MicroRNA dysregulation in manic and euthymic patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BPD) is a major psychiatric disorder with an unclear pathophysiology. Peripheral blood samples are easily drawn, making them are good candidates for diagnosing diseases. MicroRNAs are small non-coding RNA transcripts that regulate gene expression by binding to the 3'- UTR of mRNAs and directing their degradation. The aim of this study was to use blood plasma to investigate microRNA dysregulations in bipolar manic and euthymic patients. SUBJECTS AND METHODS: Blood samples were collected from 58 patients with bipolar I disorder (19 manic, 39 euthymic) and 51 healthy controls. RESULTS: Four microRNAs (miR-29a-3p, p = 0.035; miR-106b-5p, p = 0.014; miR-107, p = 0.011; and miR-125a-3p, p = 0.014) were upregulated in the entire bipolar group, compared to the healthy controls. Seven microRNAs (miR-9-5p, p = 0.032; miR-29a-3p, p = 0.001; miR-106a-5p, p = 0.034; miR-106b-5p, p = 0.003; miR-107, p < 0.001; miR-125a-3p, p = 0.016; and miR-125b-5p, p = 0.004) were more upregulated in bipolar manic patients compared to the healthy controls, and two microRNAs (miR-106a-5p, p = 0.013, and miR-107, p = 0.021) showed statistically significant upregulation in the manic patients compared to the euthymic patients. CONCLUSIONS: Our results showed greater miRNA dysregulation in the manic patients than in the euthymic patients. Two microRNAs could be more selective for bipolar manic episodes. Future studies should include depressive patients along with euthymic and manic patients.

Factorial structure and familial aggregation of the Hypomania Checklist-32 (HCL-32): Results of the NIMH Family Study of Affective Spectrum Disorders.

BACKGROUND: There is substantial evidence that bipolar disorder (BD) manifests on a spectrum rather than as a categorical condition. Detection of people with subthreshold manifestations of BD is therefore important. The Hypomania Checklist-32 (HCL-32) was developed as a tool to identify such people. PURPOSE: The aims of this paper were to: (1) investigate the factor structure of HCL-32; (2) determine whether the HCL-32 can discriminate between mood disorder subtypes; and (3) assess the familial aggregation and cross-aggregation of hypomanic symptoms assessed on the HCL with BD. PROCEDURES: Ninety-six probands recruited from the community and 154 of their adult first-degree relatives completed the HCL-32. Diagnosis was based on semi-structured interviews and family history reports. Explanatory factor analysis and mixed effects linear regression models were used. FINDINGS: A four-factor ("Activity/Increased energy," "Distractibility/Irritability", "Novelty seeking/Disinhibition, "Substance use") solution fit the HCL-32, explaining 11.1% of the total variance. The Distractibility/Irritability score was elevated among those with BP-I and BP-II, compared to those with depression and no mood disorders. Higher HCL-32 scores were associated with increased risk of BD-I (OR = 1.22, 95%CI 1.14-1.30). The "Distractibility/Irritability" score was transmitted within families (ß = 0.15, p = 0.040). However, there was no familial cross-aggregation between mood disorders and the 4 HCL factors. CONCLUSIONS: Our findings suggest that the HCL-32 discriminates the mood disorder subtypes, is familial and may provide a dimensional index of propensity to BD. Future studies should explore the heritability of symptoms, rather than focusing on diagnoses.

Effects of a Balanced Translocation between Chromosomes 1 and 11 Disrupting the DISC1 Locus on White Matter Integrity.

OBJECTIVE: Individuals carrying rare, but biologically informative genetic variants provide a unique opportunity to model major mental illness and inform understanding of disease mechanisms. The rarity of such variations means that their study involves small group numbers, however they are amongst the strongest known genetic risk factors for major mental illness and are likely to have large neural effects. DISC1 (Disrupted in Schizophrenia 1) is a gene containing one such risk variant, identified in a single Scottish family through its disruption by a balanced translocation of chromosomes 1 and 11; t(1;11) (q42.1;q14.3). METHOD: Within the original pedigree, we examined the effects of the t(1;11) translocation on white matter integrity, measured by fractional anisotropy (FA). This included family members with (n = 7) and without (n = 13) the translocation, along with a clinical control sample of patients with psychosis (n = 34), and a group of healthy controls (n = 33). RESULTS: We report decreased white matter integrity in five clusters in the genu of the corpus callosum, the right inferior fronto-occipital fasciculus, acoustic radiation and fornix. Analysis of the mixed psychosis group also demonstrated decreased white matter integrity in the above regions. FA values within the corpus callosum correlated significantly with positive psychotic symptom severity. CONCLUSIONS: We demonstrate that the t(1;11) translocation is associated with reduced white matter integrity in frontal commissural and association fibre tracts. These findings overlap with those shown in affected patients with psychosis and in DISC1 animal models and highlight the value of rare but biologically informative mutations in modeling psychosis.

Effect of the 5-HTTLPR polymorphism on affective temperament, depression and body mass index in obesity.

BACKGROUND AND AIM: Many studies show high prevalence of affective disorders in obese patients. Affective temperament is a subclinical manifestation of such conditions. The 5-HTT gene encoding the serotonin transporter may be involved in both mood and eating dysregulation. The aim of this study was to investigate the influence of a polymorphism in the 5-HTT gene on affective temperament types, depressive symptoms and Body Mass Index (BMI) in obese patients. METHODS: This study involved 390 patients (237 females, and 153 males) with obesity. The TEMPS-A questionnaire, Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS) were used to evaluate affective temperaments and prevalence of depression. DNA was obtained for serotonin transporter gene-linked polymorphism (5-HTTLPR) genotyping. RESULTS: In obese patients S/S genotype was associated with depressive and L/L with cyclothymic temperament. Subjects with L/L genotype presented significantly higher BMI and greater intensity of depressive symptoms in BDI and HDRS. Females scored higher in anxious and depressive, while males in hyperthymic, cyclothymic and irritable temperaments. Females scored higher in BDI (subjective depression) while males in HDRS (objective depression). LIMITATIONS: TEMPS-A, BDI and HDRS are frequently used in studies on affective disorders. However, these methods do not examine all dimensions of mood and personality. CONCLUSIONS: In obese patients S allele of 5-HTTLPR was associated with development of depressive temperament while L allele corresponded with greater obesity and prevalence of depression. Different mechanisms may be involved in manifestation of depression in males and females with obesity.

A genetic analysis of the validity of the Hypomanic Personality Scale.

OBJECTIVES: Studies of mania risk have increasingly relied on measures of subsyndromal tendencies to experience manic symptoms. The measures of mania risk employed in those studies have been shown to predict manic onset, to show familial associations, and to demonstrate expected correlations with psychosocial variables related to bipolar disorder. However, little work has been conducted to validate such measures against biologically relevant indices, or to consider whether early adversity, which has been shown to be highly elevated among those with bipolar disorder, is related to higher scores on mania risk measures. This study tested whether a well-used, self-report measure of vulnerability to mania is associated with several candidate genes that have previously been linked with bipolar disorder or with early adversity. Interactions of genes with early adversity in the prediction of mania vulnerability were also tested. METHODS: Undergraduate students from the University of Miami (Coral Gables, FL, USA) (N = 305) completed the Hypomanic Personality Scale and the Risky Families Scale, and provided blood for genotyping. RESULTS: Findings indicated that the Hypomanic Personality Scale was related to a number of dopamine-relevant polymorphisms and with early adversity. A polymorphism of ANKK1 appeared to specifically increase mania risk in the context of early adversity. CONCLUSIONS: These results provide additional support for the validity of the Hypomanic Personality Scale.

The significance of at-risk or prodromal symptoms for bipolar I disorder in children and adolescents.

While in the early identification and intervention of psychosis-specific instruments and risk criteria have been generated and validated, research into indicated preventive strategies for bipolar I disorder (BD I) has only recently gained momentum. As the first signs of BD I often start before adulthood, such efforts are especially important in the vulnerable pediatric population. Data are summarized regarding the presence and nature of potentially prodromal, that is, subsyndromal, symptoms prior to BD I, defined by first-episode mania, focusing on pediatric patients. Research indicates the possibility of early identification of youth at clinical high risk for BD. Support for this proposition comes from retrospective studies of BD I patients, as well as prospective studies of community samples, offspring of BD I subjects, youth with depressive disorders, and patients at high risk for psychosis or with bipolar spectrum disorders without lifetime history of mania. These data provide essential insight into potential signs and symptoms that may enable presyndromal identification of BD I in youth. However, except for offspring studies, broader prospective approaches that focus on youth at clinical high risk for BD I and on developing specific interviews and (or) rating scales and risk criteria are mostly missing, or in their early stage. More work is needed to determine valid and sufficiently specific clinical high-risk criteria, to distinguish risk factors, endophenotypes, and comorbidities from prodromal symptomatology, and to develop phase-specific interventions that titrate the risk of intervention to the risk of transition to mania and to functional impairment or distress. Moreover, studies are needed that determine potential differences in prodromal symptoms and trajectories between children, adolescents, and adults, and the best phase-specific interventions.

[Temperamental endophenotypes]. / Les endophénotypes tempéramentaux.

Temperament has been defined as the heritable biologically determined core of personality that remains stable throughout the life span and establishes the baseline level of reactivity, mood, and energy of a person. If the link between temperament and mental disorder goes back to the Greco-Roman medicine, Kraepelin was among the first authors to pay attention to the temperamental bases of bipolar disorder. He proposed four temperamental types that he described in the premorbid histories of the majority of manic-depressive patients, and found overrepresented in the biologic relatives of these patients. Building on this ancestry, Akiskal formulated the modern concept of affective temperament, and described five temperaments: depressive, hyperthymic, cyclothymic, irritable, and anxious. According to Akiskal's model, bipolar disorder lies along a continuum from temperament to full-blown episodes of affective illness. A series of recent studies have shown the role played by temperaments in the outbreak of bipolar episodes, their clinical presentation, as well as the illness course and comorbidities. Furthermore modern familial and genetic studies have confirmed the first observations of Kraepelin. It has been recently proposed that affective temperaments may carry distinct evolutionary advantages on the individual or a group level, so that affective disorders would be genetic reservoirs for adaptative temperaments and the price to be paid for the chance of exceptionality. Apart from these theoretical perspectives, paying attention to temperamental components may have important implications for the treatment of bipolar disorder. Finally recent studies confirmed as well, that the concept of affective temperament fulfilled the criteria required to be considered as an endophenotype.

[The clinical importance of affective temperaments]. / Az affektív temperamentumok klinikai jelentosége.

Intensive research on affective temperaments began no more than a decade ago as a result of Akiskal's work in the field. Based on ancient Greek and later the Kraepelinian concept of temperament Akiskal created five distinct temperament types (hyperthym, cyclothym, depressive, irritable and anxious) which are now considered to be the preclinical background of affective disorders. In collaboration with an international workgroup, a semi-structured (TEMPS-I) and a self-rated (TEMPS-A) questionnaire was developed and translated into more than 25 languages intensifying research activity in the field. Based upon search of different databases (Scopus, Web of Knowledge, OVID Medline, PubMed, Psychinfo) and hand search of relevant Hungarian language literature, our review article aims to summarize current knowledge on affective temperaments. We cover their role in psychiatric and non-psychiatric disorders, investigate the scientific knowledge on their possible genetic background, highlight their importance on intercultural differences and outline the possibilities for future research discovering the common background between depression and other - non-psychiatric - disorders.

The 5-HTTLPR polymorphism, impulsivity and suicide behavior in euthymic bipolar patients.

BACKGROUND: Suicide behavior is very frequent in Bipolar Disorder (BD) and they are both closely associated with impulsivity. Furthermore they are, impulsivity, BD and suicide behavior, associated with serotonergic function, at least partially, under genetic determinism and somewhat associated with the serotonin transporter gene polymorphism, the 5-HTTLPR. We aimed to assess different impulsivity components in BD sub-grouped by suicidal attempt and healthy controls. We hypothesized that the non-planning/cognitive impulsivity, could be more closely associated with suicidal behavior. We further associated 5-HTTLPR genotypes with neuropsychological results to test the hypothesis that this polymorphism is associated with cognitive impulsivity. METHOD: We assessed 95 euthymic bipolar patients sub-grouped by suicidal attempt history in comparison with 94 healthy controls. All subjects underwent a laboratory assessment of impulsivity (Continuous Performance Test and Iowa Gambling Test). Furthermore the genotyping of 5-HTTLPR was performed in all subjects. RESULTS: We found that bipolar patients are more impulsive than healthy controls in all impulsivity dimensions we studied. Furthermore bipolar patients with a suicide attempt history have a greater cognitive impulsivity when compared to both bipolar patients without such a history as well when compared to healthy controls. No association was found between 5-HTTLPR genotypes and neuropsychological measures of impulsive behavior. LIMITATIONS: The sample studied can be considered small and a potentially confounding variable - medication status - was not controlled. CONCLUSION: A lifetime suicide attempt seems associated with cognitive impulsivity independently of the socio-demographic and clinical variables studied as well with 5-HTTLPR genotype. Further studies in larger samples are necessary.

CHRNA7 haplotypes are associated with impaired attention in euthymic bipolar disorder.

BACKGROUND: Bipolar disorder (BD) patients show a deficit in sustained attention during euthymic periods. This deficit may be relevant for genetic studies in these patients. The α7 cholinergic receptor plays an important role in attentional deficit in humans and animal models. Moreover, there is evidence suggesting the role of the alpha 7 nicotinic cholinergic receptor subunit gene (CHRNA7) in BD susceptibility. The aim of the present study was to investigate the impact of CHRNA7 in sustained attention performance. METHODS: We studied the association of a promoter variant (-86C/T) and three intronic polymorphisms, rs883473, rs6494223 and rs904952, in the non-duplicated region of CHRNA7 with sustained attention in 143 euthymic BD patients (based on DSM-IV criteria) and 101 healthy subjects. Sustained attention was assessed by the degraded stimulus (DS-CPT) version of Continuous Performance Test. Age, gender, years of education and IQ (WAIS vocabulary subtest) were controlled in the analyses as potential confounders. RESULTS: Several candidate polymorphisms showed significant associations with different measures of the neuropsychological task for bipolar group. The CTCT haplotype was associated with an improvement in the attentional task performance in the BD group (p ≤ 0.025). On the other hand, different low frequency haplotypes showed influence in bipolar attentional performance (p ≤ 0.026). LIMITATIONS: A replication study using larger samples may be required for conclusive results. CONCLUSIONS: Our results point toward a slight association of CHRNA7 genotypes and haplotypes with sustained attention performance in euthymic patients with BD.

Association between affective temperaments and bipolar spectrum disorders: preliminary perspectives from a controlled family study.

BACKGROUND: The study aimed at determining the temperamental underpinnings of bipolar spectrum disorders (BSD) in the first-degree relatives (FDR) of patients with bipolar I disorder in comparison with control subjects. SAMPLING AND METHODS: The sample consisted of 198 subjects: 33 bipolar I probands and their 33 FDR in the experimental group, 33 schizophrenia probands and their 33 FDR in the patient control group, and 33 normal healthy controls and their 33 FDR. The affective temperament and the BSD were assessed using the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire and the criteria of Ghaemi et al. [Can J Psychiatry 2002;47:125-134], respectively. RESULTS: Among the FDR of bipolar I probands, 27.3% satisfied the diagnosis of BSD, which was significantly higher than in the other groups (relative risk = 6, 95% CI = 1.74-20.69). Bipolar probands were significantly more hyperthymic as compared to controls (relative risk = 2, 95% CI = 1.34-2.98), and both the FDR of the bipolar and the FDR of the patient control groups were significantly more hyperthymic as compared to the FDR of the normal controls (relative risk = 1.52, 95% CI = 0.93-2.51). FDR (of bipolar patients) with BSD had a significantly higher total irritable temperament score as compared to FDR (of bipolar patients) without BSD (mean difference = 2.07, 95% CI = 0.64-3.50). CONCLUSIONS: Our findings support the fact that the whole spectrum of bipolarity is transmitted in susceptible families. The graded distribution of hyperthymia suggests it to be a milder expression of bipolarity in the FDR of bipolar patients. The irritable temperament appears to be a specific vulnerability marker for the development of BSD.

Examining the validity of cyclothymic disorder in a youth sample.

BACKGROUND: Four subtypes of bipolar disorder (BP) - bipolar I, bipolar II, cyclothymia and bipolar not otherwise specified (NOS) - are defined in DSM-IV-TR. Though the diagnostic criteria for each subtype are intended for both adults and children, research investigators and clinicians often stray from the DSM when diagnosing pediatric bipolar disorder (PBD) (Youngstrom, 2009), resulting in a lack of agreement and understanding regarding the PBD subtypes. METHODS: The present study uses the diagnostic validation method first proposed by Robins and Guze (1970) to systematically evaluate cyclothymic disorder as a distinct diagnostic subtype of BP. Using a youth (ages 5-17) outpatient clinical sample (n=827), participants with cyclothymic disorder (n=52) were compared to participants with other BP spectrum disorders and to participants with non-bipolar disorders. RESULTS: Results indicate that cyclothymic disorder shares many characteristics with other bipolar subtypes, supporting its inclusion on the bipolar spectrum. Additionally, cyclothymia could be reliably differentiated from non-mood disorders based on irritability, sleep disturbance, age of symptom onset, comorbid diagnoses, and family history. LIMITATIONS: There is little supporting research on cyclothymia in young people; these analyses may be considered exploratory. Gaps in this and other studies are highlighted as areas in need of additional research. CONCLUSIONS: Cyclothymic disorder has serious implications for those affected. Though it is rarely diagnosed currently, it can be reliably differentiated from other disorders in young people. Failing to accurately diagnose cyclothymia, and other subthreshold forms of bipolar disorder, contributes to a significant delay in appropriate treatment and may have serious prognostic implications.

No association between the serotonin transporter gene polymorphism 5-HTTLPR and cyclothymic temperament as measured by TEMPS-A.

BACKGROUND: Temperaments are stable personality traits that can be considered subsyndromal risk factors of psychiatric illnesses. The 5-HTTLPR polymorphism of the serotonin transporter gene has been found to be associated with affective temperaments, particularly the cyclothymic temperament, as measured with the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A). In this study we have attempted to replicate this finding in a population-based sample which is five times as large as the sample used in the original study. METHODS: The 21 items of the cyclothymic subscale of TEMPS-A was filled in by 691 individuals (404 females, 287 males, 18-40 years) randomly recruited from the general population. DNA was isolated from saliva, and the serotonin transporter polymorphism 5-HTTLPR was genotyped using the polymerase chain reaction and fragment analysis. RESULTS: No significant association was found between 5-HTTLPR genotype and TEMPS-A score, neither when analysing by an additive allelic model nor when the different genotypes and allelic dominance were examined. Furthermore, no association was observed after gender stratification, or when TEMPS-A was analysed as a dichotomous measure, using a cut-off of ≥11 positive item responses. LIMITATIONS: Although being used in clinical settings, TEMPS-A has not been officially validated in Norway. CONCLUSIONS: This study suggests that there is no association between the 5-HTTLPR polymorphism and cyclothymic temperament as measured by TEMPS-A.

The association between oxytocin receptor gene (OXTR) polymorphisms and affective temperaments, as measured by TEMPS-A.

BACKGROUND: Oxytocin is associated with social interaction, trust, and affectivity. Affective temperaments are traits based on Kraepelin's typological definition of the "fundamental states" of manic-depressive illness. These states can be measured by the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire version (TEMPS-A). The objective of this study is to assess the association between oxytocin receptor gene (OXTR) polymorphisms and affective temperaments. METHODS: Participants consisted of 493 genetically unrelated, non-clinical Japanese subjects (307 males and 186 females). The Mini-International Neuropsychiatric Interview (MINI) was used to screen and exclude those who had a lifetime diagnosis of schizophrenia or other psychotic disorders. Fifteen OXTR tag single nucleotide polymorphisms (SNPs) were genotyped using TaqMan® or direct sequencing. The Haploview 4.1. software determined the haplotype block structure. Haplotype-based quantitative trait association analysis with Bonferroni correction using PLINK 1.06 software was used to assess the association between haplotypes and the following affective temperaments: depressive, cyclothymic, hyperthymic, irritable, and anxious. RESULTS: Two haplotype blocks were identified on the OXTR. The depressive temperament was significantly associated with the most frequent haplotype GGGTGTC (rs11131149/rs2243370/rs2243369/rs13316193/rs2254298/rs2268493/rs2268491) (corrected P<0.05). LIMITATIONS: This study consisted of participants from a corporation and the effect sizes were small. CONCLUSIONS: The findings suggest that an OXTR haplotype is associated with a discrete depressive temperament. Clarification of the biological basis of this temperamental trait may help to elucidate the pathophysiology of depressive disorder.

Cyclothymic temperament and major depressive disorder: a study on Italian patients.

BACKGROUND: Classical authors had hypothesized that affective temperaments represent the subclinical manifestations of mood disorders: in particular, cyclothymic and hyperthymic temperaments have been considered as a subthreshold variant of bipolar disorder. The aim of our study is to test the presence of affective temperaments in a group of Italian patients with major depressive disorder (MDD), and to test the association between cyclothymic temperament and well-established validators of bipolar disorder diagnosis such as age at onset and family history of bipolar disorder. METHODS: Patients with diagnosis of major depressive disorder (DSM-IV-TR) were included in the study. Affective temperaments have been evaluated through the Italian semistructured interview version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-I). In order to improve the accuracy of family history and age at onset reports, close family members of the patients were also interviewed. RESULTS: 104 of patients included in the study have completed the temperament interview. 25.5% were diagnosed with a dominant affective temperament. Cyclothymic affective temperament was the most represented in the sample of MDD patients (12.3%); depressive, hyperthymic and irritable temperaments have been detected respectively in 7.5%, 2.8% and 2.8% of patients. Patients with CT showed a significantly lower age at onset of MDD than "pure" MDD patients (31.9 vs. 40.9 years; p=0.049) and higher rates of family history of bipolar disorder in first degree relatives (15.4% vs. 0%; p=0.001). LIMITATIONS: The major limitation of this study was the lack of a group of bipolar depressives, which would have been useful in order to confirm the similarities of age at onset and bipolar family history with cyclothymic MDD. CONCLUSIONS: Our data confirm previous reports in a sample of accurately screened patients with unipolar major depression: we found that patients with a cyclothymic temperament had an earlier age at onset and a higher family history for bipolar disorder than patients without any dominant affective temperament. Further research is needed to ascertain whether patients with "unipolar" cyclothymic MDD respond to mood stabilizers.

Early mood swings as symptoms of the bipolar prodrome: preliminary results of a retrospective analysis.

BACKGROUND/AIMS: Temperament and mood swings are promising indicators for the characterization of mood spectrum vulnerability. The aim of this study was to investigate the relationship between affective temperament and mood swings in bipolar disorder. We explored these clinical features retrospectively. METHODS: Patients who met the criteria for bipolar I disorder were enrolled in the study. Exclusion criteria were partial remittance and a full affective or psychotic episode. Data concerning illness and family history, mood swings (semistructured interview for mood swings) and depression (Beck, Depression Inventory) were obtained. We examined premorbid temperament with the validated German version Temps-M of the original version Temps-A. Patients with and without mood swings were compared with respect to the dominant temperament. RESULTS: Out of 20 bipolar patients, 6 subjects reported mood swings prior to the onset of affective disorder. Subjects with mood swings prior to the onset of bipolar disorder significantly correlated with a positive family history of affective disorders. Concerning cyclothymic and irritable temperament, bipolar affective patients with mood swings had higher scores. No differences were found between males and females. CONCLUSION: Our findings go in line with previous results that mood swings, as represented by the cyclothymic temperament, are present prior to the first onset of bipolar disorder in a subset of patients. These traits may represent vulnerability markers and could presumably be used to identify individuals at high risk for developing bipolar disorder in order to prevent this illness. Further studies are indicated to clarify the correlation with genetic risk factors.

Description and validation of the Affective Temperament Questionnaire.

BACKGROUND: Akiskal and Mallya (Psychopharmacol Bull. 1987;23:68-73) proposed criteria defining 4 affective temperaments-hyperthymic, irritable, cyclothymic, and dysthymic. This study aims to develop and validate, using a 3-point rating scale, a short questionnaire that assesses these temperaments. METHODS: The Affective Temperament Questionnaire (ATQ) was administered to a family-based sample of individuals with major depressive disorder (MDD), bipolar disorder (BP), or no mood disorder (N = 378). Factor analyses, internal consistency, and analysis of variance were undertaken to examine the factorial structure and concurrent validity (relative to Axis I mood disorder diagnosis) of the ATQ. Affective Temperament Questionnaire data were evaluated with respect to raw scores and dominant affective temperament. RESULTS: Three factors emerged--hyperthymia, cyclothymia, and dysthymia--which had moderate to high internal consistency. Support for the concurrent validity of ATQ was found, whereby temperament scores and rates of dominant affective temperaments differed with respect to mood disorder diagnosis. Hyperthymia and cyclothymia were more prevalent among individuals with BP than among individuals with MDD or no history of a mood disorder. Dysthymia occurred at a relatively similar rate among individuals with MDD or BP. CONCLUSIONS: Our findings support the use of the ATQ for collecting information regarding affective temperaments and for furthering understanding regarding the links between affective temperament and mood disorders.

[Darier's disease: an evaluation of its neuropsychiatric component]. / Les manifestations neuropsychiatriques de la maladie de Darier : résultat préliminaire d'une étude epidémioclinique et génétique de huit familles.

BACKGROUND: Darrier's disease is a rare genodermatosis with a dominant autosomic penetrating variable transmission. The association between Darier's disease and neuropsychiatric disorders has been reported since 1996. Moreover, associations with mental retardation, schizophrenia, mood disorders and suicide have been reported. The discovery in 1999 of the ATP2A2 gene of Darier's disease, localised on chromosome 12, allowed significant advances notably in understanding the pathogenicity of these symptoms. MATERIAL AND METHODS: In this article, we present the preliminary results of a clinical and genetic study of eight Tunisian families, involving dermatologists, psychiatrists and geneticians. Eight patients with Darier's disease and their first degree relatives were included in the study after they had given their written consent. Thirty-five subjects were examined, 23 of them had Darier's disease. All patients were submitted to a complete clinical examination; notably dermatological screening, genetic inquiry and blood tests for haplotype analysis. Only 13 of them underwent a psychiatric examination. RESULTS: The psychiatric examination was carried out only in 13 patients with Darier's disease, who revealed neuropsychiatric symptoms with a frequency of 61.1% (8/13). Two patients presented mild mental retardation; six patients had mood disorders, three of them belonged to the same family (two had recurrent depression, four belonged to the bipolar spectrum [2 bipolar disorder type 2, 2 cyclothymia]). The coexpression of the two distinct phenotypes (Darier's disease and bipolar disease), within the same three members' of the family of our study, suggests the existence of a genetic linkage between the two diseases, as has been reported in the literature.

Prevention of bipolar disorder in at-risk children: theoretical assumptions and empirical foundations.

This article examines how bipolar symptoms emerge during development, and the potential role of psychosocial and pharmacological interventions in the prevention of the onset of the disorder. Early signs of bipolarity can be observed among children of bipolar parents and often take the form of subsyndromal presentations (e.g., mood lability, episodic elation or irritability, depression, inattention, and psychosocial impairment). However, many of these early presentations are diagnostically nonspecific. The few studies that have followed at-risk youth into adulthood find developmental discontinuities from childhood to adulthood. Biological markers (e.g., amygdalar volume) may ultimately increase our accuracy in identifying children who later develop bipolar I disorder, but few such markers have been identified. Stress, in the form of childhood adversity or highly conflictual families, is not a diagnostically specific causal agent but does place genetically and biologically vulnerable individuals at risk for a more pernicious course of illness. A preventative family-focused treatment for children with (a) at least one first-degree relative with bipolar disorder and (b) subsyndromal signs of bipolar disorder is described. This model attempts to address the multiple interactions of psychosocial and biological risk factors in the onset and course of bipolar disorder.

Suggestive linkage of a chromosomal locus on 18p11 to cyclothymic temperament in bipolar disorder families.

Attempts to identify bipolar disorder (BP) genes have only enjoyed limited success. One potential cause for this problem is that the traditional categorical BP phenotypes currently used in genetic linkage studies are not the most informative, efficient, or biologically relevant. An alternative to these strict categorical BP phenotypes is quantitative BP phenotypes. By isolating one aspect of a complex trait such as BP into a simple, intermediate, quantitative trait, genes that contribute to the larger complex trait can be more readily identified. Along these lines, we utilized a temperament-based measure (cyclothymic temperament) as a quantitative, intermediate BP phenotype in linkage analyses and hypothesized that this measure might more efficiently detect loci for BP or temperamental traits that predispose to BP. A total of 158 individuals with temperament data from 28 BP families were used in the linkage analyses. All pedigrees had a proband diagnosed with BPI or BPII and at least two other family members with a mood disorder diagnosis. An 8 cM genome scan was performed and analyzed using MERLIN nonparametric multipoint regression linkage for a cyclothymic temperament trait. The highest overall LOD score was on chromosome 18 (LOD = 2.71, P = 0.0002). Other linkage peaks which may indicate potential regions of interest were found on chromosomes 3 and 7. The temperament-based cyclothymic trait yielded a higher peak LOD score and a lower P-value than analyses using traditional, categorical phenotypes in a separate analysis including these same families.