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Biomedical subjects

N D Ryan

Publications and source records attributed to N D Ryan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Children with prepubertal-onset major depressive disorder and anxiety grown up.

BACKGROUND: The continuity in adulthood of major depressive disorder (MDD) first arising before puberty is largely unknown. This information could guide early treatment and clarify the appropriateness of including children with MDD in genetic studies. METHODS: Eighty-three subjects with onset of MDD, 44 subjects with anxiety disorder and no MDD, and 91 subjects with no evidence of past or current psychiatric disorders were assessed by two psychiatrists before puberty (Tanner stage < III) and were evaluated 10 to 15 years later as adults by an independent team without knowledge of the initial diagnosis. RESULTS: The clinical outcome of children with prepubertal-onset MDD in adulthood includes a high risk of suicide attempts (nearly 3-fold compared with normal controls and 2-fold compared with children with anxiety) and bipolar disorder. Compared with controls, both the children with MDD and those with anxiety went on to have increased risk of substance abuse and conduct disorder but not other disorders, increased use of longterm psychiatric and medical services, and overall impaired functioning. Children with prepubertal-onset MDD with a recurrence of MDD during follow-up had higher rates of MDD in their first-degree relatives. CONCLUSIONS: There is high morbidity in clinically referred children with prepubertal-onset MDD and anxiety, but continuity and specificity of MDD or anxiety disorder in adulthood is less clear. Caution is warranted in selecting clinically referred children with prepubertal-onset MDD for inclusion in genetic studies unless they have a family history of MDD and recurrence of MDD over time.

Adolescent↗
PubMed1999

Mood stabilizers in children and adolescents.

OBJECTIVE: The efficacy of mood stabilizers in children and adolescents has not been studied adequately. This article will review existing studies and highlight some important issues in designing future studies on these agents. METHOD: Electronic databases including Medline, Psycholnfo, and CRISP were searched for data in children receiving compounds that have mood-stabilizing properties in adults. RESULTS: Some open clinical data and an extremely modest amount of controlled research data suggest lithium, carbamazepine, and valproate may be effective mood stabilizers in children and adolescents. There are no controlled data on other potential mood stabilizers in children. CONCLUSIONS: The disorders that may be responsive to mood stabilizers are among the most morbid in child psychiatry. More studies are needed to clarify the efficacy of these compounds in children and adolescents and to provide a rational basis for choosing among them.

Adolescent↗
PubMed1999

Factors associated with the development of substance use disorder in depressed adolescents.

OBJECTIVE: To document rates of substance use disorders (SUD) in adolescents with unipolar major depressive disorder and to examine demographic, clinical, and biological factors associated with the development of SUD. METHOD: Twenty-eight adolescents with unipolar major depression and no SUD history and 35 group-matched normal controls who participated in a cross-sectional sleep polysomnography and neuroendocrine study were reassessed clinically 7 years later. RESULTS: The risk for SUD was high in both groups (34.6% in the depressed group and 24.2% in the controls). Depressed adolescents had earlier onset of SUD than controls. Depressed adolescents who developed SUD had more significant psychosocial impairment than depressed adolescents who did not develop SUD. More anxiety traits and elevated cortisol secretion near sleep onset were associated with SUD in depressed teenagers, whereas less emotional responsiveness to exciting stimuli and higher density of eye movements during REM sleep were related to depression without SUD. CONCLUSIONS: Depressed adolescents who have anxiety traits and whose hypothalamic-pituitary-adrenal axis is active when the system is normally quiescent may be at risk for developing SUD. Co-occurrence of depression and SUD is associated with serious psychosocial morbidity. Identification of risk factors for SUD in depressed teenagers may be helpful in developing more effective treatment and prevention programs.

Adolescent↗
PubMed1999

The Texas Children's Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder.

OBJECTIVES: To develop consensus guidelines for medication treatment algorithms for childhood major depressive disorder (MDD) based on scientific evidence and clinical opinion when science is lacking. The ultimate goal of this approach is to synthesize research and clinical experience for the practitioner and to increase the uniformity of preferred treatment for childhood MDD. A final goal is to develop an approach that can be tested as to whether it improves clinical outcomes for children and adolescents with MDD. METHOD: A consensus conference was held. Participants included academic clinicians and researchers, practicing clinicians, administrators, consumers, and families. The focus was to review and use clinical evidence to recommend specific pharmacological approaches for treatment of MDD in children and adolescents. After a series of presentations of current research evidence and panel discussion, the consensus panel met, agreed on assumptions, and drafted the algorithms. The process initially addressed strategies of treatment and then tactics to implement the strategies. RESULTS: Consensually agreed-upon algorithms for major depressions (with and without psychosis) and comorbid attention deficit disorders were developed. Treatment strategies emphasized the use of selective serotonin reuptake inhibitors. The algorithm consists of systematic strategies for treatment interventions and recommended tactics for implementation of the strategies, including medication augmentation and medication combinations. Participants recommended prospective evaluation of the algorithms in various public sector settings, and many volunteered as sites for such an evaluation. CONCLUSIONS: Using scientific and clinical experience, consensus-derived algorithms for children and adolescents with MDD can be developed.

Adolescent↗
PubMed1999

Insulin-like growth factor I in skeletal muscle after weight-lifting exercise in frail elders.

To assess muscle remodeling and functional adaptation to exercise and diet interventions, 26 men and women aged 72-98 yr underwent a vastus lateralis biopsy before and after placebo control condition, and progressive resistance training, multinutrient supplementation, or both. Type II atrophy, Z band, and myofibril damage were present at baseline. Combined weight lifting and nutritional supplementation increased strength by 257 +/- 62% (P = 0.0001) and type II fiber area by 10.1 +/- 9.0% (P = 0.033), with a similar trend for type I fiber area (+12.8 +/- 22.2%). Exercise was associated with a 2. 5-fold increase in neonatal myosin staining (P = 0.0009) and an increase of 491 +/- 137% (P < 0.0001) in IGF-I staining. Ultrastructural damage increased by 141 +/- 59% after exercise training (P = 0.034). Strength increases were largest in those with the greatest increases in myosin, IGF-I, damage, and caloric intake during the trial. Age-related sarcopenia appears largely confined to type II muscle fibers. Frail elders respond robustly to resistance training with musculoskeletal remodeling, and significant increases in muscle area are possible with resistance training in combination with adequate energy intakes.

Aged↗
PubMed1998

Serotonergic functioning in depressed abused children: clinical and familial correlates.

BACKGROUND: The goal of this study was to examine serotonergic functioning and concomitant clinical and familial correlates in depressed abused children. METHODS: L-5-Hydroxytryptophan (L-5-HTP) (0.8 mg/kg) was administered intravenously to 10 depressed abused (MDD-AB), 10 depressed nonabused (MDD-NA), and 10 normal control nonabused (NC-NA) children. The children in the two nonabused cohorts represent a small matched subset of children from a larger interlocking study of the psychobiology of depression. Blood samples for prolactin and cortisol were collected from 30 min before to 2.5 hours after L-5-HTP infusion. RESULTS: The MDD-AB children secreted significantly more prolactin post-L-5-HTP than the children in the other two groups. There were no differences in baseline prolactin or any of the cortisol measures. Total prolactin post-L-5-HTP was significantly correlated with clinical ratings of aggressive behavior (rho = .48). In addition, children with a family history positive for suicide attempt (MDD-AB: n = 7; MDD-NA: n = 5; NC-NA: n = 2) secreted significantly more prolactin post-L-5-HTP than children with no family history of suicide. CONCLUSIONS: Dysregulation in the serotonergic system in abused children appears to be related to both familial and experiential factors.

5-Hydroxytryptophan↗
PubMed1998

Child and adolescent mood disorders--experience with serotonin-based therapies.

By most measures, child and adolescent depression is much like and continuous with adult depression. Aggregating all available data, much of which is relatively new, it seems most likely that noradrenergic and mixed serotonergic/noradrenergic tricyclic antidepressants are ineffective in child and adolescent depression, whereas serotonergic antidepressants (e.g., selective serotonin reuptake inhibitors) are probably effective).

Adolescent↗
PubMed1998

Psychopathology in the relatives of depressed-abused children.

OBJECTIVE: To determine if the type of symptomatology abused children manifest is related to family history of psychopathology. METHOD: Lifetime history of psychopathology was assessed in the relatives of 26 preadolescents--13 depressed abused (MDD-AB) and 13 depressed nonabused (MDD-NA) children. Rates of disorder in the relatives of these children were compared to published rates of psychopathology in relatives of 27 normal control (NC) children. Data were obtained on 104 first-degree relatives (MDD-AB = 25, MDD-NA = 29, NC = 50) and 503 second-degree relatives (MDD-AB = 127, MDD-NA = 117, NC = 259). The Schedule for Affective Disorders and Schizophrenia was used to assess psychopathology in parents, and Family History method was used to obtain lifetime psychiatric data for all other relatives. RESULTS: When compared to first-degree relatives of NC children, first-degree relatives of MDD-AB children had approximately a nine-fold increased risk for major depression, and a three- to nine-fold increased risk for other disorders associated with the familial subtype of affective illness known as Depression Spectrum Disease (e.g., antisocial personality, alcohol and substance dependence). Similar findings were reported in second-degree relatives, and comparisons between the relatives of MDD-NA and NC children. CONCLUSION: The findings extend results of prior research and (1) suggest familial vulnerability factors influence the symptom profile of abused children; and (2) highlight the value of incorporating psychiatric formulations into multidisciplinary models of child abuse research and treatment programs.

Adolescent↗
PubMed1998

Psychoneuroendocrinology of children and adolescents.

This article reviews psychoneuroendocrinologic approaches to the understanding of internalizing disorders (depression and anxiety disorders) and externalizing disorders. This article discusses three specific psychoneuroendocrine systems: measures of the hypothalamic-pituitary-adrenal (HPA) axis, measure of the serotonergic function, and measures of the growth-hormone (GH) response to pharmacologic challenge. The hypothalamic-pituitary-adrenal (HPA) axis is the main system; understanding this system may reveal information on the permissive and etiologic relationship of stress to psychiatric disorder.

Adolescent↗
PubMed1998

Randomized, controlled trial of amitriptyline versus placebo for adolescents with "treatment-resistant" major depression.

OBJECTIVE: To assess the response to a serotonergic/noradrenergic tricyclic antidepressant, amitriptyline (AMI), in a group of adolescents with treatment-resistant major depressive disorder (MDD). METHOD: Twenty-seven depressed adolescents admitted to a state hospital underwent a 10-week randomized, controlled trial with a flexible dose of AMI or placebo. RESULTS: There were no differences between patients taking AMI (n = 13) and placebo (n = 14). Both treatment groups showed approximately 70% to 80% improvement on the clinical outcome measurements, and 65% to 70% showed functional improvement. At the end of the protocol, 30% of patients still fulfilled criteria for MDD and had impaired functioning. Patients taking AMI experienced significantly more dry mouth and tachycardia. The final AMI dose was 173.1 mg/day +/- 56.3 mg/day; blood levels were 226.2 ng/mL +/- 80.8 ng/mL. CONCLUSIONS: No significant differences were found between AMI and placebo, in part because of the high placebo response rate. Although both treatment groups showed substantial response, at the end of treatment a substantial proportion of patients still had MDD of subsyndromal symptoms of depression. This and other studies of tricyclic antidepressants question the use of this medication as first-line treatment for youths with MDD.

Adolescent↗
PubMed1997

The corticotropin-releasing hormone challenge in depressed abused, depressed nonabused, and normal control children.

Hypothalamic-pituitary-adrenal (HPA) axis disturbances in depressed children with a history of abuse were examined. Thirteen depressed abused, 13 depressed nonabused, and 13 normal control children were given 1.0 microgram/kg of human corticotropin-releasing hormone (CRH) intravenously. Blood samples for corticotropin (ACTH) and cortisol were obtained at nine intervals. When compared to depressed nonabused and normal control children, depressed abused children had significantly greater peak, total, and net ACTH secretion post-CRH. Increased ACTH secretion was only observed in depressed abused children experiencing ongoing chronic adversity (marital violence, emotional abuse, poverty, lack of supports). The pattern of findings of the depressed abused children experiencing ongoing adversity parallels the pattern of HPA axis dysregulation reported in animal studies of chronic stress. They add to a growing body of literature suggesting measures of past trauma and current adversity are important sources of variability in psychobiological correlates of major depression.

Adolescent↗
PubMed1997

Neuroendocrine response to 5-hydroxy-L-tryptophan in prepubertal children at high risk of major depressive disorder.

BACKGROUND: Altered serotonergic function has been observed in prepubertal children and adults with an acute episode of major depressive disorder (MDD). However, it is not known whether these alterations are present prior to the onset of MDD. METHODS: A serotonergic precursor, 5-hydroxy-L-tryptophan (L-5HTP) (oxitriptan) (0.8 mg/kg), was administered through an indwelling catheter to 36 children at high risk of MDD (with high family loading for MDD), 31 children with MDD, and 23 low-risk normal controls (with low family loading for mood disorders and no history of psychopathology). Blood samples for cortisol, prolactin (PRL), and growth hormone were obtained every 15 minutes for 180 minutes, beginning 30 minutes before L-5HTP infusion. RESULTS: Children at high risk of MDD and children with MDD had similar hormonal responses following L-5HTP infusion. After controlling for baseline values, both groups secreted significantly less cortisol and more PRL than did the low-risk normal controls, with the PRL finding being limited to girls. There were no between-group differences in baseline cortisol, PRL, or growth hormone secretion measures. CONCLUSIONS: Before the onset of affective illness, high-risk children had the same pattern of neuroendocrine response to the L-5HTP challenge as did children with MDD. These results extend earlier findings of altered serotonergic regulation in association with early-onset depression and indicate that these alterations may represent a trait marker for depression in children.

5-Hydroxytryptophan↗
PubMed1996

The relationship between longitudinal clinical course and sleep and cortisol changes in adolescent depression.

This study examined the relationship between longitudinal clinical course and sleep and cortisol findings in adolescent unipolar major depressive disorder (MDD). Subjects were 28 adolescents (15.4 +/- 1.3 years) systematically diagnosed with unipolar MDD and 35 group-matched normal controls who participated in EEG sleep and neuroendocrine studies. Follow-up clinical assessments were conducted 7.0 +/- 0.5 years later in 94% of the original cohort. Although initial group comparisons failed to show significant differences in biologic measures, analyses incorporating clinical follow-up reveal that changes in sleep and cortisol measures are associated with differential longitudinal course. Normal controls who would develop depression after the biologic studies had shown significantly higher density of rapid eye movements (REM) and a trend for reduced REM latency compared to controls with no psychiatric disorder at follow-up. Depressed subjects with a recurrent unipolar course showed a trend towards elevated plasma cortisol near sleep onset compared to MDD subjects with no further episodes during the follow-up interval.

Adolescent↗
PubMed1996

Sleep onset abnormalities in depressed adolescents.

Sleep measures were obtained in 16 depressed and 21 control adolescents following 1 week of adherence to a uniformly imposed and strictly enforced sleep/wake schedule. Three nights of baseline electroencephalographic (EEG) sleep on the same 10:00 PM to 7:00 AM schedule revealed prolonged sleep latency and reduced rapid eye movement (REM) latency in the depressed adolescents. Following baseline measures, sleep was restricted for 2 nights (10:00 PM-4:00 AM) and measures of recovery sleep were obtained showing further sleep latency differences. There was no evidence for delta sleep changes or sleep continuity differences in depressed adolescents. These results suggest that control over sleep/wake schedules is an important methodological issue in adolescent sleep studies. Furthermore, the findings are consistent with a larger body of evidence indicating that dysregulation near sleep onset represents a primary psychobiological change in early-onset depression.

Adolescent↗