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PubMed2005

Expression of nitric oxide synthase isoforms in hypothalamo-pituitary-adrenal axis during the development of spontaneous hypertension in rats.

This study was performed to investigate the expression of the major isoforms of nitric oxide synthase mRNA and protein in the hypothalamo-pituitary-adrenal axis (HPA axis) of spontaneously hypertensive rats (SHR) at two different postnatal ages corresponding to the development of genetic hypertension. Using RT-PCR and Western blot techniques, the mRNA and protein levels of neuronal (nNOS), endothelial (eNOS) and inducible (iNOS) isoforms were measured in 3- to 4-week-old (prehypertensive phase) and 12- to 13-week-old (established hypertension phase) SHR and age-matched normotensive Wistar-Kyoto (WKY) rats. nNOS but not eNOS mRNA levels were increased at prehypertensive and hypertensive phases in SHR HPA axis. Compared to age-matched WKY rats, significantly higher levels of nNOS protein were found in the hypothalamus, lower levels in the adrenal glands and no changes were observed in the pituitary gland. At both ages tested, there was no significant change in eNOS protein expression in SHR HPA axis. The expression of iNOS mRNA and protein was under detection limit. In the HPA axis, the expression of nNOS isoform appears to be differentially controlled at the transcriptional and translational levels in SHR. Increased mRNA levels and differential nNOS protein expression from birth in SHR HPA axis may contribute in the pathogenesis of genetic hypertension.

Animals↗
PubMed2005

Molecular heterogeneity along the dorsal-ventral axis of the murine hippocampal CA1 field: a microarray analysis of gene expression.

There has been increasing interest in functional heterogeneity along the septotemporal, dorsal-ventral (D-V) axis of the hippocampus. Although anatomical connectivity and lesion studies point to discrete roles for these sub-regions, the contribution of differential gene expression across this axis has not been systematically studied. Here we present findings from an Affymetrix microarray screen aimed at identifying genes in the CA1 region of the adult murine hippocampus that show significant differential expression along the D-V axis. Our results indicate that the vast majority of monitored genes (>90%) had tissue expression levels that differed by less than 20% between regions, while less than 0.1% of genes had expression levels that varied more than three-fold by sub-region. Only 23 probes showed a CA1 dorsoventral signal intensity ratio greater than three: 18 enriched dorsally and five enriched ventrally. Probes with the greatest difference in expression levels represent a range of genes with known functions in patterning and signaling, as well as genes without known function. Selective screening with digoxigenin-labeled in situ hybridization confirms the existence of CA1 sub-regionalized expression, with some genes exhibiting a graded expression pattern across the D-V axis, and others restricted to a discrete region. Our findings demonstrate that there are gene expression differences across the D-V axis of the adult murine hippocampus within traditionally recognized cytoarchitecturally defined boundaries. Combined with the previously recognized differences in connectivity and results from lesion studies, our data further confirm the existence of functional heterogeneity along the D-V axis.

Animals↗
PubMed2004

HPA axis activation in major depression and response to fluoxetine: a pilot study.

Hypothalamic-pituitary-adrenal (HPA) axis activation is a frequently observed phenomenon in major depression. However, whether this activation has any implications for treatment is unknown. To address this question, we examined baseline response to metyrapone and 6-week response to fluoxetine. Premenopausal women (n = 20) who met criteria for major depression with no other confounding Axis I disorders, medications, or medical illnesses and were not taking hormonal contraceptives were evaluated with an evening metyrapone challenge before the onset of treatment. Twenty-one normal women were also studied with the evening metyrapone challenge. The depressed patients then entered an open label treatment with fluoxetine for 6 weeks. Subjects were classified as responders if they demonstrated a 50% or greater decrease in Hamilton Depression Rating Scale rating. As a group, the depressed women demonstrated significantly increased ACTH secretion compared to control women before the onset of treatment, during the metyrapone challenge. Before treatment, women who were non-responders to fluoxetine showed increased HPA axis activation compared to controls, while the fluoxetine responders did not differ significantly from normal subjects in their ACTH levels during metyrapone challenge. These results suggest that overactivity of the HPA axis may be one factor associated with slower response to fluoxetine. This may reflect the greater severity of subjects with HPA axis dysregulation or the need to normalize the HPA axis with medications for optimal response.

Adolescent↗
PubMed2000

Influence of psychological variables on the activity of the hypothalamic-pituitary-adrenal axis.

Psychobiology is the discipline that attempts to integrate the impact of environmental and psychological variables on biological systems. This paper focuses on the psychobiology of the hypothalamic-pituitary-adrenal (HPA) axis and illustrates several processes that influence the response of the HPA axis. The interaction of the developing rodent or primate with their primary care giver has permanent long-term effects on the HPA axis. Manipulations that alter maternal behavior during critical periods of development permanently modify the HPA axis. The HPA axis can be programmed to be hypo-responsive or hyper-responsive as a function of time and length of maternal separation. In the adult organism, the HPA response to stress is highly dependent on specific psychological factors such as control, predictability, and feedback. In primates, social variables have been shown to diminish or exacerbate the HPA stress response. During the post-natal period of development, the mother appears to actively inhibit the pups' HPA axis. Different aspects of maternal behavior regulate different components of the HPA system.

Animals↗
PubMed1999

Articulated external fixation of the ankle: minimizing motion resistance by accurate axis alignment.

This study describes how an optimal single hinge axis position can be established for the application of articulated external fixation to the ankle joint. By deliberately introducing various amounts of relative mal-alignment between the optimal talocrural joint axis and the actual fixator hinge axis, it was possible to measure the corresponding amounts of additional resistance to joint motion. In a cadaveric study of six ankle specimens, we determined the instant axis of rotation of the talocrural joint from 3-D kinematic data. acquired by an electromagnetic motion tracking system. For each specimen, an optimal fixator hinge position was calculated from these motion data. Compared to the intact natural joint, aligning the fixator along the optimized axis position caused a moderate increase in energy (0.14 J) needed to rotate the ankle through a prescribed plantar/dorsiflexion range. However, malpositioning the hinge by 10 mm caused more than five times that amount of increase in motion resistance. While articulated external fixation with limited internal fixation can establish a favorable environment for the repair of severe injuries such as tibial pilon fractures, the large additional resistance to motion accompanying a malpositioned fixator axis suggests the development of untoward intra-articular forces that could act to disturb fragment alignment.

Ankle↗
PubMed1999

Off-axis monochromatic aberrations estimated from double pass measurements in the human eye.

Off-axis monochromatic aberrations in the human eye impose limits on peripheral vision. However, the magnitude of the aberrations off-axis, and in particular coma, has not been yet completely determined. We have developed a procedure to estimate third order aberrations in the periphery of the human eye. The technique is based on recording series of double pass retinal images with unequal entrance and exit pupil diameters (Artal, Iglesias, López-Gil & Green (1995b). J. Opt. Soc. Am. A, 12, 2358-2366.) which allows the odd asymmetries in the retinal image be assessed. The procedure that is described provides accurate estimates of the main off-axis aberrations: astigmatism, defocus and coma. We have measured these aberrations in four normal subjects. For a given eccentricity, the measured amount of coma and astigmatism are relatively similar among subjects, because the angular distance from the axis is the dominant factor in determining the magnitude of these aberrations. However, we found considerable variability in the values of peripheral defocus, probably due to a complicate combination of off-axis aberrations and fundus shape. The final off-axis optical performance of the eye for a given object location is determined by a particular mixture of defocus, astigmatism, coma and higher order aberrations.

Astigmatism↗
PubMed2004

Axis I and II comorbidity in a large sample of patients with obsessive-compulsive disorder.

BACKGROUND: No study has reported yet on the prevalence of both comorbid DSM-IV axis I and personality disorders in a large cohort of OCD patients, and little is known about differences in clinical characteristics between OCD patients with and without comorbid symptoms. OBJECTIVE: To examine the cross-sectional prevalence of comorbid DSM-IV axis I, and personality disorders in a population of patients with primary obsessive-compulsive disorder (OCD). METHOD: 420 outpatients with OCD were evaluated for comorbid pathology, demographic, and clinical characteristics. RESULTS: Forty-six percent of the patients were diagnosed with a comorbid disorder. Twenty-seven percent met the criteria for at least one comorbid axis I disorder, 15.6 percent for a comorbid personality disorder, and 20.4 percent for both a comorbid axis I disorder and a personality disorder. LIMITATIONS: A limitation of the current study is that the sample was drawn from a psychiatric department specialised in anxiety disorders, which might have underestimated the rate of comorbid diagnoses. CONCLUSION: Comorbid diagnoses occur less frequently than would be expected on the basis of comparable comorbidity studies in OCD. Associated axis I comorbidity did not affect clinical severity of OCD, but was related to higher levels of depression and anxiety, whereas axis II comorbidity impaired to a higher extent the overall functioning.

Adult↗
PubMed1999

The central amygdala modulates hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1beta administration.

In the present study we examined the role of the central nucleus of the amygdala in hypothalamic-pituitary-adrenal axis responses to an immune challenge in the form of systemic administration of the proinflammatory cytokine interleukin-1beta (1 microg/kg). We found that bilateral ibotenic acid lesions of the central amygdala substantially reduced adrenocorticotropin hormone release and hypothalamic corticotropin-releasing factor and oxytocin cell c-fos expression responses to interleukin-1,8 suggesting a facilitatory role for this structure in the generation of hypothalamic-pituitary-adrenal axis responses to an immune challenge. Since only a small number of central amygdala cells project directly to the paraventricular nucleus, we then examined the effect of central amygdala lesions on the activity of other brain nuclei that might act as relay sites in the control of the hypothalamic-pituitary-adrenal axis function. We found that bilateral central amygdala lesions significantly reduced interleukin-1beta-induced c-fos expression in cells of the ventromedial and ventrolateral subdivisions of the bed nucleus of the stria terminalis and brainstem catecholamine cell groups of the nucleus tractus solitarius (A2 noradrenergic cells) and ventrolateral medulla (A1 noradrenergic and C1 adrenergic cells). These findings, in conjunction with previous evidence of bed nucleus of the stria terminalis and catecholamine cell group involvement in hypothalamic-pituitary-adrenal axis regulation, suggest that ventromedial and ventrolateral bed nucleus of the stria terminalis cells and medullary catecholamine cells might mediate the influence of the central amygdala on hypothalamic-pituitary-adrenal axis responses to an immune challenge. Thus these data establish that the central amygdala influences hypothalamic-pituitary-adrenal axis responses to a systemic immune challenge but indicate that it primarily acts by modulating the activity of other control mechanisms.

Adrenocorticotropic Hormone↗
PubMed2002

Hypothalamic-pituitary-adrenal axis function in patients with chronic depression.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis function in patients with chronic depression has previously been shown to be normal when measured using the dexamethasone suppression test (DST). We examined patients with chronic depression using the sensitive dexamethasone/corticotropin releasing hormone (dex/CRH) test and the dexamethasone suppression test (DST) to establish whether HPA axis abnormalities are present in this group. We also compared the sensitivity of the two tests and compared the results with previous studies in depression that have not specifically selected chronic patients. METHOD: Twenty-nine patients with the chronic subtype of major depressive disorder and 28 matched controls underwent examination of HPA axis function. RESULTS: Neither the cortisol response to the DST or the dex/CRH test differed significantly between the patient and control groups. There was a trend in favour of more patients than controls having an abnormal response to the dex/CRH test (P = 0.052). Neither the patients with an abnormally enhanced response, nor the magnitude of response could be predicted by any illness or demographic variable. CONCLUSION: The HPA axis is not overtly abnormal in chronic depression. This contrasts with previous findings in acute depression and bipolar disorder and may suggest that the HPA axis abnormalities present in acute depression resolve, but are not accompanied by symptom resolution. Alternatively, a subgroup of depressives with less HPA dysfunction may progress to chronicity. This has implications for treatment and prognosis. The dex/CRH is a more sensitive test of HPA axis function than the DST in patients with chronic depression.

Adult↗
PubMed2001

Diazepam increases the hypothalamic-pituitary-adrenocortical (HPA) axis activity by a cyclic AMP-dependent mechanism.

1. Previous studies in this laboratory have shown that diazepam behaves as a phosphodiesterase 4 (PDE 4) inhibitor. It has been reported that PDE-4 inhibitors activate the hypothalamic-pituitary-adrenocortical (HPA) axis in the rat. In the present study we have examined whether activation of the cyclic AMP-dependent protein kinase (PKA) is involved in the effect of diazepam on basal HPA axis activity. 2. Acute systemic administration of diazepam (10 mg kg(-1) i.p.) was found to increase the basal HPA axis activity, increasing the plasma concentrations of corticotrophin (ACTH) and corticosterone 30 min post injection. Diazepam also elevated cyclic AMP content of the hypothalamus. 3. Pretreatment of the animals with dexamethasone (1 mg kg(-1) s.c.) for 3 days completely abolished the effect of diazepam on HPA axis activity. 4. The antagonists of central and peripheral benzodiazepine receptors, flumazenil (10 mg kg(-1) i.p.) and PK 11195 (5 mg kg(-1) i.p.) did not affect the diazepam induced increase of HPA axis activity nor did they have an effect per se. 5. The increase in ACTH and corticosterone levels was significantly reduced by the cyclic AMP-dependent protein kinase (PKA) inhibitor, H-89, given either subcutaneously (5 mg kg(-1) s.c.) or intracerebroventricularly (i.c.v.; 28 microg in 10 microl). 6. The results indicate that diazepam can stimulate basal HPA axis activity in the rat by a cyclic AMP-dependent PKA mediated pathway.

Adrenal Cortex↗
PubMed2006

Multiple-axis tomography: applications to basal bodies from Paramecium tetraurelia.

BACKGROUND INFORMATION: Transmission electron tomography is becoming a powerful tool for studying subcellular components of cells. Classical approaches for electron tomography consist of recording images along a single-tilt axis. This approach is being improved by dual-axis reconstructions and/or high-tilt devices (tilt angle>+/-60 degrees) on microscopes to compensate part of the information loss due to the 'missing wedge' phenomena. RESULTS: In the present work we have evaluated the extension of the dual-axis technique to a multiple-axis approach, and we demonstrate a freely available plug-in for the Java-based freeware image-analysis software ImageJ. Our results from phantom and experimental data sets from Paramecium tetraurelia epon-embedded sections have shown that multiple-axis tomography achieves results equivalent to those obtained by dual-axis approach without the requirement for high-tilt devices. CONCLUSIONS: This new approach allows performance of high-resolution tomography, avoiding the need for high-tilt devices, and therefore will increase the access of electron tomography to a larger community.

Algorithms↗
PubMed2001

Maternal left ventricular transverse and long-axis systolic function during pregnancy.

OBJECTIVES: Circumferential fiber shortening has been the dominant basis for conventional analysis by echocardiography of left ventricular systolic function during pregnancy. Results in the literature have been conflicting due mainly to the fact that geometric assumptions for the calculation of these indices are made that may not be valid due to changes in left ventricular shape during pregnancy. Left ventricular long-axis displacement is expected to be a useful index of systolic function, independent of the changes in left ventricular geometry. The aim of this study was to compare circumferential to long-axis shortening during left ventricular contraction in pregnant women. METHODS: This was a cross-sectional study of 125 pregnant women at 9-42 weeks of gestation and 19 non-pregnant female controls. Two-dimensional and M-mode echocardiography of the left ventricle was performed including measurement of left ventricular long-axis displacement and activation time on the lateral, septal, anterior and inferior sides of the mitral annulus. Activation time was assessed as the time from the start of the Q-wave of the electrocardiogram to the onset of left ventricular long-axis shortening. RESULTS: Mean arterial pressure and activation time decreased during pregnancy, reaching a nadir at about 19 weeks' gestational age of 4% and 13%, respectively, below non-pregnant values; they subsequently increased towards term. Left ventricular long-axis displacement mirrored the changes in mean arterial pressure and activation time and increased with gestational age at all four sites of the atrioventricular plane reaching a peak at about 23 weeks (+ 12% compared to non-pregnant levels). The ejection fraction and fractional shortening remained stable until 30 and 32 weeks, respectively, and then decreased towards term. CONCLUSION: Changes in left ventricular long-axis performance during pregnancy occur earlier than do measures of transverse function.

Adult↗
PubMed1997

Inhaled beclomethasone dipropionate suppresses the hypothalamo-pituitary-adrenal axis in a dose dependent manner.

OBJECTIVE: Little is known about the dose-response relationship of potential, unwanted, effects of inhaled beclomethasone (BDP) on the hypothalamo-pituitary-adrenal (HPA) axis, particularly in nonspecialist clinic settings. The purpose of our study was to investigate the dose-response relationship of inhaled BDP on the HPA axis in a general practice patient population. We also explored the optimal testing strategy in this population and correlated effects of inhaled BDP on the HPA axis with other systemic corticosteroid side effects. PATIENTS AND DESIGN: Controlled observational study employing 21 patients on inhaled BDP recruited from general practice, with minimal past and no present exposure to other corticosteroids, and 21 age and gender-matched controls. MEASUREMENTS: Twenty-four-hour urinary free cortisol excretion (UFC), serum cortisol before and 30 minutes after injection of 1 microgram and 250 micrograms of tetracosactrin, serum IGF-I and serum osteocalcin were measured. BDP use was estimated by inhaler weighing and prescription count. RESULTS: In subjects on inhaled BDP, 24-hour UFC (P < 0.008), serum cortisol 30 minutes after 250 micrograms tetracosactrin (P < 0.05) and the serum cortisol rise after 250 micrograms tetracosactrin (P < 0.04) were significantly lower when compared with controls. Measurements of HPA function correlated inversely with BDP dose estimated by inhaler weighing (all P < 0.03). Serum IGF-I and osteocalcin levels did not differ. CONCLUSIONS: We have demonstrated hypothalamo-pituitary-adrenal axis suppression in nonspecialist-clinic asthma patients on moderate to large doses of inhaled beclomethasone dipropionate. When accurate measurements of inhaled steroid dose are used, there is an exponential relationship between dose and hypothalamo-pituitary-adrenal axis suppression. There appears to be no 'safe' threshold, and around 15% of patients may have clinically significant suppression. However, the significance of hypothalamo-pituitary-adrenal axis suppression as a marker for concomitant corticosteroid effects on other organ systems remains uncertain.

Administration, Inhalation↗
PubMed2001

A comparison between low-dose (1 microg), standard-dose (250 microg) ACTH stimulation tests and insulin tolerance test in the evaluation of hypothalamo-pituitary-adrenal axis in primary fibromyalgia syndrome.

OBJECTIVE: Primary fibromyalgia syndrome (PFS) is a nonarticular rheumatological syndrome characterized by disturbances in the hypothalamo-pituitary-adrenal (HPA) axis. The site of the defect in the HPA axis is a matter of debate. Our aim was to evaluate the HPA axis by the insulin-tolerance test (ITT), standard dose (250 microg) ACTH test (SDT) and low dose (1 microg) ACTH test (LDT) in patients with PFS. DESIGN AND PATIENTS: Sixteen patients (13 female, three male) with PFS were included in the study. Sixteen healthy subjects (12 female, four male) served as matched controls. ACTH stimulation tests were carried out by using 1 microg and 250 microg intravenous (i.v.) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. The ITT was performed by using i.v. soluble insulin, and serum glucose and cortisol levels were measured before and after 30, 60, 90 and 120 min. The 1 microg and 250 microg ACTH stimulation tests and the ITT were performed consecutively. RESULTS: Peak cortisol responses to both the low dose test (LDT) and standard dose test (SDT) (589 +/- 100 nmol/l; 777 +/- 119 nmol/l, respectively) were lower in the PFS group than in the control group (1001 +/- 370 nmol/l; 1205 +/- 386 nmol/l, respectively) (P < 0.0001). Peak cortisol responses to ITT (730 +/- 81 nmol/l) in the PFS group were lower than in the control group (1219 +/- 412 nmol/l) (P < 0.0001). Six of the 16 patients with PFS had peak cortisol responses to LDT lower than the lowest peak cortisol response of 555 nmol/l obtained in healthy subjects after LDT. There was a significant difference between the peak cortisol responses to LDT (589 +/- 100 nmol/l) and peak cortisol responses to ITT (730 +/- 81 nmol/l) in the PFS group (P < 0.0001). Peak cortisol responses to SDT (777 +/- 119 nmol/l) were similar to peak cortisol responses to ITT (730 +/- 81 nmol/l) in the PFS group. CONCLUSION: We conclude that the perturbation of the HPA axis in PFS is characterized by underactivation of the HPA axis. Some patients with PFS may have subnormal adrenocortical function. LDT is more sensitive than SDT or ITT in the investigation of the HPA axis to determine the subnormal adrenocortical function in patients with PFS.

Adrenocorticotropic Hormone↗
PubMed1999

Acute and long-term treatments with the selective serotonin reuptake inhibitor citalopram modulate the HPA axis activity at different levels in male rats.

It is well established that the maximal therapeutic effect of selective serotonin reuptake inhibitors (SSRI) are achieved in depressive patients after several weeks of treatment, but the adaptive processes leading to the therapeutic effects are unclear. It has been shown that hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis in depressive patients is affected by long-term antidepressant treatment. These changes occur in association with the mood normalising effect, suggesting that antidepressants affect the HPA axis and this effect is associated with the therapeutic effect. Male Wistar rats were treated with the SSRI, citalopram, to investigate time-related changes in components that may be involved in the desensitization of the HPA axis. A single injection of citalopram (10 mg/kg, s.c.), increased the plasma levels of ACTH and corticosterone in a dose-dependent manner and increased the number of c-Fos containing cells in the hypothalamic paraventricular nucleus. A daily treatment with the same compound (10 mg/kg, s.c.) for 14 days decreased the expression of POMC mRNA ( approximately 40%). In addition, a blunted response to citalopram was observed in animals long-term treated with citalopram. Also CRF-stimulated cAMP accumulation in the pituitary was altered. In conclusion, acute citalopram activated the HPA-axis at the hypothalamic level and long-term citalopram treatment desensitized the HPA-axis at the pituitary level. These results support the hypothesis that the therapeutic effects of long-term antidepressant treatments reduce HPA axis responsiveness.

Adenylyl Cyclases↗
PubMed1999

Location of the hinge axis and the kinematic centre in asymptomatic and clicking temporomandibular joints.

The study aimed to compare the locations of the hinge axis and the kinematic centre in both clicking and non-clicking TMJs. The six degrees of freedom optoelectronic jaw movement recording system OKAS-3D was used to record open/close movements in 10 asymptomatic subjects and 30 subjects with a clicking joint. Movement paths of the hinge axis and the kinematic axis were calculated. A t-test was used in the analysis of the locations of the two condylar movement reference points. Variances between the values of the hinge and the kinematic axes were compared with the F-test. Locations of the hinge axis and the kinematic centre on the average did not differ significantly for the asymptomatic subjects at the group level (P>0. 05), while individually the locations differed 4.96 mm on the average. The difference between the hinge axis and the kinematic axis was significant for the group of subjects with clicking joints (P<0.01), with the average individual level difference of 9 mm. Variances differed significantly between the coordinates of the hinge and the kinematic axes between the two groups of subjects (P<0. 01). The study shows the importance of the choice of a condylar movement reference point for the study of condylar movements and suggests the use of the kinematic centre in such studies.

Adolescent↗
PubMedDate not supplied

The A/P axis in echinoderm ontogeny and evolution: evidence from fossils and molecules.

Even though echinoderms are members of the Bilateria, the location of their anterior/posterior axis has remained enigmatic. Here we propose a novel solution to the problem employing three lines of evidence: the expression of a posterior class Hox gene in the coeloms of the nascent adult body plan within the larva; the anatomy of certain early fossil echinoderms; and finally the relation between endoskeletal plate morphology and the associated coelomic tissues. All three lines of evidence converge on the same answer, namely that the location of the adult mouth is anterior, and the anterior/posterior axis runs from the mouth through the adult coelomic compartments. This axis then orients the animal such that there is but a single plane of symmetry dividing the animal into left and right halves. We tentatively hypothesize that this plane of symmetry is positioned along the dorsal/ventral axis. These axis identifications lead to the conclusion that the five ambulacra are not primary body axes, but instead are outgrowths from the central anterior/posterior axis. These identifications also shed insight into several other evolutionary mysteries of various echinoderm clades such as the independent evolution of bilateral symmetry in irregular echinoids, but do not elucidate the underlying mechanisms of the adult coelomic architecture.

Animals↗
PubMedDate not supplied

Effects of axis I and II comorbidity on behavior therapy outcome for obsessive-compulsive disorder and agoraphobia.

The impact of concurrent axis I diagnoses and axis II traits on the efficacy of a 22-session exposure-based treatment program for 43 outpatients with panic disorder and agoraphobia (PDA) and 63 with obsessive-compulsive disorder (OCD) was examined. Trained interviewers used the Structured Clinical Interview for DSM-III-R (SCID) to assess axis I diagnoses and the SCID-II to identify the number of axis II criteria met for anxious, dramatic, and odd clusters. Among axis I diagnoses, secondary major depressive disorder (MDD), dysthymia, social phobia, and generalized anxiety disorder (GAD) were present in sufficient numbers to study their effects on treatment outcome. Outcomes were assessed on self-rated target fears and functioning and on a behavioral avoidance test at post-treatment and at 6 months follow-up. Only GAD comorbidity predicted dropout, whereas MDD and all three personality cluster traits predicted post-treatment outcomes. Follow-up analyses showed significant effects of MDD and GAD, but axis II cluster criteria were not predictive.

Adolescent↗