Faculty Bibliography

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) comorbid with oppositional defiant disorder (ODD) or conduct disorder (CD) and substance abuse/dependence seems to represent a specific subset within the phenotypic ADHD spectrum. METHODS: We applied complex segregation and linkage analyses in a set of multigenerational families densely segregating ADHD comorbid with ODD, CD, alcohol abuse/dependence, and nicotine dependence. RESULTS: Our data suggest that ADHD cosegregates with disruptive behaviors as a unique, phenotypically variable trait as evidenced by highly significant pair-wise linkages among: ADHD and ODD (logarithm of odds [LOD]=14.19), ADHD and CD (LOD=5.34), ODD and CD (LOD=6.68), and CD and alcohol abuse/dependence (LOD=3.98). In addition to previously reported ADHD susceptibility loci, we found evidence of linkage for comorbid ADHD phenotypes to loci at 8q24, 2p21-22.3, 5p13.1-p13.3, 12p11.23-13.3, 8q15, and 14q21.1-22.2. These results were replicated with an affected status phenotype derived from latent class clusters. CONCLUSIONS: Patterns of cosegregation of ADHD with comorbidities can inform our understanding of the inheritance patterns not only of ADHD but also of disruptive behavioral disorders and alcohol abuse/dependence. Refining the comorbid ADHD phenotype by determining the cosegregation profile of specific comorbidities might be a powerful tool for defining significant regions of linkage

Love is one of the most desired experiences. The quest for understanding human bonds, especially love, was traditionally a domain of the humanities. Recent developments in biological sciences yield new insights into the mechanisms underlying the formation and maintenance of human relationships. Animal models of reproductive behaviors, mother-infant attachment and pair bonding complemented by human studies reveal neuroendocrine foundations of prosocial behaviors and emotions. Amongst various identified neurotransmitters and modulators, which control affiliative behaviors, the particular role of nanopeptides has been indicated. New studies suggest that these chemicals are not only involved in regulating bonding processes in animals but also contribute to generating positive social attitudes and feelings in humans

Dementia is a clinical state characterized by loss of function in multiple cognitive domains. It is a costly disease in terms of both personal suffering and economic loss. Frontotemporal dementia (FTD) is the term now preferred over Picks disease to describe the spectrum of non-Alzheimers dementias characterized by focal atrophy of the frontal and anterior temporal regions of the brain. The prevalence of FTD is considerable, though specific figures vary among different studies. It occurs usually in an age range of 35-75 and it is more common in individuals with a positive family history of dementia. The risk factors associated with this disorder include head injury and family history of FTD. Although there is some controversy regarding the further syndromatic subdivision of the different types of FTD, the three major clinical presentations of FTD include: 1) a frontal or behavioral variant (FvFTD), 2) a temporal, aphasic variant, also called Semantic dementia (SD), and 3) a progressive aphasia (PA). These different variants differ in their clinical presentation, cognitive deficits, and affected brain regions. Patients with FTD should have a neuropsychiatric assessment, neuropsychological testing and neuroimaging studies to confirm and clarify the diagnosis. Treatment for this entity consists of behavioral and pharmacological approaches. Medications such as serotonin reuptake inhibitors, antipsychotics, mood stabilizer and other novel treatments have been used in FTD with different rates of success. Further research should be directed at understanding and developing new diagnostic and therapeutic modalities to improve the patients' prognosis and quality of life

BACKGROUND: The goal of the current investigation was to examine genetic and environmental predictors of early alcohol use, a potent predictor of later alcohol dependence. METHODS: This study represents an add-on project to an investigation examining the efficacy of an intervention for maltreated children entering out-of-home care. Predictors of early alcohol use include the following: maltreatment, family loading for alcohol or substance-use disorders, and serotonin transporter genotype (5-HTTLPR; locus SLC6A4). Participants included 127 subjects: 76 maltreated children and 51 demographically matched community controls. RESULTS: At follow-up, 29% of the maltreated children reported alcohol use, a rate more than seven times the rate observed in controls. Maltreated children also drank alcohol, on average, more than 2 years earlier than controls (11.2 vs. 13.5 years). Early alcohol use was predicted by maltreatment, 5-HTTLPR, and a gene by environment interaction, with increased risk for early alcohol use associated with the s-allele. Psychopathology at baseline, severity of maltreatment, and poor mother-child relations also predicted early alcohol use. CONCLUSIONS: Maltreated children are at high risk for psychiatric, alcohol, and substance abuse problems. Examination of genetic and environmental risk and protective factors can help identify those who are most vulnerable and help guide prevention and intervention efforts

OBJECTIVES: Studies of sex differences in methylphenidate response by children with attention-deficit/hyperactivity disorder have lacked methodological rigor and statistical power. This paper reports an examination of sex differences based on further analysis of data from a comparison of two once-daily methylphenidate formulations (the COMACS study), which addresses these shortcomings. METHOD: Children (184: 48 females; mean [SD] age, 9.58 [1.83] years) entered a double-blind, crossover trial of Concerta, MetadateCD/Equasym XL, or placebo. Attention-deficit/hyperactivity disorder symptoms were recorded at seven time points across the school day on the seventh day of treatment, using a laboratory classroom setting. RESULTS: More females had comorbid anxiety disorder. Males and females did not differ with regard to other characteristics. Observed sex differences in pharmacodynamic symptom profiles persisted after controlling for placebo and time 0 hours attention-deficit/hyperactivity disorder scores and the presence of an anxiety disorder. Females had a statistically superior response at 1.5 hours post-dosing and an inferior response at the 12-hour time point relative to their male counterparts, no matter which methylphenidate formulation was being assessed. CONCLUSIONS: Dose titration of once-daily formulations of methylphenidate should ideally be based on systematic evidence of response at different periods across the day. The responses of female patients may require additional assessments later in the day to determine the optimal dose

AIMS AND METHODS: Using a birth cohort, these secondary analyses document the prevalence and correlates of depressive symptoms in mothers of young children, as well as the rates and predictors of persistent and incident elevated depressive symptoms at a 1-year follow-up. RESULTS: At the initial survey, approximately 17% of women with young children had elevated depressive symptoms. Forty-six percent of women with initial elevated depressive symptoms continued to have elevated depressive symptoms at the 1-year follow-up. Results of adjusted regression models indicated that elevated initial symptoms were associated with such factors as comorbid anxiety symptoms, parenting distress, poor physical health, financial strain, stressful life events, low social support, low family expressiveness, and younger child age. For the subset of women with partners (n = 860), quality of the relationship with the partner and partner involvement were significant correlates of initial elevated depressive symptoms. Persistent elevated depressive symptoms were significantly associated with high anxiety symptoms, high family conflict, and low maternal education. Predictors of incident cases of elevated depressive symptoms indicated that in addition to sociodemographic correlates, education and maternal race/ethnicity, physical health, parenting distress, and parent and child life events are related to the development of elevated symptoms. CONCLUSIONS: Elevated depressive symptoms are common, and almost one half of the women in our sample with elevated depressive symptoms at the initial assessment also had elevated symptoms at the 1-year follow-up. Persistent and incident elevated depressive symptoms had different predictors, suggesting that identification and treatment of maternal depression must continue beyond the immediate postpartum period to prevent negative consequences of depression for mothers and their young children.

PURPOSE: Autism spectrum disorders (ASD) are characterized by early impairments in language and related social communication skills. This investigation explored whether scores on the MacArthur-Bates Communicative Development Inventory (CDI) at ages 2 and 3 years predict outcome at age 9 years in children with ASD and developmental delay (DD). METHOD: Sixty-two children referred for possible autism at age 2 years, and 19 children with DD, were followed to age 9 years. Vocabulary, prespeech, and gestures scores on CDIs administered at ages 2 and 3 years were used to predict follow-up IQ, language, adaptive skills, and scores on diagnostic measures. RESULTS: CDI scores at ages 2 and 3 did not predict outcome for the DD group. For the ASD sample, CDI receptive and expressive language and late gestures at ages 2 and 3 years predicted a number of follow-up variables, although scores at age 3 years were generally more predictive than scores at age 2 years. CONCLUSIONS: The CDI yielded scores that were predictive of outcome, suggesting that this parent report measure may be a quick and informative assessment of early verbal and nonverbal skills in children with ASD