Beyond the Window of Risk? The Dutch Bipolar Offspring Study: 22-Year Follow-up.

OBJECTIVE: Adolescent offspring of parents with bipolar disorder (BD) are at high risk to develop BD and other psychopathology, yet how this risk continues into middle adulthood remains unknown. This study aimed to determine the window of risk for BD and other psychopathology in offspring of parents with BD followed from adolescence into adulthood. METHOD: This study reported on the 22-year follow-up assessment of the Dutch Bipolar Offspring Study, a fixed cohort study of 140 participants established in 1997. Offspring (n = 100; mean [SD] age = 38.28 [2.74] years) of parents with bipolar I disorder or bipolar II disorder were assessed at baseline and 1-, 5-, 12-, and 22-year follow-up. RESULTS: No new BD onsets occurred since the 12-year follow-up (lifetime prevalence = 11%-13%; bipolar I disorder = 4%; bipolar II disorder = 7%). Lifetime prevalence of any mood disorder was 65%; for major depressive disorder, prevalence was 36%; and for recurrent mood episodes, prevalence was 37%. Prevalence of major depressive disorder more than doubled in the past decade. Point prevalence of any psychopathology peaked between 20 and 25 years (38%-46%), subsiding to 29% to 35% per year after age 30. Overall, 71% of offspring contacted mental health services since the last assessment. CONCLUSION: The risk for homotypic transmission of BD in offspring of parents with BD is highest during adolescence. The heterotypic risk for mood disorder onset and recurrences continues over the life course. Severe mood disorders are often preceded by milder psychopathology, emphasizing the need for early identification and interventions. This study allows for better understanding of the onset and course of mood disorders and specific windows of risk in a familial high-risk population.

Neurotrophic factor levels and executive functions in children of parents with bipolar disorder: A case controlled study.

BACKGROUND: In the current study, it was aimed to evaluate neurotrophic factor levels and their relationship with executive functions in high-risk children and adolescents (high-risk group) whose parents were diagnosed with bipolar disorder (BD) but not affected by any psychiatric disease,and in order to determine possible vulnerability factors related to the disease. METHODS: The study sample consisted of 32 high-risk group and 34 healthy controls. The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version-Turkish Adaptation (KSADS-PL-T), Stroop Test, Serial Digit Learning Test (SDLT) and Cancellation Test to evaluate executive functions were administered to all participants by the clinician.Serum levels of neurotrophic factors were measured using commercial enzyme linked immunosorbent assay kits. RESULTS: Serum BDNF, NT-3, NT-4 levels and SDLT scores were significantly lower in the high-risk group for BD compared to the healthy control group. A moderate negative correlation was found between BDNF levels and the Cancellation Test scores in the high-risk group. In addition to these results, the odds ratios of age, NT-4, SDLT scores for being in the risky group in terms of BD diagnosis were 1.26, 0.99 and 0.86 respectively. LIMITATIONS: This was a cross-sectional study. Causality between study results is therefore difficult to establish. The relatively small sample size of the study is another limitation. CONCLUSION: The results of the present study suggest that BDNF, NT-3, NT-4 may play a role in the physiopathology of BD and may be associated with impaired executive function areas such as attention and response inhibition in the high-risk group.

Behavioral self-regulation in pediatric bipolar disorder and healthy offspring of bipolar patients.

OBJECTIVES: This study investigated behavioral self-regulation problems using the Children's Hostility Inventory (CHI) in pediatric bipolar disorder (PBD), healthy offspring of bipolar disorder patients (HOBD), and healthy controls (HC) without previous history of psychiatric disorders. METHODS: The CHI was administered to 41 consecutive children and adolescents diagnosed with PBD, to 16 HOBD, and to 22 HC. The inventory assessed irritability, expression, hostility, and aggression and was completed by the children with the help of their mothers. Adolescents and their respective parents were interviewed separately using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). RESULTS: All subscales of the CHI presented statistically significant differences, except for the subscale assessing feelings of suspicion. Pairwise comparisons revealed consistently significant differences between the PBD group and controls, indicating more self-regulation difficulties in the PBD group, represented by high levels of hostility and aggressive behavior. There were no significant differences between the PBD and HOBD groups. CONCLUSIONS: Future studies should further investigate if such behavior is state-dependent or a trait of bipolar juvenile expression. Expression of hostility and irritability should be considered relevant targets in psychosocial approaches addressing this population.

Functional outcomes across development in offspring of parents with bipolar disorder.

OBJECTIVE: Whereas the risk and course of psychopathology in offspring of parents with bipolar disorder (BD) have been the primary focus of high-risk offspring studies to date, functional outcomes have not been given much attention. We present a systematic review of functional outcomes and quality of life (QoL) across development in offspring of parents with BD and aim to explore the role of offspring psychopathology in these outcomes. METHOD: We searched Embase, MEDLINE, PsycINFO, Web of Science, Cochrane Central, and Google Scholar from inception to June 24, 2022, for studies referring to functional outcomes (global, social, academic or occupational) or QoL in offspring of parents with BD. RESULTS: From the 6470 records identified, 39 studies were retained (global = 17; social = 17; school = 16; occupational = 3; QoL = 5), including 13 studies that examined multiple domains. For all domains, high heterogeneity was found in study methods and quality. Only 56 % of studies adjusted for offspring psychopathology, impeding interpretation. Global and social functioning generally seemed to be impaired among older offspring (>16 years). Academic performance appeared to be unaffected. School behavior, occupational functioning, and QoL showed mixed results. Offspring psychopathology is associated with social functioning, but the relationship of offspring psychopathology with other domains is less clear. CONCLUSION: Studies on functional outcome in offspring of parents with BD show predominantly mixed results. Inconsistent adjustment of psychopathology and age limits conclusive interpretation. Functional outcomes should be prioritized as research topics in high-risk studies and the potential associations between familial risk status, offspring psychopathology, and age may inform prevention strategies.

Behavioral self-regulation in pediatric bipolar disorder and healthy offspring of bipolar patients

Objectives: This study investigated behavioral self-regulation problems using the Children's Hostility Inventory (CHI) in pediatric bipolar disorder (PBD), healthy offspring of bipolar disorder patients (HOBD), and healthy controls (HC) without previous history of psychiatric disorders. Methods: The CHI was administered to 41 consecutive children and adolescents diagnosed with PBD, to 16 HOBD, and to 22 HC. The inventory assessed irritability, expression, hostility, and aggression and was completed by the children with the help of their mothers. Adolescents and their respective parents were interviewed separately using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). Results: All subscales of the CHI presented statistically significant differences, except for the subscale assessing feelings of suspicion. Pairwise comparisons revealed consistently significant differences between the PBD group and controls, indicating more self-regulation difficulties in the PBD group, represented by high levels of hostility and aggressive behavior. There were no significant differences between the PBD and HOBD groups. Conclusions: Future studies should further investigate if such behavior is state-dependent or a trait of bipolar juvenile expression. Expression of hostility and irritability should be considered relevant targets in psychosocial approaches addressing this population.

Executive function deficit in bipolar offspring: A neurocognitive endophenotype?

BACKGROUND: Recent studies in bipolar offspring (BO) showed that a low cognitive performance, especially executive function deficit, could be an early marker of bipolar disorder (BD). Nevertheless, these findings have not been replicated (specifically attentional control, flexibility, and working memory). In addition, most studies have focused on children and adolescents, but few studies analyze the executive function performance in BO adults. OBJECTIVE: Our goal was to compare the neurocognitive performance of BO with control parent-offspring (CO) in a sample that included various age groups. METHOD: We conducted a cohort study, including subjects between six to 30 years old. We evaluated 129 BO and 113 CO subjects using validated psychiatric diagnostic interviews and an extensive neuropsychological battery. RESULTS: Compared to the CO group, the BO group presented a lower performance in several executive functioning domains, mainly in tasks of attentional control, flexibility, and working memory. All age groups exhibited these findings. CONCLUSIONS: BO group presents executive function deficits, regardless of the age group: children, adolescents, and adults. This neurocognitive deficit should be accountable as a neurocognitive endophenotype candidate in BD.

Cognitive correlates of impulsive aggression in youth with pediatric bipolar disorder and bipolar offspring.

BACKGROUND: Youth with bipolar disorder (BD) and offspring of individuals with BD (BD-OFF) are characterized by higher levels of impulsive and overt aggression. The cognitive basis underlying these aggressive behaviors are not clarified in this population. The aim of this study was to investigate the relationship between cognitive alterations and aggressive behavior in youth with BD and BD-OFF. METHODS: Forty-two youth with BD, 17 BD-OFF and 57 healthy controls (HCs) were administered the Modified Overt Aggression Scale (MOAS), the Cambridge Neuropsychological Test Automated Battery (CANTAB), the Young Mania Rating Scale (YMRS) and the Children's Depression Rating Scale (CDRS). Multiple linear regression analyses were performed in the three groups separately. In each group, tests scores from the CANTAB were predictors. MOAS subscale scores and MOAS total scores were dependent variables. Results are corrected for age, IQ and mood state. RESULTS: Both youth with BD and BD-OFF showed positive correlations between impairment in executive functions and levels of verbal aggression. In youth with BD, altered processing of either positive and negative stimuli positively correlated with MOAS total scores, whereas in BD-OFF, such relationship was negative. CONCLUSIONS: Impulsive aggressive behaviors in youth with BD arise from a combination of altered affective processing and executive dysfunction. The negative relationship between affective processing and aggression in BD-OFF suggested the presence of possible mechanisms of resilience in this population.

Traumatic experiences, family functioning, and mood disorder development in bipolar offspring.

OBJECTIVES: Studies in children of patients affected with bipolar disorder (BD; bipolar offspring) are at high risk to develop mood disorders. Our aim is to investigate how environmental factors such as childhood trauma and family functioning relate to the development of mood disorders in offspring at familial risk for BD. DESIGN: The current study is part of a longitudinal prospective cohort study among offspring of parents with BD. METHODS: The current study is part of the Dutch Bipolar Offspring Study, an ongoing prospective cohort study among adolescent offspring of a parent with BD. Bipolar offspring were psychiatrically evaluated at baseline and at 1-, 5-, and 12-year follow-up. Complete follow-up data over de 12-year follow-up were available for 102 offspring. Childhood trauma was measured with the Childhood Trauma Questionnaire (CTQ) and filled out by the offspring. Family functioning was reported by the mother with the 130-item Questionnaire for Family Problems (QFP). RESULTS: Emotional maltreatment was significantly associated (HR = 1.82, CI 1.18-2.82, p = .007) with mood disorder onset in bipolar offspring. No association was found with the family functioning total score (HR = 1.04, CI 0.94-15, p = .085) nor its subscales. CONCLUSIONS: The current study suggests that emotional maltreatment is associated with mood disorder development in bipolar offspring. Remarkably, the association of offspring-reported emotional maltreatment and mood disorder onset was not reflected in parent-reported family functioning (e.g., support and communication, openness or involvement). Possible explanations are discussed and warrant further study. PRACTITIONER POINTS: Offspring of bipolar patients are at increased risk of developing mood disorders across the life-time. Emotional trauma contributes to the likelihood of developing mood disorders in bipolar offspring. In the daily treatment of bipolar patients having children, attention should be given to parental style and difficulties. Further research using multiple informant methods on childhood trauma an family functioning is needed to further disentangle the effects of these variables on the onset of psychopathology in bipolar offspring.

The Dutch Bipolar Offspring Study: Cognitive Development and Psychopathology.

Various aspects of the relationship between cognitive impairment and bipolar disorder are not clear yet. This study examines cognitive and educational functioning prospectively in offspring at familial risk for bipolar disorder, in order to improve our understanding of the association between cognitive functioning and psychopathology. Bipolar offspring (N = 92) from the prospective Dutch bipolar offspring study were evaluated at adolescence and adulthood for IQ estimate, educational achievement and development of any psychiatric disorder. The main outcome was IQ estimate after 12 years of follow-up (offspring mean age 28 years). Generalized estimating equation (GEE) analyses showed that any lifetime DSM-IV axis I diagnosis was related to a lower cognitive outcome at adulthood as compared to unaffected bipolar offspring. No specific association was found for type of diagnosis. Early onset psychopathology (diagnosis at or before age 15 years) was significantly related to lower IQ estimate at adulthood, indicating a sensitive period for neurocognitive development.

Rostral Middle Frontal Volumetric Differences in Bipolar Offspring versus Community Controls Offspring.

Neuroanatomical findings in the anterior limbic network in bipolar disorder (BD) adults have not been replicated in other populations such as bipolar offspring (BO). The aim of this study was to compare some brain areas volumes between BO with and without a lifetime affective disorder (AD) to a group of community control offspring (CCO). Methods: A descriptive observational cross-sectional study was carried out, with multiple comparison groups. Seven subjects (11-17 years old) from the BO with AD group were compared to seven subjects from the BO without AD group and seven subjects from the CCO group (match by age, gender and Tanner stage). Magnetic resonance imaging was performed with a Philips 3 Teslas device and volumetric segmentation was performed with the Freesurfer image analysis suite. Results: A larger size was found in the right middle frontal rostral region in the BO with AD group compared to the other two groups (p = 0.041). A higher volume was also found in BO with AD group in the left pars opercularis (Cohen d = 0.63) and in the right cingulate isthmus (d = 0.53) when compared with BO without AD group, and in the right hippocampus (d = 0.53) when compared to CCO group. A smaller volume was found in the BO without AD group versus CCO group in the left anterior caudate (d = 0.6). The BO groups (with and without AD) compared to CCO have a higher volume in the right frontal pole (d = 0.52). These volumetric differences can be attributed to the condition of BO with AD.

Los hallazgos neuroanatómicos en la red límbica anterior en el trastorno bipolar (TB) en adultos no se han replicado en otras poblaciones, como en los hijos de pacientes con trastorno bipolar (HPTB). El objetivo de este estudio fue comparar los volúmenes de áreas del cerebro entre HPTB, con y sin algún trastorno afectivo (TA) a lo largo de la vida, con un grupo de hijos de padres control de la comunidad (HPC). Métodos: Se realizó un estudio observacional, descriptivo y transversal, con múltiples grupos de comparación. Siete sujetos (11-17 años) del grupo HPTB con TA se compararon con siete sujetos del grupo HPTB sin TA y siete sujetos del grupo HPC (pareados por edad, sexo y estadio Tanner). La resonancia magnética nuclear se realizó con un resonador Philips 3 Teslas y la segmentación volumétrica se realizó con el conjunto de análisis de imagen Freesurfer. Resultados: Se encontró un tamaño mayor en la región frontal rostral medial derecha en el grupo HPTB con TA en comparación con los otros dos grupos (p = 0.041). También se encontró un mayor volumen en el grupo HPTB con TA en el opérculo frontal izquierdo (Cohen d = 0, 63) y en el istmo del giro del cíngulo derecho (d = 0, 53) cuando se comparó con el grupo sin TA, y en el hipocampo derecho (d = 0, 53) en comparación con el grupo HPC. Se encontró un volumen más pequeño en el grupo HPTB sin TA versus grupo HPC en el caudado anterior izquierdo (d = 0, 6). Los grupos HPTB (con y sin TA) en comparación con HPC tienen un volumen mayor en el polo frontal derecho (d = 0.52). Estas diferencias volumétricas pueden atribuirse a la condición de HPTB con TA.

Lifetime psychiatric disorders: A comparison study between offspring of parents with bipolar disorder type-I versus the offspring of community controls parents / Trastornos psiquiátricos a través de la vida: un estudio de comparación de hijos de padres con trastorno afectivo bipolar tipo I frente a hijos de padres controles de la comunidad

Abstract Introduction: Literature reports show that bipolar offspring (BO) present with a wide range of psychiatric disorders. Comparison between BO and control parent offspring (CPO) may help to identify which psychopathological findings are specific to this high-risk group. Objective: To compare the psychopathological characteristics between a group of BO type-I and a group of CPO, by identifying the presence of psychiatric disorders according the DSM-IV-TR. Methods: A descriptive-correlational, cross-sectional and comparative study was conducted with 127 offspring of parents with bipolar disorder type-I from the multimodal intervention programme (PRISMA) and with 150 CPO between 6 and 30 years of age. Subjects were evaluated with validated diagnostic interviews (K-SADS-PL and DIGS). Results: The BO group showed higher frequencies for bipolar disorder (prevalence ratio [PR] = 17.70; 95% confidence interval [CI]; 1.02-306.83), bipolar disorder not otherwise specified (PR = 23.07, 95% CI; 2.8-189.0, p = 0.0001), disorders due to psychoactive substance use (PR = 9.52,95% CI; 2.93-30.90), oppositional defiant disorder (PR = 4.10,95% CI; 1.70-9.89), posttraumatic stress disorder (PR = 3.90, 95% CI 1.30-11.66), disorder due to alcohol use (PR = 3.84, 95% CI; 1.28-11.48), attention deficit/hyperactivity disorder (PR = 2.26, 95% CI; 1.37-3.75), and major depressive disorder (PR = 2.25, 95% CI; 1.13-4.50). Statistically significant differences were also found in the CGAS and GAF functional scales, with lower scores for the BO group. Conclusion: These findings confirm previous literature reports showing that BO have higher rates of affective and non-affective psychiatric disorders than control subjects, and also a lower level of global functioning.

Resumen Introducción: Reportes en la literatura muestran que los Hijos de Padres con Trastorno Bipolar tipo I (HPTB) manifiestan un amplio rango de trastornos psiquiátricos. La comparación entre los HPTB y los Hijos de Padres Control (HPC) permite establecer cuáles hallazgos psicopatológicos son específicos de este grupo de alto riesgo. Objetivo: Comparar las características psicopatológicas entre un grupo de HPTB tipo I y un grupo de HPC, mediante la identificación de la presencia de trastornos psiquiátricos según el DSM-IV-TR. Metodología: Se realizó un estudio descriptivo-correlacional, comparativo de corte transversal con 127 Hijos de Padres con TAB tipo I (HPTB-I) dentro de un programa de intervención multimodal (PRISMA) y 150 HPC, con edades entre los seis y 30 años. Los sujetos fueron evaluados con entrevistas diagnósticas validados (K-SADS-PL y DIGS). Resultados: El grupo de HPTB mostró mayor frecuencias de trastorno bipolar (Razón de Prevalencia [RP] = 17,70; Intervalo de Confianza [IC] del 95%, 1,02-306,83), trastorno bipolar no especificado (RP = 23,07, IC 95% 2,8 -189, p = 0.0001), trastorno por uso de sustancias psi-coactivas (RP = 9,52; IC 95%, 2,93-30,90), trastorno oposicionista desafiante (RP = 4,10; IC 95%, 1,70-9,89); trastorno de estrés postraumático (RP = 3,90; IC 95%, 1,30-11,66), trastorno por uso de alcohol (RP = 3,84; IC 95%, 1,2811,48), trastorno por déficit de atención e hiperactividad (RP = 2,26; IC 95%, 1,37-3,75) y trastorno depresivo mayor (RP = 2,25; IC 95%, 1,13-4,50). También se encontraron diferencias estadísticamente significativas en las escalas de funcionalidad CGAS y GAF, con menor puntaje en el grupo de HPB. Conclusión: Estos hallazgos confirman reportes previos de la literatura que demuestran que los HPTB presentan mayores tasas de trastornos psiquiátricos afectivos y no afectivos, y una menor nivel de funcionalidad global, al ser comparados con sujetos controles de la comunidad.

[Lifetime Psychiatric Disorders: a Comparision Study Between Offspring of Parents With Bipolar Disorder Type-I Versus the Offspring of Community Controls Parents]. / Trastornos psiquiátricos a través de la vida: un estudio de comparación de hijos de padres con trastorno afectivo bipolar tipo I frente a hijos de padres controles de la comunidad.

INTRODUCTION: Literature reports show that Bipolar Offspring (BO) present with a wide range of psychiatric disorders. Comparison between BO and Control Parent Offspring (CPO) may help to identify which psychopathological findings are specific to this high-risk group. OBJECTIVE: To compare the psychopathological characteristics between a group of BO type-I and a group of CPO, by identifying the presence of psychiatric disorders according the DSM-IV-TR. METHODS: A descriptive-correlational, cross-sectional and comparative study was conducted with 127 offspring of parents with bipolar disorder type-I from the multimodal intervention program (PRISMA) and with 150 CPO between 6 and 30 years of age. Subjects were evaluated with validated diagnostic interviews (K-SADS-PL and DIGS). RESULTS: The BO group showed higher frequencies for bipolar disorder (Prevalence Ratio [PR]=17.70; 95% confidence interval [CI]; 1.02 - 306.83), bipolar disorder not otherwise specified (PR=23.07, 95% CI; 2.8 - 189.0, P=.0001), disorders due to psychoactive substance use (PR=9.52, 95% CI; 2.93 -30.90), oppositional defiant disorder (PR=4.10, 95% CI; 1.70 -9.89), posttraumatic stress disorder (PR=3.90, 95% CI 1.30 -11.66), disorder due to alcohol use (PR=3.84, 95% CI; 1.28 -11.48), attention deficit/hyperactivity disorder (PR=2.26, 95% CI; 1.37 -3.75), and major depressive disorder (PR=2.25, 95% CI; 1.13 -4.50). Statistically significant differences were also found in the CGAS and GAF functional scales, with lower scores for the BO group. CONCLUSION: These findings confirm previous literature reports showing that BO have higher rates of affective and non-affective psychiatric disorders than control subjects, and also a lower level of global functioning.

Characteristics of depression among offspring at high and low familial risk of bipolar disorder.

OBJECTIVES: Having a parent with bipolar disorder (BP) is a very strong risk factor for developing BP. Similarly, depression among youth is a clinical risk factor for subsequent BP. We evaluated whether mood symptomatology in depressed youth is different between those at high and low familial risk to develop BP. METHODS: The most severe major depressive episode in BP offspring (N=61) and community control offspring (N=20) was evaluated using expanded depression and mania rating scales derived from the Schedule for Affective Disorders and Schizophrenia for Children Present Version. The results were adjusted for any between-group significant demographic differences and for multiple comparisons. RESULTS: The severity of depressive symptoms and the percentage of offspring with severe depressive symptoms, especially atypical depressive features, were significantly higher in the depressed offspring of BP parents compared to the depressed controls (Ps <.05). The depressive symptoms were helpful to identify a high-risk group (e.g., odds ratio [OR] for hypersomnia: 22.4, 95% confidence interval [CI]: 1.3-404, P=.04). In addition, there were significantly more depressed offspring of BP parents with subsyndromal manic symptoms than controls (52.5% vs 20%, OR: 4.2, 95% CI: 1.2-14.7, P<.01). CONCLUSIONS: Depressed BP offspring had more severe depression including atypical depressive symptoms, and were more likely to have subsyndromal mixed manic symptoms than depressed control offspring. Prospective studies to evaluate whether these youth are at high risk to develop BP are warranted. If replicated, the results of this study have important clinical (e.g., treatment of depression in depressed offspring of BP parents) and research implications.

Immune dysregulation in offspring of a bipolar parent. Altered serum levels of immune growth factors at adolescent age.

Immune dysregulation plays a role in the vulnerability for mood disorders. Immune growth factors, such as Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein-2 (IGF-BP2), Epidermal Growth Factor (EGF), IL-7 and sCD25 have repeatedly been reported altered in patients with mood disorders. The aim of this study was to investigate levels of these factors in serum of adolescent bipolar offspring, who have a heightened risk for mood disorder development and to also analyze the data combined with previously published data. Growth factors were assessed by CBA/ELISA in adolescent bipolar offspring (n=96, mean age=16years) and in age- and gender-matched healthy controls (n=50). EGF belonged to a mutually correlating cluster of mainly neurotrophic compounds including S100B and BDNF, which were in general decreased in serum. IL-7, SCF, IGF-BP2 and sCD25, belonged to a different mutually correlating cluster of immune growth factors, which were in general increased: IGF-BP2 significantly in serum of offspring without a mood disorder, IL-7 and SCF in serum of offspring who had experienced a mood episode. This pattern of de- and increases was not different between bipolar offspring that developed or did not develop a mood disorder over time, apart from the IGF-BP2 level, which was near significantly higher in offspring later developing a mood disorder. Correlations with the previously published immune-cellular abnormalities were not found. In conclusion non-affected adolescents at familial mood disorder development risk were characterized by a distinct pattern of a series of compounds operating in a network of hematopoiesis, neurogenesis and inflammation.

Validation of the Seven Up Seven Down Inventory in bipolar offspring: screening and prediction of mood disorders. Findings from the Dutch Bipolar Offspring Study.

OBJECTIVE: To validate the Seven Up Seven Down (7U7D), an abbreviated version of the General Behavior Inventory (GBI), as screener for mood disorders and test its ability to predict mood disorders over time in individuals at risk for bipolar disorder (BD). METHODS: Bipolar offspring (n=108) were followed from adolescence into adulthood and assessed at baseline, 1-, 5- and 12 years follow-up (T1-T4 respectively). Offspring were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children--Present and Lifetime Version, Structured Clinical Interview for DSM-IV Axis I Disorders and the GBI. RESULTS: Performance of the GBI and 7U7D was functionally similar for the depression (7D) scale, but variable for the mania (7U) scale. As screener for mood disorders (T4), the 7D showed fair diagnostic efficiency (area under the curve (AUC) 0.68, p<0.01, OR 1.53, 95% CI 1.15-2.03). The discriminative validity for BD and unipolar disorder was only close to significant (7D AUC 0.66, p=0.078; 7U AUC 0.67, p=0.067). In terms of prediction of mood disorder onset between T1 and T4, the 7D, but not the 7U, was associated with new onset (AUC 0.67, p<0.05; HR 1.14, 95% CI 1.07-1.23). The 7U7D did not achieve significant prediction of BD. LIMITATIONS: Relative small sample size and limited generalizability. CONCLUSIONS: Based on the current study, the 7U7D shows limited potential as screening instrument for mood disorders in bipolar offspring. The clinical utility of the 7U7D needs further exploration for use in clinical and research settings.

Categorical and dimensional psychopathology in Dutch and US offspring of parents with bipolar disorder: A preliminary cross-national comparison.

OBJECTIVE: Accumulating evidence suggests cross-national differences in adults with bipolar disorder (BD), but also in the susceptibility of their offspring (bipolar offspring). This study aims to explore and clarify cross-national variation in the prevalence of categorical and dimensional psychopathology between bipolar offspring in the US and The Netherlands. METHODS: We compared levels of psychopathology in offspring of the Pittsburgh Bipolar Offspring Study (n=224) and the Dutch Bipolar Offspring Study (n=136) (age 10-18). Categorical psychopathology was ascertained through interviews using the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), dimensional psychopathology by parental reports using the Child Behavior Checklist (CBCL). RESULTS: Higher rates of categorical psychopathology were observed in the US versus the Dutch samples (66% versus 44%). We found no differences in the overall prevalence of mood disorders, including BD-I or -II, but more comorbidity in mood disorders in US versus Dutch offspring (80% versus 34%). The strongest predictors of categorical psychopathology were maternal BD (OR: 1.72, p<.05), older age of the offspring (OR: 1.19, p<.05), and country of origin (US; OR: 2.17, p<.001). Regarding comorbidity, only country of origin (OR: 7.84, p<.001) was a significant predictor. In general, we found no differences in dimensional psychopathology based on CBCL reports. LIMITATIONS: Preliminary measure of inter-site reliability. CONCLUSIONS: We found cross-national differences in prevalence of categorical diagnoses of non-mood disorders in bipolar offspring, but not in mood disorder diagnoses nor in parent-reported dimensional psychopathology. Cross-national variation was only partially explained by between-sample differences. Cultural and methodological explanations for these findings warrant further study.

Cortical thickness in symptomatic and asymptomatic bipolar offspring.

Children of parents diagnosed with bipolar disorder are at greater risk for developing a variety of psychiatric disorders, however, the reasons remain unknown. The present study aimed to investigate gray matter integrity in high-risk bipolar offspring (HRO) and healthy offspring (HCO) using cortical thickness techniques. Here we examined healthy control offspring (HCO; n=20) and HRO with (n=17) or without (n=13) psychiatric symptoms. T1-weighted images were collected from all offspring, and cortical thickness and age-cortical thickness correlations were compared. HRO showed cortical thinning in superior and inferior temporal regions, supramarginal, and caudal and rostral middle frontal regions compared to HCO. When comparing HRO with and without psychiatric symptoms, we found cortical thinning in symptomatic offspring in the superior frontal and somatosensory related cortices. Age-thickness correlations showed a relatively consistent negative relationship in most regions in HCO, while the reverse was true for the HRO. These regions included parahippocampal, lateral orbitofrontal, and inferior temporal regions. Our study provides evidence of cortical thickness reductions among symptomatic and asymptomatic high-risk offspring during youth. Some of these alterations, found in regions of emotion processing and regulation, are evident only when associated with the presence of psychiatric symptoms.

Accuracy of emotion labeling in children of parents diagnosed with bipolar disorder.

BACKGROUND: Emotion labeling deficits have been posited as an endophenotype for bipolar disorder (BD) as they have been observed in both patients and their first-degree relatives. It remains unclear whether these deficits exist secondary to the development of psychiatric symptoms or whether they can be attributed to risk for psychopathology. To explore this, we investigated emotion processing in symptomatic and asymptomatic high-risk bipolar offspring (HRO) and healthy children of healthy parents (HCO). METHODS: Symptomatic (n:18, age: 13.8 ± 2.6 years, 44% female) and asymptomatic (n:12, age: 12.8 ± 3.0 years, 42% female) HRO and age- and sex-matched HCO (n:20, age: 13.3 ± 2.5 years, 45% female) performed an emotion-labeling task. Total number of errors, emotion category and intensity of emotion error scores were compared. Correlations between total error scores and symptom severity were also investigated. RESULTS: Compared to HCO, both HRO groups made more errors on the adult face task (pcor=0.014). The HRO group were 2.3 times [90%CI:0.9-6.3] more likely and 4.3 times [90%CI:1.3-14.3] more likely to make errors on sad and angry faces, respectively. With the exception of sad face type errors, we observed no significant differences in error patterns between symptomatic and asymptomatic HRO, and no correlations between symptom severity and total number of errors. LIMITATIONS: This study was cross-sectional in design, limiting our ability to infer trajectories or heritability of these deficits. CONCLUSIONS: This study provides further support for emotion labeling deficits as a candidate endophenotype for BD. Our study also suggests these deficits are not attributable to the presence of psychiatric symptoms.

Gray matter volumes in symptomatic and asymptomatic offspring of parents diagnosed with bipolar disorder.

Children of parents diagnosed with bipolar disorder (BD), termed high-risk offspring (HRO), are at greater risk of developing psychiatric disorders compared to healthy children of healthy parents (HCO). Gray matter volume (GMV) abnormalities have been observed in HRO, however, these reports are inconsistent. We posit that this variability may be attributed to differences in methodology among offspring studies; in particular, the presence of psychiatric symptoms in HRO. Here, we directly compared GMVs between symptomatic and asymptomatic HRO, and HCO. High-resolution T1-weighted MR images were collected from 31 HRO (18 symptomatic and 13 asymptomatic) and 20 age- and sex-matched HCO. HRO had at least one parent diagnosed with BD. Symptomatic HRO were defined as having a psychiatric diagnosis other than BD, while asymptomatic HRO were required to be free of any psychiatric diagnosis. Scans were processed using voxel-based morphometry methods and between group analyses were performed in SPM. Compared to HCO, the HRO group showed decreased GMV in the right inferior orbitofrontal, right middle frontal, and bilateral superior and middle temporal regions. Both symptomatic and asymptomatic HRO groups showed decreased GMV in these regions separately when compared to HCO. When comparing symptomatic and asymptomatic HRO, GMVs were comparable in all regions except the lateral occipital cortex. Our study compared symptomatic and asymptomatic HRO directly. In doing so, we provided further support for the presence of discrete GMV deficits in HRO, and confirmed that these deficits are present irrespective of the presence of symptoms in HRO.

[Description of Clinical and Neurocognitive Profiles in Offspring of Bipolar-Type-I Parents From a Multimodal Intervention Program: Prisma]. / Descripción de perfiles psicopatológicos y neurocognitivos de hijos de pacientes con trastorno bipolar tipo I dentro un programa de intervencion multimodal: PRISMA.

INTRODUCTION: Offspring of bipolar parents are a high risk population for the develop of mental diseases, their study allow determining the genetic risk, early symptoms, prodromes and psychopathology of bipolar disorder. OBJECTIVE: To describe the psychopathological characteristics and neurocognitives profiles of the offspring of bipolar type I parents. And to identify the presence of sub-syndromal symptoms in all the symptom domains. METHODS: A descriptive and cross-sectional study was conducted on 110 offspring between 6 and 30 years old. Semi-structured diagnostic interviews were performed. The intelectual coeficient was determined and a neuropsychological assessment was performed on 89 offspring. RESULTS: The most prevalent disorder in the offspring was ADHD (27.6%), with major depression (15.5%) and separation anxiety (14.1%) also being prevalent. Seven patients of the sample were diagnosed with bipolar disorder. There was a statistically significant difference between the age groups for ADHD prevalence. The most frequent sub-syndromal symptoms were observed in the disruptive group. Alterations in the cognitive domains: attention, verbal fluency, work memory, and speed of information processing, were observed in the group younger than 18 years. CONCLUSIONS: The offspring of bipolar parents have an elevated rate of psychopathology and cognitive alterations. They are a high risk population for the development of mental disease. These subjects also require close longitudinal observation and early and preventive therapeuthic interventions.