Parenting by individuals with fetal alcohol spectrum disorders and neurobehavioral outcomes in their offspring.

BACKGROUND: The neurobehavioral health impairments associated with prenatal alcohol exposure are now known to persist through adulthood. However, little is known about how these impairments affect individuals' parenting abilities and the neurobehavioral health of their offspring. This study compares parents with fetal alcohol spectrum disorder (FASD) with socioeconomically matched, nonexposed parents on measures of parenting and family support and assesses the neurobehavioral health of the children in both groups. METHODS: Forty-nine parent-child dyads were recruited from a longitudinal cohort of low socioeconomic status. Measures included the Parenting Styles and Dimensions Questionnaire, Family Support Scale, an in-depth psychosocial history, the Pediatric Symptom Checklist (PSC; parent and child reports), the Achenbach Child Behavior Checklist (CBCL), a screening psychiatric evaluation of the child, the NIH Toolbox Cognition Battery for Children, The Vineland Adaptive Behavior Scales-Third Edition caregiver rating form, and the Traumatic Events Screening Inventory (parent and child reports). RESULTS: Cognitive functioning was impaired for both offspring of parents with FASD ( x ¯ = 81.1, SD = 13.0) and control parents ( x ¯ = 79.9, SD = 16.1), but despite similar impairments, children of parents with FASD were less likely to have an Individualized Education Plan than controls. Adaptive functioning was adequate for both groups ( x ¯ = 92.1, SD = 15.4 in exposed vs. x ¯ = 94.3, SD = 12.3 in controls) and CBCL and PSC scores in both groups were within normal limits. Parents in both groups showed a predominantly authoritative parenting style. Despite a similar frequency of adverse childhood experiences in both groups, parents with FASD were less likely to recognize their child's adverse experiences. CONCLUSION: Parents with FASD display notable strengths including a predominantly authoritative parenting style. However, parents with FASD underrecognize child trauma and underutilize developmental services compared to socioeconomically matched controls, despite similar neurocognitive impairments. Impairments in adaptive functioning in parents with FASD may translate into difficulties with child-parent communication and limit both insight into neurobehavioral problems and advocacy skills. There is a need to identify and support parents with FASD to optimize their parenting abilities in the context of their individual strengths and difficulties.

Effectiveness of Psychotropic Medications in Children with Prenatal Alcohol and Drug Exposures: A Case Series and Model of Care.

Fetal Alcohol Spectrum Disorders affect up to 5% of the population, with additional children affected by prenatal drug exposures. The majority of these children display symptoms of ADHD and poor emotional dysregulation, a common reason for seeking psychiatric care. However, high prevalence of comorbid look-alike symptoms and limited availability of evidence-based treatments complicates psychiatric decision making in this population. The goal of the current study is to report on the effectiveness of psychotropic medications in a case series of 16 individuals with prenatal alcohol/drug exposure and propose a model for psychiatric care for this population. In addition to traditional subjective reports, an objective continuous performance test (T.O.V.A.®) was used to aid with guiding treatment. We found that T.O.V.A.®-scores improved on average from - 6.5 to - 2.9 with our psychiatric approach (p = 0.03). T.O.V.A.®-measurements were helpful in differentiating ADHD symptoms from comorbid symptoms and to guide decision-making on starting and changing medications.

Psychopharmacological Treatments in Children with Fetal Alcohol Spectrum Disorders: A Review.

Psychiatric symptoms in children with Fetal Alcohol Spectrum Disorders (FASD) present with high prevalence and morbidity, often across symptom domains, e.g. ADHD-like symptoms, emotional dysregulation and sleep problems. Polypharmacy is often used, but no empirically-based guidelines exist regarding optimal treatment for these children. Moreover, stimulant use in these children is controversial as their responsiveness may be different due to altered neural circuitry associated with prenatal alcohol exposure. The objective of this review is to give an overview of existing data on pharmacological treatments of neurobehavioral symptoms in FASD. Our literature review yielded limited and conflicting clinical data on the effectiveness of pharmacological treatments for psychiatric symptoms in children with FASD, with some symptom domains lacking data altogether. We emphasize the need for clinical trials to guide pharmacological treatments in this complex population.

The role of brain-derived neurotrophic factor in bone marrow stromal cell-mediated spinal cord repair.

The ability of intraspinal bone marrow stromal cell (BMSC) transplants to elicit repair is thought to result from paracrine effects by secreted trophic factors including brain-derived neurotrophic factor (BDNF). Here we used gene therapy to increase or silence BDNF production in BMSCs to investigate the role of BDNF in BMSC-mediated neuroprotection. In a spinal cord organotypic culture, BMSC-conditioned medium significantly enhanced spinal motoneuron survival by 64% compared with culture medium only. Only conditioned medium of BDNF-hypersecreting BMSCs sustained this neuroprotective effect. In a rat model of spinal cord contusion, a BDNF-dependent neuroprotective effect was confirmed; only with a subacute transplant of BDNF-hypersecreting BMSCs were significantly more spared motoneurons found at 4 weeks postinjury compared with vehicle controls. Spared nervous tissue volume was improved by 68% with both control BMSCs and BDNF-hypersecreting BMSCs. In addition, blood vessel density in the contusion with BDNF-hypersecreting BMSCs was 35% higher compared with BMSC controls and sixfold higher compared with vehicle controls. BDNF-silenced BMSCs did not survive the first week of transplantation, and no neuroprotective effect was found at 4 weeks after transplantation. Together, our data broaden our understanding of the role of BDNF in BMSC-mediated neuroprotection and successfully exploit BDNF dependency to enhance anatomical spinal cord repair.

The effect of a polyurethane-based reverse thermal gel on bone marrow stromal cell transplant survival and spinal cord repair.

Cell therapy for nervous tissue repair is limited by low transplant survival. We investigated the effects of a polyurethane-based reverse thermal gel, poly(ethylene glycol)-poly(serinol hexamethylene urethane) (ESHU) on bone marrow stromal cell (BMSC) transplant survival and repair using a rat model of spinal cord contusion. Transplantation of BMSCs in ESHU at three days post-contusion resulted in a 3.5-fold increase in BMSC survival at one week post-injury and a 66% increase in spared nervous tissue volume at four weeks post-injury. These improvements were accompanied by enhanced hindlimb motor and sensorimotor recovery. In vitro, we found that ESHU protected BMSCs from hydrogen peroxide-mediated death, resulting in a four-fold increase in BMSC survival with two-fold fewer BMSCs expressing the apoptosis marker, caspase 3 and the DNA oxidation marker, 8-oxo-deoxyguanosine. We argue that ESHU protected BMSCs transplanted is a spinal cord contusion from death thereby augmenting their effects on neuroprotection leading to improved behavioral restoration. The data show that the repair effects of intraneural BMSC transplants depend on the degree of their survival and may have a widespread impact on cell-based regenerative medicine.

Bone marrow stromal cell-mediated tissue sparing enhances functional repair after spinal cord contusion in adult rats.

Bone marrow stromal cell (BMSC) transplantation has shown promise for repair of the spinal cord. We showed earlier that a BMSC transplant limits the loss of spinal nervous tissue after a contusive injury. Here, we addressed the premise that BMSC-mediated tissue sparing underlies functional recovery in adult rats after a contusion of the thoracic spinal cord. Our results reveal that after 2 months BMSCs had elicited a significant increase in spared tissue volumes and in blood vessel density in the contusion epicenter. A strong functional relationship existed between spared tissue volumes and blood vessel density. BMSC-transplanted rats exhibited significant improvements in motor, sensorimotor, and sensory functions, which were strongly correlated with spared tissue volumes. Retrograde tracing revealed that rats with BMSCs had twice as many descending brainstem neurons with an axon projecting beyond the contused spinal cord segment and these correlated strongly with the improved motor/sensorimotor functions but not sensory functions. Together, our data indicate that tissue sparing greatly contributes to BMSC-mediated functional repair after spinal cord contusion. The preservation/formation of blood vessels and sparing/regeneration of descending brainstem axons may be important mediators of the BMSC-mediated anatomical and functional improvements.

Stem cells for central nervous system repair and rehabilitation.

The central nervous system (CNS) has limited capacity for self-repair. Current treatments are often incapable of reversing the debilitating effects of CNS diseases that result in permanent and/or progressive physical and cognitive impairments. One promising repair strategy is transplantation of stem cells, which can potentially replace lost neurons and/or glia or promote repair through secretion of trophic factors. Various types of stem cells exist, each with their own advantages and disadvantages. Although no consensus exists regarding the optimal cell type to use, moderate functional improvements have been shown in animal models of CNS diseases using different types of stem cells. However, the precise mechanism of action behind their beneficial effects remains unknown. In addition, many barriers to clinical use still need to be resolved before transplantation of stem cells can be used as effective biologics. These barriers include--depending on the stem cell type--possible tumor formation, difficulty with harvest, limited in vivo differentiation and integration, and ethical issues regarding use.

Reducing macrophages to improve bone marrow stromal cell survival in the contused spinal cord.

We tested whether reducing macrophage infiltration would improve the survival of allogeneic bone marrow stromal cells (BMSC) transplanted in the contused adult rat thoracic spinal cord. Treatment with cyclosporine, minocycline, or methylprednisolone all resulted in a significant decrease in macrophage infiltration at 3 days postinjury. However, when BMSC were injected at that time point, survival 7 days later was similar between treatment groups and saline-injected controls. In fact, we found that the presence of BMSC resulted in a significant increase in macrophage infiltration into the contusion.

Bone marrow stromal cells elicit tissue sparing after acute but not delayed transplantation into the contused adult rat thoracic spinal cord.

Bone marrow stromal cells (BMSC) transplanted into the contused spinal cord may support repair by improving tissue sparing. We injected allogeneic BMSC into the moderately contused adult rat thoracic spinal cord at 15 min (acute) and at 3, 7, and 21 days (delayed) post-injury and quantified tissue sparing and BMSC survival up to 4 weeks post-transplantation. BMSC survival within the contusion at 7 days post-transplantation was significantly higher with an acute injection (32%) and 3-day delayed injection (52%) than with a 7- or 21-day delayed injection (9% both; p < 0.01). BMSC survival at 28 days post-transplantation was close to 0 in all paradigms, indicating rejection. In contused rats without a BMSC transplant (controls), the volume of spared tissue gradually decreased until 46% (p < 0.001) of the volume of a comparable uninjured spinal cord segment at 49 days post-injury. In rats with BMSC, injected at 15 min, 3, or 7 days post-injury, spared tissue volume was significantly higher in grafted rats than in control rats at the respective endpoints (i.e., 28, 31, and 35 days post-injury). Acute and 3-day delayed but not 7- and 21-day delayed injection of BMSC significantly improved tissue sparing, which was strongly correlated (r = 0.79-1.0) to BMSC survival in the first week after injection into the contusion. Our data showed that neuroprotective effects of BMSC transplanted into a moderate rat spinal cord contusion depend strongly on their survival during the first week post-injection. Acutely injected BMSC elicit more tissue sparing than delayed injected BMSC.