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Biomedical subjects

J M Oldham

Publications and source records attributed to J M Oldham.

At least 19 recordsLinked to original sources

Comorbid personality disorder and treatment use in a community sample of youths: a 20-year follow-up.

OBJECTIVE: The impact of comorbid personality disorder (PD) on subsequent treatment and psychotropic drug use was examined in a representative sample of over 700 individuals. METHOD: Axis I disorders and PD were assessed by self- and mother-report at mean ages 13 and 22 years, and by self-report at mean age 33. Mothers reported treatment use by participants before mean age 33; participants reported treatment and psychotropic drug use at mean age 33. RESULTS: Individuals with multiple axis I disorders without PD, axis I disorder-PD comorbidity, and single disorders were compared simultaneously to individuals not diagnosed. Overall, odds of subsequent and past year treatment or psychotropic drug use or both were highest when PD co-occurred with a mood, an anxiety, a disruptive, or a substance use disorder. CONCLUSION: Co-occurring personality pathology may contribute to elevated mental health service use, including use of psychotropic drugs, among young adults in the community.

Adolescent↗

Prolonged underfeeding of sheep increases myostatin and myogenic regulatory factor Myf-5 in skeletal muscle while IGF-I and myogenin are repressed.

The IGF axis is nutritionally sensitive in vivo and IGFs stimulate myoblast proliferation and differentiation in vitro, while myostatin inhibits these processes in vitro. We hypothesised that underfeeding would reversibly inhibit the myogenic activity of satellite cells in vivo together with decreased IGF-I and increased myostatin in muscle. Satellite cell activity was measured indirectly from the expression of proliferating cell nuclear antigen (PCNA) and the myogenic regulatory factors (MRFs), MyoD, Myf-5 and myogenin. Young sheep were underfed (30% of maintenance) and some killed after 1, 4, 12, 17, 21 and 22 weeks. Remaining underfed animals were then re-fed a control ration of pellets and killed after 2 days, and 1, 6 and 30 weeks. Expression of PCNA and MRFs decreased during the first week of underfeeding. This coincided with reduced IGF-I and myostatin mRNA, and processed myostatin. Subsequently, Myf-5, MyoD, myostatin mRNA and processed myostatin increased, suggesting that satellite cells may have become progressively quiescent. Long-term underfeeding caused muscle necrosis in some animals and IGF-I and MRF expression was increased in these, indicating the activation of satellite cells for muscle repair. Re-feeding initiated rapid muscle growth and increased expression of PCNA, IGF-I and the MRFs concurrently with decreased myostatin proteins. In conclusion, these data indicate that IGF-I and myostatin may work in a coordinated manner to regulate the proliferation, differentiation and quiescence of satellite cells in vivo.

Adaptation, Physiological↗

Internal consistency, intercriterion overlap and diagnostic efficiency of criteria sets for DSM-IV schizotypal, borderline, avoidant and obsessive-compulsive personality disorders.

OBJECTIVE: To evaluate performance characteristics of DSM-IV Personality Disorders (PDs) criteria. METHOD: Six hundred and sixty-eight adults recruited for the Collaborative Longitudinal Personality Disorders Study (CLPS) were assessed with diagnostic interviews. RESULTS: Within-category inter-relatedness was evaluated by Cronbach's alpha and median intercriterion correlations (MIC). Cronbach's alpha ranged from 0.47 to 0.87 (median=0.71); seven of the 10 PDs had alphas greater than 0.70. Between-category criterion overlap was evaluated by "inter-category" intercriterion correlations between all PD pairs (ICMIC). ICMIC values (median=0.08) were lower than MIC values (median=0.23). Diagnostic efficiency statistics (sensitivity, specificity, positive predictive power and negative predictive power were calculated for schizotypal, borderline, avoidant and obsessive-compulsive PDs. CONCLUSION: DSM-IV PD criteria sets have some convergent validity and discriminant validity: criteria for individual PDs correlate better with each other than with criteria for other PDs. Diagnostic efficiency statistics provide guidance regarding usefulness of criteria for inclusion or exclusion.

Adolescent↗

Molecular expression of myostatin and MyoD is greater in double-muscled than normal-muscled cattle fetuses.

Excessive muscling in double-muscled cattle arises from mutations in the myostatin gene, but the role of myostatin in normal muscle development is unclear. The aim of this study was to measure the temporal relationship of myostatin and myogenic regulatory factors during muscle development in normal (NM)- and double-muscled (DM) cattle to determine the timing and possible targets of myostatin action in vivo. Myostatin mRNA peaked at the onset of secondary fiber formation (P < 0.001) and was greater in DM (P < 0.001) than in NM. MyoD expression was also elevated throughout primary and secondary fiber formation (P < 0.001) and greater in DM (P < 0.05). Expression of myogenin peaked later than MyoD (P < 0.05); however, it did not differ between NM and DM. These data show that myostatin and MyoD increase coincidentally during formation of muscle fibers, indicating a coordinated role in the terminal differentiation and/or fusion of myoblasts. Myostatin mRNA is also consistently higher in DM than NM, suggesting that a feedback loop of regulation is also disrupted in the myostatin-deficient condition.

Animals↗

Treatment utilization by patients with personality disorders.

OBJECTIVE: Utilization of mental health treatment was compared in patients with personality disorders and patients with major depressive disorder without personality disorder. METHOD: Semistructured interviews were used to assess diagnosis and treatment history of 664 patients in four representative personality disorder groups-schizotypal, borderline, avoidant, and obsessive-compulsive-and in a comparison group of patients with major depressive disorder. RESULTS: Patients with personality disorders had more extensive histories of psychiatric outpatient, inpatient, and psychopharmacologic treatment than patients with major depressive disorder. Compared to the depression group, patients with borderline personality disorder were significantly more likely to have received every type of psychosocial treatment except self-help groups, and patients with obsessive-compulsive personality disorder reported greater utilization of individual psychotherapy. Patients with borderline personality disorder were also more likely to have used antianxiety, antidepressant, and mood stabilizer medications, and those with borderline or schizotypal personality disorder had a greater likelihood of having received antipsychotic medications. Patients with borderline personality disorder had received greater amounts of treatment, except for family/couples therapy and self-help, than the depressed patients and patients with other personality disorders. CONCLUSIONS: These results underscore the importance of considering personality disorders in diagnosis and treatment of psychiatric patients. Borderline and schizotypal personality disorder are associated with extensive use of mental health resources, and other, less severe personality disorders may not be addressed sufficiently in treatment planning. More work is needed to determine whether patients with personality disorders are receiving adequate and appropriate mental health treatments.

Adolescent↗

Adolescent personality disorders associated with violence and criminal behavior during adolescence and early adulthood.

OBJECTIVE: A community-based, longitudinal prospective study was conducted to investigate whether personality disorders during adolescence are associated with elevated risk for violent behavior during adolescence and early adulthood. METHOD: A community-based sample of 717 youths from upstate New York and their mothers were interviewed in 1983, 1985-1986, and 1991-1993. Axis I and II disorders were assessed in 1983 and 1985-1986. Antisocial personality disorder was not assessed because most participants were less than 18 years of age in 1983 and 1985-1986. Violent behavior was assessed in 1985-1986 and 1991-1993. RESULTS: Adolescents with a greater number of DSM-IV cluster A or cluster B personality disorder symptoms were more likely than other adolescents in the community to commit violent acts during adolescence and early adulthood, including arson, assault, breaking and entering, initiating physical fights, robbery, and threats to injure others. These associations remained significant after controlling for the youths' age and sex, for parental psychopathology and socioeconomic status, and for co-occurring psychiatric disorders during adolescence. Paranoid, narcissistic, and passive-aggressive personality disorder symptoms during adolescence were independently associated with risk for violent acts and criminal behavior during adolescence and early adulthood after the covariates were controlled. CONCLUSIONS: Cluster A and cluster B personality disorders and paranoid, narcissistic, and passive-aggressive personality disorder symptoms during adolescence may increase risk for violent behavior that persists into early adulthood.

Adolescent↗

Charting the future of axis II.

Although there is general agreement that personality disorders are best conceptualized dimensionally, reflecting continuity with normal personality types, personality disorder traits, and personality disorders themselves, categorical systems continue to be utilized for clinical diagnostic purposes. The arguments for and against each approach are reviewed, and a proposal is presented for DSM-V that involves elements of both.

Humans↗

The Collaborative Longitudinal Personality Disorders Study: development, aims, design, and sample characteristics.

This paper describes the aims, background, design, and methods used in a collaborative longitudinal study of Axis II personality disorders (PDs). This study examines the putative stability of selected PD diagnoses and criteria, what factors affect their course, and whether their stability and course distinguishes them from a representative Axis I disorder. This article also describes the acquisition and demographics of the sample on whom the study is being done. A prospective, repeated measures investigation of the stability of PDs is now underway at multiple clinical settings in four collaborating urban sites in Boston. New Haven, New York, and Providence. Diagnostic assignments are based on semistructured interview assessments (by clinically trained raters) and confirmed by at least one additional contrasting diagnostic method. The sample consists of 668 treatment seeking and reliably diagnosed adults recruited from a broad range of clinical sites. By design, patients in the sample met standards for one of five diagnostic subgroups: (a) schizotypal (N = 86); (b) borderline (N = 175); (c) avoidant (N = 157); (d) obsessive-compulsive (N = 153) personality disorders or a control group having (e) major depressive disorder without personality disorder (N = 97).

Adolescent↗

Protection of persons with mental disorders from research risk: a response to the report of the National Bioethics Advisory Commission.

For the last several years, the National Bioethics Advisory Commission (NBAC) has considered several complex issues relating to biomedical research. Prominent among these considerations has been the protection of the rights and welfare of human research subjects, and the NBAC recently submitted to the president a report entitled Research Involving Persons With Mental Disorders That May Affect Decisionmaking Capacity. The importance of careful protection of vulnerable populations from undue or inappropriate risk in human subject research cannot be overemphasized, and the NBAC report includes recommendations that would strengthen such protection. However, the creation of workable mechanisms that allow appropriate risk-benefit judgments and that preserve respect for the autonomy of participating research subjects is challenging indeed. We believe that the NBAC has developed recommendations that strengthen protections for individual research participants. However, several key elements of the report are stigmatizing to persons with psychiatric disorders, and they could, if adopted as new federal regulations, inappropriately impede critical categories of psychiatric research.

Bioethics↗

Personality disorders in adolescence and risk of major mental disorders and suicidality during adulthood.

BACKGROUND: A community-based longitudinal study was conducted to investigate whether personality disorders (PDs) during adolescence increase the risk for Axis I psychiatric disorders and suicidality during early adulthood. METHOD: Psychosocial and psychiatric interviews were administered to a representative community sample of 717 youths and their mothers from 2 counties in the state of New York in 1975, 1983, 1985-1986, and 1991-1993. Anxiety, disruptive, eating, mood, personality, and substance use disorders and suicidal ideation and behavior were assessed in 1983 and 1985-1986, when the participants were adolescents, and in 1991-1993, when they were young adults. RESULTS: Adolescents with PDs were more than twice as likely as those without PDs to have anxiety, disruptive, mood, and substance use disorders during early adulthood. These associations remained statistically significant after co-occurring Axis I disorders during adolescence were controlled statistically. Cluster A, B, and C PDs and DSM-IV Appendix B PDs during adolescence were all associated with elevated risk for Axis I disorders during early adulthood after co-occurring Axis I and Axis II disorders during adolescence were controlled statistically. Cluster C PDs during adolescence were associated with elevated risk for suicidal ideation or behavior during early adulthood after co-occurring psychiatric disorders and suicidality during adolescence were controlled statistically. CONCLUSIONS: Adolescents in the community with personality disorders are at elevated risk for major mental disorders and suicidal ideation or behavior during early adulthood. This increase in risk is not accounted for by co-occurring Axis I disorders or suicidality during adolescence.

Adolescent↗

HIV service provision and training needs in outpatient mental health settings.

OBJECTIVE: Despite high rates of HIV infection among people with serious mental illness little is known about the provision of HIV related services in outpatient mental health settings. This study examined HIV service provision and staff training needs among New York State outpatient providers. METHODS: An anonymous survey regarding patient characteristics, provision of routine HIV risk assessment, general HIV service provision, and staff training needs regarding HIV was sent to the directors of all New York State Office of Mental Health licensed and certified outpatient programs. RESULTS: Less than one-third of respondents stated that HIV risk assessment was performed routinely upon intake. Programs that served more HIV identified patients were more likely to have staff trained in HIV service provision. The number of identified HIV infected patients also influenced the frequency with which programs stated that their staff needed additional training in HIV risk interviewing, with clinics serving over 100 known HIV infected patients annually reporting the least training need and clinics serving between 11-50 known HIV infected patients annually reporting the most training need. CONCLUSIONS: It appears that clinics with large numbers of known HIV infected patients have mobilized to deal with the unique needs of these patients by providing specialty services and training staff in HIV service provision. However, the majority of clinics have failed to realize that severe mental illness is associated with behaviors that place individuals at risk of HIV infection or else routine HIV risk assessment would be more common.

Ambulatory Care Facilities↗

Axis II comorbidity of substance use disorders among patients referred for treatment of personality disorders.

OBJECTIVE: The purpose of this study was to determine the extent of comorbid substance use disorders in patients referred for treatment of personality disorders. METHOD: Two hundred inpatients and outpatients were assessed by semistructured interviews for substance use and personality disorders. Univariate odds ratios were calculated for groups of substance use disorders and each DSM-III-R axis II disorder; comorbidity among axis II disorders was controlled in multivariate models predicting current or lifetime substance use disorder groups. The impact of personality disorder on chronicity and overall impairment associated with substance use disorders was evaluated. RESULTS: Close to 60% of subjects with substance use disorders had personality disorders. Borderline personality disorder was significantly associated with current substance use disorders, excluding alcohol and cannabis, and with lifetime alcohol, stimulant, and other substance use disorders, excluding cannabis. Antisocial personality disorder was associated with lifetime substance use disorders other than alcohol, cannabis, and stimulants. These relationships remained significant after controlling for the presence of all other personality disorders. There was no evidence that personality disorders increased the chronicity of substance use disorders, but comorbid personality disorders were associated with greater global impairment. CONCLUSIONS: Borderline personality disorder may be associated with a wide variety of substance use disorders, especially among patients seeking treatment for personality problems.

Adult↗

Postnatal growth responses to insulin-like growth factor I in insulin receptor substrate-1-deficient mice.

Organ weight was compared in adult mice with deletion of one (IRS-1-/+) or both (IRS-1-/-) copies of the insulin receptor substrate-1 (IRS-1) gene and IRS-1+/+ littermates. IRS-1-/+ mice showed modest reductions in weight of most organs in proportion to a decrease in body weight. IRS-1-/- mice showed major reductions in weight of heart, liver, and spleen that were directly proportional to a decrease in body weight. In IRS-1-/- mice, kidney and particularly small intestine and brain exhibited proportionately smaller weight reductions, and gastrocnemius muscle showed a proportionately greater weight reduction than the decrease in body weight. Growth deficits in IRS-1-/- mice could reflect impaired actions of multiple hormones or cytokines that activate IRS-1. To assess the requirement for IRS-1 in insulin-like growth factor I (IGF-I)-dependent postnatal growth, IRS-1-/+ mice were cross-bred with mice that widely overexpress a human IGF-I transgene (IGF+) to generate IGF+ and wild-type mice on an IRS-1+/+, IRS-1-/+, and IRS-1-/- background. IGF-I overexpression increased body weight and weight of brain, small intestine, kidney, spleen, heart, and gastrocnemius muscle in IRS-1+/+ mice. IGF-I overexpression could not completely reverse the body growth retardation in IRS-1-/- mice. Absolute or partial IRS-1 deficiency impaired IGF-I-induced body overgrowth more in females than in males. In males and females, IGF-I stimulated similar overgrowth of brain regardless of IRS-1 status, and intestine and spleen showed dose dependence on IRS-1 for IGF-I-induced growth. IGF-I-induced growth of gastrocnemius muscle had an absolute requirement for IRS-1. IGF-I-induced growth of kidney and heart was impaired by IRS-1 deficiency only in females. In vivo, therefore, most organs do not require IRS-1 for IGF-I-induced growth and can use alternate signaling molecules to mediate IGF-I action. Other organs, such as gastrocnemius muscle, require IRS-1 for IGF-I-induced growth in vivo.

Animals↗

Nutritional regulation of IGF-II, but not IGF-I, is age dependent in sheep.

In post-natal animals, plasma concentrations of IGF-I are tightly regulated by nutritional status. The current study reports that plasma levels of IGF-II in sheep are also regulated by nutrition, but whether plasma IGF-II is increased, decreased or remains the same, depends on the age of the animal. Ewe lambs, ranging in age from 2 days to 2 years, were fed or fasted for lengths of time between 24 and 72 h. Blood samples were taken at intervals of 24 h throughout the treatment period and immediately before slaughter. Plasma concentrations of IGF-I increased with advancing age in fed animals (P<0.001) and were reduced by fasting in all age groups (P<0.001). Plasma concentrations of IGF-II also increased as animals matured (P<0.001), but did not show an overall effect of the fasting treatment. An interaction between age and nutrition (P<0.001) resulted from a decrease in plasma IGF-II in response to fasting in neonatal animals (P<0.01) and, conversely, increased levels of plasma IGF-II in fasted mature animals (P<0.01 or P<0.001). Fasted sheep of peripubertal age showed no change in plasma levels of IGF-II. The nutritional sensitivity of serum IGF-binding proteins (BPs) also changed with age. The 29 kDa BP, which we presume to be BP1, was elevated by fasting in young animals and reduced slightly in older animals. BP2 was increased to a similar magnitude by fasting at all ages. BP3 was depressed by fasting in young animals and showed little change in adults. In contrast, a 24 kDa BP, which is probably BP4, showed little change in young animals and was reduced substantially in older sheep. In conclusion, the response of plasma IGF-II to fasting suggests that this peptide has functions in mediating nutritional stress which depend on the age of the animal, and also that the role of IGF-II may differ from that of IGF-I in adults.

Age Factors↗

Co-occurrence of mood and personality disorders: a report from the Collaborative Longitudinal Personality Disorders Study (CLPS).

The purpose of this study was to examine the relationship of subtypes and particular clinical features of mood disorders to co-occurrence with specific personality disorders. Five hundred and seventy-one subjects recruited for the Collaborative Longitudinal Personality Disorders Study (CLPS) were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and the Diagnostic Interview for DSM-IV Personality Disorders (DIPD-IV). Percent co-occurrence rates for current and lifetime mood disorders with personality disorders were calculated. Logistic regression analyses examined the effects of clinical characteristics of depressive disorders (e.g., age at onset, recurrence, symptom severity, double depression, and atypical features) on personality disorder co-occurrence. In comparison with other DSM-IV personality disorders, avoidant, borderline, and dependent personality disorders (PDs) were most specifically associated with mood disorders, particularly depressive disorders. Severity and recurrence of major depressive disorder and comorbid dysthymic disorder predicted co-occurrence with borderline and to a lesser extent research criteria depressive personality disorders. The results are consistent with the view that a mood disorder with an insidious onset and recurrence, chronicity, and progression in severity leads to a personality disorder diagnosis in young adults.

Adolescent↗

Regulation by nutrition and age of insulin-like growth factor binding sites in ovine kidney.

The insulin-like growth factors (IGFs) are considered to have a role in the regulation of renal growth and development. The purpose of the present study was to evaluate the effect of nutritional stress on IGF binding in ovine kidney at different postnatal ages. Binding of IGF-I and IGF-II to kidneys of fed and fasted sheep was characterised using histological autoradiography, competitive binding assays, and SDS-PAGE. Nutritional regulation of IGF-I binding was restricted to cells of the proximal tubules of two and 14-day-old lambs where we identified an IGF binding protein which was upregulated in response to fasting and where IGF-II binding was also slightly enhanced. Ontogenetic changes occurred in the glomeruli where IGF-I binding peaked at 6 months (P < or = 0.001), and IGF-II binding increased to 4 months and then plateaued (P < or = 0.01). In the medulla, IGF-II binding was highest at 4 and 6 months (P < or = 0.05). From these studies, we conclude that the IGF axis may play a role in the regulation of the metabolic response to fasting in the kidney of young lambs. Furthermore, the changes with age which are described may reflect a transition period at 4-6 months, from an initial promotion of kidney growth and development in young lambs to establishment of the metabolic and clearance functions in the adult animal.

Aging↗

Localisation of insulin-like growth factor receptors in skin follicles of sheep (Ovis aries) and changes during an induced growth cycle.

Pelage growth cycles are regulated by circulating prolactin in many mammals, but the intercellular mediators of this signaling are unknown. Binding sites for insulin-like growth factors (IGFs) were examined in sheep skin to show changes in distribution and abundance of IGF receptors associated with a prolactin stimulus and the subsequent hair follicle growth cycle. Follicle cycles were induced in New Zealand Wiltshire ewes by a surge in plasma prolactin following a 4-month period of prolactin suppression with bromocriptine. Eight treated and three control sheep were slaughtered at intervals over 43 days during the follicle growth cycle. At 12-20 days after the elevation of prolactin, wool follicles passed through brief catagen and telogen phases, followed by a return to anagen. IGF binding sites were localized in skin sections by incubation with 125I-IGF-I or 125I-IGF-II. Displacement with competitive binding inhibitors (unlabeled IGF-I, IGF-II, des(1-3)IGF-I, des(1-6)IGF-II, or insulin) and affinity cross-linking showed that these binding sites were predominantly IGF type 1 and type 2 (mannose-6-phosphate) receptors. The radioligands bound especially to follicle germinal cells and prekeratinocytes. Increases in specific binding of both radioligands were observed after the rise in prolactin, but prior to anatomical changes in follicles associated with cessation of growth. For IGF-I, highest binding density was observed during catagen in the germinal matrix and dermal papilla cells. For IGF-II, peak density occurred during late anagen/early catagen in the germinal matrix and during telogen in the dermal papilla. These cycle associated changes in receptor availability suggest that IGF receptors are involved in control of the wool growth.

Animals↗