Coping with the New Era: Noise and Light Pollution, Hperactivity and Steroid Hormones. Towards an Evolutionary View of Bipolar Disorders.

Human population is increasing in immense cities with millions of inhabitants, in which life is expected to run 24 hours a day for seven days a week (24/7). Noise and light pollution are the most reported consequences, with a profound impact on sleep patterns and circadian biorhythms. Disruption of sleep and biorhythms has severe consequences on many metabolic pathways. Suppression of melatonin incretion at night and the subsequent effect on DNA methylation may increase the risk of prostate and breast cancer. A negative impact of light pollution on neurosteroids may also affect mood. People who carry the genetic risk of bipolar disorder may be at greater risk of full-blown bipolar disorder because of the impact of noise and light pollution on sleep patterns and circadian biorhythms. However, living in cities may also offers opportunities and might be selective for people with hyperthymic temperament, who may find themselves advantaged by increased energy prompted by increased stimulation produced by life in big cities. This might result in the spreading of the genetic risk of bipolar disorder in the coming decades. In this perspective the burden of poor quality of life, increased disability adjusted life years and premature mortality due to the increases of mood disorders is the negative side of a phenomenon that in its globality also shows adaptive aspects. The new lifestyle also influences those who adapt and show behaviors, reactions and responses that might resemble the disorder, but are on the adaptive side.

More inclusive bipolar mixed depression definition by permitting overlapping and non-overlapping mood elevation symptoms.

OBJECTIVE: The objective of this study was to assess the strengths and limitations of a mixed bipolar depression definition made more inclusive than that of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) by counting not only 'non-overlapping' mood elevation symptoms (NOMES) as in DSM-5, but also 'overlapping' mood elevation symptoms (OMES, psychomotor agitation, distractibility, and irritability). METHODS: Among bipolar disorder (BD) out-patients assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, we assessed prevalence, demographics, and clinical correlates of mixed vs. pure depression, using more inclusive (≥3 NOMES/OMES) and less inclusive DSM-5 (≥3 NOMES) definitions. RESULTS: Among 153 depressed BD, counting not only NOMES but also OMES yielded a three-fold higher mixed depression rate (22.9% vs. 7.2%) and important statistically significant clinical correlates for mixed compared to pure depression (more lifetime anxiety disorder comorbidity, more current irritability, and less current antidepressant use), which were not significant using the DSM-5 threshold. CONCLUSION: To conclude, further studies with larger numbers of patients with DSM-5 bipolar mixed depression assessing strengths and limitations of more inclusive mixed depression definitions are warranted, including efforts to ascertain whether or not OMES should count toward mixed depression.

More inclusive bipolar mixed depression definitions by requiring fewer non-overlapping mood elevation symptoms.

OBJECTIVE: Assess strengths and limitations of mixed bipolar depression definitions made more inclusive than that of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) by requiring fewer than three 'non-overlapping' mood elevation symptoms (NOMES). METHOD: Among bipolar disorder (BD) out-patients assessed with Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, we assessed prevalence, demographics, and clinical correlates of mixed vs. pure depression, using less inclusive (≥3 NOMES, DSM-5), more inclusive (≥2 NOMES), and most inclusive (≥1 NOMES) definitions. RESULTS: Among 153 depressed BD, compared to less inclusive DSM-5 threshold, our more and most inclusive thresholds, yielded approximately two- and five-fold higher mixed depression rates (7.2%, 15.0%, and 34.6% respectively), and important statistically significant clinical correlates for mixed compared to pure depression (e.g. more lifetime anxiety disorder comorbidity, more current irritability), which were not significant using the DSM-5 threshold. CONCLUSION: Further studies assessing strengths and limitations of more inclusive mixed depression definitions are warranted, including assessing the extent to which enhanced statistical power vs. other factors contributes to more vs. less inclusive mixed bipolar depression thresholds having more statistically significant clinical correlates, and whether 'overlapping' mood elevation symptoms should be counted.

Relationship between affective temperaments and aggression in euthymic patients with bipolar mood disorder and major depressive disorder.

BACKGROUND: So far there is a scarce of studies dealing with the relationship between different aspects of aggressive behaviour and affective temperaments among various mood disorders. The aim of the present study was to explore in a group of patients with affective mood disorders the relationship between affective temperaments and aggression. METHODS: 100 consecutive outpatients in euthymic phase of mood disorders (46 with bipolar disorder-type I, 18 with bipolar disorder-type II and 36 with major depressive disorder) were self-assessed with the Aggression Questionnaire and the short version of Slovenian Temperament Evaluation of Memphis, Pisa, Paris and San Diego - Autoquestionnaire (TEMPS-A). RESULTS: The factorial analysis of the TEMPS-A subscales revealed 2 main factors: Factor 1 (prominent cyclothymic profile) consisted of cyclothymic, depressive, irritable, and anxious temperaments and Factor 2 (prominent hyperthymic profile) which was represented by the hyperthymic temperament, and by depressive and anxious temperaments as negative components. Patients with prominent cyclothymic profile got their diagnosis later in their life and had significantly higher mean scores on anger and hostility (non-motor aggressive behaviour) compared with patients with prominent hyperthymic profile. LIMITATIONS: We included patients with different mood disorders, therefore the sample selection may influence temperamental and aggression profiles. We used self-report questionnaires which can elicit sociable desirable answers. CONCLUSION: Anger and hostility could represent stable personality characteristics of prominent cyclothymic profile that endure even in remission. It seems that distinct temperamental profile could serve as a good diagnostic and prognostic value for non-motor aspects of aggressive behaviour.

Multiple sclerosis and bipolar disorders: the burden of comorbidity and its consequences on quality of life.

BACKGROUND: The purpose is to measure the worsening of the Quality of Life (QoL) in people with Multiple Sclerosis (MS) and the concomitant role of co-morbid Major Depressive Disorder (MDD) and Bipolar Disorder (BD), the latter not yet studied even though it was found strictly associated with MS. CASES: 201 consecutive-MS-patients. CONTROLS: 804 sex-and-age-matched subjects without MS, randomly selected from an epidemiological database study. Psychiatric diagnoses according to DSM-IV were determined by physicians using structured interview tools (ANTAS-SCID). Bipolar Spectrum Disorders were identified by Mood Disorders Questionnaire (MDQ). QoL was measured by SF-12. RESULTS: MS was the strongest determinant in worsening the QoL in the overall sample. Both MDD and BD type-II lifetime diagnoses were significantly associated with a poorer quality of life in the total sample as in cases of MS. In MS the impairment of the QoL attributable to BD type-II was even greater than that in MDD. LIMITATIONS: The MS diagnosis was made differently in cases and controls. Although this may have produced false negatives in controls, it would have reinforced the null hypothesis (no role of MS in worsening the QoL); therefore, it does not invalidate the study. CONCLUSIONS: MDD as well BD type-II are co-determinants in worsening QoL in MS. Clinicians should consider depressive symptoms as well as the hypomanic and mixed components in MS. Additional research is required to confirm our results and further clarify the manner in which BD and the mixed symptoms of BD type-II may affect awareness of both the underlying disease and psychiatric component and finally to what extent they impact treatment adherence with the available therapies for MS.

Gender differences in DSM-5 versus DSM-IV-TR PTSD prevalence and criteria comparison among 512 survivors to the L'Aquila earthquake.

BACKGROUND: Post-traumatic Stress Disorder (PTSD) has demonstrated gender-specific prevalence and expressions across the different DSM definitions, since its first introduction in DSM-III. The DSM-5 recently introduced important revisions to PTSD symptomatological criteria. Aim of the present study is to explore whether gender moderates rates of DSM-5 PTSD expression in a non-clinical sample of survivors to a massive earthquake in Italy. METHODS: 512 survivors of the L'Aquila 2009 earthquake, previously investigated for the presence DSM-IV-TR PTSD, were reassessed according to DSM-5 criteria in order to explore gender differences. All subjects completed the Trauma and Loss Spectrum-Self Report (TALS-SR). RESULTS: Females showed significantly higher DSM-5 PTSD rates and rates of endorsement of almost all DSM-5 PTSD criteria. Significant gender differences emerged in almost half of PTSD symptomatological criteria with women reporting higher rates in 8 of them, while men in only one (a new symptom in DSM-5: reckless or self-destructive behavior). Considering the impact of the three new DSM-5 symptoms on the diagnosis, significant gender differences emerged with these being crucial in almost half of the PTSD diagnoses in males but in about one-fourth in females. By using ROC curves, DSM-5 criteria E and D showed the highest AUC values in males (.876) and females (.837), respectively. LIMITATIONS: The use of self-report instrument; no information on comorbidity; homogeneity of study sample; lack of assessment on functional impairment. CONCLUSIONS: This study provides a contribution to the ongoing need for reassessment on how gender moderates rates of expression of particular disorders such as PTSD.

Post-traumatic stress disorder in DSM-5: estimates of prevalence and criteria comparison versus DSM-IV-TR in a non-clinical sample of earthquake survivors.

BACKGROUND: The latest edition of DSM (DSM-5) introduced important revisions to PTSD symptomatological criteria, such as a four-factor model and the inclusion of new symptoms. To date, only a few studies have investigated the impact that the proposed DSM-5 criteria will have on prevalence rates of PTSD. METHODS: An overall sample of 512 adolescents who survived the L'Aquila 2009 earthquake and were previously investigated for the presence of full and partial PTSD, using DSM-IV-TR criteria, were reassessed according to DSM-5 criteria. All subjects completed the Trauma and Loss Spectrum-Self Report (TALS-SR). RESULTS: A DSM-5 PTSD diagnosis emerged in 39.8% of subjects, with a significant difference between the two sexes (p<0.001), and an overall 87.1% consistency with DSM-IV-TR. Most of the inconsistent diagnoses that fulfilled DSM-IV-TR criteria but not DSM-5 criteria can be attributed to the subjects not fulfilling the new criterion C (active avoidance). Each DSM-5 symptom was more highly correlated with its corresponding symptom cluster than with other symptom clusters, but two of the new symptoms showed moderate to weak item-cluster correlations. Among DSM-5 PTSD cases: 7 (3.4%) endorsed symptom D3; 151 (74%) D4; 28 (13.7%) both D3 and D4; 75 (36.8%) E2. LIMITATIONS: The use of a self-report instrument; no information on comorbidity; homogeneity of study sample; lack of assessment on functional impairment; the rates of DSM-IV-TR qualified PTSD in the sample was only 37.5%. CONCLUSIONS: This study provides an inside look at the empirical performance of the DSM-5 PTSD criteria in a population exposed to a natural disaster, which suggests the need for replication in larger epidemiological samples.

Do Akiskal & Mallya's affective temperaments belong to the domain of pathology or to that of normality?

BACKGROUND: Kraepelin and Kretschmer hypothesized a continuum between full-blown affective pathology and premorbid temperaments. More recently Akiskal proposed a putative adaptive role for the four fundamental temperaments: the hyperthymic one characterized by emotional intensity, the cyclothymic one by emotional instability, the depressive one by a low energy level, and the irritable one by an excessive response to stimuli. Today it is widely debated whether affective temperaments belong to the domain of pathology or to that of normality. PURPOSE: To make clear, by applying an integrated model, the position of affective temperaments within the continuum between normality and pathology. METHODS: We reviewed several papers that explore the distribution of affective temperaments among the general population, and their involvement both in pathological conditions (somatic and psychiatric) and in human activities (professions and other occupations). RESULTS: Far from being intrinsically pathological conditions, affective temperaments seem to represent adaptive dispositions whose dysregulation can lead to full-blown affective pathology. All the temperamental types display some impact on people's lives by influencing personal skills and professional choices over a wide field of human activities. CONCLUSIONS: Affective temperaments are not problematic when they appear in a mild form, but when they occur in extreme form we have observed a gap between the hyperthymic temperament, which represents the most functional and desirable, and the cyclothymic, depressive, irritable and phobic anxious ones, which are closer to mood, anxiety, and substance use disorders, and imply a component of somatic diseases and life stressors.

Age, gender and epicenter proximity effects on post-traumatic stress symptoms in L'Aquila 2009 earthquake survivors.

BACKGROUND: Earthquakes are among the most frequently occurring natural disasters affecting the general population and inducing Post-Traumatic Stress Disorder (PTSD). Thus, increasing effort has been devoted to explore risk factors for PTSD onset after exposure. The aim of the present study was to investigate the impact of gender, degree of exposure and age on PTSD and post-traumatic stress symptoms in the general population exposed to the L'Aquila 2009 earthquake (Richter Magnitude 6.3). METHODS: A total sample of 1488 subjects (721 women and 767 men) was assessed by means of the Trauma and Loss Spectrum Self Report (TALS-SR): 939 subjects have been directly and 549 not-directly exposed to the earthquake. We performed a random extraction of units from the population in order to have 8 homogenous comparable subgroups. RESULTS: A main significant effect of exposure (exposed>non exposed subjects) and gender (women>men) emerged on the TALS-SR domain scores. Further significant interaction effects of exposure(⁎)age and gender(⁎)age emerged with significantly more TALS-SR symptoms being reported in younger with respect to older non-exposed subjects and in younger with respect to older women. LIMITATIONS: Social support was not examined systematically as well as major depression. Further limitations are the relatively small sample size and the use of lifetime instruments. CONCLUSIONS: Our results corroborate literature on female gender and proximity to the epicenter being correlated to PTSD after earthquake exposure and suggest a possible secondary effect of age.

Suicidal ideation and temperament: an investigation among college students.

BACKGROUND: Suicide is a major health problem accounting for up to 1.5 percent of all deaths worldwide and represents one of the most common causes of death in adolescents and young adults. A number of studies has been performed to establish risk factors for suicide in patients with psychiatric disorders including temperamental features. This study set out to assess the relationship between suicidal ideation and temperament in young adults. METHODS: A cross-sectional sample of healthy college students (n=1381) was examined using a self-rating questionnaire. Suicidal ideation, social background, educational status, substance abuse, and affective temperament according to TEMPS-M were assessed. Predictors of lifetime suicidal ideation were examined in multivariate logistic regression analyses. RESULTS: Suicidal ideation was reported by 12.5% of all subjects at some point in their life and was higher in nicotine dependents, youth with alcohol related problems and users of illicit substances as well as in youth with lower educational status. Lifetime suicidal ideation was associated with the anxious, depressive and cyclothymic temperament in both sexes and the irritable temperament in males. These results remained significant after adjustment for smoking status, frequency of alcohol consumption, drug experience and educational status in a multivariate logistic regression analysis. LIMITATIONS: The use of self-rating instruments always reduces objectivity and introduces the possibility of misreporting. CONCLUSIONS: Considering the fact that many subjects completing suicide have never been diagnosed with mental disorders it might be reasonable to include an investigation of temperament in screenings for risk of suicide. This might be especially useful for health care professionals without mental health care background.

The influence of affective temperaments and psychopathological traits on the definition of bipolar disorder subtypes: a study on bipolar I Italian national sample.

UNLABELLED: Affective temperament and psychopathological traits such as separation anxiety (SA) and interpersonal sensitivity (IPS) are supposed to impact on the clinical manifestation and on the course of Bipolar Disorder (BD); in the present study we investigated their influence on the definition of BD subtypes. METHOD: : Among 106 BD-I patients with DSM-IV depressive, manic or mixed episode included in a multi-centric Italian study and treated according to the routine clinical practice, 89 (84.0%) were in remission after a follow-up period ranging from 3 to 6 months (Clinical Global Impression-BP [CGI-BP] <2). Remitting patients underwent a comprehensive evaluation including self-report questionnaires such as the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A) scale, Separation Anxiety Symptom Inventory (SASI), Interpersonal Sensitivity Measure (IPSM) and the Semi-structured interview for Mood Disorder (SIMD-R) administered by experienced clinicians. Correlation and factorial analyses were conducted on temperamental and psychopathological measures. Comparative analyses were conducted on different temperamental subtypes based on the TEMPS-A, SASI and IPSM profile. RESULTS: : Depressive, cyclothymic and irritable TEMPS-A score and SASI and IPSM total scores were positively and statistically correlated with each other. On the contrary, hyperthymic temperament score was negatively correlated with depressive temperament and not significantly correlated with the other temperamental and psychopathological dimensions. The factorial analysis of the TEMPS-A subscales and SASI and IPSM total scores allowed the extraction of 2 factors: the cyclothymic-sensitive (explaining 46% of the variance) that included, as positive components, depressive, cyclothymic, irritable temperaments and SASI and IPSM scores; the hyperthymic (explaining the 19% of the variance) included hyperthymic temperament as the only positive component and depressive temperament and IPSM, as negative components. Dominant cyclothymic-sensitive patients (n=49) were more frequently females and reported higher number of depressive, hypomanic and suicide attempts when compared to the dominant hyperthymic patients (n=40). On the contrary, these latter showed a higher number of manic episodes and hospitalizations than cyclothymic-sensitive patients. The rates of first-degree family history for both mood and anxiety disorders were higher in cyclothymic-sensitive than in hyperthymic patients. Cyclothymic sensitive patients also reported more axis I lifetime co-morbidities with Panic Disorder/Agoraphobia and Social Anxiety Disorder in comparison with hyperthymics. As concerns axis II co-morbidity the cyclothymic-sensitive patients met more frequently DSM-IV criteria 1, 5 and 7 for borderline personality disorder than the hyperthymics. On the contrary, antisocial personality disorder was more represented among hyperthymic than cyclothymic patients, in particular for DSM-IV criteria 1 and 6. LIMITATION: : No blind evaluation and uncertain validity of personality inventory. CONCLUSION: : Our results support the view that affective temperaments influence the clinical features of BD in terms of both clinical and course characteristics, family history and axis I and II co-morbidities. Hypothetical temperamental subtypes as measured by TEMPS-A presented important interrelationships that permit to reliably isolate two fundamental temperamental disposition: the first characterized by rapid fluctuations of mood and emotional instability, and the second by hyperactivity, high level of energy and emotional intensity. Dominant cyclothymic and hyperthymic bipolar I patients reported important differences in terms of gender distribution, number and polarity of previous episodes, hospitalizations, suicidality, rates of co-morbid anxiety and personality traits and disorders. Our data are consistent with the hypothesis that affective temperaments, and in particular cyclothymia, could be utilized as quantitative, intermediate phenotypes in order to identify BD susceptibility genes.

A genome-wide association study of bipolar disorder and comorbid migraine.

Both migraine and bipolar affective disorder (BPAD) are complex phenotypes with significant genetic and nongenetic components. Epidemiological and clinical studies have showed a high degree of comorbidity between migraine and BPAD, and overlapping regions of linkage have been shown in numerous genome-wide linkage studies. To identify susceptibility factors for the BPAD/migraine phenotype, we conducted a genome-wide association study (GWAS) in 1001 cases with bipolar disorder collected through the NIMH Genetics Initiative for Bipolar Disorder and genotyped at 1 m single-nucleotide polymorphisms (SNPs) as part of the Genetic Association Information Network (GAIN). We compared BPAD patients without any headache (n = 699) with BPAD patients with doctor diagnosed migraine (n = 56). The strongest evidence for association was found for several SNPs in a 317-kb region encompassing the uncharacterized geneKIAA0564 {e.g. rs9566845 [OR = 4.98 (95% CI: 2.6-9.48), P = 7.7 × 10(-8)] and rs9566867 (P = 8.2 × 10(-8))}. Although the level of significance was significantly reduced when using the Fisher's exact test (as a result of the low count of cases with migraine), rs9566845 P = 1.4 × 10(-5) and rs9566867 P = 1.5 × 10(-5), this region remained the most prominent finding. Furthermore, marker rs9566845 was genotyped and found associated with migraine in an independent Norwegian sample of adult attention deficit hyperactivity disorder (ADHD) patients with and without comorbid migraine (n = 131 and n = 324, respectively), OR = 2.42 (1.18-4.97), P = 0.013. This is the first GWAS examining patients with bipolar disorder and comorbid migraine. These data suggest that genetic variants in the KIAA0564 gene region may predispose to migraine headaches in subgroups of patients with both BPAD and ADHD.

Hyperthymic temperament may protect against suicidal ideation.

BACKGROUND: The aim of this study was to investigate the role of hyperthymic temperament in suicidal ideation between a sample of patients with affective disorders (unipolar and bipolar). METHOD: We investigated affective disorders outpatients (unipolar, bipolar I, II and NOS) treated in eleven participating centres during at least a six-month period. DSM-IV diagnosis was made by psychiatrists experienced in mood disorders, using the corresponding modules of the Mini International Neuropsychiatric Interview (MINI). In addition, bipolar NOS diagnoses were extended by guidelines for bipolar spectrum symptoms as proposed by Akiskal and Pinto in 1999. Thereby we also identified NOS III (switch by antidepressants) and NOS IV (hyperthymic temperament) bipolar subtypes. All patients completed the Beck Depression Inventory (BDI). We screened a total sample of 411 patients (69% bipolar), 352 completed all the clinical scales without missing any item. RESULTS: No statistical significant difference in suicidal ideation (measure by BDI item 9 responses) was found between bipolar and unipolar patients (4.5% vs. 9.1%, respectively). On the group of bipolar patients, suicidal ideation was slightly more frequent among bipolar NOS compared with bipolar I and II (p value 0.094 and 0.086, respectively), interestingly we found a statistical significant less common suicidal ideation among bipolar subtype IV (with hyperthymic temperament) compared with bipolar NOS patients (p value 0.048). CONCLUSIONS: Our results indicate that those subjects with hyperthymic temperament displayed less suicidal ideation. This finding supports the hypothesis that this particular affective temperament could be a protective factor against suicide among affective patients. LIMITATION: The original objective of the national study was the cross validation between MDQ and BSDS in patients with affective disorders in our country. This report arises from a secondary analysis of the original data.

A genome-wide linkage study of bipolar disorder and co-morbid migraine: replication of migraine linkage on chromosome 4q24, and suggestion of an overlapping susceptibility region for both disorders on chromosome 20p11.

Migraine and Bipolar Disorder (BPAD) are clinically heterogeneous disorders of the brain with a significant, but complex, genetic component. Epidemiological and clinical studies have demonstrated a high degree of co-morbidity between migraine and BPAD. Several genome-wide linkage studies in BPAD and migraine have shown overlapping regions of linkage on chromosomes, and two functionally similar voltage-dependent calcium channels CACNA1A and CACNA1C have been identified in familial hemiplegic migraine and recently implicated in two whole genome BPAD association studies, respectively. We hypothesized that using migraine co-morbidity to look at subsets of BPAD families in a genetic linkage analysis would prove useful in identifying genetic susceptibility regions in both of these disorders. We used BPAD with co-morbid migraine as an alternative phenotype definition in a re-analysis of the NIMH Bipolar Genetics Initiative wave 4 data set. In this analysis we selected only those families in which at least two members were diagnosed with migraine by a doctor according to patients' reports. Nonparametric linkage analysis performed on 31 families segregating both BPAD and migraine identified a linkage signal on chromosome 4q24 for migraine (but not BPAD) with a peak LOD of 2.26. This region has previously been implicated in two independent migraine linkage studies. In addition we identified a locus on chromosome 20p11 with overlapping elevated LOD scores for both migraine (LOD=1.95) and BPAD (LOD=1.67) phenotypes. This region has previously been implicated in two BPAD linkage studies, and, interestingly, it harbors a known potassium dependant sodium/calcium exchanger gene, SLC24A3, that plays a critical role in neuronal calcium homeostasis. Our findings replicate a previously identified migraine linkage locus on chromosome 4 (not co-segregating with BPAD) in a sample of BPAD families with co-morbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a gene for the migraine/BPAD phenotype. Together these data suggest that some genes may predispose to both bipolar disorder and migraine.

Bipolar disorder with frequent mood episodes in the national comorbidity survey replication (NCS-R).

Virtually nothing is known about the epidemiology of rapid cycling bipolar disorder (BPD) in community samples. Nationally representative data are reported here for the prevalence and correlates of a surrogate measure of DSM-IV rapid cycling BPD from the National Comorbidity survey Replication (NCS-R), a national survey of the US household population. DSM-IV disorders were assessed in the NCS-R with the WHO Composite International Diagnostic Interview (CIDI). Although the CIDI did not assess rapid cycling, it did assess the broader category of 12-month BPD with frequent mood episodes (FMEs), having at least four episodes of mania/hypomania or major depression in the 12 months before interview. Roughly one-third of NCS-R respondents with lifetime DSM-IV BPD and half with 12-month BPD met criteria for FME. FME was associated with younger age-of-onset (of BP-I, but not BP-II) and higher annual persistence (73% of the years since first onset of illness with an episode) than non-FME BPD. No substantial associations of FME vs non-FME BPD were found with socio-demographics, childhood risk factors (parental mental disorders, other childhood adversities) or comorbid DSM-IV disorders. However, FME manic episodes had greater clinical severity than non-FME episodes (assessed with a fully structured version of the Young Mania Rating Scale) and FME hypomanic episodes had greater role impairment than non-FME episodes (assessed with the Sheehan Disability Scales). Whether these indicators of severity merely reflect attenuated effects of rapid cycling or independent effects of sub-threshold rapid cycling warrants further study given the high proportion of lifetime cases who met criteria for FME.

[Predicting risk of suicide in bipolar and unipolar depression: correlation between temperament and personality]. / Prädiktion des Suizidrisikos bei bipolar und unipolar depressiven Patienten: Wechselwirkung von Temperament und Persönlichkeit.

OBJECTIVE: The aim of this study was to evaluate the roles of personality and affective temperament traits in the prediction of suicide risk in mood disorders. METHODS: The participants were 147 psychiatric inpatients with bipolar disorders I and II and major depressive disorder. Patients undertook the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego self-rating questionnaire, the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), and the Beck Hopelessness Scale. RESULTS: Sixty-four subjects were diagnosed with increased suicidal risk based on the Mini International Neuropsychiatric Interview (MINI). Logistic regression analysis resulted in two models predictive of MINI-based suicidal risk: irritable temperament and the MMPI-2 scale. Multiple regression analysis further indicated that higher hyperthymic values are protective against hopelessness, while MINI-based suicidal intent is a predictor of hopelessness. CONCLUSIONS: Personality and affective temperament traits may have a role in the prediction of suicide.

Towards a genetically validated new affective temperament scale: a delineation of the temperament phenotype of 5-HTTLPR using the TEMPS-A.

BACKGROUND: Although it has been described that affective temperaments are associated with the 5-HTTLPR, less attention was paid to the association between this polymorphism and subscales and items related to each affective temperament. The aim of our study was to investigate the association of affective temperament subscales and individual items with the s allele of the 5-HTTLPR. METHOD: 138 psychiatrically healthy women completed the TEMPS-A questionnaire and were genotyped for 5-HTTLPR. Scores of subjects on the temperament scales, subscales and items in the three genotype and the two phenotype groups were compared using ANOVA. We selected items with significantly different mean scores between the three genotype groups and the two phenotype groups separately and performed item analysis. RESULTS: Subjects in the different 5-HTTLPR genotype and phenotype groups have significantly different score on scales measuring depressive, cyclothymic, irritable and anxious temperaments, and several subscales composing these temperamental scales. Subjects in the three genotype groups scored significantly different on 11 items, 8 of these remained in a derived genotype scale after item analysis. Subjects in the two phenotype groups had significantly different scores on 12 items, 9 of them were retained in a derived phenotype scale after item analysis. LIMITATIONS: Our sample was relatively small and included only women. CONCLUSIONS: Our data provide support for the association of affective temperaments with the s allele. Although the cyclothymic temperament shows the strongest association, all temperaments within the depressive superfactor have a similar share in this association. The newly derived 5-HTTLPR Phenotype Scale shows strong association with 5-HTTLPR genotype and phenotype, therefore this scale should be further investigated in relation to psychiatric disorders, as well as psychological traits and temperaments.

A mixed state core for melancholia: an exploration in history, art and clinical science.

OBJECTIVE: We argue for a mixed state core for melancholia comparing concepts of melancholia across centuries using examples from art, history and scientific literature. METHOD: Literature reviews focusing on studies from Kraepelin onward, DSM-IV classification and view-points from clinical experience highlighting phenomenologic and biologic features as predictors of bipolar outcome in prospective studies of depression. RESULTS: Despite the implied chemical pathology in the term endogenous/melancholic depression, frequently reported glucocortical and sleep neurophysiologic abnormalities, there is little evidence that melancholia is inherited independently from more broadly defined depressions. Prospective follow-up of 'neurotic' depressions have shown melancholic outcomes in as many as a third; hypomania has also been observed in such follow-up. CONCLUSION: These findings and considerations overall do suggest that melancholia as defined today is more closely aligned with the depressive and/or mixed phase of bipolar disorder. Given the high suicidality from many of these patients the practice of treating them with antidepressant monotherapy needs re-evaluation.

Validating the soft bipolar spectrum in the French National EPIDEP Study: the prominence of BP-II 1/2.

BACKGROUND: Much of the current literature on bipolar disorder is focused on bipolar I (BP-I), and to a much lesser extent on bipolar II (BP-II). The French multi-center national EPIDEP study has, among its objectives, the feasibility of validating a broader spectrum of bipolarity (the so-called "soft spectrum") by practicing clinicians. In this report we test aspects of a bipolar schema proposed earlier by Akiskal and Pinto [Akiskal, H.S., Pinto, O., 1999. The evolving bipolar spectrum: Prototypes I, II, III, IV. Psychiatr. Clin. North Am. 22: 517-534.]. METHODS: EPIDEP was scheduled in three phases: Phase 1 to recruit DSM-IV major depressives; Phase 2 to assess hypomania and affective temperaments; and Phase 3 to obtain history on course of illness, family history, and comorbidity. Comparative analyses are presented between affective subgroups constructed on a hierarchical basis: spontaneous hypomania (BP-II), cyclothymic temperament (BP-II 1/2), antidepressant-associated hypomania (BP-III), hyperthymic temperament (BP-IV), versus "strict unipolar" (UP). RESULTS: We present data on 490 patients for whom we obtained full assessment during all three phases of the study, classified as BP-II 1/2 (N=164), II (N=61), III (N=28), IV (N=22), as well as UP (N=174) as the reference nonbipolar group. Systematic inter-group comparison among the soft spectrum showed significant differences along clinical, descriptive, course, pharmacologic response and familial affective disorder patterns, which confirm the heterogeneity of the soft bipolar spectrum, with special characteristics for each of the subgroups. In terms of external validation, familial bipolar loading characterized all soft bipolar subgroups except type IV. LIMITATION: Data collection conducted in a practice setting, clinicians cannot be entirely held "blind" to all measures. This is an exploratory attempt, with many variables examined, to help characterize the clinical terrain of soft bipolarity. CONCLUSION: This is nonetheless the first systematic clinical attempt to validate the bipolar spectrum beyond mania (BP-I). BP-II 1/2, BP-III and BP-IV appeared distinct from BP-II and strict UP -- along most of the variables examined. BP-II 1/2 -- with early onset complex temperament structure, and high mood instability, rapid switching, irritable ("dark") hypomania and suicidality -- emerged as the most prevalent and severe expression of the bipolar spectrum, and accounting for 33% of all MDE. These results, which are of great public health relevance, testify to the cyclic nature of bipolarity in its softest expressions. The soft phenotypes are also of interest for genetic investigations of bipolar disorder.