Diana I. Simeonova

Cortical magnetic resonance imaging findings in familial pediatric bipolar disorder

BACKGROUND Morphometric magnetic resonance imaging (MRI) studies of pediatric bipolar disorder (BD) have not reported on gray matter volumes but have reported increased lateral ventricular size and presence of white matter hyperintensities (WMH). We studied gray matter volume, ventricular-to-brain ratios (VBR), and number of WMH in patients with familial, pediatric BD compared with control subjects. METHODS Twenty subjects with BD (aged 14.6 +/- 2.8 years; 4 female) according to the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, each with a parent with BD, and 20 age-, gender-, and intelligence quotient-matched healthy control subjects (aged 14.1 +/- 2.8 years; 4 female) were scanned at 3 T. Most subjects were taking psychotropic medications. A high-resolution T1-weighted spoiled gradient echo three-dimensional MRI sequence was analyzed by BrainImage for volumetric measurements, and T2-weighted images were read by a neuroradiologist to determine presence of WMH. RESULTS After covarying for age and total brain volume, there were no significant differences between subjects with BD and control subjects in volume of cerebral (p = .09) or prefrontal gray matter (p = .34). Subjects with BD did not have elevated numbers of WMH or greater VBR when compared with control subjects. CONCLUSIONS Children and adolescents with familial BD do not seem to have decreased cerebral grey matter or increased numbers of WMH, dissimilar to findings in adults with BD. Gray matter decreases and development of WMH might be later sequelae of BD or unique to adult-onset BD.

A Pilot Study of Antidepressant-Induced Mania in Pediatric Bipolar Disorder: Characteristics, Risk Factors, and the Serotonin Transporter Gene

BACKGROUND Antidepressant-induced mania (AIM) has been described in bipolar disorder (BD) and has been associated with the short-allele of the serotonin transporter gene (5-HTT). We wished to investigate the frequency of and risk factors for AIM in pediatric patients with or at high risk for BD. METHODS Fifty-two children and adolescents (30 with BD and 22 with subthreshold manic symptoms, 15.1 +/- 3.4 years old), all with a parent with BD, were interviewed with their parents for manic/depressive symptoms occurring before and after past antidepressant treatment. The 47 subjects with serotonin reuptake inhibitor (SSRI) exposure were genotyped for the 5-HTT polymorphism. RESULTS Fifty percent of subjects were AIM+ and 25.5% had new onset of suicidal ideation. The AIM+ and AIM- groups did not differ significantly in relation to allele (p = .36) or genotype (p = .53) frequencies of the 5-HTT polymorphism. The AIM+ subjects were more likely to have more comorbidities (3.2 vs. 2.4; p = .02) and be BD type I (p = .04) than AIM- subjects. CONCLUSIONS Youth with or at high risk for BD may be particularly vulnerable to SSRI AIM and thus should be monitored if given SSRIs. In this preliminary study, we did not find that the 5-HTT polymorphism significantly influenced vulnerability to AIM.

Somatic and Social: Chinese Americans Talk about Emotion

Empirical findings suggest that Chinese and Americans differ in the ways that they describe emotional experience, with Chinese using more somatic and social words than Americans. No one, however, has investigated whether this variation is related to differences between Chinese and American conceptions of emotion or to linguistic differences between the English and Chinese languages. Therefore, in two studies, the authors compared the word use of individuals who varied in their orientation to Chinese and American cultures (European Americans [EA], more acculturated Chinese Americans [CA], and less acculturated CA) when they were speaking English during emotional events. Across both studies, less acculturated CA used more somatic (e.g., dizzy) and more social (e.g., friend) words than EA. These findings suggest that even when controlling for language spoken, cultural conceptions of emotion may shape how people talk about emotion.

Amygdalar, hippocampal, and thalamic volumes in youth at high risk for development of bipolar disorder☆

Children of parents with bipolar disorder (BD), especially those with attention deficit hyperactivity disorder (ADHD) and symptoms of depression or mania, are at significantly high risk for developing BD. As we have previously shown amygdalar reductions in pediatric BD, the current study examined amygdalar volumes in offspring of parents (BD offspring) who have not yet developed a full manic episode. Youth participating in the study included 22 BD offspring and 22 healthy controls of comparable age, gender, handedness, and IQ. Subjects had no history of a manic episode, but met criteria for ADHD and moderate mood symptoms. MRI was performed on a 3T GE scanner, using a 3D volumetric spoiled gradient echo series. Amygdalae were manually traced using BrainImage Java software on positionally normalized brain stacks. Bipolar offspring had similar amygdalar volumes compared to the control group. Exploratory analyses yielded no differences in hippocampal or thalamic volumes. Bipolar offspring do not show decreased amygdalar volume, possibly because these abnormalities occur after more prolonged illness rather than as a preexisting risk factor. Longitudinal studies are needed to determine whether amygdalar volumes change during and after the development of BD.

Psychotropic Medication Exposure and Age at Onset of Bipolar Disorder in Offspring of Parents with Bipolar Disorder

OBJECTIVE Exposure to psychotropic medications before the onset of bipolar disorder (BD) in children may have profound effects on the course of illness. Both antidepressant and stimulant exposure have been proposed to hasten the course of BD development, whereas mood stabilizers have been proposed as protective. We sought to describe psychotropic medication exposure in a cohort of children at risk for BD and retrospectively determine the effect of medication exposure on age at onset (AAO) of BD. METHODS Subjects were 106 children and adolescents who had at least 1 parent with BD. Of these, 63 had BD I or BD II and 43 had subsyndromal symptoms of BD. AAO was determined as nearest month of first manic or hypomanic episode. Past psychotropic medication exposure prior to AAO was determined through interview and chart review. RESULTS Both groups had high rates of exposure to psychotropic medications. Antidepressant or stimulant exposure was not correlated with an earlier AAO of BD. However, mood stabilizer exposure was associated with a later AAO. CONCLUSIONS Children with full or subsyndromal BD are frequently exposed to a variety of psychotropic medications before their first manic episode. Our findings do not support that early stimulant or antidepressant exposure leads to an earlier AAO of BD. However, early mood stabilizer exposure may be associated with delayed AAO. Longitudinal studies are needed to clarify these results.

Subcortical volumetric correlates of anxiety in familial pediatric bipolar disorder: A preliminary investigation☆

Anxiety is a common comorbid condition in pediatric bipolar disorder (BD). However, there is little known about the effects of comorbidity on brain morphometry in this population. The aim of the present study was to examine subcortical correlates of anxiety in familial pediatric BD. The subject group comprised 120 children (mean age=12+/-3.3 years) with at least one parent diagnosed with BD. Bipolar offspring with BD were compared with bipolar offspring without BD on a measure of overall lifetime anxiety. A sub-sample of 20 bipolar offspring with BD (mean age=14.6+/-2.8 years) underwent magnetic resonance imaging (MRI) with a 3-T scanner. Correlational analyses were conducted between hippocampal and amygdalar volumes, and anxiety scores. The results showed significantly higher anxiety in bipolar offspring with BD compared to bipolar offspring without BD. There was a significant negative association between total hippocampal volume and anxiety scores. No significant association was found between total amygdalar volume and anxiety scores. Clinically, these findings suggest that anxiety comorbidity needs to be properly assessed and treated in the management of pediatric BD. This is the first study to show a negative association between hippocampal volume and anxiety in this population. The overlap between anxiety and familial pediatric BD suggests that anxiety may be one important area of future research in parsing out the heterogeneous nature and complex etiology of early-onset BD.

Psychosis risk screening in clinical high-risk adolescents: A longitudinal investigation using the Child Behavior Checklist

This is the first study to investigate whether parent-reported social and behavioral problems on the Child Behavior Checklist (CBCL) can be used for psychosis risk screening and the identification of at-risk youth in the general population. This longitudinal investigation assessed 122 adolescent participants from three groups (at-risk, other personality disorders, non-psychiatric controls) at baseline and one year follow-up. The findings indicate that two individual CBCL rating scales, Withdrawn/Depressed and Thought Problems, have clinical and diagnostic utility as an adjunctive risk screening measure to aid in early detection of at-risk youth likely to develop psychosis. Furthermore, the findings shows that a cost-effective, general screening tool with a widespread use in community and pediatric healthcare settings has a promise to serve as a first step in a multi-stage risk screening process. This can potentially facilitate increased screening precision and reduction of high rate of false-positives in clinical high-risk individuals who present with elevated scores on psychosis-risk measures, but ultimately do not go on to develop psychosis. The findings of the present study also have significant clinical and research implications for the development of a broad-based psychosis risk screening strategy, and novel prevention and early intervention approaches in at-risk populations for the emergence of severe mental illness.

Does a Parent-Report Measure of Behavioral Problems Enhance Prediction of Conversion to Psychosis in Clinical High-Risk Adolescents?

Recent research on risk for psychosis has focused on youth who manifest subclinical signs that are often associated with the prodrome to psychosis. Standardized measures of prodromal symptoms have been shown to significantly enhance prediction of risk for conversion to an Axis I psychotic disorder. In the present study, a widely used parent-report measure of behavioral problems, the Child Behavior Checklist (CBCL) was administered to examine the clinical and diagnostic utility of the measure as an adjunctive screening instrument in the identification of at-risk youth. The CBCL, the Structured Interview for Prodromal Syndromes (SIPS), and other diagnostic measures were administered at baseline and at one year follow-up assessments to adolescents (n=41) at clinical high-risk for the development of a psychotic disorder. Analyses were conducted to compare the 14 at-risk adolescents who subsequently converted to psychosis to the 27 who did not. Conversion to psychosis was defined as conversion to an Axis I psychotic disorder or affective disorder with psychotic features. Consistent with expectations, at one year follow-up, compared to the Non-Converted participants, the Converted participants manifested significantly higher scores on the prodromal symptom scales of the SIPS. There were, however, no differences in CBCL social and behavioral ratings as a function of conversion status. It is concluded that the CBCL does not show promise as an alternative or adjunctive predictor of conversion to psychosis in at-risk adolescents.

Anxiety and physical health problems increase the odds of women having more severe symptoms of depression.

Severely depressed women incur substantial disability and suicide risk, necessitating an understanding of factors that may contribute to severe depression. The purpose of this research was to determine the degree to which age, physical morbidity, anxiety, and hormonal status predict the likelihood of severe depression among women with mood disorders (n = 298). Data arose from a standardized battery of measures in a multi-center clinical registry of patients with mood disorders. The women were being treated at 17 participating sites of the National Network of Depression Centers. Results of logistic regression analyses indicate that a woman’s level of anxiety was the strongest predictor of her likelihood of having severe depression (Exp(B) = 1.33, p = .000), including thoughts of death or suicide. The number of physical health problems that a woman reported was also a significant predictor (Exp(B) = 1.09, p = .04). Neither age nor hormonal status was significant in the final model, although a trend was observed for women with surgically induced menopause to have more severe depression. Findings support the need to work closely with medical practitioners to address physical health problems as part of the treatment plan for depression and to give comorbid anxiety and depression equal priority in symptom management.

Longitudinal investigation of the relationship between family history of psychosis and affective disorders and Child Behavior Checklist ratings in clinical high-risk adolescents

This is the first study to investigate whether positive family history (FH) of psychosis and affective disorders moderates the relationship between child diagnostic status and parent-reported social and behavioral problems on the Child Behavior Checklist (CBCL) in clinical high-risk adolescents. This longitudinal investigation assessed 122 participants (mean age=14.25±1.8years) from three groups (at-risk, other personality disorders, non-psychiatric controls) at baseline and one year follow-up. As predicted, there was a main effect of FH for a number of CBCL scales indicating higher scores for adolescents with positive FH. The findings also demonstrate a significant Diagnostic Status×Family History interaction for several behavioral scales providing support for FH as a concurrent and longitudinal moderator of the relationship between diagnostic status and CBCL scales. The moderating effect is present for areas of functioning associated with depression, anxiety, social adjustment, thought problems, attention problems, and aggressive behavior. The findings also indicate that both positive and negative symptoms are related to the genetic vulnerability for developing psychosis in clinical high-risk individuals, particularly those symptoms reflective of emotional, attentional, and interpersonal functioning. The present findings are novel and have significant clinical and research implications. This investigation provides a platform for future studies to clarify further the role of FH in clinical high-risk individuals and contributes to integration of this knowledge in the development of early intervention and prevention approaches in at-risk populations for the emergence of severe mental illness.