Infants later diagnosed with autism have lower canonical babbling ratios in the first year of life.

BACKGROUND: Canonical babbling-producing syllables with a mature consonant, full vowel, and smooth transition-is an important developmental milestone that typically occurs in the first year of life. Some studies indicate delayed or reduced canonical babbling in infants at high familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis, but evidence is mixed. More refined characterization of babbling in the first year of life in infants with high likelihood for ASD is needed. METHODS: Vocalizations produced at 6 and 12 months by infants (n = 267) taking part in a longitudinal study were coded for canonical and non-canonical syllables. Infants were categorized as low familial likelihood (LL), high familial likelihood diagnosed with ASD at 24 months (HL-ASD) or not diagnosed (HL-Neg). Language delay was assessed based on 24-month expressive and receptive language scores. Canonical babble ratio (CBR) was calculated by dividing the number of canonical syllables by the number of total syllables. Generalized linear (mixed) models were used to assess the relationship between group membership and CBR, controlling for site, sex, and maternal education. Logistic regression was used to assess whether canonical babbling ratios at 6 and 12 months predict 24-month diagnostic outcome. RESULTS: No diagnostic group differences in CBR were detected at 6 months, but HL-ASD infants produced significantly lower CBR than both the HL-Neg and LL groups at 12 months. HL-Neg infants with language delay also showed reduced CBR at 12 months. Neither 6- nor 12-month CBR was significant predictors of 24-month diagnostic outcome (ASD versus no ASD) in logistic regression. LIMITATIONS: Small numbers of vocalizations produced by infants at 6 months may limit the reliability of CBR estimates. It is not known if results generalize to infants who are not at high familial likelihood, or infants from more diverse racial and socioeconomic backgrounds. CONCLUSIONS: Lower canonical babbling ratios are apparent by the end of the first year of life in ASD regardless of later language delay, but are also observed for infants with later language delay without ASD. Canonical babbling may lack specificity as an early marker when used on its own.

Genetic counseling as preventive intervention: toward individual specification of transgenerational autism risk.

BACKGROUND: Although autism spectrum disorders (ASD) are among the most heritable of all neuropsychiatric syndromes, most affected children are born to unaffected parents. Recently, we reported an average increase of 3-5% over general population risk of ASD among offspring of adults who have first-degree relatives with ASD in a large epidemiologic family sample. A next essential step is to investigate whether there are measurable characteristics of individual parents placing them at higher or lower recurrence risk, as this information could allow more personalized genetic counseling. METHODS: We assembled what is to our knowledge the largest collection of data on the ability of four measurable characteristics of unaffected prospective parents to specify risk for autism among their offspring: (1) sub clinical autistic trait burden, (2) parental history of a sibling with ASD, (3) transmitted autosomal molecular genetic abnormalities, and (4) parental age. Leveraging phenotypic and genetic data in curated family cohorts, we evaluate the respective associations between these factors and child outcome when autism is present in the family in the parental generation. RESULTS: All four characteristics were associated with elevation in offspring risk; however, the magnitude of their predictive power-with the exception of isolated rare inherited pathogenic variants -does not yet reach a threshold that would typically be considered actionable for reproductive decision-making. CONCLUSIONS: Individual specification of risk to offspring of adults in ASD-affected families is not straightforwardly improved by ascertainment of parental phenotype, and it is not yet clear whether genomic screening of prospective parents in families affected by idiopathic ASD is warranted as a clinical standard. Systematic screening of affected family members for heritable pathogenic variants, including rare sex-linked mutations, will identify a subset of families with substantially elevated transmission risk. Polygenic risk scores are only weakly predictive at this time but steadily improving and ultimately may enable more robust prediction either singly or when combined with the risk variables examined in this study.

Hallux Pronation in Hallux Valgus: Experimental and Radiographic Study.

Toe pronation is a frequent sign in hallux valgus (HV), but it is difficult to assess and quantify. The aim of this study was to evaluate the relation between big toe pronation with both radiological and clinical findings and to determine if toe pronation is an influential factor in severity of HV. Six big toe donor proximal phalanges were used to create a radiographic calibrating system controlling their pronation at 0° to 60°. A linear regression model was used to predict proximal phalanx pronation in radiographs. Big toe pronation in HV was clinically evaluated with a prospective study using 132 patients from our surgical waiting list and a control group of 30 patients without HV. Patients standing barefoot on a rigid platform were used to obtain the nail-floor angle. We obtained the following angles: HV, intermetatarsal, interphalangeal, distal articular set angle, proximal articular set angle, first metatarsal pronation, proximal phalanx pronation, and sesamoid bones displacement. We obtained an equation to predict proximal phalanx pronation according to the proportion of the rotated phalanx (p < .001, r = 0.98), and used an intraclass reliability test to assess the intra-/interobserver reliability (p < .001, intraclass correlation [ICC] = 0.89/p < .001, ICC = 0.82). We found that the relation between HV severity and proximal phalanx pronation, nail-floor angle, and first metatarsal pronation was statistically significant (p < .0001, r = 0.64). Proximal phalanx pronation and nail-floor angle should be considered to classify the severity of HV. Using a mathematical formula, we can predict proximal phalanx pronation on radiographs. Clinical Level of Evidence.

Language delay aggregates in toddler siblings of children with autism spectrum disorder.

BACKGROUND: Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype. METHODS: We implemented two approaches: (1) a meta-analysis of studies comparing language delay, a categorical indicator of language function, and language scores, a continuous metric, in unaffected toddlers at high and low familial risk for ASD, and (2) a parallel analysis of 350 unaffected 24-month-olds in the Infant Brain Imaging Study (IBIS), a prospective study of infants at high and low familial risk for ASD. An advantage of the former was its detection of group differences from pooled data across unique samples; an advantage of the latter was its sensitivity in quantifying early manifestations of language delay while accounting for covariates within a single large sample. RESULTS: Meta-analysis showed that high-risk siblings without ASD (HR-noASD) were three to four times more likely to exhibit language delay versus low-risk siblings without ASD (LR-noASD) and had lower mean receptive and expressive language scores. Analyses of IBIS data corroborated that language delay, specifically receptive language delay, was more frequent in the HR-noASD (n = 235) versus LR-noASD group (n = 115). IBIS language scores were continuously and unimodally distributed, with a pathological shift towards decreased language function in HR-noASD siblings. The elevated inherited risk for ASD was associated with lower receptive and expressive language scores when controlling for sociodemographic factors. For receptive but not expressive language, the effect of risk group remained significant even when controlling for nonverbal cognition. CONCLUSIONS: Greater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms.

Increased Extra-axial Cerebrospinal Fluid in High-Risk Infants Who Later Develop Autism.

BACKGROUND: We previously reported that infants who developed autism spectrum disorder (ASD) had increased cerebrospinal fluid (CSF) in the subarachnoid space (i.e., extra-axial CSF) from 6 to 24 months of age. We attempted to confirm and extend this finding in a larger independent sample. METHODS: A longitudinal magnetic resonance imaging study of infants at risk for ASD was carried out on 343 infants, who underwent neuroimaging at 6, 12, and 24 months. Of these infants, 221 were at high risk for ASD because of an older sibling with ASD, and 122 were at low risk with no family history of ASD. A total of 47 infants were diagnosed with ASD at 24 months and were compared with 174 high-risk and 122 low-risk infants without ASD. RESULTS: Infants who developed ASD had significantly greater extra-axial CSF volume at 6 months compared with both comparison groups without ASD (18% greater than high-risk infants without ASD; Cohen's d = 0.54). Extra-axial CSF volume remained elevated through 24 months (d = 0.46). Infants with more severe autism symptoms had an even greater volume of extra-axial CSF from 6 to 24 months (24% greater at 6 months, d = 0.70; 15% greater at 24 months, d = 0.70). Extra-axial CSF volume at 6 months predicted which high-risk infants would be diagnosed with ASD at 24 months with an overall accuracy of 69% and corresponding 66% sensitivity and 68% specificity, which was fully cross-validated in a separate sample. CONCLUSIONS: This study confirms and extends previous findings that increased extra-axial CSF is detectable at 6 months in high-risk infants who develop ASD. Future studies will address whether this anomaly is a contributing factor to the etiology of ASD or an early risk marker for ASD.

Accuracy of ultrasound in the diagnosis of acute cholecystitis with coexistent acute pancreatitis.

PURPOSE: Acute cholecystitis and pancreatitis are acute forms of cholecystolithiasis. The presence of acute cholecystitis can lead to important changes in therapy in the early course of acute pancreatitis. The aim of this study was to identify the accuracy of ultrasonography in diagnosing acute cholecystitis with coexistent acute pancreatitis. METHODS: Subjects were all those patients admitted to our hospital with a diagnosis of acute pancreatitis between 1998 and 2015 who underwent cholecystectomy within 15 days of the ultrasonography performed on admittance. Patient data were analyzed retrospectively to compare the ultrasound findings with the pathological findings of the resected gallbladders. Patients were allocated to two groups according to the signs of acute cholecystitis on ultrasonography: group 1 negative and group 2 positive. RESULTS: One hundred and twenty patients were enrolled in the study: 77 in group 1 and 43 in group 2. Similar results were found for the two groups with respect to the pathological diagnosis of acute cholecystitis, i.e., 31.2 % for group 1 and 27.9 % for group 2. Analysis indicated that there was no correlation between the ultrasonography data and pathological findings (p = 0.708). CONCLUSIONS: On the basis of our study, ultrasound findings alone cannot be used to accurately diagnose acute cholecystitis in the setting of acute pancreatitis.

In vivo bactericidal efficacy of farnesol on Ti6Al4V implants. / Eficacia bactericida in vivo del farnesol sobre implantes de Ti6Al4V.

OBJECTIVE: To evaluate the in vivo anti-staphylococcal bactericidal activity of farnesol on Ti6Al4V surfaces. MATERIAL AND METHODS: An experimental model of infection in biomaterials was developed by inoculation of Staphylococcus aureus ATCC 29213 into the canal of both femurs of 15 Wistar rats. A Ti6Al4V pin impregnated with 30mM of farnesol was inserted into study femur, and a Ti6Al4V control was inserted into the control femur. To evaluate the bactericidal efficacy, a comparison was made between the median of the colony forming units recovered after inoculation in the study group and the control group for different times of euthanasia and inoculum size. RESULTS: The median expressed as Log10 CFU counts obtained with farnesol titanium pin was 4.26, and in control group, it was 4.86, which was statistically significant (P=.001) on applying the Student t test for related samples. The median reduction obtained in farnesol pins relative to the control was 74%. CONCLUSIONS: Treatment with farnesol 30mM on Ti6Al4V pins appears to decrease the rate of colonisation by Staphylococcus aureus.

Quantitative autistic traits ascertained in a national survey of 22 529 Japanese schoolchildren.

OBJECTIVE: Recent epidemiologic studies worldwide have documented a rise in prevalence rates for autism spectrum disorders (ASD). Broadening of diagnostic criteria for ASD may be a major contributor to the rise in prevalence, particularly if superimposed on an underlying continuous distribution of autistic traits. This study sought to determine the nature of the population distribution of autistic traits using a quantitative trait measure in a large national population sample of children. METHOD: The Japanese version of the Social Responsiveness Scale (SRS) was completed by parents on a nationally representative sample of 22 529 children, age 6-15. RESULTS: Social Responsiveness Scale scores exhibited a skewed normal distribution in the Japanese population with a single-factor structure and no significant relation to IQ within the normal intellectual range. There was no evidence of a natural 'cutoff' that would differentiate populations of categorically affected children from unaffected children. CONCLUSION: This study provides evidence of the continuous nature of autistic symptoms measured by the SRS, a validated quantitative trait measure. The findings reveal how paradigms for diagnosis that rest on arbitrarily imposed categorical cutoffs can result in substantial variation in prevalence estimation, especially when measurements used for case assignment are not standardized for a given population.

[Ileocolic intussusception in an adult caused by inverted Meckel's diverticulum]. / Intususcepción ileocólica en un adulto causado por divertículo de Meckel invertido.

Meckel's diverticulum is the most common congenital abnormality of the gastrointestinal tract. It is found in 2.00% of the population and is more frequent in children. Invagination is an unusual complication that can cause secondary intestinal intussusception. This event is extremely rare and only a few cases have been reported. We present the case of a 19-year-old male who presented with chronic abdominal pain and weight loss of 23 Kg 6 months prior to hospital admittance. The last episode manifested as intense abdominal pain, nausea, vomiting, and diarrhea with a 6-hour progression. Imaging studies established the diagnosis of bowel obstruction and ileocolic intussusception. Laparotomy with ileocolic resection was performed without reducing the intussusception. The histopathologic study reported inverted Meckel's diverticulum at the base of the ileocolic intussusception. Intestinal intussusception in adults, secondary to inverted Meckel's diverticulum is rare and should be considered in the differential diagnosis of patients presenting with abdominal pain and bowel obstruction.

Distribution of electromechanical delay in the heart: insights from a three-dimensional electromechanical model.

In the intact heart, the distribution of electromechanical delay (EMD), the time interval between local depolarization and myocyte shortening onset, depends on the loading conditions. The distribution of EMD throughout the heart remains, however, unknown because current experimental techniques are unable to evaluate three-dimensional cardiac electromechanical behavior. The goal of this study was to determine the three-dimensional EMD distributions in the intact ventricles for sinus rhythm (SR) and epicardial pacing (EP) by using a new, to our knowledge, electromechanical model of the rabbit ventricles that incorporates a biophysical representation of myofilament dynamics. Furthermore, we aimed to ascertain the mechanisms that underlie the specific three-dimensional EMD distributions. The results revealed that under both conditions, the three-dimensional EMD distribution is nonuniform. During SR, EMD is longer at the epicardium than at the endocardium, and is greater near the base than at the apex. After EP, the three-dimensional EMD distribution is markedly different; it also changes with the pacing rate. For both SR and EP, late-depolarized regions were characterized with significant myofiber prestretch caused by the contraction of the early-depolarized regions. This prestretch delays myofiber-shortening onset, and results in a longer EMD, giving rise to heterogeneous three-dimensional EMD distributions.

Optical properties and application of a reactive and bioreducible thiol-containing tetramethylrhodamine dimer.

Thiolated dimeric tetramethylrhodamine (TAMRA) was synthesized in a straightforward procedure utilizing commercially available 5(6)-succinimidyl TAMRA and cystamine hydrochloride. The thiol-containing TAMRA dimer displayed distinct spectral properties in reduced and oxidized forms; covalent dimer formation produced greater effects on the spectral properties than previously reported for noncovalent TAMRA dimers or dimers formed with shorter carbon spacers. The resulting TAMRA disulfide dimer exhibited a hypsochromic shift of 34 nm relative to the reduced monomer species and an isosbestic point at 532 nm between reduced monomeric and oxidized dimeric forms. Molar extinction coefficients of the monomer and dimer relative to moles of TAMRA were similar (6.61 x 10(4) M(-1) cm(-1) and 6.42 x 10(-4) M(-1) cm(-1), respectively). However, fluorescence emission was altered with >93% of dye fluorescence quenched in phosphate buffered saline upon dimer formation. A 520:554 nm absorbance intensity ratio of 2.64 was observed for the oxidized ssTAMRA dimer, almost twice as high as values reported for noncovalent TAMRA dimers. The resulting disulfide dye was easily reduced using both soluble and agarose gel immobilized tris(2-carboxyethyl) phosphine and fresh cell lysate from cultured RAW 264.7 macrophage cells. Absorbance intensity ratios at 554 and 520 nm were used to determine the oxidation half-life of a 1.2 x 10(-5) M solution of reduced TAMRA stored in ambient atmosphere to be approximately 50 h at 22 degrees C. The free thiol dye was further reacted with maleimide-derivatized poly(hydroxypropyl methacrylamide) to yield the dye-labeled polymer conjugate. This dye derivative should prove useful as a dithiol reduction-sensitive fluorescent probe in cellular tracking systems, as well as a thiol-based dye-labeling reagent due to its easy preparation from readily available materials, environmental sensitivity, and simple activation to produce distinct spectral states. The enhanced spectral properties of the covalent TAMRA dimer described here could be useful to prepare more advanced reporter molecules and bioconjugates.

Shape mapping of the hippocampus in young children with autism spectrum disorder.

BACKGROUND AND PURPOSE: We hypothesized the occurrence of characteristic hippocampal-shape alterations in young children with autistic spectrum disorder (ASD) who also exhibit deficits on neuropsychologic tests of medial temporal lobe (MTL) function. MATERIALS AND METHODS: Coronal 3D MR images were acquired from 3- to 4-year-old children with ASD (n = 45) and age-matched children with typical development (n = 13). Children with ASD were further subclassified into those with autism disorder (AD, n = 29) or pervasive developmental disorder-not otherwise specified (PDD-NOS) (n = 16). Variations in hippocampal shape were evaluated by using large-deformation high-dimensional brain mapping. RESULTS: Hippocampal shape measures distinguished children with ASD from those with typical development; within the ASD sample, children with AD were distinguished from those with PDD-NOS. Hippocampal-shape alterations in children with ASD were correlated with degree of mental retardation and performance deficits on tests of MTL function. CONCLUSIONS: Children with ASD exhibited an alteration of hippocampal shape consistent with inward deformation of the subiculum. This pattern of hippocampal-shape deformations in the children with ASD was accentuated in the more severely affected subgroup of children with AD and was associated with deficits on neuropsychologic tests of MTL but not prefrontal function. Hippocampal-shape deformation in the children with ASD was observed to be similar to a pattern of hippocampal shape deformation previously reported in adults with MTL epilepsy. Although the children with ASD, and those with AD in particular, PDD-NOS are at high risk for epilepsy as they enter adolescence, the specificity and causal relationship of this pattern of hippocampal-shape deformation to the development of seizures is not yet known.

Supplementation of urban home visitation with a series of group meetings for parents and infants: results of a "real-world" randomized, controlled trial.

OBJECTIVE: Home visitation has been shown to be effective in reducing rates of child maltreatment and in enhancing psychosocial outcomes in children and their parents. Even when available, however, it is underutilized by parents in some urban settings. We tested a supplemental 10-session group intervention for its ability to increase active participation in home visitation, enhance the quality of caregiving behavior of parents, and improve social developmental outcome in children. METHOD: A randomized controlled design was utilized, involving two separate cohorts of parents of 3- to 18-month old infants, totaling 148 parent-child dyads. The intervention focused on practical experience in promoting parent-infant attachment relationships. RESULTS: At 6 months follow-up, there was a substantial increase in the proportion of intervention group parents participating in home visitation, compared to parents in the control group (Fisher's exact p = .008). Parents in the intervention group exhibited a trend for improvement in their capacity to appropriately interpret infants' emotional cues (p = .08), independent of the effects of home visitation itself. Attrition in both the treatment and control groups was inversely associated with income and level of education. CONCLUSIONS: Group meetings may constitute an effective means of engaging stressed urban families in home visitation.

Genetic structure of reciprocal social behavior.

OBJECTIVE: The study examined the genetic structure of deficits in reciprocal social behavior in an epidemiologic sample of male twins. METHOD: Parents of 232 pairs of 7-15-year-old male twins completed the Social Reciprocity Scale to provide data on their children's reciprocal social behavior. Scale scores were analyzed by using structural equation modeling. RESULTS: Intraclass (twin-twin) correlations for scores on the Social Reciprocity Scale were 0.73 for monozygotic twins (N=98 pairs) and 0.37 for dizygotic twins (N=134 pairs). The best fitting model of causal influences on reciprocal social behavior incorporated additive genetic influences and unique environmental influences. CONCLUSIONS: For school-age boys in the general population, reciprocal social behavior is highly heritable, with a genetic structure similar to that reported for autism in clinical samples. Continuous measures of reciprocal social behavior may be useful for characterizing the broader autism phenotype and may enhance the statistical power of genetic studies of autism.

HIV as a chronic disease: implications for long-term care at an AIDS-dedicated skilled nursing facility.

OBJECTIVE: To describe the characteristics and outcomes of the first 3 years of admissions to a dedicated skilled nursing facility for people with acquired immunodeficiency syndrome (AIDS). METHODS: Systematic chart review of consecutive admissions to a 30-bed, AIDS-designated long-term care facility in New Haven, Connecticut, from October 1995 through December 1998. RESULTS: The facility has remained filled to 90% or more of its bed capacity since opening. Of 180 patients (representing 222 admissions), 69% were male; mean age was 41 years; 57% were injection drug users; 71% were admitted directly from a hospital. Leading reasons for admission were (1) the need for 24-hour nursing/medical supervision, (2) completion of acute medical treatment, and (3) terminal care. On admission, the median Karnofsky score was 40, and median CD4+ cell count was 24/mm3; 48% were diagnosed with serious neurologic disease, 44% with psychiatric illness; patients were receiving a median of 11 medications on admission. Of 202 completed admissions, 44% of patients died, 48% were discharged to the community, 8% were discharged to a hospital. Median length of stay was 59 days (range 1 to 1,353). Early (< or = 6 months) mortality was predicted by lower admission CD4+ count, impairments in activities of daily living, and the absence of a psychiatric history; long-term stay (> 6 months) was predicted by total number of admission medications, neurologic disease, and dementia. Comparison of admissions from 1995 to 1996 to those in 1997 to 1998 indicated significantly decreased mortality rates and increased prevalence of psychiatric illness between the two periods (P < .01). CONCLUSIONS: A dedicated skilled nursing facility for people with AIDS can fill an important service need for patients with advanced disease, acute convalescence, long-term care, and terminal care. The need for long-term care may continue to grow for patients who do not respond fully to current antiretroviral therapies and/or have significant neuropsychiatric comorbidities. This level of care may be increasingly important not only in reducing lengths of stay in the hospital, but also as a bridge to community-based residential options in the emerging chronic disease phase of the AIDS epidemic.

Psychiatric comorbidity and the long-term care of people with AIDS.

OBJECTIVES: To examine the association of comorbid psychiatric disorders with admission and discharge characteristics for patients residing at a long-term care facility designated for acquired immunodeficiency syndrome (AIDS). METHODS: Demographic and clinical characteristics were obtained by systematic chart review for all patients (N = 180) admitted to the facility from its opening in October 1995 through December 1999. Lifetime history of severe and persistent psychiatric disorders (major depression, bipolar and psychotic disorders) was determined by current diagnosis on baseline clinical evaluation or a documented past history. RESULTS: Forty-five patients (25%) had comorbid psychiatric disorders. At admission, patients with comorbidity were more likely to be ambulatory (80% vs. 62%, P = .03) and had fewer deficits in activities of daily living (27% vs. 43%, P = .05). After controlling for human immunodeficiency virus (HIV) disease severity, patients with comorbidity had significantly lower discharge rates (relative risk = 0.43, 95% confidence interval 0.23-0.78, P = .0001) and death rates (relative risk = 0.53, 95% confidence interval 0.42-0.68, P = .009). CONCLUSIONS: Patients with AIDS and comorbid psychiatric disorders at this facility had more favorable admission characteristics and were less likely to be discharged or to die. They may have been admitted earlier in their disease course for reasons not exclusively due to HIV infection. Once admitted, community-based residential alternatives may be unavailable as a discharge option. These findings are unlikely to be an anomaly and may become more pronounced with prolonged survival due to further therapeutic improvements in HIV care. Health services planners must anticipate rising demands on the costs of care for an increasing number of patients who may require long-term care and expanded discharge options for the comanagement of HIV disease and chronic psychiatric disorders.

Reciprocal social behavior in children with and without pervasive developmental disorders.

An invariant feature of pervasive developmental disorders (PDDs) is a relative deficit in the capacity for reciprocal social behavior (RSB). The authors acquired teacher reports of RSB in 287 schoolchildren and parent reports of RSB in 158 child psychiatric patients using a new research instrument, the Social Reciprocity Scale. Total scores on this measure of RSB were continuously distributed in all groups of subjects; children with PDDs scored significantly higher for the degree of deficits in RSB than did clinical or nonclinical controls. Latent class analysis and factor analysis failed to demonstrate separate categories of deficiency for core autistic symptomatology and more general impairments in RSB, consistent with the notion of a "broader autism phenotype." Assessments of RSB on a continuous scale may be useful clinically for characterizing the behavior of children whose social deficits fall below the threshold for a full diagnosis of autism. They may also be useful in genetic-linkage studies of autistic spectrum disorders.

Serotonin and externalizing behavior in young children.

Considerable evidence suggests that there is a relationship between pathologic aggressive behavior and low cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in both humans and non-human primates. The purpose of this investigation is to examine the relationship between CSF concentrations of human newborn 5-HIAA and subsequent aggressive behavior observed at 30 months of age. Leftover portions of culture negative CSF drawn from febrile infants (age, birth to 3 months) were assayed for 5-HIAA. Family environment and child behavior were assessed at 30 months by parent report. Subjects with 5-HIAA levels below the median of the distribution had higher externalizing behavior scores at 30 months than did subjects whose 5-HIAA levels fell above the median (P = 0.02). While it is likely that serotonin mediates one component of genetic liability to antisocial outcome, the magnitude of that component may be less than what has been inferred from previously published reports.

Family psychiatric history, cerebrospinal fluid monoamine metabolites, and temperament in infants.

BACKGROUND: Variations in cerebrospinal fluid (CSF) levels of the monoamine metabolites 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol, and homovanillic acid have been associated with behavioral abnormalities in nonhuman primates, and with psychopathology in studies of children and adults. METHODS: We assayed monoamine metabolites in "left-over" spinal fluid from 167 neurologically normal newborn infants (0-3 months of age), and later (at age 18-21 months of age) obtained their family psychiatric histories and assessed their temperament using the Colorado Childhood Temperament Inventory (CCTI). RESULTS: Family history of antisocial personality disorder predicted significantly lower scores for soothability (p = .003) at 18-21 months. There were no statistically significant associations between newborn monoamine metabolite levels and any aspect of temperament on the CCTI. CONCLUSIONS: These findings suggest complex relationships between genetic liability for psychiatric disorders and CSF monoamine metabolite levels; those relationships do not seem to be mediated by infant temperament. It appears likely that interindividual differences in monoamine metabolite levels change over the course of development in humans.