Metyrapone tests in patients with panic disorder.

BACKGROUND: Studies of hypothalamic secretion of corticotropin-releasing hormone (CRH) in patients with panic disorder in the nonpanic state (using CRH tests) are contradictory. No data about the hypothalamic-pituitary response to metyrapone are available. METHODS: Study participants included 14 patients with panic disorder (DSM-IV criteria) and 14 healthy control subjects who underwent a standard overnight metyrapone test and a combined metyrapone/low-dose dexamethasone test. RESULTS: Significant treatment effects of metyrapone and combined metyrapone/dexamethasone were found on plasma corticotropin, cortisol, and 11-deoxycortisol, but no differences between patients and control subjects emerged. Considering visual analogue scale ratings of anxiety, tension, restlessness, and Beck Depression Inventory scores as covariates, no group effects were detected. CONCLUSIONS: Standard overnight metyrapone tests do not support a hypersecretion of hypothalamic CRH in panic disorder. Furthermore, no evidence for increased glucocorticoid negative feedback in panic was found. Hypothalamic CRH secretion in the nonpanic state needs further research.     

Pituitary volumes in hypochondriac patients

To date, no study has examined the pituitary volumes in patients with hypochondriasis. In the present study, we evaluated pituitary volumes in patients with hypochondriasis and healthy controls. Twenty individuals with hypochondriasis (ten males, ten females), aged 20 to 48 years, and healthy controls were included into the study. The pituitary volumes were obtained. Volumetric measurements were made with T1-weighted coronal MRI images, with 2.4-mm-thick slices, at 1.5 T, and were done blindly. Volumetric measurements did not demonstrate group differences in the brain measurements, i.e., whole brain volume, white, and gray matter volumes (P > 0.05). We found significantly smaller pituitary volumes of the whole group of hypochondriac patients compared to healthy controls (age and ICV as covariates). To conclude, the results from the current investigation suggest that hypochondriac patients had smaller pituitary volumes compared with healthy controls. This could be the keystone to a better understanding of the neurobiological basis of hypochondriasis.     

Illumination perception in photophobic patients suffering from panic disorder with agoraphobia

Ten (6.9%) of a sample of 144 patients with panic disorder and agoraphobia developed photophobic behaviour in the course of their anxiety disorder. Their illumination ratings were characterized before and after cognitive behaviour therapy and compared to 10 age- and sex-matched normal control subjects. The illumination of a sheet of printed paper by a continuously adjustable reading lamp was rated by the subjects as ‘too dark’, ‘comfortable’ or ‘too bright’. The ratings for comfortable luminance were significantly lower in the photophobic patients than in the controls, and renormalized after cognitive behavioural therapy. No differences were observed in the ratings for ‘too dark’ and ‘too bright’. Photophobia in a subsample of patients with panic disorder is a state-dependent phenomenon that can be influenced by cognitive behavioural therapy. The role of neurotransmitters, conditioning processes and a concomitant neurasthenic syndrome requires further characterization.     

Coping behavior in patients with panic disorder

The purpose of the present paper was to investigate the role of coping behavior in patients with panic disorder (PD). This was done by evaluating three items of coping behavior (seeking of social support, wishful thinking and avoidance) in the Ways of Coping Checklist. The subjects consisted of 30 patients with PD (26 with agoraphobia). Coping behavior and the severity of PD was investigated at baseline and at 24 months (the final outcome). At baseline there were no gender differences in coping behavior. The severity of panic attacks significantly correlated with that of agoraphobia. The baseline severity of PD (panic attacks and agoraphobia) did not correlate with coping behavior. At the outcome assessment there was no significant correlation between the severity of panic attack and coping behavior. The severity of agoraphobia at final outcome and the coping behavior (seeking of social support) at baseline were significantly correlated. In the group that had remission in agoraphobia (the good outcome group), the severity of agoraphobia at baseline was significantly lower and the seeking of social support coping behavior was significantly higher than that of the poor outcome group. No significant difference in panic attack severity was noted between the good and poor outcome groups. Discriminant analysis revealed that seeking of social support coping behavior was a significant discriminant factor of agoraphobia. Although these are preliminary data, special coping behavior might be related to improvement of agoraphobia in patients with PD.     

DSM-III-R Axis I and II disorders in agoraphobic patients with and without panic disorder

Patients attending an inpatient phobia treatment program were diagnosed for DSM-III-R Axis I and II disorders, using the Structured Clinical Interview for DSM-III-R Disorders, and completed a set of self-report instruments. They were divided into 3 groups: (a) those who met the criteria for panic disorder with agoraphobia (n= 57), (b) those who met the criteria for agoraphobia without a history of panic disorder (n= 21), and (c) those who met criteria for other anxiety disorders, but not for panic/agoraphobia (n= 14). On Axis I, more of the panic with agoraphobia than of the agoraphobia without panic patients had obsessive-compulsive disorder. On Axis II, no significant differences between the agoraphobic patients with and without panic occurred. However, the number of hysterical traits was related to the presence of panic disorder among the agoraphobic patients. Avoidant and dependent traits were related to symptom severity.     

Relationship between perfectionism,personality disorders and agoraphobia in patients with panic disorder

OBJECTIVE: In earlier reports, we found that perfectionism might be involved in the development and/or maintenance of agoraphobia in panic disorder. The present report extends this work by examining the relationship between perfectionism and comorbidity with personality disorders in panic disorder patients with agoraphobia (PDA) and those without agoraphobia (PD). METHOD: We examined comorbidity of personality disorders by Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) and assessed perfectionism using multidimensional perfectionism scale in 56 PDA and 42 PD patients. RESULTS: The PDA group met criteria for at least one personality disorder significantly more often than the PD group. With stepwise regression analyses, avoidant and obsessive-compulsive personality disorders emerged as significant indicators of perfectionism in patients with panic disorder. CONCLUSION: These findings suggest that perfectionism in panic disorder patients may be more common in those with comorbid personality disorders, and may be an important target for preventive and therapeutic efforts.     

Effect of pharmacotherapy on serum cholesterol levels in patients with panic disorder

Shioiri T, Fuji K, Someya T, Takahashi S. Effect of pharmacotherapy on serum cholesterol levels in patients with panic disorder. Acta Psychiatr Scand 1996: 93: 164–167. © Munksgaard 1996. It is unclear whether elevated cholesterol level is a complication of panic disorder (PD) or is associated with pharmacotherapy. We compared the total cholesterol (TC) level in 47 PD patients with that in 47 gender- and age-matched normal controls (NC), and we also examined the pre- and post-treatment TC levels. There was no sex difference in TC. Before pharmacotherapy, the mean TC level in the PD group (194.9 ± 39.6 mg/dl) was non-significantly higher than that in the NC group (190.5±26.7 mg/dl). The mean TC level in the PD group was significantly reduced following the pharmacotherapy (post-TC: 184.7± 31.0 mg/dl; t= 2.44, P<0.02), and the subgroup treated with alprazolam (n = 26) showed markedly significant decrease of TC after the treatment (t= 2.36, P<0.03). The TC level in the PD subgroup with agoraphobia (n= 24, 198.9 ± 37.9 mg/dl) was slightly higher than that in the group without agoraphobia (n= 23, 190.8±41.6 mg/dl). These findings suggest that there is a relationship between cholesterol levels and treatment in PD.     

Midbrain volume increase in patients with panic disorder

Aim: Although recent studies suggest abnormalities of the cerebral cortex, limbic structures, and brain stem regions in panic disorder (PD), the extent to which the midbrain is associated with PD pathophysiology is unclear. The aim of this study was to investigate structural abnormalities of the midbrain using magnetic resonance imaging and to determine if there is a clinical correlation between midbrain volume and clinical measurements in patients with PD. Methods: Thirty‐eight patients with PD (PD group) and 38 healthy controls (HC group) participated in this study. The midbrain was measured with a manual tracing method with high spatial resolution magnetic resonance imaging. The Panic Disorder Severity Scale and Global Assessment of Functioning were used to examine the correlation between volume abnormality and clinical symptoms and functioning in the PD group. Results: Relative midbrain volume was larger in the PD group than in the HC group. The relative volume of the dorsal midbrain was larger in the PD group, while the volume of the ventral midbrain was not. We found a significant positive correlation between relative dorsal midbrain volume and total Panic Disorder Severity Scale score, and a significant negative correlation between relative dorsal midbrain volume and Global Assessment of Functioning score in the PD group. Conclusions: Our findings suggest that the dorsal midbrain is associated with PD pathophysiology. The midbrain volume increase may reflect PD severity.     

Evaluation of cerebral blood flow volume using color duplex sonography in patients with untreated panic disorder

The aim of this study was to compare cerebral blood flow (CBF) using color duplex sonography in panic disorder and normal controls. We report 24 untreated patients and 20 healthy subjects. State-Trait Anxiety Inventory, Beck Depression Inventory, Beck Anxiety Inventory, and Symptom Check List-90 were completed on each subject. The internal carotid artery (ICA) and vertebral artery (VA) of both sides were explored with a 7.5-Mhz linear array transducer. CBF volume and mean ICA flow velocity were significantly higher in patients than normal subjects adjusted for age. However, we could not find a statistically significant difference in flow volume and velocity of VA and the sum of bilateral ICA volume between patients and controls adjusted for age. There was also no correlation between CBF volume and the other radiological data with STAI scores. In conclusion, we found that independent of anxiety levels, CBF volume has increased in panic disorder patients. In addition, color duplex sonography is a non-invasive and easily applicable technique and it is a preferable alternative to quantify CBF volume.     

Anterior cingulate cortex volume reduction in patients with panic disorder

Aim:  Recent neuroimaging studies have suggested that the anterior cingulate cortex (ACC) has an important role in the pathology of panic disorder. Despite numerous functional neuroimaging studies that have elucidated the strong relationship between functional abnormalities of the ACC and panic disorder and its symptoms and response to emotional tasks associated with panic disorder, there has been no study showing volumetric changes of the ACC or its subregions.
Methods:  To clarify the structural abnormalities of ACC and its subregions, the combination of region of interest (ROI) and optimized voxel-based morphometry (VBM) methods were performed on 26 patients with panic disorder, and 26 age and sex-matched healthy subjects. In the ROI study, ACC was divided into four subregions: dorsal, rostral, subcallosal and subgenual ACC.
Results:  The results of the manually traced ROI volume comparison showed significant volume reduction in the right dorsal ACC. VBM also showed a volume reduction in the right dorsal as well as a part of the rostral ACC as a compound mass.
Conclusions:  Both manual ROI tracing and optimized VBM suggest a subregion-specific pattern of ACC volume deficit in panic disorder. In addition to functional abnormalities, these results suggest that structural abnormalities of the ACC contribute to the pathophysiology of panic disorder.     

Heart rate variability in drug-naïve patients with panic disorder and major depressive disorder

Power spectral analysis of electrocardiogram (ECG) R–R intervals is useful for the detection of autonomic dysfunction in various clinical disorders. Although both panic disorder (PD) and major depressive disorder (MDD) are known to have effects on the cardiac autonomic nervous system, no previous study has tested this among drug-naïve (i.e. no history of treatment) patients with MDD and PD in the same study. The purpose of this study was to compare cardiac autonomic functions among drug-naïve patients with MDD and PD and those of healthy controls. Subjects were 17 drug-naïve PD patients, 15 drug-naïve MDD patients and 15 normal controls. ECGs were recorded under both supine resting and supine deep-breathing conditions (10–12 breaths/min; 0.17–0.20 Hz). We measured the low-frequency power (LF; 0.05–0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15–0.40 Hz), which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. As expected, deep breathing induced an increase in HF power and a decrease in the LF/HF ratio in healthy controls. Compared to these controls, however, the MDD group had a lower response to regular deep breathing in LF power and in LF/HF ratio. PD patients showed intermediate results between normal controls and MDD patients. The results indicate that the reactivity to deep breathing revealed diminished cardiac autonomic reactivity in drug-naïve MDD patients.     

Anterior insular volume is larger in patients with obsessive-compulsive disorder

There has been increasing evidence indicating gray matter abnormalities in patients with obsessive-compulsive disorder (OCD). Several voxel-based morphometry (VBM) studies have reported volume changes in the insular cortex. Although there are distinct differences in the connectivity and functions in the anterior and posterior insular cortices, these two regions have never been distinguished in previous VBM studies. In this study, we adopted a region of interest (ROI) method to measure insular volume separately. We investigated insular volume in 32 drug-free patients with OCD and in 34 healthy controls using magnetic resonance imaging (MRI). Repeated measures multivariate analysis of covariance (MANCOVA) was conducted to examine the difference between the patients and the controls. Compared with the healthy controls, the patients had a significantly larger gray matter volume in the anterior insular cortex bilaterally (post hoc test, p = 0.036; left, p = 0.047; right). This is the first volumetric MRI study to separately investigate the anterior and posterior insular cortex volumes in non-medicated patients with OCD. The results suggest that the anterior insular cortex may be related to the pathophysiology of OCD.     

High plasma nesfatin-1 level in patients with major depressive disorder

Aim

In the present study, our aim was to determine the changes in the plasma concentrations of a recently discovered peptide hormone nesfatin-1 in patients with major depressive disorder and then to make a comparison with the control group.

Method

Subjects in the patient group were randomly selected from Mustafa Kemal University, Medical School, Research and Training Hospital, Psychiatry Department, Outpatient Clinic and subjects in the control group were selected from healthy volunteers. Healthy control subjects were matched in terms of weight and body mass index. Hamilton Depression Rating Scale (HAM-D) was applied to both groups. ELISA method was used for measurement of plasma nesfatin-1 levels.

Results

The average nesfatin-1 level was statistically higher in patients with major depressive disorder than in the control group (p < 0.001). A positive correlation was observed between plasma nesfatin-1 levels and HAM-D scores both in the patient group (r = 0.59, p < 0.001) and in the control group (r = 0.58, p < 0.001).

Conclusion

Our findings suggest a possible relationship between major depressive disorder and high plasma nesfatin-1 level.     

Hippocampus and amygdalar volumes in patients with somatization disorder

In regard to somatization disorder which covers an important section of our patient population, there is no systematic structural magnetic resonance imaging (MRI) study in the literature. Therefore, we aimed to use structural MRI to evaluate the hippocampus amygdalar complex which is associated with both stress and regulation of emotion that are main basis clinical presentation of somatization disorder in the patients with somatization disorder. Totally 40 subjects (20 patients with somatization disorder and 20 healthy controls) were enrolled. Intracranial volume (ICV), whole brain volume, gray and white matter volumes, and hippocampus and amygdalar volumes of the subjects were measured. In regard to unadjusted mean volumes of measured structures, the patients had significantly smaller mean volumes of the left and right amygdala. However, two groups did not differ significantly in terms of whole brain, total gray and white matter or hippocampus volumes. The repeated measures ANCOVA predicting left and right amygdala volumes demonstrated a significant main effect of diagnostic group. In conclusion, the findings of the present study revealed that the patients with somatization disorder had significantly smaller mean volumes of the left and right amygdala without any differences in regard to whole brain, total gray and white matter or hippocampus volumes. On the basis of the current findings, it seems reasonable to evaluate that abnormalities in connectivity and/or metabolism dimensions and to examine the effects of drugs or psychotherapeutic approaches could be especially informative.     

Longitudinal volume changes of the pituitary gland in patients with schizotypal disorder and first-episode schizophrenia

An enlarged volume of the pituitary gland has been reported in the schizophrenia spectrum, possibly reflecting the hypothalamic-pituitary-adrenal (HPA) hyperactivity. However, it remains largely unknown whether the pituitary size longitudinally changes in the course of the spectrum disorders. In the present study, longitudinal magnetic resonance imaging (MRI) data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The pituitary volume was measured at baseline and follow-up (mean, 2.7 years) scans and was compared across groups. The pituitary volume was larger in the schizophrenia patients than controls at baseline, and both patient groups had significantly larger pituitary volume than controls at follow-up. In a longitudinal comparison, both schizophrenia (3.6%/year) and schizotypal (2.7%/year) patients showed significant pituitary enlargement compared with controls (− 1.8%/year). In the schizophrenia patients, greater pituitary enlargement over time was associated with less improvement of delusions and higher scores for thought disorders at the follow-up. These findings suggest that the pituitary gland exhibits ongoing volume changes during the early course of the schizophrenia spectrum as a possible marker of state-related impairments.     

Insular cortex volume and impulsivity in teenagers with first-presentation borderline personality disorder

Fronto-limbic neural dysfunction has been implicated in the emotional dysregulation and impulsivity seen in borderline personality disorder (BPD). However, it remains unclear whether affected individuals exhibit morphologic changes of the insular cortex, a fronto-limbic integration cortex engaged in emotional regulation and impulse control. This magnetic resonance imaging study examined the insular cortex volume and its relationship to clinical characteristics in a first-presentation teenage BPD sample. No significant difference was found in the insular volume between 20 BPD participants (5 males) and 20 healthy control participants (5 males). There was no association between the insular volume and parasuicidal episodes, trauma exposure, or comorbid Axis I disorders, but the BPD participants with violent episodes during the previous 6 months had a smaller insular volume bilaterally compared with those without such episodes. Furthermore, right anterior insular volume in the BPD participants was negatively correlated with impulsivity score. These preliminary findings suggest that insular cortex volume does not significantly differ in early BPD, but that there might be a relationship with violent and impulsive behavior that is often seen in the disorder. Further studies are needed to clarify whether the potential relationship between the insular cortex volume and impulsivity is specific to BPD.     

Reduced cortical thickness in non-medicated patients with obsessive-compulsive disorder

Increasing evidence suggests the presence of grey matter volume abnormalities in patients with obsessive-compulsive disorder (OCD) and the mediation of the expression of different OCD symptoms by discrete neural systems of the brain. However, limited studies have investigated the abnormalities of cortical thickness, and their results are comparatively inconsistent, possibly owing to the inclusion of medicated patients. Therefore, this study investigated cortical thickness abnormalities using surface-based analysis to identify distinct neural correlates of each symptom dimension in non-medicated patients with OCD. Thirty non-medicated patients with OCD and 30 age- and gender-matched healthy controls underwent magnetic resonance imaging. Group comparison of cortical thickness was performed using surface-based analysis. We also conducted correlation analysis between cortical thickness and each symptom dimension score. Compared to the healthy controls, the OCD patients had statistically significant reduction in cortical thickness in the cluster that contained the left superior temporal gyrus and posterior insular cortex (p<.05, corrected); no areas of the brain had significantly greater cortical thickness. Negative correlation was also found between cortical thickness and "cleaning" dimension scores in the left postcentral and right superior parietal gyri. The present results suggest that cortical thinning in the region that contains the left superior temporal gyrus and posterior insula may underlie pathophysiology of OCD and that discrete neural systems may mediate the "cleaning" symptom dimension.     

Ghrelin and leptin levels in patients with obsessive-compulsive disorder

To examine the importance of ghrelin and leptin in the pathogenesis of obsessive-compulsive disorder (OCD), we measured serum ghrelin and leptin levels, lipid profile and body mass index (BMI) in 43 patients with OCD and 20 healthy controls. The patients were divided into two subgroups according to whether DSM-IV OCD was accompanied with major depressive disorder (MDD) (OCD+MDD) or not (OCD-MDD). There was no statistically significant difference in ghrelin and leptin levels between groups. The OCD+MDD group had a trend of higher ghrelin levels and lower leptin levels than the OCD-MDD and control groups. There was a negative correlation between change in serum ghrelin and leptin levels only in the OCD+MDD group. Neither ghrelin nor leptin showed any correlation with severity of MDD and OCD. In conclusion, our results suggest that OCD is not associated with leptin or ghrelin levels. More comprehensive and detailed studies are needed to decipher the exact role of ghrelin and leptin in OCD.     

Volumetric differences in the pituitary between drug-naïve and medicated male patients with obsessive–compulsive disorder

Objective

Obsessive–compulsive symptoms are induced or aggravated by stress, and the pituitary is a key component of the hypothalamic-pituitary-adrenal axis. We examined pituitary volume in drug-naïve and medicated male patients with obsessive–compulsive disorder (OCD).

Methods

Volumetric magnetic resonance imaging studies were conducted on 62 male control subjects, medicated male patients (N = 50) and drug-naïve male patients (N = 12) with OCD.

Results

Pituitary volume was significantly smaller in drug-naïve patients with OCD (464.97 ± 55.82 mm³) compared to medicated patients (577.84 ± 129.11 mm³, P = 0.004) and control subjects (543.04 ±113.70 mm³, P = 0.027), and no difference between control subjects and medicated patients (P = 0.174).

Conclusion

The results indicate that drug-naïve male patients with OCD exhibit decreased pituitary volume. This finding suggests that dysregulation of the HPA axis in OCD may influence pituitary volume. In addition, the increased pituitary volume in medicated patients may reflect the effect of drugs on the pituitary.     

Potential peripheral biological predictors of suicidal behavior in major depressive disorder

Previous studies have shown that dysfunctions in the serotonin system and hypothalamic-pituitary-adrenal axis (HPA) are associated strongly with suicidal behavior and suicide, especially among individuals with major depressive disorder. Suicidal behavior has been explained using both the stress-diathesis model and the state-trait interaction model. Specifically, diatheses, or trait-dependent risk factors, are associated with dysfunctions in the serotonin system; however, stress responses, or state-dependent factors, are associated with HPA hyperactivity. Decreases in cholesterol and brain-derived neurotrophic factor (BDNF) levels have been associated with impaired brain plasticity among individuals with suicidal behavior. Decreased serotonin functioning has been measured using cerebral spinal fluid (CSF) 5-HIAA, fenfluramine challenge studies, and platelet 5-HT2A receptors. HPA axis dysfunction has been evaluated with the dexamethasone suppression test. Cholesterol and BDNF levels have been measured in blood serum or plasma.Nevertheless, challenges to finding promising and accessible neurobiological predictors of suicide and suicidal behavior remain. As suicide behavior is a complex phenomenon, a combined or multidimensional approach, including each of the aforementioned methods, may be required to predict suicide risk among individuals with major depressive disorder.