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PubMed2004

Gene expression in aggressive fibromatosis.

Aggressive fibromatosis represents a group of tumors with heterogeneous patterns of biologic behavior. In this study, gene expression in 12 samples of aggressive fibromatosis, as well as that in samples of normal skeletal muscle and a variety of normal tissues, was determined at Gene Logic Inc (Gaithersburg, MD), with the use of Affymetrix GeneChip U_133 arrays containing approximately 33,000 genes. Gene-expression analysis was performed with the Gene Logic Gene Express software system. Differences in gene expression were quantified as the fold change in gene expression between the sets of fibromatosis tissue and normal skeletal muscle. A set of genes was then identified that was significantly overexpressed in aggressive fibromatosis compared with expression in normal muscle. This set of genes was then further examined for expression in a variety of normal tissues. We identified genes that were selectively overexpressed in aggressive fibromatosis compared with expression in 448 samples comprising 16 different nonneoplastic tissues. In particular, ADAM12, WISP-1, SOX-11, and fibroblast activation protein-alpha were uniquely overexpressed in aggressive fibromatosis compared with expression in normal tissues. In addition, the technique of Eisen clustering identified 2 distinct subgroups of aggressive fibromatosis with regard to gene expression. We conclude that gene-expression patterns may be useful in the further classification of subtypes of aggressive fibromatosis and that such classification could have clinical significance.

Adolescent↗

PubMed1999

The effect of aggressive and moderate lowering of LDL-cholesterol and low dose anticoagulation on plasma lipids, apolipoproteins and lipoprotein families in post coronary artery bypass graft trial.

The reported results (The Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. New Engl J Med 1997;336:153-162) of the Post Coronary Artery Bypass Graft (Post CABG) trial have shown that aggressive lowering was more effective than moderate lowering of low density lipoprotein (LDL) cholesterol in reducing the progression of atherosclerosis in saphenous-vein grafts (27 vs. 39%; P < 0.001); low dose warfarin had no effect on the progression of atherosclerosis. The present report describes the effect of long-term (an average of 4.3 years) aggressive treatment with high (40-80 mg/day) and moderate treatment with low (2.5-5 mg/day) doses of lovastatin on lipids, apolipoproteins (apo) and apoA- and apoB-containing lipoprotein families. To achieve the target LDL-cholesterol levels (60-85 mg/dl for aggressive group and 134-140 mg/dl for moderate group), cholestyramine (8 g/day) was given to 25% of subjects on aggressive and 5% of subjects on moderate treatment. Although with both treatment strategies there were significant decreases (P<0.001) in the levels of total cholesterol, LDL-cholesterol, apoB, LDL-apoB and cholesterol-rich Lp-B family, percent changes in the levels of these variables were greater in the aggressive- than in the moderate-treatment groups. These treatments had only marginal effects in increasing the levels of high density lipoprotein cholesterol, apoA-I and Lp-A-I and Lp-A-I:A-II families. The long-term aggressive treatment exerted no effect on the concentrations of triglycerides, apoC-IlI, apoC-III in VLDL + LDL and triglyceride-rich Lp-Bc families. Neither treatment affected the levels of Lp(a). The potentially modifying influence of warfarin and apoE phenotypes on lovastatin-induced changes in lipoprotein variables was found to be of little significance. It is likely that the beneficial effect of lovastatin in reducing the progression of atherosclerosis in grafts is mediated through its specific lowering effect on cholesterol-rich Lp-B particles.

Anticholesteremic Agents↗

PubMed2003

Alcohol intoxication and self-aggressive behavior.

Nonexperimental field studies have demonstrated an association between alcohol intoxication and self-aggressive behaviors across the spectrum of lethality. Although these results are suggestive, it is not yet known whether alcohol intoxication is causally related to self-aggression. The authors therefore experimentally examined the effects of alcohol intoxication (mean blood alcohol concentration of .10) on a behavioral measure of self-aggression in men (N = 40). After consuming either an alcohol or a placebo drink, participants were provided the opportunity to self-administer shock during a task disguised as a reaction-time game, with self-aggression defined by the intensity of shock chosen. Half of the participants observed a self-aggressive model (a potential moderator of alcohol-related self-aggression). Independent alcohol and model effects were found, with alcohol accounting for over 30% of the self-aggression variance.

Adult↗

PubMed2006

Risk factors for the incidence of endometrial cancer according to the aggressiveness of disease.

There is a wide range of aggressiveness of endometrial tumors, some being indolent and easily treated while others metastasize and prove fatal. The authors used data from three population-based, case-control studies to determine if etiologic factors differ for aggressive disease. Interview data were obtained from 1,304 female residents of western Washington State who were 45-74 years of age and diagnosed with endometrial cancer during 1985-1991, 1994-1995, and 1997-1999 and from 1,779 controls who were of similar ages and selected primarily by random digit dialing. As a means of gauging aggressiveness, tumor characteristics were abstracted from the population-based cancer registry that serves western Washington State. The risk of endometrial cancer among long-term users (> or = 8 years) of unopposed estrogens was particularly high for the least aggressive tumors (odds ratio = 18.6, 95% confidence interval: 12.2, 28.6) but was elevated for moderate and highly aggressive tumors as well (odds ratios = 6.6 and 7.1, respectively). Women who were obese, had a history of diabetes, and had fewer than two children were also at increased risk, regardless of tumor aggressiveness, while oral contraceptive users were at decreased risk of only relatively more aggressive disease. In general, a woman's risk of endometrial cancer appears to be influenced by similar risk factors regardless of disease severity.

Aged↗

PubMed2001

Aggressive digital papillary adenocarcinoma: a case report and review of the literature.

We report a case of an aggressive digital papillary adenocarcinoma (ADPA) on the right thumb of a 48-year-old white man. Histologic evaluation of the initial biopsy demonstrated features consistent with those proposed for aggressive digital papillary adenoma; however, re-excision of the remaining lesion revealed histologic features consistent with aggressive digital papillary adenocarcinoma. These tumors have a high rate of local recurrence and can metastasize, occasionally resulting in mortality. Our case demonstrates that even if the histologic criteria of aggressive digital papillary adenocarcinoma are met, the lesion may still represent an aggressive digital papillary adenocarcinoma (ADPAca). In agreement with a recent study by Duke et al., this case supports the idea that aggressive digital papillary lesions should be classified as aggressive digital papillary adenocarcinoma.

Adenocarcinoma, Papillary↗

PubMed2000

FDG PET in the evaluation of the aggressiveness of pulmonary adenocarcinoma: correlation with histopathological features.

2-[Fluorine-18]fluoro-2-deoxy-d-glucose (FDG) uptake within the primary lesion correlates with survival on positron emission tomography (PET) studies of patients with non-small cell lung cancer. The more metabolically active the tumour, the worse the outcome. The aim of this study was to determine whether a correlation exists between aggressiveness as determined by pathology and the findings of FDG PET in pulmonary adenocarcinoma. Thirty-five patients with 38 adenocarcinomas of the lung were studied. All patients underwent thoracotomy within 4 weeks of the FDG PET study. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. Patients were classified into high SUV (> or = 4.0) and low SUV (<4.0) groups. The degree of FDG uptake (SUVs) in primary lung lesions was correlated with the histopathological features of aggressiveness (pleural involvement, vascular invasion or lymphatic permeation). The mean SUV of aggressive adenocarcinomas (4.36+/-1.94, n = 22) was higher than that of non-aggressive ones (1.53+/-0.88, n = 16) (P < 0.0001). Tumours with a high FDG uptake have a significantly higher likelihood of aggressiveness than those with a low FDG uptake (P = 0.0004). Analysis by the Kaplan-Meier methods revealed that the groups had different prognoses (log-rank test, P = 0.0099). The high SUV group had a significantly worse prognosis. In conclusion, a correlation was seen between aggressiveness as determined by pathology and glucose metabolism as measured by FDG PET in adenocarcinoma of the lung. FDG PET may be used as a non-invasive diagnostic technique in measuring aggressiveness and prognosis in patients with pulmonary adenocarcinoma.

Adenocarcinoma↗

PubMed2003

Does aggressive care following acute myocardial infarction reduce mortality? Analysis with instrumental variables to compare effectiveness in Canadian and United States patient populations.

BACKGROUND: Previous U.S. studies suggest that the incremental ("marginal") use of the aggressive approach to care for acute myocardial infarction (AMI) in patients differing only in their distance to hospitals offering aggressive care may be associated with small mortality benefits. We hypothesized that the marginal benefits should be larger in Canada, as the country is operating on a lower margin because the approach to care is more conservative overall. METHODS: This retrospective study used administrative data of hospital admissions and health services for all patients admitted for a first AMI in Quebec in 1988 (n = 8,674). We used differential distances to hospitals offering aggressive care as instrumental variables when measuring mortality up to four years after AMI. RESULTS: Of the 4,422 subjects who were > or = 65 years old, 11 percent received cardiac catheterization within 90 days after admission. In a previous study that applied similar methodology to the 1987 U.S. Medicare population, 23 percent of subjects received catheterization within 90 days. As in the U.S. study, we found that subjects living closer to hospitals offering aggressive care were more likely to receive aggressive care than subjects living further away (26 percent versus 19 percent received cardiac catheterization within 90 days; 95 percent CI: 5 percent to 9 percent). Unlike the U.S. study, we found no differences in mortality across the "close" versus "far" differential distance groups (unadjusted differences at one year: 1 percent; 95 percent CI: -1 percent to 3 percent). This absence of association held in elderly (> or = 65 years) and younger age groups. Adjusted results also showed no differences between subjects receiving aggressive versus conservative care (at one year: 4 percent; 95 percent CI: -11 percent to 20 percent). CONCLUSIONS: Contrary to our hypothesis, but consistent with results from numerous randomized trials and observational studies, we cannot confirm that, on the margin, the aggressive approach to post-AMI care is associated with mortality benefits in Canada.

Aged↗

PubMedDate not supplied

The epigenetic reprogramming of poorly aggressive melanoma cells by a metastatic microenvironment.

A dynamic, complex relationship exists between tumor cells and their microenvironment, which plays a pivotal role in cancer progression, yet remains poorly understood. Particularly perplexing is the finding that aggressive melanoma cells express genes associated with multiple cellular phenotypes, in addition to their ability to form vasculogenic-like networks in three-dimensional matrix--called vasculogenic mimicry, which is illustrative of tumor cell plasticity. This study addressed the unique epigenetic effect of the microenvironment of aggressive melanoma cells on the behavior of poorly aggressive melanoma cells exposed to it. The data show significant changes in the global gene expression of the cells exposed to 3-D matrices preconditioned by aggressive melanoma cells, including the acquisition of a vasculogenic cell phenotype, upregulation of ECM remodeling genes, and increased invasive ability--indicative of an epigenetic, microenvironment-induced reprogramming of poorly aggressive melanoma cells. However, this epigenetic effect was completely abrogated when a highly cross-linked collagen matrix was used, which could not be remodeled by the aggressive melanoma cells. These findings offer an unique perspective of the inductive properties associated with an aggressive melanoma microenvironment that might provide new insights into the epigenetic regulation of tumor cell plasticity and differentiation, as well as mechanisms that could be targeted for novel therapeutic strategies.

Cell Line, Tumor↗

PubMed2005

Clear cell renal cell carcinoma: gene expression analyses identify a potential signature for tumor aggressiveness.

PURPOSE: The objective of this study was to use gene expression profiling to identify novel biomarkers that are predictive of aggressive behavior in clear cell renal cell carcinoma (CCRCC). EXPERIMENTAL DESIGN: Candidate genes were discovered using Human Genome U133 Plus 2 Arrays and validated on independent samples by quantitative reverse transcription-PCR (RT-PCR). Both the discovery and the validation cohorts included nonaggressive primary CCRCC, aggressive primary CCRCC, metastatic CCRCC, and nonneoplastic kidney adjacent to tumor. RESULTS: Aggressive primary and metastatic CCRCC displayed no significant differences in gene expression. In contrast, we identified significant differences in gene expression between nonaggressive and aggressive CCRCC (including metastatic CCRCC). Thirty-four of the 35 transcripts that displayed the most significant differential expression by microarray analysis also displayed significant differential expression in independent validation studies using quantitative RT-PCR (P < 0.001 for 31 candidates and P < 0.005 for the remaining three candidates). Hierarchical clustering of the quantitative RT-PCR data using our candidate markers accurately grouped 88% (23 of 26) of aggressive and metastatic CCRCC samples, 100% (14 of 14) of nonaggressive CCRCC samples, and 100% (15 of 15) of nonneoplastic samples into separate clusters. Finally, we evaluated the ability of protein expression levels of one of our candidate markers (survivin) to predict survival among a cohort of 183 CCRCC patients treated surgically at Mayo Clinic from 1990 to 1992. In multivariate analysis, expression of survivin (BIRC5) was inversely associated with cancer-specific survival (P = 0.017). CONCLUSION: We used a combination of genomic profiling and validation by quantitative PCR to identify a panel of candidate biomarkers for determining CCRCC aggressiveness. Our data also indicate that the gene expression alterations that result in aggressive behavior and metastatic potential can be identified in the primary tumor.

Biomarkers, Tumor↗

PubMed1998

The role of cytotoxic chemotherapy in the management of aggressive and malignant pituitary tumors.

Pituitary tumors are mostly benign lesions, although 5-35% are locally invasive. A small number exhibit a more aggressive course, infiltrating dura, bone and sinuses, and are designated highly aggressive. However, the presence of metastases separate from the pituitary in the central nervous system or at a distance is necessary to designate pituitary tumors as carcinomas, i.e. truly malignant. When conventional therapeutic modalities fail, systemic chemotherapy remains the last option. We report seven such patients, three with highly aggressive and four with malignant pituitary tumors (n=4) four women; median age, 32 yr; range, 23-48 yr), who received one or more courses of chemotherapy with lomustine and 5-fluorouracil (median, two courses; range, one to six courses). Three patients with systemic metastatic disease had a shorter survival (median, 5 months; range, 1-14 months) than the one patient with central nervous system metastases alone (10 yr). A patient with an aggressive nonmetastatic prolactinoma who initially responded to chemotherapy died from another nondisease-associated cause. Two patients, one with an aggressive and one with a metastatic tumor, achieved symptomatic improvement with a median duration of 6 months. A hormonal reduction greater than 50% was observed in two of seven patients; only one patient who had an aggressive tumor obtained an objective tumor response. The median survival from the time of initiation of chemotherapy in patients with malignant tumors ranged from 3-65 months. Two patients with malignant tumors developed disease progression while receiving chemotherapy; no patient with extracranial metastases showed a response. Treatment was well tolerated, with minimal individual side-effects. Three patients with no response to initial treatment received different chemotherapeutic regimens with no additional response. All patients with metastatic malignant tumors eventually died. Treatment with cytotoxic chemotherapy is noncurative, and current experience is limited. Until another more specific form of treatment is available, chemotherapy may still be of some value in patients with highly aggressive and malignant pituitary tumors, at least in achieving a temporary remission or delay in progression. The combination of lomustine/5-fluorouracil proved easy to administer with minimal toxicity, although the response rate was only 14%. Until a more specific treatment is found, an optimal chemotherapeutic regimen needs to be established.

Adult↗

PubMed2002

The relationship between driver aggression, violence, and vengeance.

A distinction is made between mild driver aggression and driver violence as unique constructs that differ mainly in frequency of occurrence and severity of outcome. Drivers completed questionnaires assessing the likelihood of engaging in mild driver aggression, the frequency of past driver violence, driving vengeance, and willful violations. Violence was predicted by the interaction of mild aggression and vengeance, such that violence was greater among aggressive drivers, but only for those with elevated levels of vengeance. Driver violence was also predicted by the interaction of mild aggression and violations. Specifically, violence was greater among aggressive drivers reporting traffic violations. The present findings suggest that mild driver aggression and driver violence are linked within a small group of drivers that hold other dangerous driving attitudes and behaviors as part of their typical driving repertoire.

Adult↗

PubMed2003

Prevalence of periodontopathic bacteria in aggressive periodontitis patients in a Japanese population.

BACKGROUND: Actinobacillus actinomycetemcomitans is considered a major etiologic agent of aggressive periodontitis. Other periodontopathic bacteria such as Porphyromonas gingivalis are also suspected of participating in aggressive periodontitis, although the evidence is controversial. The aim of the present study was to investigate the prevalence of periodontopathic bacteria and to clarify the microbiological features of aggressive periodontitis in Japanese patients. METHODS: Subgingival plaque was collected from 50 aggressive periodontitis (AgP) patients (localized 10, generalized 40). Samples from 35 generalized chronic periodontitis (CP) patients and 18 healthy subjects were examined as controls. Plaque samples were examined using culture and polymerase chain reaction (PCR) method. RESULTS: The prevalence of A. actinomycetemcomitans was relatively low in the localized (20%) and generalized (17.5%) AgP patients, with no significant difference observed in detection frequencies between AgP and the control groups (CP 8.6%, healthy 0%). On the other hand, Tannerella forsythensis (formerly Bacteroides forsythus), Campylobacter rectus, P. gingivalis, and Treponema denticola were frequently detected in localized as well as generalized aggressive periodontitis patients. The prevalence and proportion of P. gingivalis correlated with severity of clinical attachment loss in both localized and generalized aggressive periodontitis. CONCLUSIONS: T. forsythensis, C. rectus, P. gingivalis, and T. denticola were the predominant periodontopathic bacteria of aggressive periodontitis patients in Japan. Although A. actinomycetem- comitans was also detected in AgP patients, the prevalence of this bacterium was much lower than that of P. gingivalis.

Adolescent↗

PubMed2005

The British Rheumatoid Outcome Study Group (BROSG) randomised controlled trial to compare the effectiveness and cost-effectiveness of aggressive versus symptomatic therapy in established rheumatoid arthritis.

OBJECTIVES: To examine the effectiveness and cost-effectiveness of symptomatic versus aggressive treatment in patients with established, stable rheumatoid arthritis (RA). DESIGN: A randomised observer-blinded controlled trial and economic evaluation with an initial assessment at randomisation and follow-ups at 12, 24 and 36 months. SETTING: Five rheumatology centres in England. The 'symptomatic care' patients were managed predominantly in primary care with regular visits by a rheumatology specialist nurse. The 'aggressive care' patients were managed predominantly in the hospital setting. PARTICIPANTS: Patients with RA for more than 5 years were screened in rheumatology clinics. INTERVENTIONS: The symptomatic care patients were seen at home every 4 months by a rheumatology specialist nurse and annually by the rheumatologist. The aim of treatment was symptom control. The aggressive care patients were seen at least every 4 months in hospital. Their treatment was altered (following predefined algorithms) with the aim of suppressing both clinical and laboratory evidence of joint inflammation. MAIN OUTCOME MEASURES: The main outcome measure was the Health Assessment Questionnaire (HAQ). Others included the patient and physician global assessment, pain, tender and swollen joint counts, the erythrocyte sedimentation rate and the OSRA (Overall Status in Rheumatoid Arthritis) score. X-rays of the hands and feet were performed at the beginning and end of the study. The EQ-5D was used in the health economic evaluation. Comprehensive costs were also estimated and were combined with measures of outcome to examine between-group differences. RESULTS: A total of 466 patients were recruited; 399 patients completed the 3 years of follow-up. There was a significant deterioration in physical function (HAQ) in both arms. There was no significant difference between the groups for any of the clinical outcome measures except the physician global assessment [adjusted mean difference 3.76 (95% CI 0.03 to 7.52)] and the OSRA disease activity component [adjusted mean difference 0.41 (95% CI 0.01 to 0.71)], both in favour of the aggressive arm. During the trial, second-line drug treatment was changed in 77.1% of the aggressive arm and 59.0% of the symptomatic arm. There were instances when the rheumatologist should have changed treatment but did not do so, usually because of mild disease activity. The symptomatic arm was associated with higher costs and higher quality-adjusted life-years (QALYs). There was a net cost of 1517 Pounds Sterling per QALY gained for the symptomatic arm. Overall, the primary economic analysis and sensitivity analyses of the cost and QALY data indicate that symptomatic treatment is likely to be more cost-effective than aggressive treatment in 58-90% of cases. CONCLUSIONS: This trial showed no benefit of aggressive treatment in patients with stable established RA. However, it was difficult to persuade the rheumatologist and/or the patient to change treatment if the evidence of disease activity was minimal. Patients in the symptomatic arm were able to initiate changes of therapy when their symptoms deteriorated, without frequent hospital assessment. Approximately one-third of current clinic attenders with stable RA could be managed in a shared care setting with annual review by a rheumatologist and regular contact with a rheumatologist nurse. Further research is needed into disease progression and the use of biological agents, minimum disease activity level below which disease progression does not occur, cost-effectiveness through shared care modelling, the development of a robust and fail-safe system of primary-care based disease-modifying anti-rheumatic drug (DMARD) monitoring, and predicting response to DMARDs.

Adult↗

PubMed1998

The relationship between personality psychopathology and aggressive behavior in research volunteers.

Theorists and clinicians have long believed that personality psychopathology is a risk factor for aggressive behavior. Previous investigations in this area, however, have provided mixed results. In this study, the relationship between personality psychopathology and aggressive behavior was examined in 137 research volunteers. The influences of gender and coexisting major mental disorders were statistically controlled. Aggressive behavior was associated with criteria for 7 of the 11 personality disorders listed in the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.). Except for schizoid criteria, all relationships with aggressive behavior were in the positive direction. When all personality disorders were considered simultaneously, paranoid and passive-aggressive criteria were significant predictors of aggressive behavior.

Adolescent↗

PubMed1981

Intensive monitoring of epileptic patients with a history of episodic aggression.

Nineteen epileptic patients with significant history of episodic aggressive behavior were subjected to intensive behavioral and electrophysiologic monitoring for an average period of six weeks in a specialized inpatient facility. Numerous seizures were recorded in these patients but none disclosed ictal aggression. Only two patients showed episodic aggressive behavior but in neither case could seizures be implicated causally. The majority of patients showed a remarkable progressive improvement in aggressive tendencies during hospitalization. It is concluded that ictal aggression is rare and that, in most cases, the aggressive behavior in epileptics is a multifactorially determined interictal phenomenon.

Adolescent↗

PubMed2001

The 5-HTTPRS/L polymorphism and aggressive behavior in Alzheimer disease.

BACKGROUND: Aggressive behavior in Alzheimer disease (AD) has been linked to dysfunction of serotonin neurotransmission. Homozygosity for the long variant (*L) of an identified biallelic polymorphism of the serotonin transporter promoter region (5-HTTPR) is associated with increased expression of the transporter protein and increased speed of response to serotonin reuptake inhibitor treatment. OBJECTIVE: To determine whether the *L/*L genotype and the *L allele are associated with an increased risk of aggressive symptoms in patients with AD. DESIGN: Case-control study. SETTING: University hospital geriatric psychiatry inpatient program and Alzheimer disease research center. SUBJECTS: Fifty-eight patients with AD with a history of aggressive behavior and 79 never-aggressive patients with AD with comparable severity of cognitive impairment. MAIN OUTCOME MEASURES: The 5-HTTPR genotype and allele frequency. RESULTS: The *L/*L genotype was significantly associated with aggression in patients with AD (odds ratio, 2.8; 95% confidence interval, 1.2-6.5). Similar results were obtained for *L allele frequency. CONCLUSION: The 5-HTTPR*L allele and *L/*L genotype may predispose patients with AD to develop aggressive behavior.

Aged↗

PubMed2006

Short-term and long-term effects of violent media on aggression in children and adults.

OBJECTIVES: To test whether the results of the accumulated studies on media violence and aggressive behavior are consistent with the theories that have evolved to explain the effects. We tested for the existence of both short-term and long-term effects for aggressive behavior. We also tested the theory-driven hypothesis that short-term effects should be greater for adults and long-term effects should be greater for children. DESIGN: Meta-analysis. PARTICIPANTS: Children younger than 18 years and adults. MAIN EXPOSURES: Violent media, including TV, movies, video games, music, and comic books. MAIN OUTCOME MEASURES: Measures of aggressive behavior, aggressive thoughts, angry feelings, physiological arousal (eg, heart rate, blood pressure), and helping behavior. RESULTS: Effect size estimates were combined using meta-analytic procedures. As expected, the short-term effects of violent media were greater for adults than for children whereas the long-term effects were greater for children than for adults. The results also showed that there were overall modest but significant effect sizes for exposure to media violence on aggressive behaviors, aggressive thoughts, angry feelings, arousal levels, and helping behavior. CONCLUSIONS: The results are consistent with the theory that short-term effects are mostly due to the priming of existing well-encoded scripts, schemas, or beliefs, which adults have had more time to encode. In contrast, long-term effects require the learning (encoding) of scripts, schemas, or beliefs. Children can encode new scripts, schemas, and beliefs via observational learning with less interference and effort than adults.

Adult↗

PubMed2000

Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: a randomized controlled trial.

BACKGROUND: Field studies of illicit anabolic-androgenic steroid users suggest that some develop manic or aggressive reactions to these drugs-a potential public health problem. However, controlled laboratory evaluations of these effects remain limited. METHODS: In a randomized, placebo-controlled, crossover trial, we administered testosterone cypionate for 6 weeks in doses rising to 600 mg/wk and placebo for 6 weeks, separated by 6 weeks of no treatment, to 56 men aged 20 to 50 years. Psychiatric outcome measures included the Young Mania Rating Scale (YMRS), the Point Subtraction Aggression Paradigm (a computerized provocation test of aggression), the Aggression Questionnaire of Buss and Perry, the Symptom Checklist-90-R, daily diaries of manic and depressive symptoms, and similar weekly diaries completed by a "significant other" who knew the participant well. RESULTS: Testosterone treatment significantly increased manic scores on the YMRS (P = .002), manic scores on daily diaries (P = .003), visual analog ratings of liking the drug effect (P = .008), and aggressive responses on the Point Subtraction Aggression Paradigm (P = .03). Drug response was highly variable: of 50 participants who received 600 mg/wk of testosterone cypionate, 42 (84%) exhibited minimal psychiatric effects (maximum YMRS score, <10), 6 (12%) became mildly hypomanic (YMRS score, 10-19), and 2 (4%) became markedly hypomanic (YMRS score, > or =20). The 8 "responders" and 42 "nonresponders" did not differ significantly on baseline demographic, psychological, laboratory, or physiological measures. CONCLUSIONS: Testosterone administration, 600 mg/wk increased ratings of manic symptoms in normal men. This effect, however, was not uniform across individuals; most showed little psychological change, whereas a few developed prominent effects. The mechanism of these variable reactions remains unclear.

Adult↗