and Phobia Questionnaire (APPQ), Anxiety Sensitivity Inventory-Revised (ASI-R), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) were administered at baseline of the study. Fractional anisotropy (FA) data were compared using tract-based spatial statistics (TBSS). RESULTS: TBSS results showed that the FA values of the patients with NRPD were significantly higher than of those with RPD in the WM regions such as the precentral gyrus, parahippocampal gyrus, posterior corona radiata, posterior thalamic radiation, posterior parts of the corpus callosum, and precuneus. Symptom severity scales, such as ASI-R scores, showed significant positive correlations of the FA values with the fronto-temporal WM regions in NRPD. CONCLUSIONS: These results suggest that structural changes to areas such as the fronto-limbic regions and the posterior part of default mode network, could influence medication response in PD. Further studies with a larger number of patients should be performed to confirm our findings.

Common and different neural markers in major depression and anxiety disorders: A pilot structural magnetic resonance imaging study.

Although anxiety and depression often co-occur and share some clinical features, it is still unclear if they are neurobiologically distinct or similar processes. In this study, we explored common and specific cortical morphology alterations in depression and anxiety disorders. Magnetic Resonance Imaging data were acquired from 13 Major Depressive Disorder (MDD), 11 Generalized Anxiety Disorder (GAD), 11 Panic Disorder (PD) patients and 21 healthy controls (HC). Regional cortical thickness, surface area (SA), volume and gyrification were measured and compared among groups. We found left orbitofrontal thinning in all patient groups, as well as disease-specific alterations. MDD showed volume deficits in left precentral gyrus compared to all groups, volume and area deficits in right fusiform gyrus compared to GAD and HC. GAD showed lower SA than MDD and PD in right superior parietal cortex, higher gyrification than HC in right frontal gyrus. PD showed higher gyrification in left superior parietal cortex when compared to MDD and higher SA in left postcentral gyrus compared to all groups. Our results suggest that clinical phenotypic similarities between major depression and anxiety disorders might rely on common prefrontal alterations. Frontotemporal and parietal abnormalities may represent unique biological signatures of depression and anxiety.

Symptom trajectories in patients with panic disorder in a primary care intervention: Results from a randomized controlled trial (PARADISE).

This analysis aims to identify and characterize symptom trajectories in primary care patients with panic disorder with/without agoraphobia (PD/AG) who participated in a primary care team based training involving elements of cognitive behavioural therapy (CBT). Growth Mixture Modeling was used to identify different latent classes of change in patients with PD/AG (N = 176) who underwent treatment including CBT elements. We identified three patient classes with distinct similar trajectories. Class 1 (n = 58, mean age: 46.2 years ± 13.4 years, 81% women) consisted of patients with an initially high symptom burden, but symptoms declined constantly over the intervention period. Symptoms of patients in class 2 (n = 89, mean age: 44.2 years ± 14.5 years, 67.4% women) declined rapidly at the beginning, then patients went into a plateau-phase. The third class (n = 29, mean age: 47.0 years ± 12.4 years, 65.5% women) was characterized by an unstable course and had the worse outcome. Our findings show that only a minority did not respond to the treatment. To identify this minority and refer to a specialist would help patients to get intensive care in time.

Comparison of Cortisol Stress Response in Patients with Panic Disorder, Cannabis-Induced Panic Disorder, and Healthy Controls.

BACKGROUND/AIMS: Little research effort has so far been dedicated to the analysis of the hypothalamic-pituitary-adrenal axis of aetiologically differing subgroups of patients with panic disorder (PD). The current study aimed at a deeper understanding of the cortisol stress response in cannabis-induced PD (CIPD) patients. METHODS: Matched groups of 7 PD patients (mean age ± SD: 32.95 ± 9.04 years), 7 CIPD patients (31.94 ± 8.40 years), and 7 healthy controls (HC) (31.13 ± 8.57 years) were included in the study. The Trier Social Stress Test (TSST) was used for stress induction. Salivary cortisol samples were collected and panic- and depression-related questionnaires were applied. RESULTS: A stress response to the TSST was found in 28.6% of PD patients, in 51.1% of CIPD patients, and in 100% of HC subjects. Statistical analyses revealed a cortisol hyporesponsiveness in PD and CIPD patients. While cortisol values of PD patients and HC participants differed significantly, CIPD patients' cortisol courses balanced between those of PD patients and HC subjects. CONCLUSIONS: Current findings show a distinctive pattern of the stress-induced cortisol reaction in CIPD patients, which is markedly different from the hormonal response in PD patients as well as HC subjects. Previous findings of cortisol hyporesponsiveness in PD patients compared to HC subjects were confirmed.

Thalamic shape and volume abnormalities in female patients with panic disorder.

The thalamus is believed to play crucial role in processing viscero-sensory information, and regulating the activity of amygdala in patients with panic disorder (PD). Previous functional neuroimaging studies have detected abnormal activation in the thalamus in patients with PD compared with healthy control subjects (HC). Very few studies, however, have investigated for volumetric abnormalities in the thalamus in patients with PD. Furthermore, to the best of our knowledge, no previous study has investigated for shape abnormalities in the thalamus in patients with PD. Twenty-five patients with PD and 25 HC participants (all female) were recruited for the study. A voxel-wise volume comparison analysis and a vertex-wise shape analysis were conducted to evaluate structural abnormalities in the PD patients compared to HC. The patients with PD demonstrated significant gray matter volume reductions in the thalamus bilaterally, relative to the HC. The shape analysis detected significant inward deformation in some thalamic regions in the PD patients, including the anterior nucleus, mediodorsal nucleus, and pulvinar nucleus. PD patients showed shape deformations in key thalamic regions that are believed to play a role in regulating emotional and cognitive functions.

Smaller volumes in the lateral and basal nuclei of the amygdala in patients with panic disorder.

The amygdala plays an important functional role in fear and anxiety. Abnormalities in the amygdala are believed to be involved in the neurobiological basis of panic disorder (PD). Previous structural neuroimaging studies have found global volumetric and morphological abnormalities in the amygdala in patients with PD. Very few studies, however, have explored for structural abnormalities in various amygdala sub-regions, which consist of various sub-nuclei, each with different functions. This study aimed to evaluate for volumetric abnormalities in the amygdala sub-nuclei, in order to provide a better understanding neurobiological basis of PD. Thirty-eight patients with PD and 38 matched healthy control (HC) participants underwent structural MRI scanning. The volume of the whole amygdala, as well as its consistent sub-nuclei, were calculated using FreeSurfer software. Relative volumes of these amygdala sub-regions were compared between the two groups. Results showed significantly smaller volumes in the right lateral and basal nuclei in the patients with PD compared with the HC. Lateral and basal nuclei are thought to play crucial role for processing sensory information related with anxiety and fear. Our results suggest that these particular amygdala sub-regions play a role in the development of PD symptoms.

Cortical thickness reductions in the middle frontal cortex in patients with panic disorder.

BACKGROUND: Panic disorder (PD), an anxiety disorder characterized by the recurrence of panic attacks, has been reported to be associated with volumetric changes in several brain regions. There are, however, very few studies investigating abnormalities in cortical thickness, and little is known about the relationship between cortical thickness and social dysfunction in PD. METHODS: Thirty-eight patients with PD and 38 healthy control participants (HC) were recruited for this study. A whole-brain analysis was performed to evaluate groupwise differences in cortical thickness using the FreeSurfer software. Symptom severity and social functioning were evaluated with the Panic Disorder Severity Scale (PDSS) and the Global Assessment of Functioning (GAF) scale. RESULTS: The patients with PD demonstrated a significant reduction in cortical thickness in the left rostral middle frontal cortex (MFC), compared with the HC. Correlational analyses revealed that cortical thickness in the left rostral MFC showed a significant negative relationship with PDSS score and a significant positive relationship with GAF scores in the PD patients. LIMITATIONS: All the patients received medication. CONCLUSION: PD patients showed reduced cortical thickness in the left rostral MFC compared with HC. Furthermore, cortical thickness in this region was associated with patients' symptom severity and degree of social dysfunction.

The Rodent-versus-wild Snake Paradigm as a Model for Studying Anxiety- and Panic-like Behaviors: Face, Construct and Predictive Validities.

Using an innovative approach to study the neural bases of psychiatric disorders, this study investigated the behavioral, morphological and pharmacological bases of panic attack-induced responses in a prey-versus-coral snake paradigm. Mesocricetus auratus was chronically treated with intraperitoneal administration of the selective serotonin uptake inhibitor paroxetine or the gamma aminobutyric acid (GABA)/benzodiazepine receptor agonist alprazolam at three different doses and were then confronted with a venomous coral snake (Micrurus frontalis, Reptilia, Elapidae). The threatened rodents exhibited defensive attention, flat back approaches, defensive immobility, and escape defensive responses in the presence of the venomous snake, followed by increases in Fos protein in limbic structure neurons. Chronic administration of both paroxetine and alprazolam decreased these responses with morphological correlates between the panicolytic effect of both drugs administered at the highest dose and decreases in Fos protein-immunolabeled perikarya found in the amygdaloid complex, hypothalamus and periaqueductal gray matter columns, which are structures that make up the encephalic aversion system. These findings provide face, construct and predictive validities of this new experimental model of anxiety- and panic attack-like behavioral responses displayed by threatened prey confronted with venomous coral snakes.

Reduced Cortical Thickness in the Temporal Pole, Insula, and Pars Triangularis in Patients with Panic Disorder.

PURPOSE: Recent neuroimaging findings have revealed that paralimbic and prefrontal regions are involved in panic disorder (PD). However, no imaging studies have compared differences in cortical thickness between patients with PD and healthy control (HC) subjects. MATERIALS AND METHODS: Forty-seven right-handed patients with PD who met the diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders-4th edition-text revision, and 30 HC subjects were enrolled. We used the FreeSurfer software package for estimating the cortical thickness of regions of interest, including the temporal pole, insula, and pars triangularis (mid-ventrolateral prefrontal cortex). RESULTS: Cortical thickness of the temporal pole (p=0.033, right), insula (p=0.017, left), and pars triangularis (p=0.008, left; p=0.025, right) in patients with PD was significantly lower, compared with HC subjects (Benjamini-Hochberg false discovery rate correction). Exploratory analysis revealed a significant negative correlation between the cortical thickness of the right temporal pole and Beck Depression Inventory scores (r=-0.333, p=0.027) in patients with PD and positive correlations between the cortical thickness of the left pars triangularis and Panic Disorder Severity Scale (r=0.429, p=0.004), Anxiety Sensitivity Index-Revised (r=0.380, p=0.011), and Beck Anxiety Inventory (r=0.421, p=0.004) scores using Pearson's correlation. CONCLUSION: Ours study is the first to demonstrate cortical thickness reduction in the temporal pole, insula, and pars triangularis in patients with PD, compared with the HC subjects. These findings suggest that reduced cortical thickness could play an important role in the pathophysiology of PD.

A magnetoencephalography investigation of coherence source imaging in panic disorder.

Limbic and frontal structures are largely implicated in panic disorder (PD). Decreased coherence imaging values, as determined by magnetoencephalography (MEG), are suggestive of decreased or inefficient communication among these structures. We have previously demonstrated that coherence source imaging (CSI) values could be similar or higher in some PD patients. The purpose of the current investigation was to replicate these finding in a larger sample. Nine strictly diagnosed PD patients and nine age-matched and sex-matched healthy controls were examined. The CSI-MEG values of 26 frontotemporal regions (FTRs) and 28 extra-frontotemporal regions (ex-FTR; Brodmann areas) were determined for each participant. MEG scans were acquired using a 151-channel whole-head biomagnetometer system. Despite the relatively small sample size, CSI values were significantly lower in a number of FTRs in PD patients. In none of the ex-FTRs (i.e. posterior regions) were there differences between panic and control groups. The above data add to the complexity of understanding the nature of the pathophysiology of PD. Our finding of decreased focal coherence imaging values may reflect decreased excitability in these areas. The preliminary finding could be interpreted as an inhibitory process guarding against the spread of activity in closer hyperexcitable areas as seen in epilepsy. The current data provide evidence for dysfunctional communication within the frontotemporal structures. The findings have implications for the understanding of the neural circuitry underlying PD.

Commonalities and differences in the neural substrates of threat predictability in panic disorder and specific phobia.

Different degrees of threat predictability are thought to induce either phasic fear or sustained anxiety. Maladaptive, sustained anxious apprehension is thought to result in overgeneralization of anxiety and thereby to contribute to the development of anxiety disorders. Therefore, differences in threat predictability have been associated with pathological states of anxiety with specific phobia (SP) representing phasic fear as heightened response to predictable threat, while panic disorder (PD) is characterized by sustained anxiety (unpredictable threat) and, as a consequence, overgeneralization of fear. The present study aimed to delineate commonalities and differences in the neural substrates of the impact of threat predictability on affective processing in these two anxiety disorders. Twenty PD patients, 20 SP patients and 20 non-anxious control subjects were investigated with an adapted NPU-design (no, predictable, unpredictable threat) using whole-head magnetoencephalography (MEG). Group independent neural activity in the right dlPFC increased with decreasing threat predictability. PD patients showed a sustained hyperactivation of the vmPFC under threat and safety conditions. The magnitude of hyperactivation was inversely correlated with PDs subjective arousal and anxiety sensitivity. Both PD and SP patients revealed decreased parietal processing of affective stimuli. Findings indicate overgeneralization between threat and safety conditions and increased need for emotion regulation via the vmPFC in PD, but not SP patients. Both anxiety disorders showed decreased activation in parietal networks possibly indicating attentional avoidance of affective stimuli. Present results complement findings from fear conditioning studies and underline overgeneralization of fear, particularly in PD.

Mobilization of Peripheral Blood Stem Cells and Changes in the Concentration of Plasma Factors Influencing their Movement in Patients with Panic Disorder.

In this paper we examined whether stem cells and factors responsible for their movement may serve as new biological markers of anxiety disorders. The study was carried out on a group of 30 patients diagnosed with panic disorder (examined before and after treatment), compared to 30 healthy individuals forming the control group. We examined the number of circulating HSCs (hematopoetic stem cells) (Lin-/CD45 +/CD34 +) and HSCs (Lin-/CD45 +/AC133 +), the number of circulating VSELs (very small embryonic-like stem cells) (Lin-/CD45-/CD34 +) and VSELs (Lin-/CD45-/AC133 +), as well as the concentration of complement components: C3a, C5a and C5b-9, SDF-1 (stromal derived factor) and S1P (sphingosine-1-phosphate). Significantly lower levels of HSCs (Lin-/CD45 +/AC133 +) have been demonstrated in the patient group compared to the control group both before and after treatment. The level of VSELs (Lin-/CD45-/CD133 +) was significantly lower in the patient group before treatment as compared to the patient group after treatment.The levels of factors responsible for stem cell movement were significantly lower in the patient group compared to the control group before and after treatment. It was concluded that the study of stem cells and factors associated with their movement can be useful in the diagnostics of panic disorder, as well as differentiating between psychotic and anxiety disorders.

White matter correlates of anxiety sensitivity in panic disorder.

BACKGROUND: Anxiety sensitivity (AS) refers to a fear of anxiety-related sensations and is a dispositional variable especially elevated in patients with panic disorder (PD). Although several functional imaging studies of AS in patients with PD have suggested the presence of altered neural activity in paralimbic areas such as the insula, no study has investigated white matter (WM) alterations in patients with PD in relation to AS. The objective of this study was to investigate the WM correlates of AS in patients with PD. METHODS: One-hundred and twelve right-handed patients with PD and 48 healthy control (HC) subjects were enrolled in this study. The Anxiety Sensitivity Inventory-Revised (ASI-R), the Panic Disorder Severity Scale (PDSS), the Albany Panic and Phobia Questionnaire (APPQ), the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) were administered. Tract-based spatial statistics were used for diffusion tensor magnetic resonance imaging analysis. RESULTS: Among the patients with PD, the ASI-R total scores were significantly correlated with the fractional anisotropy values of the WM regions near the insula, the splenium of the corpus callosum, the tapetum, the fornix/stria terminalis, the posterior limb of the internal capsule, the retrolenticular part of the internal capsule, the posterior thalamic radiation, the sagittal striatum, and the posterior corona radiata located in temporo-parieto-limbic regions and are involved in interoceptive processing (p<0.01; threshold-free cluster enhancement [TFCE]-corrected). These WM regions were also significantly correlated with the APPQ interoceptive avoidance subscale and BDI scores in patients with PD (p<0.01, TFCE-corrected). Correlation analysis among the HC subjects revealed no significant findings. LIMITATIONS: There has been no comparative study on the structural neural correlates of AS in PD. CONCLUSIONS: The current study suggests that the WM correlates of AS in patients with PD may be associated with the insula and the adjacent temporo-parieto-limbic WM regions, which may play important roles in interoceptive processing in the brain and in depression in PD.

Subregional Shape Alterations in the Amygdala in Patients with Panic Disorder.

BACKGROUND: The amygdala has been known to play a pivotal role in mediating fear-related responses including panic attacks. Given the functionally distinct role of the amygdalar subregions, morphometric measurements of the amygdala may point to the pathophysiological mechanisms underlying panic disorder. The current study aimed to determine the global and local morphometric alterations of the amygdala related to panic disorder. METHODS: Volumetric and surface-based morphometric approach to high-resolution three-dimensional T1-weighted images was used to examine the structural variations of the amygdala, with respect to extent and location, in 23 patients with panic disorder and 31 matched healthy individuals. RESULTS: There were no significant differences in bilateral amygdalar volumes between patients with panic disorder and healthy individuals despite a trend-level right amygdalar volume reduction related to panic disorder (right, ß = -0.23, p = 0.09, Cohen's d = 0.51; left, ß = -0.18, p = 0.19, Cohen's d = 0.45). Amygdalar subregions were localized into three groups including the superficial, centromedial, and laterobasal groups based on the cytoarchitectonically defined probability map. Surface-based morphometric analysis revealed shape alterations in the laterobasal and centromedial groups of the right amygdala in patients with panic disorder (false discovery rate corrected p < 0.05). CONCLUSIONS: The current findings suggest that subregion-specific shape alterations in the right amygdala may be involved in the development and maintenance of panic disorder, which may be attributed to the cause or effects of amygdalar hyperactivation.

Serotonin Transporter and COMT Polymorphisms as Independent Predictors of Health-related Quality of Life in Patients with Panic Disorder.

There is growing evidence of poor health-related quality of life (HRQOL) in patients with panic disorder (PD). However, little is known about the factors affecting HRQOL in patients with PD. The authors examined whether 5-HTTLPR tri-allelic approach and Cathechol-O-methyltransferase (COMT) Val(158)Met polymorphism can predict HRQOL in patients with PD controlling for sociodemographic factors and disorder-related symptom levels. The sample consisted of 179 patients with PD consecutively recruited from an outpatient clinic and age- and gender ratio-matched 110 healthy controls. The SF-36 was used to assess multiple domains of HRQOL. Hierarchical multiple regression analysis was performed to determine the independent effect of the 5-HTTLPR and COMT Val(158)Met on the SF-36 in panic patients. Patients with PD showed lowered HRQOL in all sub-domains of the SF-36 compared to healthy controls. The 5-HTTLPR independently and additively accounted for 2.2% of variation (6.7% of inherited variance) of perceived general health and the COMT Val(158)Met independently and additively accounted for 1.5% of variation (5.0% of inherited variance) of role limitation due to emotional problems in patient group. The present study suggests that specific genetic polymorphisms are associated with certain domains of HRQOL and provides a new insight on exploring the factors that predict HRQOL in patients with PD.