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: To describe and compare the relative merits of different identification strategies for individuals at risk for bipolar disorder (BPD). METHODS: Selective review of data that support early identification in BPD, with a particular focus on emerging clinical high-risk strategies. RESULTS: Early detection of individuals at risk for BPD can utilize genetic, endophenotypic and clinical methods. Most published work focuses on genetic familial endophenotypic risk markers for BPD. However, despite encouraging results, problems with specificity and sensitivity limit the application of these data to early prevention programs. In addition, offspring studies of BPD patients systematically exclude the majority of subjects without a first-degree bipolar relative. On the other hand, emerging work in the clinical-high-risk arena has already produced encouraging results. Although still preliminary, the identification of individuals in subsyndromal or attenuated symptom 'prodromal' stages of BPD seems to be an under-researched area that holds considerable promise deserving increased attention. Required next steps include the development of rating tools for attenuated and subsyndromal manic and depressive symptoms and of prodromal criteria that will allow prodromal symptomatology to be systematically studied in patients with recent-onset bipolar, as well as in prospective population-based phenomenology trials and attenuated symptom-based high-risk studies. CONCLUSIONS: Given the current limitations of each early identification method, combining clinical, endophenotypic and genetic strategies will increase prediction accuracy. Since reliable biological markers for BPD have not been established and since most patients with BPD lack a first-degree relative with this disorder, clinical high-risk approaches have great potential to inform early identification and intervention programs.

OBJECTIVE: Research has found low concordance of personality disorder diagnoses made during depression versus after remission and made using patient versus collateral informants, but little is known about the reliability of personality disorder (PD) diagnoses made during depression using patient and collateral reports. METHOD: A total of 168 patients were evaluated for PDs during depression and following response using patient and close informant reports. kappa coefficients of inter-informant and test-retest reliability were calculated. RESULTS: After depression response, the proportion diagnosed with cluster A and C PDs fell by both patient and close informant report, and overall inter-informant reliability declined. Overall test-retest reliability did not differ between patients and informants. CONCLUSION: Collateral informants do not improve the reliability of PD diagnoses made during depressive episodes

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.

This study explored the factor structure and developmental trajectory of effortful control (EC), its relations with child adjustment, and the moderating role of age and gender in 75 4- to 6-year-old children at risk for psychopathology. Confirmatory factor analyses revealed two subcomponents of effortful control: Suppress/Initiate (the ability to inhibit a dominant response while initiating a new response) and Motor Control (inhibiting fine and gross motor activity). EC performance improved with age, and both subcomponents were associated with greater social competence at all ages. Associations with internalizing problems were moderated by child age such that greater EC was linked to fewer problems at age 4 but did not relate to problems at ages 5 or 6