Corticotropin releasing hormone increases apparent potency of adrenocorticotropic hormone stimulation of cortisol secretion.

HYPOTHESIS: Corticotropin releasing hormone (CRH) has a regulatory effect on cortisol secretion in addition to its classic effect of stimulating adrenocorticotropic hormone (ACTH) secretion. REVIEW: There is growing evidence of "long-loop" and paracrine adrenal stimulation by CRH. Data from a study of the ovine-corticotropin releasing hormone (oCRH) stimulation test in 13 sexually abused girls and 13 normal controls was used in Montecarlo simulations of the hypothalamic-pituitary-adrenal axis, to get estimates of adrenal sensitivity to ACTH and cortisol elimination kinetics before and after oCRH administration. In both controls and sexually abused girls, ACTH had an apparent greater effect on cortisol secretion after administration of oCRH compared to its effect during the baseline period. This lends support to the hypothesis and suggests that it should be tested experimentally.

Variants of intrafamilial sexual abuse experience: implications for short- and long-term development.

This study examines short- and long-term maladaptive outcomes in a sample of sexually abused females and a comparison group. The sample consists of intrafamilial sexual abuse victims ages 6-16 years at entry into the study and a demographically similar comparison group. The outcomes examined included measures of behavior and psychological problems such as aggressive behavior, depression, dissociation, and low self-esteem; and measures at two time points, first at entry into the study (median age 11 years) and approximately 7 years later (median age 18 years). The specific questions being addressed were (a) whether subgroups or profiles. based on the specific characteristics of the sexual abuse experienced, can be identified in this sample of abused females; and (b) whether these profile groups predict different patterns of adverse short- or long-term outcomes.

Social network constellation and sexuality of sexually abused and comparison girls in childhood and adolescence.

This longitudinal study examines how childhood and early adolescent (age 6 to 15) peer and nonpeer social networks relate to sexual attitudes and behaviors in adolescence and young adulthood (age 12 to 25) for sexually abused and comparison girls. A large number of male peers in childhood is related to heightened sexual activity, sexual preoccupation, increased sexual pressure, and risky sexual behavior in adolescence. High-quality, female, nonpeer relationships have a positive effect on attitudes toward casual sex. Multiple group models illuminate several cross-lag group moderators: (a) Abused girls who are happier with male nonpeers are less preoccupied with sex; (b) abused girls who are happier with male peers are more likely to use birth control; and (c) abused girls who have early physical relationships are more likely to engage in risky sexual behavior. Treatment implications include monitoring the effects of low-status peer groups, encouraging contact with female role models, and encouraging the formation of high-quality relationships with male peers and nonpeers.

The motivations for self-injury in psychiatric inpatients.

Nonsuicidal self-injurious behavior (SIB) occurs in both culturally appropriate and culturally inappropriate forms. It is one of the diagnostic criteria for borderline personality disorder, but it occurs in several psychiatric and neurological populations. The personal intent of SIB in psychiatric populations is incompletely understood. A self-report scale (Self-Injury Motivation Scale; SIMS) to assess motivation for self-injury was developed. Relationships among motivation for SIB, characteristics of SIB, and psychopathology were explored. A semistructured interview and the SIMS, Dissociative Experiences Scale, Beck Depression Inventory, Davidson Trauma Scale, and Millon Clinical Multiaxial Inventory-II were given to 99 consecutively admitted inpatients. The SIMS had good reliability and validity. A high SIMS score suggested distinct psychopathology. Several factors on the SIMS differentiated motivations for SIB. Patients with different SIMS factor profiles had different psychopathology.

The Atomic Bomb Casualty Commission in retrospect.

For 50 years, the Atomic Bomb Casualty Commission (ABCC) and its successor, the Radiation Effects Research Foundation (RERF), have conducted epidemiological and genetic studies of the survivors of the atomic bombs and of their children. This research program has provided the primary basis for radiation health standards. Both ABCC (1947-1975) and RERF (1975 to date) have been a joint enterprise of the United States (through the National Academy of Sciences) and of Japan. ABCC began in devastated, occupied Japan. Its mission had to be defined and refined. Early research revealed the urgent need for long term study. In 1946, a Directive of President Truman enjoined the National Research Council of the National Academy of Sciences to develop the program. By 1950, ABCC staff exceeded 1,000, and clinical and genetic studies were underway. Budgetary difficulties and other problems almost forced closure in 1953. In 1955, the Francis Report led to a unified epidemiological study. Much progress was made in the next decade, but changing times required founding of a binational nonprofit organization (RERF) with equal participation by Japan and the United States. New programs have been developed and existing ones have been extended in what is the longest continuing health survey ever undertaken.

Structural characterization of three genetic variants of human serum albumin modified in subdomains IIB and IIIA.

Three new genetic variants of human serum albumin have been detected in Italy by routine clinical electrophoresis. Albumin Milano Slow is common in Northern Italy, while albumins Liprizzi and Trieste, which are fast migrating, are rare and local variants. Isoelectric focusing analysis of the CNBr fragments obtained from the carboxymethylated alloalbumins in all cases localized the mutation to fragment CB5 (residues 330-446). The modified CNBr fragments were isolated on a preparative scale and subjected to tryptic digestion. Sequence determination of the abnormal tryptic peptides revealed that all the variants are caused by single point mutations: Trieste, Lys359-->Asn, Milano Slow, Asp375-->His, and Liprizzi, Arg410-->Cys. These results were confirmed by sequence determination of a variant V8 peptide in the case of Trieste, and by DNA sequence analysis for the other two variants. The DNA analysis showed a G-->C transversion at nucleotide position 11969 for albumin Milano Slow, and a C-->T transition at position 13251 for Liprizzi. The latter represents a mutation at a hypermutable CpG dinucleotide site. Albumins Trieste and Milano Slow, as most of the variants thus far described, have mutations involving residues on the surface of the molecule. In contrast, albumin Liprizzi represents the first example of a mutation in the most active binding pocket of the molecule, placed in subdomain IIIA.

Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS).

The purpose of this study was to develop an instrument for the measurement of present-state dissociative symptoms, the Clinician Administered Dissociative States Scale (CADSS). Reported here are interrater reliability and internal consistency of the CADSS, validity as assessed by comparisons with other instruments for the assessment of dissociation, and sensitivity of the CADSS to discriminate patients with dissociative disorders from patients with other psychiatric disorders and healthy subjects. Initial analyses indicated good interrater reliability and construct validity for the CADSS. Scores on the CADSS discriminated patients with dissociative disorders from the other groups.

Development and validation of a measure of adolescent dissociation: the Adolescent Dissociative Experiences Scale.

This study describes the initial reliability and validity data on the Adolescent Dissociative Experiences Scale (A-DES), a screening measure for pathological dissociation during adolescence. The A-DES showed good scale and subscale reliability, and, as hypothesized, increased scores were associated with reported trauma in a patient population. A-DES scores were able to distinguish dissociative disordered adolescents from a normal sample and from a patient sample with a variety of diagnoses.

Structural characterization of four genetic variants of human serum albumin associated with alloalbuminemia in Italy.

A long-term electrophoretic survey on plasma proteins, which was carried out in several clinical laboratories in Italy, identified 28 different genetic variants of human serum albumin and four cases of analbuminemia. We have previously characterized 16 point mutations, 3 C-terminal mutants, and the genetic defects in two analbuminemic subjects. Here, we report the molecular defects of four alloalbumins that have been characterized by protein structural analysis. Of these, three represent new single-point mutations: albumins Tregasio, Val122-->Glu, Bergamo, Asp314-->Gly, and Maddaloni, Val533-->Met. The fourth, albumin Besana Brianza, has the same Asp494-->Asn mutation that introduces a glycosylation site which has been previously reported in a variant from New Zealand, albumin Casebrook. However, in contrast to albumin Casebrook, albumin Besana Brianza is only partially glycosylated and the oligosaccharide is heterogeneous, consisting of a biantennary complex type N-glycan with either two or one sialic acid residue(s) on the antennae. Both albumin Maddaloni and Besana Brianza represent mutations at hypermutable CpG dinucleotide sites; albumin Maddaloni is a mutant that does not involve a charged amino acid.

Disclosure patterns of sexual abuse and psychological functioning at a 1-year follow-up.

This study describes the disclosure processes of a sample of 68 sexually abused girls, with a focus on the manner in which abuse was revealed--on purpose, accidentally, or resulting from a precipitating event. This categorization is a more descriptive conceptualization of the disclosure process than has been proposed or assessed in previous studies. The circumstances surrounding disclosure are found to be related to long term psychological functioning. Children who disclosed accidentally were younger, experienced abuse for shorter durations, and received the most therapy. At follow-up, children who purposely disclosed had greater anxiety and greater difficulties coping. Discussion focuses on ways in which identifying and encouraging the least traumatic methods of disclosure would contribute to better outcomes for victims of sexual abuse.

Factors affecting utilization of treatment services by sexually abused girls.

This study describes the naturalistic therapy experiences of a sample of sexually abused girls and the relationship of these experiences to demographic factors, abuse experiences, psychopathology, and family functioning. The sample consisted of 81 sexually abused girls, aged 6 to 16, participating in a longitudinal study of the effects of sexual abuse. Results indicated strong effects for abuse experiences and child psychopathology on the total amount of therapy received. Patterns of treatment utilization were associated with ethnic minority status, but these differences are confounded by differing abuse experiences for racial groups in the sample. Other patterns of treatment utilization are discussed, as well as issues for further research and implications for treatment providers.

Patterns of dissociation in clinical and nonclinical samples.

Research has consistently found elevated mean dissociation scores in particular diagnostic groups. In this study, we explored whether mean dissociation scores for different diagnostic groups resulted from uniform distributions of scores within the group or were a function of the proportion of highly dissociative patients that the diagnostic group contained. A total of 1566 subjects who were psychiatric patients, neurological patients, normal adolescents, or normal adult subjects completed the Dissociative Experience Scale (DES). An analysis of the percentage of subjects with high DES scores in each diagnostic group indicated that the diagnostic group's mean DES scores were a function of the proportion of subjects within the group who were high dissociators. The results contradict a continuum model of dissociation but are consistent with the existence of distinct dissociative types.

Antinuclear antibodies and thyroid function in sexually abused girls.

Sexually abused girls manifest dysregulation of physiological stress response systems. In this exploratory investigation, 14 sexually abused and 13 control girls, ages 8-15 years, recruited from a prospective, longitudinal study, underwent plasma antinuclear antibody and thyroid function tests. Thyroid function tests and plasma antinuclear antibody titers did not differ between sexually abused and control girls. However, a significantly higher incidence of plasma antinuclear antibody titers was seen in abused subjects when compared with the frequency of positive antinuclear antibody titers in a sample of 22 adult healthy female volunteers, ages 20-58 years. These findings suggest that sexually abused girls may show evidence of an alteration in normal immune homeostatic function.

Thyroid hormone concentrations in depressed and nondepressed adolescents: group differences and behavioral relations.

OBJECTIVE: To examine thyroid hormone concentrations and the influence of these hormones on mood and problem behaviors in adolescents with depression. METHOD: The sample included 21 depressed adolescents and 20 matched control adolescents. Blood was drawn to measure thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), and triiodothyronine (T3). Major depression (MD), attention deficit (AD), and obsessive-compulsive (OC) symptom scores were abstracted from the Diagnostic Interview Schedule for Children. Total behavior problem scores from the Youth Self-Report also were obtained. RESULTS: Paired analysis revealed there were no significant group or gender differences or group by gender interactions for TSH, T4, or T3. For FT4, however, there were significant group differences (p = .008) showing lower concentrations in depressed adolescents than control subjects, suggesting that the former might be functionally hypothyroid. Although there were no significant correlations of TSH with any of the psychological measures obtained, in the depressed group correlations were negative (although not always significant) with FT4 and total behavior problems (r = -.40, p = .09), as well as with symptom scores of MD (r = -.25, p = .288), OC (r = -.56, p = .011), and AD behaviors (r = -.57, p = .008). Higher numbers of symptom scores of OC and AD were related to lower concentrations of FT4. CONCLUSIONS: FT4 concentrations were lower in depressed adolescents. These findings suggest a relationship between negative behaviors and dysfunction of the hypothalamic-pituitary-thyroid axis in adolescents with depression.

Structural study of the glycosylated and unglycosylated forms of a genetic variant of human serum albumin (63 Asp-->Asn).

A genetic variant of human serum albumin (alloalbumin) exhibited atypical electrophoretic mobility and chromatographic behavior apparently because of the effect of a point substitution on the molecular conformation. Three forms of albumin were isolated by DEAE HPLC chromatography: normal albumin, and two variant forms V1 and V2. The point substitution (Asp-63-->Asn) generated a canonical tripeptide acceptor sequence for glycosylation with an N-linked oligosaccharide (Asn-Lys-Ser). Neuraminidase digestion followed by electrophoresis showed that the V2 variant form was glycosylated and the V1 form was not. Time-of-flight mass spectrometry yielded a molecular weight of about 2000 for the carbohydrate. Structural analysis of the carbohydrate was done by chromatographic comparison of the pyridylaminated derivatives with standards and was confirmed by proton NMR of the three pronase glycopeptides and of the pyridylaminated oligosaccharide. The oligosaccharide had a complex biantennary structure with two sialic acid residues. In normal albumin Asp-63 is exposed and is adjacent to the first disulfide bond, Cys-62-->Cys-53. The apparent effect on molecular conformation resulting in incomplete glycosylation and atypical electrophoretic mobility suggests that glycosylation may interfere with disulfide bond formation at this site.

Hypnotizability and dissociativity in sexually abused girls.

Research on the relation between hypnotizability and clinical dissociation has led to contradictory findings. Measures of hypnotizability and dissociation are only weakly correlated in general population samples, but studies of posttraumatic stress and dissociative disorders patients have found elevated levels of clinical dissociation and hypnotizability respectively. This study assesses the relationships among hypnotizability, clinical dissociation and traumatic antecedents in 54 sexually abused girls, ages 6-15 years, and 51 matched controls. Hypnotizability was assessed on initial evaluation and again in matched subsamples at one year using the Stanford Hypnotic Clinical Scale for Children. Clinical dissociation was assessed using the Child Dissociative Checklist. Abuse variables were extracted from Child Protective Services reports. There were no significant differences in hypnotizability between abuse and control subjects. There were significant differences in clinical dissociation initially and on 1-year retest. Hypnotizability and clinical dissociation were only weakly correlated (r(105) = .118, p = NS). However, in the abuse group, highly hypnotizable subjects were significantly more dissociative. Higher levels of clinical dissociation were associated with abuse by multiple perpetrators and co-presence of physical abuse independent of the sexual abuse. A small subgroup of "double dissociative" subjects, high in both hypnotizability and dissociativity, was identified. Double dissociation was associated with multiple perpetrators and earlier onset of sexual abuse.

A genetic variant of albumin (albumin Asola; Tyr140-->Cys) with no free -SH group but with an additional disulfide bridge.

A slow migrating variant of human serum albumin, present in lower amount than the normal protein, has been detected by routine clinical electrophoresis at pH 8.6 in two members of a family living in Asola (Lombardia, Italy). Ion-exchange chromatography of serum samples failed to separate the normal protein from the variant. Analysis of the albumin peak by SDS/PAGE revealed that the variant had a lower apparent molecular mass than its normal counterpart. However, the abnormal band was not detectable when the separation was performed under reducing conditions or when both albumins were carboxymethylated. Isoelectric-focusing analysis of CNBr fragments localized the mutation to fragment CNBr 3 (residues 124-298). This fragment was isolated on a preparative scale and subjected to tryptic digestion. Sequence determination of the abnormal tryptic peptide revealed that the variant arises from a Tyr140--> Cys substitution. This result was confirmed by DNA sequence analysis, which showed a single transition of TAT-->TGT at nucleotide position 5074. Despite the presence of an additional cysteine residue, several lines of evidence indicated that albumin Asola has no free -SH group; therefore, we propose the formation of a new S-S bond between Cys140 and Cys34, the only free sulphydryl group present in the normal protein. The relatively low level of the variant in serum and its abnormal mobility on cellulose acetate electrophoresis and SDS/PAGE are probably caused by a gross conformational change of the molecule induced by the new S-S bridge.