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Suppression of the HPA axis stress-response: implications for relapse.

This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October 2004. This symposium explored the potential role of hypothalamic-pituitary-adrenal (HPA) axis dysregulation upon relapse. HPA axis stimulation induces the release of the glucocorticoid cortisol, a compound with profound effects upon behavior and emotion. Altered stress-responses of the HPA axis in abstinent alcohol-dependent subjects, therefore, may influence their affective and behavioral regulation, thus impacting their potential for relapse. Bryon Adinoff began the symposium with a review of HPA axis dysfunction in alcohol-dependent subjects, including recent studies from his lab demonstrating an attenuated glucocorticoid response to both endogenous and exogenous stimulation in one-month abstinent men. Klaus Junghanns presented his work demonstrating that a blunted ACTH or cortisol response to subjective stressors (social stressor or alcohol exposure) is predictive of a return to early drinking. The final two presenters examined the interaction between naltrexone and HPA responsiveness in alcohol-dependent or at-risk subjects, as naltrexone induces an increase in ACTH and cortisol. Falk Kiefer discussed the relationship between basal HPA axis responsivity and clinical outcome following treatment with naltrexone or acamprosate. Plasma ACTH significantly decreased over the course of the study in the placebo group, but not the medication groups [corrected] Lower basal concentrations of ACTH and cortisol were associated with quicker relapse in the placebo group only. Suchitra Krishnan-Sarin described her preliminary work, in which family-history positive (FH+) and family history negative (FH-) subjects were administered naltrexone, followed by an assessment of alcohol-induced craving. The cortisol response to alcohol was significantly and inversely related to craving in the FH+, but not the FH-, subjects. Alterations in HPA axis responsivity may therefore have a negative impact upon clinical outcome in alcohol-dependent subjects, and disinhibition of the axis with medication may have therapeutic potential.

Adrenocorticotropic Hormone↗

Right ventricular long-axis function in relation to left ventricular systolic function.

A decrease in left ventricular (LV) systolic function is accompanied by a decrease in maximal relaxation velocity in LV long-axis direction, but is it also accompanied by a decrease in right ventricular (RV) long-axis function? To study this 35 consecutive patients were examined by echocardiography. Ejection fraction (LVEF) and mitral annulus motion (MAM) were used as indices of LV systolic function and tricuspid annulus motion (TAM), that is the systolic shortening in RV long-axis direction, was used as an index of RV systolic long-axis function. In the same way the maximal relaxation velocity in LV long-axis direction, that is the maximal diastolic velocity of MAM (MDV MAM), has been suggested as an index of LV diastolic function the maximal diastolic velocity of TAM (MDV TAM) can be supposed to be an index of RV diastolic function measuring the maximal relaxation velocity in the RV long-axis direction. A significant positive correlation was found between MDV TAM and MAM (r = 0.64, P<0001) and LVEF (r = 0.54, P = 0.001) and between TAM and the two studied indices of LV systolic function, with the highest correlation to MAM (r = 0.68, P<0.001) and the lowest to LVEF (r = 0.57, P<0.001). Thus, a decrease in LV systolic function is accompanied by a decrease in both systolic and diastolic RV long-axis function, findings that probably are due to the close anatomical connection between the ventricles and to changes that occur in afterload of the RV secondary to LV systolic dysfunction.

Aged↗

Head scatter off-axis for megavoltage x rays.

Our objective in this study has been to investigate how head scatter varies with the off-axis position in a 6 MV x-ray beam. We define the head-scatter off-axis ratio, HOA, as the ratio of the kerma due to head-scatter photons at the off-axis position x to the kerma from direct primary photons on the central axis. "Direct primary" are those photons that come from the source without interactions in the intervening structures. We determined HOA from measurements with an ionization chamber in a miniphantom. Head-scatter and direct primary photons contribute to a measurement of the ionization per mu Q(x) at the off-axis position x in the open field cx x cy. The ionization per mu QP(x), measured in the same position but with the field collimated to the smallest possible opening (cx x 3 cm), is intended to include only direct primary photons. Head-scatter photons cannot be completely eliminated, and the errors due to remaining head scatter and radiation back-scattered by the movable collimators into the monitor were estimated. For normalization of the final results, ionization due to direct primary photons was also measured on the central axis, QP(0). HOA was derived from these three measurements as HOA(cx,cy,x)=(Q(cx,cy,x) - QP(cx,cy,x))/QP(cx,cy,0). On the central axis (x=y=0), HOA represents the "scatter-to-primary ratio" between head scatter and the direct primary dose. Monte Carlo simulations were made to help with the interpretation and evaluation of the results. HOA could be fitted to a Gaussian model with two components corresponding to sources of widths 1.8 and 14 cm, projected on a plane 5 cm below the x-ray source. The narrow Gaussian component is interpreted as the source of photons scattered in the flattening filter and the primary collimator. The broad component is attributed to photons scattered in the secondary (variable) collimators. Conventional head-scatter models (e.g., a single Gaussian source model) do not fit the measured HOA data for large collimator settings (c>20 cm) or outside beam collimation. The full width at half-maximum (FWHM) of HOA(x) across the field increased with the field width (cx) in the direction of the measurements in a manner consistent with the field of view of the two sources. It was not sensitive to the field measure in the orthogonal direction (cy). Head scatter outside the field also increased with field size, reflecting an increased contribution of photons scattered at large angles. It exceeds the leakage through the collimator 2 cm outside the edge for square fields c>10 cm. Monte Carlo calculations showed considerably less head scatter outside the field than measurements.

Air↗

Long axis excursion in aortic stenosis.

OBJECTIVES: To examine long axis excursion in patients with all grades of aortic stenosis and preserved transverse systolic function, and to compare long axis excursion in symptomatic with that in asymptomatic severe aortic stenosis. DESIGN: Prospective comparative study. SETTING: Regional cardiothoracic centre. PATIENTS: 78 patients with all grades of aortic stenosis and normal fractional shortening and ejection fraction were studied. There were two comparison groups, 10 age matched normal subjects and 14 patients with aortic stenosis and fractional shortening < 26%. METHODS: Aortic valve function and left ventricular mass were assessed echocardiographically. M mode measurements of long axis excursion at the septal and lateral sides of the mitral annulus were taken. RESULTS: There were significant differences between the groups in long axis excursion at both the septal (p < 0.0001) and lateral sides of the mitral annulus (p = 0.002 by analysis of variance). Long axis excursion was independently related to both left ventricular mass index (p = 0.001) and the grade of aortic stenosis (p = 0.002). Comparing patients with severe aortic stenosis with and without symptoms, there were significant differences in effective orifice area (p = 0.02 ) and long axis excursion at the lateral side of the mitral annulus (p = 0.04), but not in fractional shortening, ejection fraction, or peak or mean pressure difference. CONCLUSION: In patients with aortic stenosis, long axis excursion is reduced even in the presence of normal fractional shortening or ejection fraction. It is lower in patients with symptomatic compared with asymptomatic severe aortic stenosis and may be of use in predicting the onset of symptoms.

Acute Disease↗

Detection of urinary tract stones at low-radiation-dose CT with z-axis automatic tube current modulation: phantom and clinical studies.

PURPOSE: To evaluate depiction of urinary tract calculi at computed tomography (CT) with a z-axis modulation technique at various noise indexes to reduce radiation dose and preserve image quality. MATERIALS AND METHODS: Sixteen radiopaque kidney stones (2.5-19.2 mm in diameter) were embedded in the collecting systems of two bovine kidneys immersed in a water bath. A kidney phantom was made by placing the kidneys in an elliptical Plexiglas phantom (32 x 20 x 20 cm) filled with physiologic saline. The phantom was scanned at 16-detector row CT with a fixed tube current (300 mA) and z-axis modulation at noise indexes of 14, 20, 25, 35, and 50; remaining imaging parameters were held constant. Two abdominal radiologists reviewed images from most to least noisy. Images were evaluated for presence of stones and size, site, and attenuation value of each stone. Readers also graded conspicuity and margins of each stone on a five-point scale. In addition, follow-up studies of 22 patients (mean age, 46 years; range, 26-57 years; male-female ratio, 14:8) with kidney and ureteral stones who underwent CT with z-axis modulation (noise index, 14 and 20) were evaluated in the same manner. Statistical analysis was performed with the Student t test, Wilcoxon signed rank test, and kappa test of interobserver agreement. Institutional review board approval was obtained, and informed consent was not needed. RESULTS: In the phantom study, all 16 stones were identified on images obtained with a fixed tube current and z-axis modulation at noise indexes of 14, 20, and 25 (with a reduction in radiation dose of up to 77% compared with that of fixed tube current scanning). Three stones (<5 mm) were not visualized with z-axis modulation at noise indexes of 35 and 50. No significant difference was shown for conspicuity of kidney stones in 22 patients who underwent CT with z-axis modulation (with a 43%-66% reduction in radiation dose) when compared with results of previous fixed tube current studies (P > .05). CONCLUSION: Kidney stones (< or =2.5 mm) can be adequately depicted with the z-axis modulation technique, with a 56%-77% reduction in radiation dose. In patients with urinary tract stones, the technique results in a 43%-66% reduction in radiation dose at noise indexes of 14 and 20 without compromising stone depiction.

Adult↗

Influence of posture on left ventricular long- and short-axis shortening.

End-diastolic volume and left ventricular stroke volume are increased in the supine compared with upright position, but the contribution of long-axis (LAS) and short-axis shortening (SAS) to these changes with change in posture has not been established. We examined long- and short-axis motion and dimensions with echocardiography in 10 healthy subjects in the upright and supine position. Long-axis length at end diastole was almost identical, whereas the diastolic short-axis diameter was increased in the supine position. At end systole, there was a decreased long-axis length and increased short-axis length in the supine vs. upright position. Both LAS and SAS were enhanced in supine vs. upright positions [LAS: 9.3 +/- 2.2 vs. 15.1 +/- 3.1 mm (P < 0.001); SAS: 12.7 +/- 3.2 vs. 16.3 +/- 2.8 mm (P < 0.001)], presumably via Starling mechanisms. LAS increased more in the lateral part of the mitral annulus than in the septal part [7.7 +/- 2.6 vs. 4.0 +/- 2.8 mm (P < 0.006)], which implies that the more spherical form, in the supine position, induces more stretch at the lateral free wall than in the ventricular septum. These findings support the notion that Starling mechanisms affect systolic LAS.

Adult↗

Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. I. Linear acceleration responses during off-vertical axis rotation.

1. The dynamic properties of otolith-ocular reflexes elicited by sinusoidal linear acceleration along the three cardinal head axes were studied during off-vertical axis rotations in rhesus monkeys. As the head rotates in space at constant velocity about an off-vertical axis, otolith-ocular reflexes are elicited in response to the sinusoidally varying linear acceleration (gravity) components along the interaural, nasooccipital, or vertical head axis. Because the frequency of these sinusoidal stimuli is proportional to the velocity of rotation, rotation at low and moderately fast speeds allows the study of the mid-and low-frequency dynamics of these otolith-ocular reflexes. 2. Animals were rotated in complete darkness in the yaw, pitch, and roll planes at velocities ranging between 7.4 and 184 degrees/s. Accordingly, otolith-ocular reflexes (manifested as sinusoidal modulations in eye position and/or slow-phase eye velocity) were quantitatively studied for stimulus frequencies ranging between 0.02 and 0.51 Hz. During yaw and roll rotation, torsional, vertical, and horizontal slow-phase eye velocity was sinusoidally modulated as a function of head position. The amplitudes of these responses were symmetric for rotations in opposite directions. In contrast, mainly vertical slow-phase eye velocity was modulated during pitch rotation. This modulation was asymmetric for rotations in opposite direction. 3. Each of these response components in a given rotation plane could be associated with an otolith-ocular response vector whose sensitivity, temporal phase, and spatial orientation were estimated on the basis of the amplitude and phase of sinusoidal modulations during both directions of rotation. Based on this analysis, which was performed either for slow-phase eye velocity alone or for total eye excursion (including both slow and fast eye movements), two distinct response patterns were observed: 1) response vectors with pronounced dynamics and spatial/temporal properties that could be characterized as the low-frequency range of "translational" otolith-ocular reflexes; and 2) response vectors associated with an eye position modulation in phase with head position ("tilt" otolith-ocular reflexes). 4. The responses associated with two otolith-ocular vectors with pronounced dynamics consisted of horizontal eye movements evoked as a function of gravity along the interaural axis and vertical eye movements elicited as a function of gravity along the vertical head axis. Both responses were characterized by a slow-phase eye velocity sensitivity that increased three- to five-fold and large phase changes of approximately 100-180 degrees between 0.02 and 0.51 Hz. These dynamic properties could suggest nontraditional temporal processing in utriculoocular and sacculoocular pathways, possibly involving spatiotemporal otolith-ocular interactions. 5. The two otolith-ocular vectors associated with eye position responses in phase with head position (tilt otolith-ocular reflexes) consisted of torsional eye movements in response to gravity along the interaural axis, and vertical eye movements in response to gravity along the nasooccipital head axis. These otolith-ocular responses did not result from an otolithic effect on slow eye movements alone. Particularly at high frequencies (i.e., high speed rotations), saccades were responsible for most of the modulation of torsional and vertical eye position, which was relatively large (on average +/- 8-10 degrees/g) and remained independent of frequency. Such reflex dynamics can be simulated by a direct coupling of primary otolith afferent inputs to the oculomotor plant. (ABSTRACT TRUNCATED)

Acceleration↗

Food intake-induced leptin secretion modulates hypothalamo-pituitary-adrenal axis response and hypothalamic Ob-Rb expression to insulin administration.

The mutation of the ob gene is known to induce a phenotype of obesity accompanied by symptoms including enhanced production of glucocorticoid. Chronic administration to ob/ob mice of leptin, the ob gene product, reverses hypercorticosteronemia. This establishes a clear relation between adipocyte and hypothalamo-pituitary-adrenal (HPA) axis functions. In the present study we investigated the acute modulatory effects of food intake-stimulated leptin secretion on HPA axis activity and hypothalamic leptin receptor (Ob-Rb) expression in 24-hour fasting, adult female, BALB/c mice after insulin-induced hypoglycemia. Our results indicate that: (1) food supply for 45 min to 24-hour fasting mice increased plasma glucose levels and reversed both hypercorticosteronemia and hypoleptinemia; (2) the insulin-induced hypoglycemia produced a marked HPA axis activation in animals with no access to food but this response was fully prevented by food intake and the consecutive increase in plasma leptin levels; (3) the inhibitory effect of leptin on the HPA axis response to insulin-induced hypoglycemia was corroborated by i.p. administration of murine leptin, and (4) fasting-induced hypothalamic Ob-Rb overexpression is not modulated by insulin itself but by leptin, since increase in leptin levels by food intake or by administration of exogenous leptin completely reversed this Ob-Rb overexpression. These results confirm the inhibitory effect of leptin on the HPA axis response to various stress stimuli. They clearly demonstrate that acute food intake in 24-hour fasting mice: (a) rapidly reduced fasting-induced hypercorticosteronemia by enhancing both spontaneous and insulin-elicited endogenous leptin secretion; (b) fully prevented HPA axis response to insulin administration, by rapidly increasing endogenous leptin secretion and probably also by diminishing the extent and the duration of insulin-induced hypoglycemia, and (c) abolished hypothalamic Ob-Rb overexpression induced by fasting itself combined with insulin treatment. The present data strongly suggests an inhibitory effect of endogenous leptin on insulin-induced HPA axis response, an interaction relevant to the physiological adaptation to starvation and caloric excess, and further supports the pivotal role played by the hypothalamus in restoring homeostasis in different allostatic states.

Adrenocorticotropic Hormone↗

Decreased hypothalamo-pituitary-adrenal axis response to neuroendocrine challenge under repeated endotoxemia.

It has been established that in vivo administration of bacterial lipopolysaccharide (LPS) enhances hypothalamo-pituitary-adrenal (HPA) axis function by a mechanism involving endotoxin-stimulated cytokine release. Since under chronic LPS treatment a tolerance of the HPA axis response takes place, the aim of the present study was to determine whether mice submitted to repeated LPS administration could present an impairment in the HPA response to insulin (INS) administration, a pure neuroendocrine challenge. For this purpose, adult female BALB/c mice were injected with 200 microliters i.p. of sterile saline solution (VEH) containing 25 micrograms of LPS in a single or repeated (at 24-hour intervals, during 5 consecutive days) fashion. Animals were then killed at either 45 min after INS (0.3 IU/mouse, i.p.) or 2 h after LPS (25 micrograms/mouse) administration on experimental day 1 (D1; without any previous LPS injection), 3 (D3; mice having received 2 previous LPS injections) or 5 (D5; mice having received 4 previous LPS administrations). Control groups were injected a similar volume of VEH alone on experimental day 1 (D1; without any previous LPS injection), 3 (D3; mice having received 2 previous LPS injections) or 5 (D5; mice having received 4 previous LPS administrations); in each group, mice were killed at either 45 min or 2 h after VEH injection. Immediately after decapitation, trunk blood was collected. Plasma tumor necrosis factor alpha (TNF), ACTH and corticosterone (B) levels were determined by specific assays. Plasma TNF, ACTH and B levels were significantly increased 2 h after the first LPS treatment (D1). Although no significant increase in plasma TNF concentration was found 2 h after the third LPS injection (D3), the corticotrope response was still significant and induced a full effect on adrenal B output. Two hours after the fifth LPS administration (D5) TNF output was minimal and the HPA axis response was significantly diminished. Finally, the pattern of the HPA axis response to INS-induced hypoglycemia was similar to that elicited after LPS challenge although somewhat delayed. Our results indicate that: (1) TNF seems to play an important role in stimulating HPA axis function after single but not after repeated endotoxin administration; and (2) an impairment in the HPA axis response to both immuneneuroendocrine (LPS) and neuroendocrine (INS) stimuli takes place after repeated LPS administration. This study further suggests that the tolerance of the HPA axis response under recurrent endotoxemia could be, at least partially, due to an impairment in both immune (TNF output) and neuroendocrine functions.

Adrenal Glands↗

Sexual dimorphism in the mouse hypothalamic-pituitary-adrenal axis function after endotoxin and insulin stresses during development.

Bidirectional communication between the immune and the endocrine systems is now widely accepted as essential for the survival of the organism. Since a classical nonresponsive period of the hypothalamic-pituitary-adrenal (HPA) axis takes place shortly after birth and because endogenous sex hormones modulate immune function, the aim of the present work was to determine whether sex steroids regulate the PHA axis response to immune (bacterial, lipopolysaccharide, LPS) and nonimmune (insulin, INS) stressors in mice during development. For this purpose 7-, 15-, 30-, 45- and 60-day-old mice of both sexes were intraperitoneally injected with either vehicle alone (basal) or containing LPS (2 mg/kg body weight) or INS (12 IU/kg body weight). The animals were then killed by decapitation, 2 h or 45 min after LPS or INS, respectively. Plasma samples were assayed to measure corticosterone concentrations. The results indicated that: (a) there was a transient increase in basal plasma corticosterone levels during development, with a peak value at the juvenile age, regardless of sex; (b) a higher basal plasma corticosterone concentration in females than in males characterized the adult age; (c) the infantile age is a period of the HPA axis function nonresponsive to purely neuroendocrine but not to inflammatory stimuli; (d) during the juvenile age, females showed a hyporesponsive HPA axis to neurendocrine and immune stress, whereas male mice were fully unresponsive to both challenges; (e) animals of both sexes showed a maximal HPA axis response to purely neuroendocrine stress at the prepubertal age; this response to the immune stimulus was also maximal in 30-day-old males, while it was found in females after puberty (45-day-old mice); (f) sexual dimorphism in the HPA axis response to a purely neuroendocrine stimulus was found at 30 days of age or later, while this characteristic of the response to endotoxin was not present until puberty. These data clearly suggest that these are gender-dependent characteristics of the ontogeny of the HPA and HP-gonadal axes that are responsible for the sexual dimorphism of HPA axis function in mice.

Animals↗

Revising axis V for DSM-IV: a review of measures of social functioning.

OBJECTIVE: Axis V, which uses the Global Assessment of Functioning Scale in the multiaxial system of DSM-III-R, is under review for DSM-IV. This article examines what is known about axis V and selectively reviews the literature on measures of social functioning to identify potential alternatives to the Global Assessment of Functioning Scale. METHOD: About 25 studies on the use, reliability, and validity of axis V in DSM-III and DSM-III-R are reviewed. In addition, nearly 30 measures of social functioning are reviewed and analyzed as potential substitutes for the Global Assessment of Functioning Scale. The analysis focuses on the strengths and weaknesses of each measure for assessing functioning on axis V. RESULTS: Axis V measures are modestly reliable and valid but not widely used. The authors identify and discuss two particular limitations of the Global Assessment of Functioning Scale: 1) the combination of measures of symptoms and measures of social functioning on a single axis and 2) the exclusion of physical impairments from the rating of functioning. CONCLUSIONS: None of the measures of social functioning reviewed is clearly superior to the Global Assessment of Functioning Scale for use on axis V. A modified version of the Global Assessment of Functioning Scale, separating the measures of social and occupational functioning from the measures of symptoms and psychological functioning, is proposed for field testing, along with a new set of instructions permitting the rating of limitations due to both physical and mental impairments.

Persons with Disabilities↗

DSM-III-R axis II comorbidity in dysthymia and major depression.

OBJECTIVE: Dysthymia is generally believed to be associated with a high rate of DSM-III-R axis II comorbidity. However, it is unclear whether this rate is higher than that for other axis I disorders, how many dysthymic patients have personality disorders, and what the most common co-occurring axis II conditions are. METHOD: Ninety-seven outpatients with early-on-set dysthymia and 45 with episodic major depression were administered structured diagnostic interviews for axis I and II disorders. In addition, knowledgeable informants were independently interviewed about axis II conditions in the patients. RESULTS: A significantly greater proportion of dysthymic patients (60%) than patients with episodic major depression (18%) met criteria for a personality disorder. The most common axis II conditions among dysthymic patients were borderline, histrionic, and avoidant personality disorder. Informants' reports yielded similar results. CONCLUSIONS: These data indicate that early-onset dysthymia is associated with significantly greater axis II comorbidity than episodic major depression. Further work is necessary to elucidate the processes underlying this association.

Adult↗

Axis I comorbidity in patients with borderline personality disorder: 6-year follow-up and prediction of time to remission.

OBJECTIVE: The purpose of this study was to assess the prevalence of axis I disorders among patients with borderline personality disorder over 6 years of prospective follow-up. METHOD: A semistructured interview of demonstrated reliability was used to assess presence or absence of comorbid axis I disorders in 290 patients who met Revised Diagnostic Interview for Borderlines criteria and DSM-III-R criteria for borderline personality disorder and 72 patients who did not meet these criteria but did meet DSM-III-R criteria for another axis II disorder. Over 94% of surviving patients were reinterviewed about their axis I disorders at 2-year, 4-year, and 6-year follow-up periods. RESULTS: Although the patients with borderline personality disorder experienced declining rates of many axis I disorders over time, the rates of these disorders remained high, particularly the rates of mood and anxiety disorders. Patients whose borderline personality disorder remitted over time experienced substantial decline in all comorbid disorders assessed, but those whose borderline personality disorder did not remit over time reported stable rates of comorbid disorders. When the absence of comorbid axis I disorders was used to predict time to remission, the absence of substance use disorders was a far stronger predictor of remission from borderline personality disorder than was the absence of posttraumatic stress disorder, mood disorders, other anxiety disorders, or eating disorders, respectively. CONCLUSIONS: The results of this study suggest that axis I disorders are less common over time in patients with initially severe borderline personality disorder, particularly for patients whose borderline personality disorder remits over time. The findings also suggest that substance use disorders are most closely associated with the failure to achieve remission from borderline personality disorder.

Adult↗

A DSM-IV Axis I comorbidity study of males (n = 120) with paraphilias and paraphilia-related disorders.

One hundred and twenty consecutively evaluated outpatient males with paraphilias (PAs; n = 88, including 60 sex offenders) and paraphilia-related disorders (PRDs; n = 32) were systematically assessed for certain developmental variables and DSM-IV-defined Axis I comorbidity. In comparison with the PRDs, the PA group was statistically significantly more likely to self-report a higher incidence of physical (but not sexual) abuse, fewer years of completed education, a higher prevalence of school-associated learning and behavioral problems, more psychiatric/substance abuse hospitalizations, and increased employment-related disability as well as more lifetime contact with the criminal justice system. In both groups, the most prevalent Axis I disorders were mood disorders (71.6%), especially early onset dysthymic disorder (55%) and major depression (39%). Anxiety disorders (38.3%), especially social phobia (21.6%), and psychoactive substance abuse (40.8%), especially alcohol abuse (30%), were reported as well. Cocaine abuse was statistically significantly associated with PA males (p = .03). There was a statistically significant correlation between the lifetime prevalence of Axis I nonsexual diagnoses and hypersexual diagnoses (PAs and PRDs). The prevalence of retrospectively diagnosed attention deficit hyperactivity disorder (ADHD) was 35.8%, the third most prevalent Axis I disorder. ADHD (p = .01), especially ADHD-combined subtype (p = .009), was statistically significantly associated with PA status. ADHD was statistically significantly associated with conduct disorder, and both of these Axis I disorders were associated with the propensity for multiple PAs and a higher likelihood of incarceration. When the diagnosis of ADHD was controlled, the differences reported above between PAs and PRDs either became statistically nonsignificant or remained as only statistical trends. Thus, ADHD and its associated developmental sequellae and Axis I comorbidities was the single most common nonsexual Axis I diagnosis that statistically significantly distinguished males with socially deviant sexual arousal (PAs) from a nonparaphilic hypersexual comparison group (PRDs). Sex offender paraphiliacs were more likely to be diagnosed with conduct disorder, alcohol abuse, cocaine abuse, and generalized anxiety disorder. The prevalence of any ADHD in the sex offender paraphiliacs was 43.3%, and nearly 25% of offenders were diagnosed with ADHD-combined subtype.

Adolescent↗

The association of spatial T wave axis deviation with incident coronary events. The ARIC cohort.

BACKGROUND: Although current evidence suggests that the spatial T wave axis captures important information about ventricular repolarization abnormalities, there are only a few and discordant epidemiologic studies addressing the ability of the spatial T wave axis to predict coronary heart disease (CHD) occurrence. METHODS: This prospective study analyzed data from 12,256 middle-aged African American and white men and women, from the Atherosclerosis Risk in Communities Study (ARIC). Following a standardized protocol, resting standard 12-lead, 10-second electrocardiograms were digitized and analyzed with the Marquette GE program. The median follow-up time was 12.1 years; incident coronary heart disease comprised fatal and non-fatal CHD events. RESULTS: The incidence rate of CHD was 4.26, 4.18, 4.28 and 5.62 per 1000 person-years respectively, across the spatial T wave axis quartiles. Among women for every 10 degrees increase in the spatial T wave axis deviation, there was an estimated increase in the risk of CHD of 1.16 (95% CI 1.04-1.28). After adjustment for age, height, weight, smoking, hypertension, diabetes, QRS axis and minor T wave abnormalities, this hazard rate ratio for women fell to 1.03 (0.92-1.14). The corresponding crude and adjusted hazard ratios for men were 1.05 (95% CI 0.96-1.15) and 0.95 (0.86-1.04) respectively. CONCLUSIONS: In conclusion, this prospective, population-based, bi-ethnic study of men and women free of coronary heart disease at baseline shows that spatial T wave axis deviation is not associated with incident coronary events during long-term follow up. It is doubtful that spatial T wave axis deviation would add benefit in the prediction of CHD events above and beyond the current traditional risk factors.

Black or African American↗

Risk factors for suicide independent of DSM-III-R Axis I disorder. Case-control psychological autopsy study in Northern Ireland.

BACKGROUND: The vast majority of suicides suffer from at least one mental disorder at the time of death. AIMS: To identify risk factors for suicide, particularly those independent of current DSM-III-R Axis I disorder(s). METHOD: A case-control psychological autopsy study comparing suicides with matched community controls. RESULTS: Independent risk factors for suicide included: Axis II (personality) disorder (particularly antisocial, avoidant and dependent); at least one of 12 life events (from the List of Threatening Experiences) during the previous 52 or 4 weeks (in particular, a 'serious problem with close friend, neighbour or relative'); current unemployment; previous history of deliberate self-harm; and contact with a GP within 26 weeks. Relative to individuals with no current mental disorder, the estimated risk of suicide in those with Axis I-Axis II comorbidity (OR 346.0) was significantly greater than that in those with Axis I disorder(s) only (OR 52.4). CONCLUSIONS: Suicide risk assessment may be enhanced by enquiry about the aforementioned independent risk factors, and attention to Axis I-Axis II comorbidity.

Case-Control Studies↗

Differential menstrual cycle regulation of hypothalamic-pituitary-adrenal axis in women with premenstrual syndrome and controls.

Previous studies in animals indicate that reproductive steroids are potent modulators of the hypothalamic-pituitary-adrenal (HPA) axis, a physiologic system that is typically dysregulated in affective disorders, such as major depression. Determination of the role of reproductive steroids in HPA axis regulation in humans is of importance when attempting to understand the pathophysiology of premenstrual syndrome (PMS), a disorder characterized by affective symptoms during the luteal phase of the menstrual cycle. We performed two studies using treadmill exercise stress testing to determine the effect of menstrual cycle phase and diagnosis on the HPA axis in women with PMS and controls and the role of gonadal steroids in HPA axis modulation in control women. The results of these studies indicate that women with PMS fail to show the normal increased HPA axis response to exercise during the luteal phase and that progesterone, not estradiol, produces increased HPA axis response to treadmill stress testing in control women. These data demonstrate that women with PMS, when symptomatic, appear to have an abnormal response to progesterone and, furthermore, do not display the HPA axis abnormalities characteristic of major depression.

Adrenocorticotropic Hormone↗

A comparison between the 1-microg adrenocorticotropin (ACTH) test, the short ACTH (250 microg) test, and the insulin tolerance test in the assessment of hypothalamo-pituitary-adrenal axis immediately after pituitary surgery.

The short ACTH stimulation test is an easy, reliable, and extensively used test in the assessment of the hypothalamo-pituitary-adrenal (HPA) axis. However, its use immediately after pituitary surgery is a matter of debate. The insulin tolerance test (ITT) is the gold standard in the evaluation of the HPA axis, but it is not always without side effects and may be unpleasant early after pituitary surgery. Our aim was to investigate the value of the 1-microg ACTH test in the assessment of the HPA axis early after pituitary surgery. We also aimed to determine the value of the 1-microg and 250-microg ACTH tests and the ITT in the estimation of HPA axis status after 3 months postoperatively. Nineteen patients subjected to pituitary tumor surgery were included in the study, and the ITT and the 1-microg and 250-microg ACTH tests were performed between the 4th and 11th days of surgery. The tests were repeated at the first month in 3 patients with subnormal peak cortisol responses (454, 125, and 301 nmol/L) and in 18 patients at the third month postoperatively. ACTH stimulation tests were performed by using 1 microg and 250 microg ACTH iv as a bolus injection, and blood samples were drawn at 0, 30, and 60 min for measurement of serum cortisol levels. The ITT was performed by using iv regular insulin, and serum glucose and cortisol levels were measured. The 1-microg and 250-microg ACTH stimulation tests and the ITT were performed consecutively. At least 48 h were allowed between each test. A peak serum cortisol level of 550 nmol/L or greater was considered as a normal response for both the ITT and the ACTH tests. The serum cortisol level was measured by RIA using commercial kits. Serum glucose was determined by glucose oxidase method. There were correlations between the peak cortisol response to the ITT and the 1-microg ACTH test (r = 0.39, P < 0.05) in the early postoperative period. No correlation was found between the ITT and the 250-microg ACTH test responses. In the early postoperative period, two patients showed normal cortisol responses (> or =550 nmol/L) to the 1-microg ACTH test and five patients showed normal cortisol responses to the 250-microg ACTH test among the six patients with subnormal cortisol responses to the ITT. Three patients with subnormal cortisol responses to ITT and baseline cortisol values less than 240 nmol/L showed normal HPA axis at the end of the first month. In the late postoperative period, at the third month, all the patients showed normal HPA axis. In the early postoperative period of pituitary surgery, the 1-microg ACTH test results are more concordant than the 250-microg ACTH test in comparison with the ITT. Our results also indicate that HPA axis dysfunction shown by ACTH stimulation tests and the ITT in early postoperative period may be normalized 1-3 months after surgery. For this reason, we think that dynamic tests including the ITT may not be useful early after pituitary surgery.

Adrenocorticotropic Hormone↗