Personality Assessment Inventory suicidality scales: Suicidal Ideation (SUI), Suicide Potential Index (SPI), and S_Chron in an Afghanistan/Iraq-era active and Veteran military sample.

INTRODUCTION: This study validated Personality Assessment Inventory (PAI) Suicidal Ideation (SUI), Suicide Potential Index (SPI), and S_Chron scales against chronic and acute suicide risk factors and symptom validity measures. METHODS: Afghanistan/Iraq-era active-duty and Veteran participants completed a prospective study on neurocognition (N = 403) that included the PAI. The Beck Depression Inventory-II (specifically item 9) administered at two time points assessed acute and chronic suicide risk; the Beck Scale for Suicide Ideation item 20 identified history of suicide attempts. Major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and traumatic brain injury (TBI) were evaluated using structured interviews and questionnaires. RESULTS: All three PAI suicide scales were significantly related to independent indicators of suicidality, with the largest effect for SUI (AUC 0.837-0.849). All three suicide scales were significantly related to MDD (r = 0.36-0.51), PTSD (r = 0.27-0.60), and TBI (r = 0.11-0.30). The three scales were not related to suicide attempt history for those with invalid PAI protocols. CONCLUSIONS: Although all three suicide scales do show significant relationships to other indicators of risk, SUI showed the highest association and greatest resistance to response bias.

Origin of the left coronary artery from the right pulmonary artery.

Origin of the left coronary artery from the right pulmonary artery has rarely been documented. This is the first such case in a heart with an intact ventricular septum and paraductal coarctation of the aorta. Although an antemortem diagnosis was made and the anomalous left coronary artery was ligated, the patient, a 3 1/2 month old infant, died 1 day after surgery. Autopsy confirmed the diagnosis, but revealed that the left coronary artery was dominant. It is believed that the fatal outcome in the infant was, in part, due to the dominance of the left coronary artery and the effects of the coarctation on the already ischemic left ventricle.

Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder.

Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala-calcarine (P=0.01) and amygdala-thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala-ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.

Performance feedback deficit in geriatric depression.

BACKGROUND: The orbital frontal cortex is involved with processing of performance feedback. This study tests the hypothesis that older depressed subjects, compared with elderly control subjects, commit more subsequent errors after receiving feedback from an initial error. METHODS: We administered 116 older depressed patients and 139 control subjects the Trail Making Test Part B (TRAILS-B). Subjects who committed an error on TRAILS-B were immediately given feedback on performance. We then measured the frequency of making an error on the subsequent three tries. The likelihood of making any subsequent error was examined. RESULTS: After controlling for the overall initial error rate, more depressed patients than control subjects made subsequent errors. This association remained significant in later regression models. When the depressed group was examined in additional models, severity of depression was not associated with increased subsequent errors. CONCLUSIONS: These results extend previous findings suggesting a performance feedback deficit in geriatric depression. The findings support previous studies linking the orbital frontal cortex and depression.

Evidence of white matter tract disruption in MRI hyperintensities.

BACKGROUND: Diffusion tensor imaging (DTI) of brain tissue measures the apparent diffusion coefficient (ADC), or isotropic diffusion, and anisotropy, or diffusion as influenced by tissue structure. We hypothesized that hyperintensities, when compared with normal tissue by DTI, would show evidence of damage through an increased ADC and decreased anisotropy. We also hypothesized that DTI changes in hyperintensities would be similar between depressed subjects and control subjects. METHODS: Fourteen depressed geriatric patients and nineteen control subjects received DTI. The ADC and aniso-tropy of normal tissue from standard regions were compared with hyperintensities from these regions. The Students' t test compared individual regions and averaged white matter results. RESULTS: Hyperintensities showed higher ADC and lower anisotropy than normal regions. Gray matter exhibited similar trends. There was no significant difference in diffusion characteristics of hyperintensities between subjects and control subjects. CONCLUSIONS: Hyperintensities damage the structure of brain tissue, and do so comparably in depressed subjects and control subjects.

The relationship between insurance coverage and psychiatric disorder in predicting use of mental health services.

OBJECTIVE: This study investigated how insurance coverage for mental health services affects outpatient mental health service utilization among those with and among those without a DSM-III psychiatric diagnosis. The authors used a representative community sample to compare the regression effects of insurance coverage on utilization of mental health services among these subjects. METHOD: Data are from the second wave of the Piedmont, North Carolina, site of the Epidemiologic Catchment Area project. These data contain DSM-III diagnostic measures derived from the National Institute of Mental Health Diagnostic Interview Schedule as well as measures of insurance coverage and utilization. Responses from 2,889 community residents were analyzed using both ordinary least squares and logistic regression. RESULTS: In both models, insurance coverage was strongly associated with care among those with as well as among those without a psychiatric disorder. The association between coverage and the probability of care was strongest among those with a disorder. CONCLUSIONS: The findings are not consistent with the claim that failing to provide insurance coverage will reduce discretionary but not necessary mental health care utilization. They provide evidence that failing to provide insurance coverage will reduce utilization as much or more among those with a psychiatric disorder as among those without. This result has important implications for health care reform.

Violence and severe mental illness: the effects of substance abuse and nonadherence to medication.

OBJECTIVE: Violent behavior among individuals with severe mental illness has become an important focus in community-based care. This study examines the joint effect of substance abuse and medication noncompliance on the greater risk of serious violence among persons with severe mental illness. METHOD: Involuntarily admitted inpatients with severe mental illness who were awaiting a period of outpatient commitment were enrolled in a longitudinal outcome study. At baseline, 331 subjects underwent an extensive face-to-face interview. Complementary data were gathered by a review of hospital records and a telephone interview with a family member or other informant. These data included subjects' sociodemographic characteristics, illness history, clinical status, medication adherence, substance abuse, insight into illness, and violent behavior during the 4 months that preceded hospitalization. Associations between serious violent acts and a range of individual characteristics and problems were analyzed by using multivariable logistic regression. RESULTS: The combination of medication noncompliance and alcohol or substance abuse problems was significantly associated with serious violent acts in the community, after sociodemographic and clinical characteristics were controlled. CONCLUSIONS: Alcohol or other drug abuse problems combined with poor adherence to medication may signal a higher risk of violent behavior among persons with severe mental illness. Reduction of such risk may require carefully targeted community interventions, including integrated mental health and substance abuse treatment.

Can involuntary outpatient commitment reduce hospital recidivism?: Findings from a randomized trial with severely mentally ill individuals.

OBJECTIVE: The goal of this study was to evaluate the effectiveness of involuntary outpatient commitment in reducing rehospitalizations among individuals with severe mental illnesses. METHOD: Subjects who were hospitalized involuntarily were randomly assigned to be released (N = 135) or to continue under outpatient commitment (N = 129) after hospital discharge and followed for 1 year. Each subject received case management services plus additional outpatient treatment. Outpatient treatment and hospital use data were collected. RESULTS: In bivariate analyses, the control and outpatient commitment groups did not differ significantly in hospital outcomes. However, subjects who underwent sustained periods of outpatient commitment beyond that of the initial court order had approximately 57% fewer readmissions and 20 fewer hospital days than control subjects. Sustained outpatient commitment was shown to be particularly effective for individuals with nonaffective psychotic disorders, reducing hospital readmissions approximately 72% and requiring 28 fewer hospital days. In repeated measures multivariable analyses, the outpatient commitment group had significantly better hospital outcomes, even without considering the total length of court-ordered outpatient commitments. However, in subsequent repeated measures analyses examining the role of outpatient treatment among psychotically disordered individuals, it was also found that sustained outpatient commitment reduced hospital readmissions only when combined with a higher intensity of outpatient treatment. CONCLUSIONS: Outpatient commitment can work to reduce hospital readmissions and total hospital days when court orders are sustained and combined with intensive treatment, particularly for individuals with psychotic disorders. This use of outpatient commitment is not a substitute for intensive treatment; it requires a substantial commitment of treatment resources to be effective.

Chronic levodopa or pergolide administration induces down-regulation of dopamine receptors in denervated striatum.

Refractory response to dopamine (DA) agonists is a common problem in the treatment of Parkinson's disease. In rats with unilateral lesions of the substantia nigra, denervation induced significant increases in striatal 3(H)-spiperone binding sites ipsilateral to the lesion. Chronic treatment with levodopa or with pergolide mesylate significantly decreased the number of 3(H)-spiperone striatal binding sites. Agonist-induced decreases were approximately equivalent in intact and denervated striata and did not appear to be affected by lesions. These results suggest that the poor response to DA agonist in certain parkinsonian patients with chronic drug exposure may be mediated by drug-induced DA receptor down-regulation.

Clonazepam-induced up-regulation of serotonin1 binding sites in frontal cortex of rat.

Chronic administration of the benzodiazepine, clonazepam, increased the number of [3H]5-hydroxytryptamine (5-HT1) binding sites in the frontal cortex of the rat. The increase reflected a change in the maximum density of binding sites (Bmax) with no change in ligand affinity (Kd). Increased binding occurred after continued exposure (10 days) to large (5.0 mg/kg) doses of clonazepam. The changes in [3H]5-HT binding were regional in that they occurred in membranes from the frontal cortex but not the brainstem. The effects were also at least partially selective for 5-HT receptors since the binding of the beta-adrenergic radioligand, [3H]dihydroalprenolol, was not affected by clonazepam. A second benzodiazepine, diazepam, did not affect the binding of [3H]5-HT at doses of 30 mg/kg per day. The latter data suggest that the effects of benzodiazepines on serotonin 5-HT1 receptors are unique to clonazepam.

Biochemical and behavioral evaluation of pergolide as a dopamine agonist in the rat brain.

The ergot derivative pergolide was evaluated as a dopamine agonist using various behavioral and biochemical analyses. Spontaneous motor activity was decreased by small doses (0.1 mg/kg) of pergolide and increased with larger doses (above 0.5 mg/kg). Hypermotility after larger doses persisted for as long as 24 hr and was succeeded by a period of hypomotility. The doses of drug, sufficient to produce hypermotility, also produced stereotypy. With repeated daily injections (2 weeks), the period of hypermotility decreased and the ensuing period of hypomotility increased. Stereotyped behavior was similarly affected. Chronic administration of pergolide did not alter the magnitude of the behavioral responses. Levels of the dopamine (DA) metabolites, dihydroxyphenylacetate (DOPAC) and homovanillic acid (HVA), in the striatum and mesolimbic regions were decreased during the periods of hypermotility but returned to control levels during subsequent hypomotility. Activation of putative inhibitory presynaptic dopamine receptors by pergolide was studied by following accumulation of DOPA in rats treated with the dopamine neuron inhibiting agent, gamma-butyrolactone (GBL) and a DOPA-decarboxylase inhibitor. Pergolide significantly inhibited both striatal and mesolimbic accumulation of DOPA. In contrast, with changes in behavioral and metabolic indices, pergolide-induced inhibition of tyrosine hydroxylase was not affected by chronic treatment with pergolide. On the basis of both behavioral and biochemical data it is proposed that pergolide acts as a dopamine agonist with particularly long-lasting effects.

Q-oTc interval and blood calcium levels in newborn infants.

The interval from the beginning of the Q wave to the origin of the T wave (Q-oTc interval) and total and ionized serum calcium levels were measured in 27 full-term and 77 premature infants. The correlation between Q-oTc and total and ionized calcium levels was significant in both full-term and normal premature infants. No correlation was found in a group of critically ill premature infants, most of whom had evidence of CNS involvement. Constant infusion of calcium gluconate in a number of infants belonging to the latter group produced a significant shortening of the Q-oTc interval. It is speculated that the lack of correlation of Q-oTc interval and total or ionized calcium levels in sick premature infants could be explained on the basis of a dysfunction in cardiac sympathetics or alternatively by marked variations in serum catecholamines.

Deep hypothermia in infant cardiac surgery.

The value of infant cardiac surgery using deep hypothermia remains a debate. A steady number of cardiac centers have consented to this approach in spite of some filibuster. Physiologists are frightened, anesthetists may find it cumbersome, but surgeons using it enjoy the ease of correction in a bloodless and relaxed heart. The cardiologists may document acceptable results, but we also need the alert feedback from the provider of long-term health care--the pediatrician--to document possible flaws of this pristine modality. This article is intended to familiarize the pediatrician with the method of deep hypothermia: its origin, application, and appeal for consumer protection.

Congenital valvular aortic stenosis: clinical detection of small pressure gradient. Prepared for the joint study on the joint study on the natural history of congenital heart defects.

Clinical variables (from the history, physical examination, electrocardiogram and chest radiograph) were related to the pressure gradient measured between the left ventricle and the aorta in 434 young patients with congenital valvular aortic stenosis admitted to a national collaborative study. The aim was to devise a composite clinical criterion for the recognition of patients with a small pressure gradient, so as to expand the opportunity for avoiding cardiac catheterization in such patients. Flattened or inverted T waves in lead V6 were found to be inconsistent with mild disease. Therefore, a composite criterion, providing an estimate of pressure gradient, was developed for patients without T wave changes. The final criterion, based on multivariate analysis, involved only the intensity of the systolic murmor, the presence or absence of an early diastolic murmur, and voltages of the Q and R waves in lead V6. Patients with a low estimate by this procedure rarely had a large measured gradient. Only 3.7 percent (6 of 161) with an estimated gradient of less than 45 mm Hg had a gradient at cardiac catheterization of 80 or more mm Hg; none (0 of 32) with an estimated gradient of less than 30 mm Hg had a gradient of 50 or more mm Hg. This criterion should be helpful in avoiding unnecessary catheterization by identifying some patients with valvular aortic stenosis who have a small pressure gradient.

Transposition of the great arteries with aortic arch obstruction. Anatomical review and report of surgical management.

Transposition of the great arteries (S,D,D) is a common congenital cardiovascular malformation that is occasionally associated with ventricular septal defect and left ventricular outflow tract obstruction. Recently right ventricular outflow tract obstruction associated with an aortic arch anomaly has been recognized as an infrequent but important variant of transposition of the great arteries, and this constellation presents a unique surgical challenge. Five infants with this constellation whose systemic circulation was dependent on flow through the ductus arteriosus have undergone definitive surgical treatment with four survivors. An anatomical review of 129 specimens with transposition of the great arteries revealed that 17% had right ventricular outflow tract obstruction and 7% had associated aortic arch obstruction as well. All specimens with aortic arch obstruction and ventricular septal defect except one had a malalignment type ventricular septal defect. Although several treatment options may be considered, recent experience with arterial switch repair in the neonate with transposition of the great arteries (S,D,D) prompted repair in these patients by arterial switch, ventricular septal defect closure, repair of aortic arch obstruction, and augmentation of the right ventricular outflow tract.

Pneumothorax during positive-pressure mechanical ventilation.

The hemodynamic and respiratory effects of unilateral pneumothorax were studied during positive-pressure mechanical ventilation in five sheep. The sheep were anesthetized, intubated, and placed on mechanical ventilation with positive end-expiratory pressure (5 cm H2O). After baseline studies, including chest roentgenograms, were taken, increments of air were injected into the right pleural cavity. Measurements were repeated at pneumothoraces of 500, 1,000, and 1,500 ml. There was a steady fall in cardiac output (p less than 0.02) at pneumothoraces of 1,000 and 1,500 ml. The decrease in cardiac stroke volume paralleled that of cardiac output. Heart rate rose (p less than 0.05) at a pneumothorax of 1,500 ml. There appeared to be a linear relationship between the percent increase in pneumothorax as estimated by roentgenogram and the percent fall in cardiac output (r = 0.991). There was a steady rise in mean pulmonary arterial, pulmonary arterial capillary wedge, superior vena caval, and inferior vena caval pressures, although the changes in inferior vena caval pressure were not statistically different from baseline. Peak airway pressure increased from baseline at pneumothoraces of 1,000 and 1,500 ml. Both right and left end-expiratory intrapleural pressures increased and were statistically different (p less than 0.01) from baseline. However, there was a substantially greater rise in right intrapleural pressure than left. Arterial oxygen tension remained physiological throughout the study. This study indicates that cardiac output decreases as the amount of pneumothorax increases in sheep during mechanical ventilation. This study also demonstrates that, during positive-pressure mechanical ventilation, a relatively benign-appearing pneumothorax by chest roentgenogram may be associated with a significantly depressed cardiac output. In addition, arterial oxygen tension may not be useful in predicting the onset of pneumothorax during mechanical ventilation.

Surgical closure of patent ductus arteriosus in 268 preterm infants.

Over a 2 year period ending in April, 1981, 268 premature infants with birth weight below 1,750 gm underwent operation for a "hemodynamically significant" patent ductus arteriosus. Operations were performed in 13 centers participating in a collaborative study, which was primarily designed to evaluate the role of indomethacin in the management of patent ductus arteriosus. No patient died during the operations, which were done at a median age of 10 days. Eight infants (3%) died within 36 hours after operation. In only one was the death directly attributable to the operative procedure. Hospital mortality (23%) and postoperative morbidity, which included bronchopulmonary dysplasia, pneumothorax, and sepsis, were unrelated to birth weight, age at operation, and degree of preexisting pulmonary disease or preoperative treatment of the infant with indomethacin. Results indicate that surgical ligation is a safe and effective procedure for treating patent ductus arteriosus with large left-to-right shunting in small premature infants.

Electroconvulsive treatment and haloperidol: effects on pre- and postsynaptic dopamine receptors in rat brain.

Electroconvulsive treatment (ECT) has a transitory beneficial effect on patients with Parkinson's disease (PD). The possibility that this effect is mediated by dopamine (DA) receptors was investigated in the rat brain. Repeated ECT or chronic haloperidol treatment induced supersensitivity of putative autoreceptors in the nigrostrital and mesolimbic DA pathways as reflected by enhanced apomorphine-induced inhibition of DA synthesis. Effect of simultaneous administration of ECT plus haloperidol on DA receptor sensitivity were not additive. Chronic haloperidol treatment induced significant elevations in the density of 3[H]-spiperone striatal binding sites. Concurrent administration of ECT had no effect on the neuroleptic-induced supersensitivity. ECT alone was also without effect on 3[H]-spiperone binding. Thus, ECT-induced increases in the sensitivity of presynaptic autoinhibition of DA release was not reflected by changes in the striatal 3[H]-spiperone binding sites. This suggests that effects of ECT on the DA system are not mediated by dopamine D2 receptors.

Neurotensin interacts with dopaminergic neurons in rat brain.

Neurotensin (NT) injected intracerebroventricularly in rat increases dopamine (DA) turnover in the corpus striatum and nucleus accumbens. Significant increases in 3,4-dihydroxyphenylacetic acid (DOPAC) levels occurred within 15 minutes after injection with peak levels at 60 minutes. The effect on NT on DOPAC and homovanillic acid (HVA) accumulation was dose-dependent at 3-100 micrograms. NT, like haloperidol, stimulated 3,4-dihydroxyphenylalanine (DOPA) accumulation in striatal neurons, in the presence of DOPA decarboxylase inhibitor, after injection of gamma-butyrolactone (GBL). NT had a similar stimulatory effect on DOPA levels in the accumbens while haloperidol (0.25 mg.kg-1) had no significant effect in this brain region. NT did not block the inhibitory effect of apomorphine on DOPA accumulation in both the striatum and accumbens, while haloperidol inhibited apomorphine effect in both regions. NT also failed to displace 3H-spiperone from DA receptors and the presence of NT in the binding assay did not alter the ability of DA to displace 3H-spiperone in either brain region. These experiments demonstrate that NT increases DA turnover in both the nigrostriatal and mesolimbic pathways.

Chlorpromazine methiodide-induced barrel rotation: an antimuscarinic effect.

Barrel rotation is a motor response observed in rats in which the animal twists about its long axis and rolls laterally. This response was first described following intracerebroventricular injection of somatostatin. The pharmacologic specificity of the response has been questioned, and its physiologic basis is unknown. Recently, barrel rotation following intraventricular injection of quaternary chlorpromazine, chlorpromazine methiodide (CPZMI), has been reported. We have studied the specificity and pharmacologic basis of CPZMI-induced barrel rotation. The response was not induced by 26 compounds injected as controls, and was induced by 6 anti-muscarinic compounds. Dose-response relationships for onset, duration and magnitude of CPZMI-induced barrel rotation response were studied; number of rotations increased linearly with CPZMI dose up to 20 micrograms, after which number of rotations decreased and toxic effects (sedation, seizures) occurred. CPZMI barrel rotation was inhibited by intraventricular injection of the muscarinic agonist carbachol and enhanced by intraventricular or systemic atropine. Muscarinic and dopamine receptor studies indicated that CPZMI has high affinity for the muscarinic cholinergic receptor and low affinity for the spiperone binding site. Modified Scatchard analysis of CPZMI displacement of [3H]QNB at the muscarinic receptor is consistent with muscarinic antagonist properties. We conclude that CPZMI-induced barrel rotation has a specific pharmacologic basis, that of muscarinic cholinergic antagonism.