Kimberly A. Dienes

Decreased N-Acetylaspartate in children with familial bipolar disorder

BACKGROUND Relatively low levels of brain N-acetylaspartate, as measured by magnetic resonance spectroscopy, may indicate decreased neuronal density or viability. Dorsolateral prefrontal levels of N-acetylaspartate have been reported to be decreased in adults with bipolar disorder. We used proton magnetic resonance spectroscopy to investigate dorsolateral prefrontal N-acetylaspartate levels in children with familial bipolar disorder. METHODS Subjects were 15 children and adolescents with bipolar disorder, who each had at least one parent with bipolar disorder, and 11 healthy controls. Mean age was 12.6 years for subjects and controls. Subjects were allowed to continue current medications. Proton magnetic resonance spectroscopy at 3-Tesla was used to study 8 cm(3) voxels placed in left and right dorsolateral prefrontal cortex. RESULTS Bipolar subjects had lower N-acetylaspartate/Creatine ratios only in the right dorsolateral prefrontal cortex (p <.02). No differences in myoinositol or choline levels were found. CONCLUSIONS Children and adolescents with bipolar disorder may have decreased dorsolateral prefrontal N-acetylaspartate, similar to adults with BD, indicating a common neuropathophysiology. Longitudinal studies of at-risk children before the onset and during the early course of bipolar disorder are needed to determine the role of prefrontal N-acetylaspartate as a possible risk marker and/or indication of early bipolar illness progression.

Characterization of children of bipolar parents by parent report CBCL

In past research the Child Behavior Checklist (CBCL) has differentiated among various diagnostic categories for children and adolescents. However, research has not been conducted on whether the CBCL differentiates among diagnostic categories for children at high risk for development of psychopathology. This study compares four diagnostic groups [bipolar disorder (BD), attention/deficit-hyperactivity disorder (ADHD), Depressed/Anxious and No Diagnosis] within a cohort of 58 children of bipolar parents to determine whether their CBCL scores will replicate the scores of children not at high risk for bipolar disorder. The cohort of children of bipolar parents received elevated scores on the CBCL scales in comparison with non-clinical populations. In addition, the CBCL distinguished between children of bipolar parents with and without clinical disorders. Finally the BD group differed from the ADHD group only on the Aggressive Behaviors, Withdrawn and Anxious/Depressed subscales of the CBCL. Therefore the CBCL did not discriminate between the BD and ADHD groups as it had in previous studies of children with BD and unspecified family history. It is possible that this discrepancy is due to a group of children of bipolar parents with ADHD who are currently prodromal for bipolar disorder and therefore received higher scores on the CBCL based on prodromal symptomatology. A longitudinal follow-up of this cohort is necessary to ascertain whether this is the case.

Bipolar offspring: a window into bipolar disorder evolution

Children of parents with bipolar disorder (bipolar offspring) represent a rich cohort for study with potential for illumination of prodromal forms of bipolar disorder. Due to their high-risk nature, bipolar offspring may present phenomenological, temperamental, and biological clues to early presentations of bipolar disorder. This article reviews the evidence for establishing bipolar offspring as a high-risk cohort, the studies which point to possible prodromal states in bipolar offspring, biological findings in bipolar offspring which may be indicators of even higher risk for bipolar disorder, initial attempts at early intervention in prodromal pediatric bipolar disorder, and implications for future research.

Cortisol secretion in depressed, and at-risk adults

Distinct patterns of cortisol secretion have been associated with depression in past research, but it remains unclear whether individuals at-risk for depression may also have similar patterns of cortisol secretion. This is the first study to date of both naturalistic diurnal cortisol secretion and cortisol reactivity to a psychosocial laboratory stressor in depressed and at-risk adults. Cortisol secretion patterns were compared for 57 currently depressed, at-risk (based on trait-level positive and negative affect), and control participants over 5 days and in response to a laboratory stressor. After controlling for potentially confounding biobehavioral variables, the depressed group had a larger cortisol awakening response (CAR) and higher average diurnal cortisol compared to control participants. Individuals at-risk for depression also had significantly higher waking cortisol levels than control participants. Results for the psychosocial laboratory stressor did not show the predicted elevations in cortisol for depressed and at-risk participants compared to controls. The at-risk group recovered more quickly when compared to the depressed group both in levels of cortisol and concurrent measures of negative affect. The at-risk and depressed participants were similar on the diurnal cortisol measures, but differed on response to the laboratory social stressor, suggesting divergence in cortisol secretion patterns between currently depressed and temperamentally at-risk individuals. Further investigation of HPA functioning of individuals at-risk for depression may clarify the stress processes involved in risk for depression onset.

Generalized Anxiety Disorder and Depression: A Learning Theory Connection

This paper offers a new learning theory-based conceptualization of worry in Generalized Anxiety Disorder (GAD). The authors suggest that the processes that produce GAD symptoms may vary across GAD sufferers and that treatment effectiveness may be enhanced if the process that likely produced symptoms in a given individual is understood. Specifically, they suggest that a “worry as adjunctive behavior” hypothesis be added to the “worry as anxiety” and “worry as avoidance behavior” hypotheses currently considered. This new hypothesis suggests that for some worriers, worry may function as an adjunctive behavior; that is, a way of accessing quick satisfaction when daily living produces too little response contingent reinforcement. The authors explain that life events that give rise to adjunctive behavior are the same as those that contribute to depression and that this might help explain the high comorbidity between GAD and depression. In cases in which worry appears to serve an adjunctive function, treating GAD symptoms as depression would be treated (e.g., with behavioral activation) may be the most successful course of action.

Chronic stress exposure, diurnal cortisol slope, and implications for mood and fatigue: Moderation by multilocus HPA-Axis genetic variation

Chronic stress exposure has been shown to alter hypothalamic-pituitary-adrenal (HPA) axis functioning, which may mediate its effects on psychopathology and negative health outcomes. The nature of the chronic stress-HPA axis dysregulation is unclear and individuals likely vary in the extent to and manner in which indices of HPA axis regulation, such as diurnal cortisol slope, are influenced by chronic stress. We examined whether HPA-axis-linked genetic variation moderates the association between chronic stress and diurnal cortisol slope, and potential implications for mood and fatigue (possible manifestations of negative clinical outcomes). 211 adolescents (M age 15.89, 54.5% female) completed chronic stress interviews and provided DNA samples. Participants then provided saliva samples at waking and 12 h post-waking for two consecutive weekdays. HPA-axis genetic variation was calculated using a multilocus genetic profile score (MGPS) approach, using ten SNPs from CRHR1, NR3C1, NR3C2, and FKBP5 to generate an additive score of HPA-axis-linked genetic risk. Neither chronic stress nor MGPS directly predicted diurnal slope, but MGPS moderated the association between chronic stress and diurnal slope, with stress predicting a high waking cortisol followed by steep slope among youth with low but not high MGPS scores. MGPS also interacted with chronic stress to predict both negative affect and fatigue, and moderated the indirect effect of chronic stress on mood and fatigue via diurnal slope. Results suggest that diurnal cortisol regulation may be one mechanism by which genetic risk intensifies the association between chronic stress and negative outcomes.

Sunscreen sales, socio-economic factors, and Melanoma incidence in Northern Europe: A population-based ecological study

In this ecological study, we drew upon recently published melanoma prevalence data, and compared them with historical market data and published socio-economic data to test for an association between historical sunscreen sales (1997-1999) and recent melanoma incidences (2008 and 2012) in 24 countries in Northern Europe. We also explored associations between current melanoma incidences and historical data on the following socio-demographic indicators: income, urbanization, and population aging. Melanoma incidences were higher in high-income countries where sales of sunscreen were also higher. Our results show that, at the population level, income was significantly associated with melanoma incidences, β = 0.0003, t(19) = 3.104, p < .006, and that increased sunscreen sales has not prevented higher income populations from being at higher risk of melanoma.