Effectiveness of attachment based STEEP™ intervention in a German high-risk sample.

STEEP(TM) was one of the first attachment-based early intervention programs. The program applied findings from the Minnesota Longitudinal Study on Risk and Adaptation to the development of a supportive program for young high-risk mothers and their infants. STEEP's effectiveness was evaluated first in a randomized controlled study launched in 1987. The study showed effects of the one-year intervention on important individual and parenting variables, but not on quality of mother-infant attachment. In the current German study with young mothers at risk for abuse and neglect, a two-year adaptation of STEEP was evaluated within a quasi-experimental design. STEEP mother-infant pairs (N = 78) were compared with pairs who received standard services of the German Child Welfare System (GCWS, N = 29). Compared with GCWS pairs, significantly more mother-infant pairs in the intervention group showed secure attachment patterns in Ainsworth´s Strange Situation when the infants were 12 months of age. At the end of the intervention (infant age = 24 month), attachment security scores derived from Waters' Attachment Q-Sort were in the predicted direction and showed a medium effect size, but did not reach criteria of statistical significance. At both time points, the STEEP group showed significantly fewer signs of attachment disorganization than the comparison group.

Effects of elevated temperature and nickel pollution on the immune status of Japanese medaka.

Changes in a host's environment (i.e. physical or chemical) can alter normal immune function. In aquatic organisms, exposure to stress can result in significant changes in innate immunity. In the natural environment, fish are exposed to multiple stressors simultaneously. Temperature change and/or chemical exposure as individual environmental stressors have been shown in various fish species to alter all aspects of the immune response. These same stressors have also been shown to alter plasma steroid levels in exposed fish. For this study, the effects of elevated temperature and nickel pollution on specific immune parameters of Japanese medaka (Oryzias latipes) were determined. Fish were exposed for 1, 7 or 14d to either: waterborne nickel (Ni) at the nominal concentration of 125ppb; a 5 degrees C (+/-0.5 degrees C) rapid increase in water temperature; or, both potential stressors in combination. Medaka maintained at room temperature (25 degrees C+/-1 degrees C) served as the controls. Altered function of the innate and adaptive arms of the immune response was evaluated by assessing kidney macrophage-mediated superoxide (O(2)(-)) production and splenic T-cell proliferation, respectively. Plasma cortisol levels were analysed in the same fish as a marker of the physiological stress response. While kidney cell number was unaffected by exposure of fish to either stressor alone or both factors in combination, spleen cellularity was decreased (compared to control fish) in medaka exposed for 1d to thermal stress in combination with Ni, and to a lesser extent to thermal stress alone. T-lymphocyte proliferation by medaka splenocytes was not affected by any exposure paradigm. Unstimulated intracellular O(2)(-) production by kidney phagocytes was significantly elevated (compared to control) in medaka exposed for 1d to either thermal stress alone or temperature change in combination with Ni; by 7d, only the stressor combination significantly increased baseline O(2)(-) production. Resting levels of extracellular O(2)(-) production was significantly reduced in fish maintained for 1d at the elevated temperature. Effects on phorbol 12-myristate 13 acetate (PMA)-stimulated intracellular and extracellular O(2)(-) production were less dramatic than those observed for resting phagocytes. Exposure of medaka to elevated temperature for 14d tended (p<0.06) to reduce PMA-stimulated intracellular O(2)(-) production (compared to the time-matched control). Although exposure of fish for 14d to elevated temperature only slightly reduced stimulated extracellular O(2)(-) production, exposure for the same duration to Ni alone significantly depressed oxyradical production by kidney phagocytes (compared to the time-matched controls). Decreased plasma cortisol levels were observed in fish exposed for 7d to either an elevated water temperature or Ni (compared to the time-matched control); by 14d of exposure, no significant treatment-induced effects on cortisol levels were observed. These findings add to the growing body of literature seeking to determine what effects, if any, exposure to multiple aquatic pollution-induced effects have upon fish health and the health of impacted ecosystems.

Benzo[a]pyrene-induced immunotoxicity in Japanese medaka (Oryzias latipes): relationship between lymphoid CYP1A activity and humoral immune suppression.

Exposure to the environmental contaminant benzo[a]pyrene (BaP) results in suppression of immune function in both mammalian and fish species. This laboratory has previously demonstrated that a single intraperitoneal (IP) injection of BaP reduced lymphocyte proliferation, phagocyte-mediated superoxide generation, and antibody-forming cell (AFC) numbers in Japanese medaka (Oryzias latipes). The objective of the current study was to determine the role of BaP metabolism in the observed immunosuppression. Results from rodent studies have suggested that BaP elicits its immunotoxic effects via upregulation of cytochrome P4501A1 (CYP1A1) and the subsequent production of immunosuppressive BaP metabolites. In this study, exposure of medaka to 200 microg BaP/g BW significantly induced CYP1A expression or activity within lymphoid tissue 48 h post-IP injection; induction was observed specifically within distinct subpopulations of kidney mononuclear cells. Concurrent injection of fish with BaP and the CYP1A1 inhibitors alpha-naphthoflavone (ANF) or dehydroepiandrosterone (DHEA) resulted in inhibition of renal EROD activity and amelioration of BaP-induced suppression of medaka AFC numbers. Results of this study suggest that (1) BaP-induced suppression of medaka humoral immunity relies upon the CYP1A-catalyzed production of immunotoxic BaP metabolites and (2) BaP metabolites may be created in situ, directly by specific cells within kidney lymphoid tissue. Thus, apparently, mechanisms involved in BaP-induced immunosuppression have been phylogenetically conserved from fish to mammals.

Suppressive effects of benzo[a]pyrene upon fish immune function: evolutionarily conserved cellular mechanisms of immunotoxicity.

Knowledge gained through the use of alternative animal models has significantly enhanced our understanding of life at all levels of biological organization. The discipline of toxicology is under considerable pressure to develop such models due to increasing public concern regarding the experimental use of mammals. Studies in this laboratory have focused on the utility of a small laboratory fish model, the Japanese medaka (Oryzias latipes), to investigate immunotoxicological effects of benzo[a]pyrene (BaP). BaP is a ubiquitous environmental contaminant and known mammalian immunotoxicant. This laboratory has demonstrated that in vivo exposure of medaka to BaP (2-200 microg/g BW) significantly depresses both innate and humoral immunity. Further studies have indicated that BaP activates its own biotransformation pathway within medaka immune cells following both in vivo and in vitro exposure. In addition, reduction of BaP metabolism with alpha-naphthoflavone results in the reversal of BaP-induced suppression of antibody production in vitro. Inhibition of CYPlA-mediated metabolism within medaka immune cells also alleviates the immunotoxicity induced by benzo[a]pyrene-7,8-dihydrodiol, but not benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). This suggests that BPDE may be an ultimate immunotoxicant. Results from this study in medaka are in agreement with previously conducted rodent studies that indicated a role for immunotoxic BaP metabolites in BaP-induced suppression of humoral immunity.

Age-related differences in the sensitivity of the fish immune response to a coplanar PCB.

Polychlorinated biphenyls (PCBs) are widespread environmental pollutants. Because of their persistence and bioaccumulation in aquatic organisms (among other factors), the biological impact of PCB exposure on resident fish populations is of particular concern. To assess the effect(s) of an environmentally relevant coplanar PCB congener on the fish immune response, juvenile and aged Japanese medaka (Oryzias latipes) were injected i.p. with either vehicle or PCB 126 (at 0.01 or 1.0 microg/g BW) and examined after 3 and 14 days. CYP1A protein levels, examined as an indicator of PCB exposure, were significantly increased (compared to controls) in all fish treated with the highest PCB dose. Kidney phagocyte superoxide (O2*-) production was examined to indicate effects upon innate immune function. After 14 days, unstimulated O2*- production by kidney phagocytes from juvenile and aged medaka treated with the highest PCB dose was significantly increased compared to controls. Stimulated O2*- production by aged PCB-treated fish was unaffected (compared to controls) at both post-exposure timepoints. However, phagocytes from PCB-treated juvenile medaka demonstrated reduced O2*- production at 3 days post-exposure and increased levels after 14 days (compared to controls). These results demonstrate the sensitivity of medaka phagocyte function for examining PCB-induced immunotoxicity.

The Japanese medaka (Oryzias latipes) model: applicability for investigating the immunosuppressive effects of the aquatic pollutant benzo[a]pyrene (BaP).

Despite the fact that BaP is a carcinogen, mammalian immunosuppressant, and ubiquitous aquatic pollutant, knowledge regarding the effects of BaP on the immune system of fish is still lacking. To begin to fill this gap, studies were conducted in medaka to examine the effects and mechanisms by which BaP exposure might alter host immunocompetence. Fish, exposed by IP injection of BaP (2-600 microg/g BW), were examined after 48 h for effects upon immune function and CYP1A expression/activity. Benzo[a]pyrene, at a concentration below that which increased levels of CYPIA expression/activity (2 microg BaP/g BW) suppressed lymphocyte proliferation. Concentrations of BaP at 20 and 200 microg/g BW. suppressed antibody-forming cell (AFC) numbers, superoxide production, and host resistance against bacteria. In contrast, exposure to the low affinity aryl hydrocarbon receptor (AhR) agonist, benzo[e]pyrene (BeP), neither induced CYP1A expression nor altered immune function. Given the lack of immunosuppressive effects produced by BeP, and the fact that exposure to the AhR antagonist (and CYP1A inhibitor) alpha-naphthoflavone (ANF) ameliorated the suppressive effects of BaP upon AFC numbers, the AhR pathway (including CYP1A-mediated production of reactive BaP metabolites) appears important in mediating BaP-induced immunotoxicity in fish, as in mammals. In the past, the medaka has proven a successful model for assessing carcinogenic agents. These studies have demonstrated its utility for also determining the immunosuppressive effects of an important aquatic contaminant.

Exposure of Japanese medaka (Oryzias latipes) to benzo[a]pyrene suppresses immune function and host resistance against bacterial challenge.

Besides being a potent chemical carcinogen, benzo[a]pyrene (BaP) has also been shown to suppress the immune response of mammals. However, even though BaP is a ubiquitous environmental contaminant to which aquatic species may be directly exposed, information regarding the effects of BaP on the immune system of fish is still lacking. Therefore, laboratory studies were conducted using Japanese medaka (Oryzias latipes) to examine the effects of BaP on host immune status. A single IP injection of BaP at 2, 20 or 200 microg/g BW had no effect upon medaka survival or condition factors for up to 7 days post-injection. Forty-eight hours after injection of either BaP or the vehicle control, fish were sacrificed and the appropriate organs/cells used to assess effects upon: splenic lymphocyte proliferation; kidney phagocyte intracellular superoxide (*O(2)(-)) production; and, CYP1A protein level/activity. In separate experiments, fish were injected with either sheep red blood cells or the bacterial pathogen Yersinia ruckeri at 48 h post-BaP exposure for later determination of antibody-forming cell (AFC) numbers and bacterial host resistance, respectively. Results demonstrated that in the absence of effects upon host survival or condition factors, a single exposure to a relatively low dose of BaP (2 microg/g BW) significantly suppressed mitogen-stimulated T- and B-lymphocyte proliferation (in the absence of elevated hepatic CYP1A expression/activity). At higher concentrations, BaP also reduced AFC numbers, phagocyte-mediated *O(2)(-) production, and host resistance against bacterial infection. These results clearly demonstrate the ability of BaP to compromise the immune response of fish and indicate the utility of the fish immune response to serve as an early indicator of BaP exposure/effects in exposed feral populations.

Depressive symptomatology in childhood and adolescence.

Antecedents of depressive symptomatology in childhood and adolescence were examined in a prospective longitudinal study of at-risk youth (n = 168) from families of lower socioeconomic status. Relations between family context factors, maternal depressive symptoms, and depressive symptoms in childhood and adolescence were examined, with a focus on early family relationship factors rarely available for analysis in longitudinal data sets. Results suggest the possibility of etiological differences between depressive symptoms in childhood and in adolescence. Depressive symptomatology in childhood was predicted by the overall family context. Cumulative effects of maternal depressive symptomatology, early care lacking in emotional supportiveness, abuse, and family stressors were observed. Depressive symptomatology in adolescence, on the other hand, was specifically associated with maternal depression and early care lacking in emotional supportiveness. Moreover, an intriguing sex difference emerged: maternal depressive symptomatology was strongly associated with depressive symptomatology in adolescence for females, but for males supportive early care appeared more relevant.

Implications of attachment theory for developmental psychopathology.

Bowlby's attachment theory is a theory of psychopathology as well as a theory of normal development. It contains clear and specific propositions regarding the role of early experience in developmental psychopathology, the importance of ongoing context, and the nature of the developmental process underlying pathology. In particular, Bowlby argued that adaptation is always the joint product of developmental history and current circumstances (never either alone). Early experience does not cause later pathology in a linear way; yet, it has special significance due to the complex, systemic, transactional nature of development. Prior history is part of current context, playing a role in selection, engagement, and interpretation of subsequent experience and in the use of available environmental supports. Finally, except in very extreme cases, early anxious attachment is not viewed as psychopathology itself or as a direct cause of psychopathology but as an initiator of pathways probabilistically associated with later pathology.

A prospective longitudinal study of attachment disorganization/disorientation.

The research explores the antecedents and consequences of attachment disorganization from a prospective longitudinal perspective. The relations of attachment disorganization/disorientation to endogenous (e.g., maternal medical history, infant temperament) and environmental (e.g., maternal caregiving quality, infant history of abuse) antecedents and to behavioral consequences from 24 months to 19 years are examined. For the 157 participants in the longitudinal study, attachment disorganization was correlated significantly with environmental antecedents (e.g., maternal relationship and risk status, caregiving quality, and infant history of maltreatment), but not with available endogenous antecedents. Infant history of attachment disorganization was correlated with consequent variables related to mother-child relationship quality at 24 and 42 months, child behavior problems in preschool, elementary school and high school, and psychopathology and dissociation in adolescence. Structural models suggest that disorganization may mediate the relations between early experience and later psychopathology and dissociation. The findings are considered within a developmental view of psychopathology, that is, pathology defined in terms of process, as a pattern of adaptation constructed by individuals in their environments.

Children's representations of attachment relationships in family drawings.

Children's representational models of self and attachment figures were investigated in family drawings at age 8-9 in a high-risk, racially mixed sample. Drawings were scored using a series of specific signs and a group of theoretically derived, global rating scales. When specific signs were treated in a combined way (versus separately), they were significantly related to early attachment history in predicted ways. Similarly, specific rating scales were found to be significantly related to early relationship history. Analyses exploring the relative contributions of early attachment history and contemporary measures of child IQ, life stress, and emotional functioning revealed that even after contemporary influences were taken into account, attachment history made a significant contribution to the prediction of negative drawing outcome. Results were interpreted as supporting an organizational perspective on development where qualitative differences in early relationships are hypothesized to shape core representational models of the self and to exert an ongoing influence on later representational processes.

Development and the fragmented self: longitudinal study of dissociative symptomatology in a nonclinical sample.

Dissociative behaviors and their relation to both the self and self-organization were examined using the developmental psychopathology perspective in a prospective longitudinal study of high-risk children. Participants were 168 young adults (n = 79 females, n = 89 males, age = 18-19 years) considered high-risk for poor developmental outcomes at birth due to poverty. The present study investigated whether trauma, sense of self, quality of early mother-child relationship, temperament, and intelligence were related to dissociative symptomatology measured at four times across 19 years. Findings were (a) age of onset, chronicity and severity of trauma were highly correlated and predicted level of dissociation; (b) both the avoidant and disorganized patterns of attachment were strong predictors of dissociation; (c) dissociation in childhood may be a more normative response to disruption and stress, while dissociation in adolescence and young adulthood may be more indicative of psychopathology; (d) preliminary support was found for a model proposed by G. Liotti that links disorganized attachment, later trauma, and dissociation in adulthood; and (e) strong support was found for N. Waller, F. W. Putnam, and E. B. Carlson's contention that psychopathological dissociation should not be viewed as the top end of a continuum of dissociative symptomatology, but as a separate taxon that represents an extreme deviation from normal development.

A developmental investigation of inattentiveness and hyperactivity.

The development of inattentiveness and hyperactivity in middle childhood was investigated using a prospective longitudinal approach. Endogenous and exogenous predictors measured in infancy and in early and middle childhood were examined independently and in combination. In early childhood, quality of caregiving more powerfully predicted distractibility, an early precursor of hyperactivity, than did early biological or temperament factors. Caregiving and contextual factors together with early distractibility significantly predicted hyperactivity in middle childhood. While environmental variables also predicted hyperactivity in later elementary years, these factors did not improve the prediction beyond the influence of hyperactivity in early elementary years. The findings support a developmental view of the origins and course of hyperactivity in childhood, that is, that the emergence and persistence of AD/HD symptoms depend on developmental history along with current circumstances.

Associations among adult attachment representations, maternal sensitivity, and infant-mother attachment in a sample of adolescent mothers.

Associations among adolescent attachment organization, maternal sensitivity, and infant attachment organization were examined prospectively in 74 teenaged mother-infant dyads. Pregnant teenagers' attachment organizations predicted both sensitivity and infant-mother attachments. Mothers classified autonomous (F) in the prenatal period showed higher levels of sensitivity at both 3 and 9 months than mothers classified dismissing (Ds), preoccupied (E), or unresolved (U). Correspondence between maternal attachment (F vs. Ds/E/U) and infant attachment (secure [B] vs. avoidant [A]/resistant [C]/disorganized [D]) was observed in 58 of 74 (78%) dyads. Exact 4-group (Ds/E/F/U and A/B/C/D) agreement was observed in 50 of 74 (68%) families. In contrast, associations between maternal sensitivity and infant attachment were not significant, leading to questions about the processes that link attachment representations, maternal behavior, and infant attachment in adolescent mothers.

Differences in the responses of heterozygous carriers of colorblindness and normal controls to briefly presented stimuli.

Two experiments were conducted in order to investigate the possible effects of X-inactivation (Lyon, 1961) on female carriers of colorblindness. The results of the first experiment, like those of Grützner et al. (1976), were consistent with the prediction of the Lyon (1961) hypothesis that the retinas of female carriers are composed of mosaic patches of colorblind and normal areas. In this first experiment, rows and columns of colored spots were presented tachistoscopically, and subjects were asked to identify the colors of the spots. In the second experiment, plates from the Ishihara test of colorblindness were presented tachistoscopically and subjects were asked to identify the number which was embedded in the pattern of colored dots. Both experiments support the Lyon hypothesis in that female carriers were found to have more difficulty in perceiving patterns of colored stimuli than did control subjects, and they suggest that the amount of time that a carrier has to scan colored stimuli plays an important role in her ability to accurately perceive them.