Faster Serotonin Clearance in CA3 Region of Hippocampus and Antidepressant-like Effect of Decynium-22 in Juvenile Mice Are Putatively Linked to Increased Plasma Membrane Monoamine Transporter Function: Implications for Efficacy of Antidepressants in Juveniles.

Selective serotonin reuptake inhibitors (SSRIs) are less efficacious in treating depression in children than in adults. SSRIs block serotonin uptake via the high-affinity, low-capacity serotonin transporter. However, the low-affinity, high-capacity organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT) are emerging as important players in serotonin uptake. We hypothesized that OCT3 and/or PMAT are functionally upregulated in juveniles, thereby buffering SSRIs' ability to enhance serotonergic neurotransmission. Unlike in adult mice, we found the OCT/PMAT blocker, decynium-22, to have standalone antidepressant-like effects in juveniles. Using in vivo high-speed chronoamperometry, we found that juveniles clear serotonin from the CA3 region of the hippocampus ~2-fold faster than adult mice. Cell density did not differ between ages, suggesting that faster serotonin clearance in juveniles is unrelated to faster diffusion through the extracellular matrix. Western blot and immunohistochemistry showed that juvenile mice have modestly greater expression of PMAT than adults, whereas OCT3 expression in the CA3 region of the hippocampus was similar between ages. Together, these data suggest that faster serotonin clearance and antidepressant-like effects of decynium-22 in juvenile mice may be due to functionally upregulated PMAT. Faster serotonin clearance via PMAT in juveniles may contribute to reduced therapeutic efficacy of SSRIs in children relative to adults.

Misdiagnosis and missed diagnoses in foster and adopted children with prenatal alcohol exposure.

OBJECTIVE: The purpose of this article is to assess the rate of misdiagnosis and missed diagnoses of fetal alcohol spectrum disorders (FASD) among a population of foster and adopted youth referred to a children's mental health center. METHODS: Data were collected from a sample of 547 children who underwent a comprehensive multidisciplinary diagnostic evaluation. Utilizing current diagnostic criteria, children were diagnosed, as appropriate, with fetal alcohol syndrome, partial fetal alcohol syndrome, alcohol-related neurodevelopmental disorder, or alcohol-related birth defects. Changes in rates of alcohol exposure-related diagnoses and cooccurring mental health disorders pre- and postassessment were analyzed by using McNemar's test for dependent proportions. RESULTS: Among 156 children and adolescents who met criteria for a diagnosis within the fetal alcohol spectrum, 125 had never been diagnosed as affected by prenatal alcohol exposure, a missed diagnosis rate of 80.1%. Of the 31 who had been recognized before referral as affected by prenatal alcohol exposure, 10 children's FASD diagnoses were changed within the spectrum, representing a misdiagnosis rate of 6.4%. The remaining 21 (13.5%) children's diagnoses stayed the same. There also were significant changes in the rate of mental health diagnosis, and learning disorders, communication disorders, and intellectual disability, objective signs of neurocognitive damage, were not recognized in a significant number of children with FASD. CONCLUSIONS: Within this clinical sample, 86.5% of youth with FASD had never been previously diagnosed or had been misdiagnosed. These high rates of missed diagnoses and misdiagnosis have significant implications for intervention and therapeutic services.

Mental Health Disorders among Children within Child Welfare who have Prenatal Substance Exposure: Rural vs. Urban Populations.

This study analyzed differences in mental health diagnoses among Illinois child welfare-involved youth who have had prenatal substance exposure. Results indicate that youth from the rural area had a significantly higher rate of co-occurring mental health disorders. A multiple regression analysis revealed five significant predictors: living in a rural area, a history of neglect, having Fetal Alcohol Syndrome or an alcohol-related neurodevelopmental disorder, and age. These results have implications for adapting existing treatment models.

Neurocognitive habilitation therapy for children with fetal alcohol spectrum disorders: an adaptation of the Alert Program®.

OBJECTIVE: This study evaluated the effectiveness of neurocognitive habilitation, a group therapy intervention for foster and adoptive caregivers and their children who were prenatally exposed to alcohol. METHOD: Participants were recruited from clients seeking evaluation for fetal alcohol syndrome (FAS) and alcohol-related neurodevelopmental disorder (ARND) and were randomly assigned to treatment and no-treatment control groups. Forty children participated in the treatment program and were compared with 38 control participants using the Behavior Rating Inventory of Executive Function (BRIEF) and the Roberts Apperception Test for Children (RATC). RESULTS: Significant differences between the treatment and control groups were demonstrated on the BRIEF and on the RATC, suggesting that the intervention improved executive functioning and emotional problem-solving skills. CONCLUSION: These findings yield promising evidence of the effectiveness of the neurocognitive habilitation intervention in improving executive functioning and emotional problem solving in children with FAS or ARND.

Neurodevelopmental functioning in children with FAS, pFAS, and ARND.

OBJECTIVE: The purpose of this article is to compare the neurodevelopmental profiles of 78 foster and adopted children with fetal alcohol syndrome (FAS), partial FAS (pFAS), or alcohol-related neurodevelopmental disorder (ARND). METHOD: Seventy-eight foster and adopted children underwent a comprehensive diagnostic evaluation. By using criteria more stringent than those required by current guidelines, the children were placed in 1 of 3 diagnostic categories: FAS, pFAS, or ARND. Each child was evaluated across the domains of neuropsychological functioning most frequently affected by prenatal exposure to alcohol. Multivariate analyses of variance were conducted to examine differences in neuropsychological functioning between the 3 diagnostic groups. Descriptive discriminant analyses were performed in follow-up to the multivariate analyses of variance. RESULTS: The children in the 3 diagnostic categories were similar for descriptive and child welfare variables. Children with FAS had significantly decreased mean weight, height, and head circumference. Children with FAS exhibited the most impaired level of general intelligence, significantly worse language-based memory compared with children with ARND, and significantly poorer functional communication skills than children with pFAS. On executive functioning, the FAS group of children performed significantly worse on sequencing and shift than either the pFAS or ARND groups. Children with pFAS and ARND were similar in all neurodevelopmental domains that were tested. CONCLUSION: The children who met tightly defined physical criteria for a diagnosis of FAS demonstrated significantly poorer neurodevelopmental functioning than children with pFAS and ARND. Children in these latter 2 groups were similar in all neurodevelopmental domains that were tested.

The role of perceptual bias in complex figure recall.

Several studies have demonstrated that constructional and organizational abilities affect how well visual stimuli are remembered. The purpose of the present study was to determine whether perceptual bias, independent of constructional ability, influenced visual memory performance. Participants were 118 normal adults who were administered the Rey-Osterrieth Complex Figure (ROCF) and a similarity judgement task requiring then to decide which of two hierarchically constructed comparison figures most resemble a standard figure. The initial steps of a multiple regression analysis indicated that delayed recall of the ROCF was directly related to copy accuracy, inversely related to age, and better in males than females. In the final step of the regression model, performance on the similarity judgement task also predicted ROCF recall, with a more global perceptual bias predicting better recall. Results indicate that even when copy accuracy and demographic variables are accounted for, components of visual perception influence how well visual stimuli are encoded and recalled. Findings are consistent with research correlating global processing and spatial ability, and suggest that in addition to copy ability and organization, visuoperceptual bias must be considered as a moderator variable when interpreting performance as a visual memory test.