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Background Depression is the leading cause of disease burden among women worldwide. However, an understanding of symptom profiles among women at risk of mood disorders is limited. We determined distinct profiles of affective symptoms among high risk women, along with their distinguishing characteristics. Methods Women were recruited from 17 clinical sites affiliated with the National Network of Depression Centers. They completed measures of depression (Patient Health Questionnaire – 9) and anxiety (Generalized Anxiety Disorder – 7) as well as questions regarding demographics, reproductive status, behavioral/mental health history, and life stress/adversity. Latent class analysis and multinomial logistic regression were used to identify and characterize symptom profiles. Results 5792 women participated, ages 18 to 90 (M = 38). Three latent classes were identified: generally asymptomatic (48%), elevated symptoms of comorbid anxiety and depression (16%), and somatic symptoms (36%). Financial security and greater social support were protective factors that distinguished asymptomatic women. The profile of the class with elevated anxiety/depressive symptoms constituted a complex mix of adverse social determinants and potentially heritable clinical features, including a diagnosis of Bipolar Disorder. Women in the 3rd latent class were characterized by menstrual irregularity and a stronger expression of neurovegetative symptoms, especially sleep disturbance and fatigue. Limitations Limitations included less than optimal racial diversity of our sample and reliance on self-report. Conclusions Different symptom profiles may reflect distinct subtypes of women at risk of mood disorders. Understanding the etiology and mechanisms underlying clinical and psychosocial features of these profiles can inform more precisely targeted interventions to address women's diverse needs.

Although men are more likely to die by suicide, women experience a greater and more rapidly increasing rate of suicidal ideation (SI) and are 3 times more likely to attempt suicide than men. Despite this increased risk, little is known about factors that contribute to SI or suicide attempts (SA) among women. We examined factors associated with SI and SA among women and identified mood-related symptoms that differentiate women who reported attempting suicide from those who did not. Women at elevated risk for depression from across the U.S. (N = 3372; age 18 to 90) completed a survey regarding depression, anxiety, sociodemographic and reproductive status, behavioral/mental health history, and exposure to adversity. Structural equation modeling and logistic regression were used to analyze the data. Variables with the most significant relationships to SI were severity of depression (OR = 5.2, p = 0.000) and perceived stress (OR = 1.18, p = 0.000) while frequency of suicidal thoughts (OR = 3.3, p = 0.000), family history of a depression diagnosis (OR = 1.6, p = 0.000) and exposure to violence (OR = 1.9, p = 0.000) had the strongest association with SA. Childhood abuse/trauma was associated with SA (OR = 1.13, p = 0.000) but not SI. 'Feeling bad about themselves, a failure, or having let themselves or their family down' was the symptom that most clearly differentiated women who attempted suicide from women who reported suicidal ideation but no SA. The salience of childhood abuse and domestic/community violence to women's risk for a suicide attempt reinforces previous findings that these adversities may differentiate suicide risk for women versus men. Continued research is essential to understand varied paths that may lead to suicidal behavior among women, some which appear unrelated to the frequency or intensity of their suicidal thoughts.

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 ± 1.8 years) 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.

There are no published studies examining concurrent associations between temperament and behavior during toddlerhood in offspring of parents with bipolar disorder (OBD), a population at high familial risk for psychopathology. Better understanding of early determinants contributing to well-being or mental illness in this high-risk population has the potential to aid in the identification of problem domains to be targeted clinically, and facilitate the development of early intervention and prevention initiatives for an appropriate subgroup of children at the youngest possible age.A total of 30 offspring of mothers with BD (mean age=25.4±4.9 months) participated in this study at Emory University. The mothers completed the Early Childhood Behavior Questionnaire (ECBQ) and the Child Behavior Checklist (CBCL).The results of the correlational analyses indicated that the broad temperament dimension Negative Affectivity and the individual ECBQ scales Sadness and Shyness were positively associated with the broad CBCL dimension Internalizing Problems, whereas Sociability was negatively associated with Internalizing Problems. In addition, the temperament scales Soothability and Frustration were negatively and positively associated with Internalizing Problems, respectively. All ECBQ scales included in the broad temperament dimension Effortful Control, except for Cuddliness, were significantly negatively associated with the broad CBCL dimension Externalizing Problems. A significant sex difference was found for the ECBQ scale Positive Anticipation and the CBCL scale Sleep Problems, with a higher mean rank score for girls than for boys.This is the first systematic investigation of temperament and behavior and concurrent associations between these two domains in toddlers of mothers with BD. The present findings provide a platform for future investigations of the contribution of temperament and early behavior to potential well-being or mental illness in OBD.

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.

[Clin Psychol Sci Prac 17: 169–186, 2010] Children of bipolar parents (CBP) are at increased risk to develop psychopathology, especially a mood disorder. Several factors may contribute to the increased risk for psychopathology in CBP, including family environmental variables (e.g., high levels of family conflict and dysfunctional parenting) and socioemotional cue processing deficits (e.g., inaccurate detection of facial social cues). A proposed model posits that family risk factors and socioemotional cue processing deficits may interact in conferring risk for psychopathology for CBP via their effects on the development of emotion regulation and the neural circuitry that governs this development. A developmental, transactional perspective on the impact of these risk factors provides a framework within which to examine their dynamic interaction.

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.

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.

Children of parents with bipolar disorder (BD), especially those with attention deficit hyperactivity disorder (ADHD) and symptoms of depression or mania, are significantly at 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 with (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 amygdala 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.

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.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.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.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.

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.

The link between movement abnormalities and psychotic disorders is presumed to reflect common neural mechanisms that influence both motor functions and vulnerability to psychosis. The prodromal period leading to psychotic disorders represents both a viable point for intervention and a developmental period that, if studied, could shed light on etiology; however, no published studies have examined the temporal progression of this link. A group with high levels of prodromal symptomatology (i.e., adolescents with schizotypal personality disorder [SPD]; n = 42) and both psychiatric controls (with other personality disorders or conduct disorder [OD]; n = 30) and nonpsychiatric controls ([NC]; n = 49) were recruited. Videotapes of structured psychiatric interviews were coded for movement abnormalities by raters blind to participants' diagnostic status, and follow-up assessments were conducted 1 year later. Controlling for psychotropic medications, the authors found that adolescents with SPD exhibited significantly more motor abnormalities in the face and upper body than did OD and NC controls. At baseline, movement abnormalities were positively correlated with the severity of positive, negative, and total prodromal symptoms. Within the SPD group, baseline movement abnormalities predicted symptom severity 1 year later. Movement abnormalities represent an early risk indicator that may be predictive of later symptom severity and potentially of psychosis onset.

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.

Objective: Subcortical limbic structures have been proposed to be involved in the pathophysiology of adult and pediatric bipolar disorder (BD). We sought to study morphometric characteristics of these structures in pediatric subjects with familial BD compared with healthy controls. Method: Twenty children and adolescents with BD I (mean age = 14.6 years, four females) and 20 healthy age, gender, and IQ-matched controls underwent high-resolution magnetic resonance imaging at 3 T. Patients were mostly euthymic and most were taking medications. Amygdala, hippocampus, thalamus, and caudate volumes were determined by manual tracings from researchers blinded to diagnosis. Analyses of covariance were performed, with total brain volume, age, and gender as covariates. Results: No differences were found in the volumes of hippocampus, caudate, and thalamus between subjects with BD and controls. Subjects with BD had smaller volumes in the left and right amygdala, driven by reductions in gray matter volume. Exploratory analyses revealed that subjects with BD with past lithium or valproate exposure tended to have greater amygdalar gray matter volume than subjects with BD without such exposure. Conclusions: Children and adolescents with early-onset BD may have reduced amygdalar volumes, consistent with other studies in this population. Prolonged medication exposure to lithium or valproate may account for findings in adults with BD of increased amygdalar volume relative to controls. J. Am. Acad. Child Adolesc. Psy

Studies have demonstrated relationships between creativity and bipolar disorder (BD) in individuals, and suggested familial transmission of both creativity and BD. However, to date, there have been no studies specifically examining creativity in o!spring of bipolar parents and clarifying mechanisms of intergenerational transmission of creativity. We compared creativity in bipolar parents and their o!spring with BD and bipolar o!spring with attention-deficit/hyperactivity disorder (ADHD) with healthy control adults and their children. 40 adults with BD, 20 bipolar o!spring with BD, 20 bipolar o!spring with ADHD, and 18 healthy control parents and their healthy control children completed the Barron‐Welsh Art Scale (BWAS), an objective measure of creativity. Adults with BD compared to controls scored significantly (120%) higher on the BWAS Dislike subscale, and non-significantly (32%) higher on the BWAS Total scale. Mean BWAS Dislike subscale scores were also significantly higher in o!spring with BD (107% higher) and o!spring with ADHD (91% higher) than in healthy control children. Compared to healthy control children, o!spring with BD had 67% higher and o!spring with ADHD had 40% higher BWAS Total scores, but these di!erences failed to reach statistical significance when adjusted for age. In the bipolar o!spring with BD, BWAS Total scores were negatively correlated with duration of illness. The results of this study support an association between BD and creativity and contribute to a better understanding of possible mechanisms of transmission of creativity in families with genetic susceptibility for BD. This is the first study to show that children with and at high risk for BD have higher creativity than healthy control children. The finding in children and in adults was related to an enhanced ability to experience and express dislike of simple and symmetric images. This could reflect increased access to negative a!ect, which could yield both benefits with respect to providing a!ective energy for creative achievement, but also yield liabilities with respect to quality of interpersonal relationships or susceptibility to depression. ! 2005 Elsevier Ltd. All rights reserved.

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.

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.

Background The neurobiological features of pediatric bipolar disorder (BD) are largely unknown. Children and adolescents with BD may be important to study with functional neuroimaging techniques because of their unique status of early-onset BD and high familial loading for the disorder. Neuroimaging studies of adults with BD have implicated the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in the development of this disorder. Objectives To study children and adolescents with BD via functional magnetic resonance imaging using cognitive and affective tasks and to examine possible abnormalities in the DLPFC and ACC, as well as selected subcortical areas, in pediatric familial BD. Design We evaluated 12 male subjects aged 9 to 18 years with BD who had at least 1 parent with BD as well as 10 age- and IQ-matched healthy male controls. Stimulants were discontinued for at least 24 hours; other medications were continued. Subjects underwent functional magnetic resonance imaging at 3 T while performing a 2-back visuospatial working memory task and an affective task involving the visualization of positively, neutrally, or negatively valenced pictures. Setting An academic referral setting, drawing from the Bay Area of San Francisco, Calif. Results Compared with controls, for the visuospatial working memory task, subjects with BD had greater activation in several areas including the bilateral ACC, left putamen, left thalamus, left DLPFC, and right inferior frontal gyrus. Controls had greater activation in the cerebellar vermis. In viewing negatively valenced pictures, subjects with BD had greater activation in the bilateral DLPFC, inferior frontal gyrus, and right insula. Controls had greater activation in the right posterior cingulate gyrus. For positively valenced pictures, subjects with BD had greater activation in the bilateral caudate and thalamus, left middle/superior frontal gyrus, and left ACC, whereas controls had no areas of greater activation. Conclusions Children and adolescents with BD may have underlying abnormalities in the regulation of prefrontal-subcortical circuits. Further functional magnetic resonance imaging studies of attention and mood with greater sample sizes are needed.