Pedro E. Martinez

Attention Deficit-Hyperactivity Disorder in People with Generalized Resistance to Thyroid Hormone

BACKGROUND Attention deficit-hyperactivity disorder is a well-recognized psychiatric disorder of childhood. Its cause is unknown, but there is evidence of a familial predisposition. Symptoms suggestive of this disorder have been reported in subjects with generalized resistance to thyroid hormone, a disease caused by mutations in the thyroid receptor-beta gene and characterized by reduced responsiveness of peripheral and pituitary tissues to the actions of thyroid hormone. We systematically evaluated the presence and severity of attention deficit-hyperactivity disorder in 18 families with a history of generalized resistance to thyroid hormone. METHODS We studied 49 affected and 55 unaffected family members; 52 were adults, and 52 were children. All subjects were evaluated with structured psychiatric questionnaires by interviewers who were unaware of the medical diagnosis. The number of symptoms of attention deficit-hyperactivity disorder was calculated for each subject. RESULTS Among the adults, 11 of 22 subjects with generalized resistance to thyroid hormone (50 percent) and 2 of 30 unaffected subjects (7 percent) had met the criteria for attention deficit-hyperactivity disorder as children (P < 0.001). Among the children, 19 of 27 subjects resistant to thyroid hormone (70 percent) and 5 of 25 unaffected subjects (20 percent) met the criteria for the disorder (P < 0.001). The odds of having attention deficit-hyperactivity disorder were 3.2 times higher for affected male subjects than for affected female subjects and were 2.7 times higher for unaffected male subjects than for unaffected female subjects. The mean symptom score was 2.5 times higher in the affected group than in the unaffected group (7.0 vs. 2.8, P < 0.001). The frequency of other psychiatric diagnoses was similar in the two groups. CONCLUSIONS In our study sample, attention deficit-hyperactivity disorder is strongly associated with generalized resistance to thyroid hormone.

Violent communities, family choices, and children's chances: An algorithm for improving the odds

Data are presented concerning the early predictors of adaptational success and failure among 72 children attending their 1st years of elementary school in a violent Washington, D.C., neighborhood. Adaptational failures were defined as those children who were doing poorly or failing in school and rated by their parents as suffering clinically significant levels of behavior problems. Adaptational successes were defined as children whose performance as students was rated in the average to excellent range and whose parent-rated levels of behavior problems were within the normal range. Despite the fact that these children were being raised in violent neighborhoods, had been exposed to relatively high levels of violence in the community, and were experiencing associated distress symptoms, community violence exposure levels were not predictive of adaptational failure or success. Instead, adaptational status was systematically related to characteristics of the childrens homes. More specifically, the childrens chances of adaptational failure rose dramatically as a function of living in unstable and/or unsafe homes. Moreover, it was not the mere accumulation of environmental adversities that gave rise to adaptational failure in these children. Rather, it was only when such adversities contaminated or eroded the stability and/or safety levels of the childrens homes that the odds of their adaptational failure increased. We argue that this erosion of the quality of the childs microsystem (i.e., family) by adversities and pressures in the exosystem (i.e., community) is not an inevitable process. Although not yet well understood, it is a process over which families have and must exercise control. The implications of these data for improving childrens chances of physical, psychological, and academic survival in violent neighborhoods are considered.

Young children of affectively ill parents: a longitudinal study of psychosocial development.

The course of social-emotional development of young children of affectively ill and well parents was assessed. The families were classified by mothers diagnosis: bipolar illness (N = 22), unipolar depression (N = 41), and normal (N = 37). Fathers diagnosis also was obtained. Pairs of siblings were studied; the younger was between 1 1/2 and 3 1/2 years and the older between 5 and 8 years when the study began. They were seen again 3 years later. Psychiatric assessment and mothers report were used to evaluate childrens disruptive behavior, anxiety, and depressive characteristics. The frequency of problem-level behavior changed over time in relation to mothers diagnosis. By middle and late childhood, significantly more children of affectively ill than well mothers had depressive and disruptive problems and multiple behavior problems. Offspring of unipolar mothers developed problems earlier and both siblings were more likely to have behavior problems.

A prospective study of the association among impaired executive functioning, childhood attentional problems, and the development of bipolar disorder

Studies of adults who have been diagnosed with, and treated for, bipolar disorder have shown that these patients exhibit impairment on measures of executive functioning. However, it is unclear whether executive dysfunction precedes the diagnosis of bipolar illness, or develops subsequent to its onset. Moreover, investigators have failed to control for the effects of premorbid attentional problems on cognitive performance in these patients. The present authors explored these questions using data from a longitudinal prospective study of individuals at risk for major mood disorder. Results revealed that 67% of participants who met criteria for bipolar disorder in young adulthood showed impairment on the Wisconsin Card Sorting Test (WCST) when they were assessed during adolescence, as compared with 17% of individuals with no major mood diagnosis, and 19% with unipolar depression. This association between performance on the WCST and bipolar illness was not accounted for by high rates of premorbid attentional disturbance. In fact, among participants with early attentional problems, only those who ultimately developed bipolar disorder exhibited impairment on the WCST. Early attentional problems that preceded unipolar depression or no mood disorder were not associated with executive dysfunction.

Long-term outcomes of youth who manifested the CBCL-Pediatric Bipolar Disorder phenotype during childhood and/or adolescence.

OBJECTIVE Recent studies have identified a Child Behavior Checklist (CBCL) profile that characterizes children with severe aggression, inattention, and mood instability. This profile has been coined the CBCL-Pediatric Bipolar Disorder (PBD) phenotype, because it is commonly seen among children with bipolar disorder. However, mounting evidence suggests that the CBCL-PBD may be a better tool for identifying children with severe functional impairment and broad-ranging psychiatric comorbidities rather than bipolar disorder itself. No studies have followed individuals with the CBCL-PBD profile through adulthood, so its long-term implications remain unclear. The present authors examined diagnostic and functional trajectories of individuals with the CBCL-PBD profile from early childhood through young adulthood using data from a longitudinal high-risk study. METHOD Participants (n=101) are part of a 23-year study of youth at risk for major mood disorder who have completed diagnostic and functional assessments at regular intervals. RESULTS Across development, participants with the CBCL-PBD phenotype exhibited marked psychosocial impairment, increased rates of suicidal thoughts and behaviors and heightened risk for comorbid anxiety, bipolar disorder, cluster B personality disorders and ADHD in young adulthood, compared to participants without this presentation. However, diagnostic accuracy for any one particular disorder was found to be low. CONCLUSIONS Children with the CBCL-PBD profile are at risk for ongoing, severe, psychiatric symptomatology including behavior and emotional comorbidities in general, and bipolar disorder, anxiety, ADHD, cluster B personality disorders in particular. However, the value of this profile may be in predicting ongoing comorbidity and impairment, rather than any one specific DSM-IV diagnosis.

Neuropsychological Functioning in Adolescent Children of Mothers with a History of Bipolar or Major Depressive Disorders

BACKGROUND Growing evidence demonstrates an association of neuropsychological deficits with mood disorders, but it is not yet clear whether these deficits are risk factors or are concomitant with the symptoms. This study examines the neuropsychological functioning of a group of adolescent offspring who are at risk for a mood disorder by virtue of being raised by mothers who have been diagnosed with major depressive disorder (MDD) or bipolar disorder (BPD). METHODS Adolescent offspring of mothers with BPD (n = 43) or MDD (n = 72) and of psychiatrically well parents (n = 50) completed a battery of neuropsychological tests to assess executive functioning, memory, and attention. RESULTS Children of mothers with BPD showed deficits in executive functioning and selective deficits in spatial memory and attention, in comparison with children of well mothers. Deficits were not found for children of MDD mothers. CONCLUSIONS Knowledge of these neurocognitive processes could aid ultimately in determining whether neurocognitive deficits precede BPD, whether unique profiles are associated with various types of mood disorders, and who may benefit from interventions.

Clinical Subtypes of Depression Are Associated with Specific Metabolic Parameters and Circadian Endocrine Profiles in Women: The Power Study

Background Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes. Methods Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin. Results Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup. Conclusions Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences. Trial Registration ClinicalTrials.gov NCT00006180

Heterogeneity of postpartum depression: a latent class analysis

BACKGROUND Maternal depression in the postpartum period confers substantial morbidity and mortality, but the definition of postpartum depression remains controversial. We investigated the heterogeneity of symptoms with the aim of identifying clinical subtypes of postpartum depression. METHODS Data were aggregated from the international perinatal psychiatry consortium Postpartum Depression: Action Towards Causes and Treatment, which represents 19 institutions in seven countries. 17,912 unique subject records with phenotypic data were submitted. We applied latent class analyses in a two-tiered approach to assess the validity of empirically defined subtypes of postpartum depression. Tier one assessed heterogeneity in women with complete data on the Edinburgh postnatal depression scale (EPDS) and tier two in those with postpartum depression case status. FINDINGS 6556 individuals were assessed in tier one and 4245 in tier two. A final model with three latent classes was optimum for both tiers. The most striking characteristics associated with postpartum depression were severity, timing of onset, comorbid anxiety, and suicidal ideation. Women in class 1 had the least severe symptoms (mean EPDS score 10·5), followed by those in class 2 (mean EPDS score 14·8) and those in class 3 (mean EPDS score 20·1). The most severe symptoms of postpartum depression were significantly associated with poor mood (mean EPDS score 20·1), increased anxiety, onset of symptoms during pregnancy, obstetric complications, and suicidal ideation. In class 2, most women (62%) reported symptom onset within 4 weeks postpartum and had more pregnancy complications than in other two classes (69% vs 67% in class 1 and 29% in class 3). INTERPRETATION PPD seems to have several distinct phenotypes. Further assessment of PPD heterogeneity to identify more precise phenotypes will be important for future biological and genetic investigations. FUNDING Sources of funding are listed at the end of the article.

Maternal and environmental factors influence the hypothalamic-pituitary-adrenal axis response to corticotropin-releasing hormone infusion in offspring of mothers with or without mood disorders.

Individuals with melancholic major depression exhibit basal hypercortisolism and an attenuated ACTH response to exogenous corticotropin-releasing hormone (CRH) infusion. Given the greater incidence of depression in children of depressed parents, we examined the ACTH and cortisol responses to ovine CRH (oCRH) infusion in 63 adolescent offspring of mothers with major depression, bipolar illness, or no psychiatric illness. Psychiatric and observational assessments of these families had been conducted over the course of 10 years preceding this study. We examined the childrens responses to CRH in relation to maternal characteristics and family environment and found the following: (a) cortisol responses were negatively related to chronic family stress and (b) offspring of depressed mothers with an avoidant personality disorder showed an exaggerated ACTH response. In addition, adolescents in late puberty (Tanner 4 and 5) had lower ACTH and cortisol responses to oCRH infusion than those in early puberty. Further, offspring with early histories of mood problems, and those who developed major depressive disorder as young adults, did not exhibit basal hypercortisolism but did show an attenuated ACTH response to CRH. Our results add to the growing body of literature showing the influence of maternal characteristics and environmental factors on hypothalamic-pituitary-adrenal axis patterns in children.

Dialogues with preadolescents and adolescents: Mother-child interaction patterns in affectively ill and well dyads

This study examined affective/communicative patterns in the interactions of unipolar, bipolar, and well mothers with their preadolescent and adolescent children. As part of a large longitudinal project, mother-child interaction was assessed for two siblings ages 8 to 11 and 12 to 16. Interactional difficulties were linked to both maternal affective illness and child problem status. Preadolescent children appeared more comfortable/happy with well mothers than with affectively ill mothers. Mothers and their preadolescents were more critical/irritable with each other when the child had a psychiatric disorder. Gender differences were apparent, particularly in regard to mothers current psychiatric status. Interactions in adolescent-daughter dyads were more critical when mothers met criteria for a major depressive episode within the month. The results illuminate interactive processes through which psychopathology may be perpetuated in families.