Faculty Bibliography

OBJECTIVE: To examine the persistence of parent-reported social-emotional and behavioral problems in infants and toddlers. METHOD: The sample comprised 1,082 children ascertained from birth records. Children were 12 to 40 months old in year 1 (1998-1999) and 23 to 48 months old in year 2 (1999-2000). Eighty percent participated in year 1 and 91% were retained in year 2. Social-emotional and behavioral problems were measured by high scores (> or=90th percentile) on the Internalizing, Externalizing, and/or Dysregulation domains of the Infant-Toddler Social and Emotional Assessment (ITSEA). Parents reported on sociodemographic factors, family life impairment, parenting stress, and family functioning. RESULTS: Among children with any high ITSEA domain score in year 1, 49.9% had persistent psychopathology, as indicated by the continued presence of a high score in year 2. In multivariate analyses, persistence was significantly more likely when parents reported co-occurring problems (i.e., problems in multiple ITSEA domains), high family life disruption, and high parenting distress in year 1. Homotypic persistence rates (i.e., same domain persistence) ranged from 38% to 50%. Only for dysregulation was homotypic persistence greater when co-occurring problems were present than for dysregulation alone. Persistence patterns were similar for boys and girls. CONCLUSION: Findings indicate that infant-toddler social-emotional/behavioral problems are not transient and highlight the need for early identification, multidomain and family assessment, and effective early intervention.

Emerging evidence suggests that individuals who receive morphine while hospitalized demonstrate a decrease in symptoms of posttraumatic stress disorder (PTSD). However, the mechanisms of effects are not yet well understood. The goal of the current study was to examine three possible mediators for this effect. Sixty-one injured (burns, motor vehicle accidents, falls, and assaults) children were assessed during hospitalization and again 3 months post discharge. Assessment included acute and follow-up child report measures of pain, PTSD, and anxiety symptoms, as well as a medical record review for medication administration and pulse during hospitalization. Pathway analyses were conducted to test the potential mediating roles of pain reduction, noradrenergic attenuation, and separation anxiety on the association between morphine and PTSD. Results suggest that a reduction in separation anxiety may mediate the association between morphine administration and PTSD symptom reduction at 3 months. These findings have implications for our understanding of morphine's effects on psychological functioning following an acute injury and for direct clinical care

Slow oscillations originating in the prefrontal neocortex during slow-wave sleep (SWS) group neuronal network activity and thereby presumably support the consolidation of memories. Here, we investigated whether the grouping influence of slow oscillations extends to hippocampal sharp wave-ripple (SPW) activity thought to underlie memory replay processes during SWS. The prefrontal surface EEG and multiunit activity (MUA), along with hippocampal local field potentials (LFP) from CA1, were recorded in rats during sleep. Average spindle and ripple activity and event correlation histograms of SPWs were calculated, time-locked to half-waves of slow oscillations. Results confirm decreased prefrontal MUA and spindle activity during EEG slow oscillation negativity and increases in this activity during subsequent positivity. A remarkably close temporal link was revealed between slow oscillations and hippocampal activity, with ripple activity and SPWs being also distinctly decreased during negative half-waves and increased during slow oscillation positivity. Fine-grained analyses of temporal dynamics revealed for the slow oscillation a phase delay of approximately 90 ms with reference to up and down states of prefrontal MUA, and of only approximately 60 ms with reference to changes in SPWs, indicating that up and down states in prefrontal MUA precede corresponding changes in hippocampal SPWs by approximately 30 ms. Results support the notion that the depolarizing surface-positive phase of the slow oscillation and the associated up state of prefrontal excitation promotes hippocampal SPWs via efferent pathways. The preceding disfacilitation of hippocampal events temporally coupled to the negative slow oscillation half-wave appears to serve a synchronizing role in this neocorticohippocampal interplay

OBJECTIVE: This study examined whether outcomes in housing, clinical status, and well-being of persons with severe mental illness and a history of homelessness differ between those in supported housing and those in community residences, two housing arrangements that substantially differ in the level of independence that is offered to its tenants. METHODS: A quasi-experimental 18-month follow-up study was conducted with 157 persons newly entering supported housing and community residences. The housing models accepted persons with similar illness characteristics and homelessness histories, so that the inability to randomly assign tenants to housing types could be compensated for by propensity scoring methods. Tenure in housing was examined by using survival models. Analyses of other outcomes used hierarchical linear and regression models in both intent-to-treat (N=139) and true-stayer (N=80) analyses. RESULTS: Tenure in housing did not differ by housing type. Substantial proportions of tenants in both models remained housed during the follow-up period. Tenants in supported housing reported greater housing satisfaction in terms of autonomy and economic viability. Over time some tenants in supported housing reported greater feelings of isolation. Independent of housing type, symptoms of depression or anxiety at housing entry increased the risk of poorer outcomes. CONCLUSIONS: The models of supported housing were viable portals of entry into community housing for homeless persons, even for consumers with characteristics indicating that they would have been more likely to be placed in community residences. The results suggest that greater clinical attention should be paid to persons who exhibit depression or anxiety when entering housing

CONTEXT: The first 2 independent linkage studies for obsessive-compulsive disorder (OCD) identified a region on 9p24 with suggestive evidence for linkage. The glutamate transporter gene solute carrier family 1, member 1 (SLC1A1) is a promising functional candidate in this region because altered glutamatergic concentrations have been found in the striatum and anterior cingulate in neuroimaging studies of pediatric OCD. OBJECTIVE: To determine whether genotypes at polymorphisms in the SLC1A1 gene region are associated with early-onset OCD. DESIGN: Family-based analysis of association using the transmission disequilibrium test, confirmed using the family-based association test. SETTING: Anxiety disorders program in an academic medical center. PARTICIPANTS: Seventy-one probands with DSM-III-R or DSM-IV OCD and their parents. METHODS: Nine single nucleotide polymorphisms spaced throughout the SLC1A1 gene region were genotyped. RESULTS: Significant association was detected at rs3780412 (P = .04) and rs301430 (P = .03), 2 common adjacent single nucleotide polymorphisms in the 3' region of SLC1A1. Analysis by sex revealed that association at rs3780412 was limited to male probands (P = .002). Significant association was also detected for the T/C haplotype at rs301430-rs301979 (P = .03), the only haplotype block identified among the 9 single nucleotide polymorphisms. Analysis by sex also revealed that the haplotype association was limited to male probands (P = .003). A deletion in the 3' flanking region of SLC1A1 was also detected that imperfectly segregated with OCD in a large, multigenerational family with multiple affected individuals. CONCLUSIONS: The 3' region of SLC1A1 may contain a susceptibility allele for early-onset OCD, with differential effects in males and females. The results also provide further support for the involvement of a glutamatergic dysfunction in the pathogenesis of early-onset OCD

Gender differences for adolescents in residential care were examined for a sample of 2,067 youths in a large residential facility. At admission, female youths were more troubled than male youths, as shown in significantly higher Diagnostic Interview Schedule for Children (DISC) diagnoses and comorbidity rates, higher internalizing and externalizing Child Behavior Checklist scores, and significantly higher Suicide Prevention Scale hopelessness, negative self-evaluation, and suicide ideation scores. Girls had higher rates of depressive and anxiety diagnoses on the DISC at both admission and 1 year. Both genders demonstrated significant reductions in both externalizing and internalizing problem behaviors over the first year in the program. Girls had significantly higher rates of internalizing problem behavior but showed a significantly greater reduction in these behaviors than did boys. At departure, girls were rated as being more successful than boys by clinical staff. Youths did not differ by gender in their behavior on a 6-month follow-up success scale. Implications for prioritizing research addressing the needs of female adolescents in residential care are discussed

BACKGROUND: Divalproex (DVP) and oxcarbazepine (OXC) are used to treat pediatric bipolar disorder (PBPD) with severe aggression but these agents have not been compared in head to head trials. METHODS: Electronic medical records were reviewed for those (age < 18) who received DVP (n = 20) or OXC (n = 11) for the treatment of PBPD with severe aggression. Change in prospectively rated Clinical Global Impressions-Severity (CGI-S) scores that measured global improvement of mental illness from baseline and rates of discontinuation due to adverse effects at approximately 4 months were the primary outcomes. CGI-S specific to aggression (CGI-Ag-S), which was rated retrospectively and blinded to treatment, was a secondary outcome. RESULTS: Greater reduction in CGI-S scores occurred with DVP compared with OXC at 4 months (p = 0.007). Both CGI-S and CGI-Ag-S scores improved significantly from baseline to the 4-month timepoint with DVP but not OXC. There were no significant differences in weight changes between the groups. Rates of discontinuation due to adverse events were similar. However, more discontinuations due to worsening aggression occurred with OXC (DVP 0%, OXC 27.3%, p = 0.037). More patients receiving DVP had a decrease of 1 point or more on the CGI-S and had not discontinued due to adverse events as of the patient's last recorded visit on the index medication (DVP 13 (65%), OXC 2 (18%), p = 0.023). CONCLUSIONS: OXC appeared less effective than DVP for PBPD with aggression in this study. Limitations included the small sample size and the open, nonrandomized, retrospective study design. Future prospective, double-blind studies are warranted to determine the place of OXC in the treatment of PBPD.

OBJECTIVE: This longitudinal study examined whether responsiveness of the neurotransmitter serotonin (5-HT) in childhood predicts adolescent aggression. METHOD: Boys (N = 33) with disruptive behavior disorders who received assessments of central 5-HT function via the prolactin response to fenfluramine between 1990 and 1994 when they were 7 to 11 years old were re-evaluated clinically on average 6.7 years later. RESULTS: After accounting for baseline aggression, early 5-HT function accounted for a significant proportion of variance in adolescent aggression. This prospective relationship of childhood 5-HT function with adolescent aggression (r = -0.71) and antisocial behavior (r = -0.59) was found primarily in adolescents who were aggressive during childhood. Irrespective of childhood aggression, no child with high 5-HT function was particularly aggressive at follow-up. CONCLUSIONS: Low childhood 5-HT function appears important, but not sufficient, for the emergence of adolescent aggression. However, early high 5-HT function may protect against adolescent violence and aggression.

Rat pups must learn maternal odor to support attachment behaviors, including nursing and orientation toward the mother. Neonates have a sensitive period for rapid, robust odor learning characterized by increased ability to learn odor preferences and decreased ability to learn odor aversions. Specifically, odor-0.5 mA shock association paradoxically causes an odor preference and coincident failure of amygdala activation in pups until postnatal day 10 (P10). Because sensitive-period termination coincides with a declining 'stress hyporesponsive period' when corticosterone release is attenuated, we explored the role of corticosterone in sensitive-period termination. Odor was paired with 0.5 mA shock in either sensitive-period (P8) or postsensitive-period (P12) pups while manipulating corticosterone. We then assessed preference/aversion learning and the olfactory neural circuitry underlying its acquisition. Although sensitive-period control paired odor-shock pups learned an odor preference without amygdala participation, systemic (3 mg/kg, i.p.; 24 h and 30 min before training) or intra-amygdala corticosterone (50 or 100 ng; during training) permitted precocious odor-aversion learning and evoked amygdala neural activity similar to that expressed by older pups. In postsensitive-period (P12) pups, control paired odor-shock pups showed an odor aversion and amygdala activation, whereas corticosterone-depleted (adrenalectomized) paired odor-shock pups showed odor-preference learning and activation of an odor learning circuit characteristic of the sensitive period. Intra-amygdala corticosterone receptor antagonist (0.3 ng; during training) infused into postsensitive-period (P12) paired odor-shock pups also showed odor-preference learning. These results suggest corticosterone is important in sensitive-period termination and developmental emergence of olfactory fear conditioning, acting via the amygdala as a switch between fear and attraction. Because maternal stimulation of pups modulates the pups' endogenous corticosterone, this suggests maternal care quality may alter sensitive-period duration