home

Irritability AND BIPOLAR
Walk the Road of Bipolar II-
These abstracts show how irritability and bipolar seem to go hand and hand. What I found missing was treatment research in treatment of irritability with atypical antipsychotics and except for one anticonvulsants and bipolar irritability. Other studies on irritability are also brought in. Little mention is correlation between stress and irritability. We bipolars generally do very badly with stress.
One study I found suggested indirectly a possible treatment with atypical antipsychotic. What is fascinating that already in the medical community, many psychiatrists are already giving their clients atypical antipsychotics in smaller dosages to help with the irritability and the mania. I have found that risperdal really helps my irritability.
The study below was done over six years ago. You can go to atypical antipsychotics to see later research on atypical antipsychotics and bipolar disorder
Psychiatr Clin North Am. 1997 Jun;20(2):427-51. : Psychopharmacologic treatment of pathologic aggression.
Fava M.
Depression Clinical and Research Program, Massachusetts General Hospital, USA

Several drugs are apparently effective in treating pathologic anger and aggression. Because many of the studies on aggressive populations allowed the use of concomitant medications, it is unclear whether the efficacy of each drug in a particular population is dependent on the presence of other medications, such as antipsychotic agents. Finally, one needs to be circumspect in inferring efficacy of a particular drug in aggressive patients with neuropsychiatric conditions other than the ones in which some efficacy has been established. Lithium appears to be an effective treatment of aggression among nonepileptic prison inmates, mentally retarded and handicapped patients, and among conduct-disordered children with explosive behavior. Certainly, lithium would be the treatment of choice in bipolar patients with excessive irritability and anger outbursts, and it has been shown to be effective in this population. Anticonvulsant medications are the treatment of choice for patients with outbursts of rage and abnormal EEG findings. The efficacy of these drugs in patients without a seizure disorder, however, remains to be established, with the exception perhaps of valproate and carbamazepine. In fact, dyphenylhydantoin did not appear to be effective in treating aggressive behavior in children with temper tantrums and was found to be effective in only a prison population. There is some evidence for the efficacy of carbamazepine and valproate in treating pathologic aggression in patients with dementia, organic brain syndrome, psychosis, and personality disorders. As Yudofsky et al point out in their review of the literature, although traditional antipsychotic drugs have been used widely to treat aggression, there is little evidence for their effectiveness in treating aggression beyond their sedative effect in agitated patients or their antiaggressive effect among patients whose aggression is related to active psychosis. Antipsychotic agents appear to be effective in treating psychotic aggressive patients, conduct-disordered children, and mentally retarded patients, with only modest effects in the management of pathologic aggression in patients with dementia. Furthermore, at least in one study, these drugs were found to be associated with increased aggressiveness in mentally retarded subjects. On the other hand, atypical antipsychotic agents (i.e., clozapine, risperidone, and olanzapine) may be more effective than traditional antipsychotic drugs in aggressive and violent populations, as they have shown efficacy in patients with dementia, brain injury, mental retardation, and personality disorders. Similarly, benzodiazepines can reduce agitation and irritability in elderly and demented populations, but they also can induce behavioral disinhibition. Therefore, one should be careful in using this class of drugs in patients with pathologic aggression. Beta-blockers appear to be effective in many different neuropsychiatric conditions. These drugs seem effective in reducing violent and assaultive behavior in patients with dementia, brain injury, schizophrenia, mental retardation, and organic brain syndrome. As pointed out by Campbell et al in their review of the literature, however, systematic research is lacking, and little is known about the efficacy and safety of beta-blockers in children and adolescents with pathologic aggression. Although widely used in the management of pathologic aggression, the use of this class of drugs has been limited partially by marked hypotension and bradycardia, which are side effects common at the higher doses. The usefulness of the antihypertensive drug clonidine in the treatment of pathologic aggression has not been assessed adequately, and only marginal benefits were observed with this drug in irritable autistic and conduct disorder children. Psychostimulants seem to be effective in reducing aggressiveness in brain-injured patients as well as in violent adolescents with oppositional or conduct disorders, particu

  • Hum Psychopharmacol. 2003 Jul;18(5):379-84. :
    Fluvoxamine Maleate( Luvox ) In Canada fluoxetine Prozac
    Fluvoxamine versus fluoxetine in major depressive episode: a double-blind randomised comparison.
    Dalery J, Honig A.
    Hopital Neurologique Pierre Wertheimer, F-69003 Lyon, France.

    A double-blind, multinational study was conducted to compare the efficacy and safety of fluvoxamine and fluoxetine in outpatients with major depressive episode; 184 patients were randomised to fluvoxamine (100 mg/day) or fluoxetine (20 mg/day) for 6 weeks. Both drugs were effective and there were no statistically significant differences between them in the area under the curve of change from baseline in the Hamilton depression rating scale (HAMD) total score. However, the percentage of HAMD responders (>/= 50% decrease in HAMD total score) at week 2, the clinical global improvement severity of illness score at week 2 and the depression subscale of the irritability, depression and anxiety scale at weeks 1, 2 and 4, all showed significant advantages for fluvoxamine. During the last 2 weeks, fluvoxamine was significantly more effective in improving the HAMD sleep disturbance scale. Both drugs were well tolerated and there were no marked differences in their side effect profiles which were typical of SSRIs. Fluvoxamine and fluoxetine have similar efficacy and safety profiles in the treatment of major depressive episode; the findings of this study indicate that fluvoxamine may have a faster onset of action with respect to resolution of depressive symptoms and result in a better improvement in sleep quality.


    Divalproex Sodium Brand name: Epival, Depakote
    Mol Psychiatry. 2002;7(9):1023-9. : Association of anger-related traits with SNPs in the TPH gene.
    Rujescu D, Giegling I, Bondy B, Gietl A, Zill P, Moller HJ.
    Molecular Neurobiology, Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany.
    Dan.Rujescu@psy.med.uni-muenchen.de

    Since both aggression-related traits and serotonergic activity are partially heritable and correlate inversely, variations in genes of the serotonergic system might then, to some extent, account for variations in aggression-related behavior. Tryptophan hydroxylase (TPH) is the rate limiting biosynthetic enzyme in the serotonin pathway and regulates levels of serotonin. Recently, a genetic variation in TPH has been associated with aggression and anger-related traits in volunteers. We investigated a sample of community-based healthy volunteers (n = 154) and suicide attempters (n = 86), a clinical population with a high risk for elevated impulsive aggression and related traits. The subjects were genotyped for a A218C and a A779C single nucleotide polymorphism (SNP) located in the TPH gene. All subjects were administered standard psychiatric interviews as well as self-report questionnaires for aggression, irritability and anger-related traits. For anger-related traits, a multivariate effect of the tryptophan hydroxylase genotype and an interaction effect for genotype and diagnosis was observed in healthy volunteers and suicide attempters after controlling for age and educational level. U-carriers in both groups showed higher scores for State Anger, Trait Anger and Angry Temperament. These findings support the hypothesis that the A218C and the A779C SNP in the TPH gene may be associated with anger-related traits in German samples.
  • J Clin Psychiatry. 2002 May;63(5):442-6. : Divalproex sodium treatment of women with borderline personality disorder and bipolar II disorder: a double-blind placebo-controlled pilot study.
    Frankenburg FR, Zanarini MC.
    Laboratory for the Study of Adult Development, McLean Hospital, Belmont, MA 02478, USA.
    ffrankenburg@mclean.harvard.edu

    BACKGROUND: The intent of this study was to compare the efficacy and safety of divalproex sodium and placebo in the treatment of women with borderline personality disorder and comorbid bipolar II disorder. METHOD: We conducted a placebo-controlled double-blind study of divalproex sodium in 30 female subjects aged 18 to 40 years who met Revised Diagnostic Interview for Borderlines and DSM-IV criteria for borderline personality disorder and DSM-IV criteria for bipolar II disorder. Subjects were randomly assigned to divalproex sodium or placebo in a 2:1 manner. Treatment duration was 6 months. Primary outcome measures were changes on the interpersonal sensitivity, anger/hostility, and depression scales of the Symptom Checklist 90 (SCL-90) as well as the total score of the modified Overt Aggression Scale (MOAS). RESULTS: Twenty subjects were randomly assigned to divalproex sodium; 10 subjects to placebo. Using a last-observation-carried-forward paradigm and controlling for baseline severity, divalproex sodium proved to be superior to placebo in diminishing interpersonal sensitivity and anger/hostility as measured by the SCL-90 as well as overall aggression as measured by the MOAS. Adverse effects were infrequent. CONCLUSION: The results of this study suggest that divalproex sodium may be a safe and effective agent in the treatment of women with criteria-defined borderline personality disorder and comorbid bipolar II disorder, significantly decreasing their irritability and anger, the tempestuousness of their relationships, and their impulsive aggressiveness

  • Int J Neuropsychopharmacol. 2002 Jun;5(2):147-51. : Emotional blunting associated with SSRI-induced sexual dysfunction. Do SSRIs inhibit emotional responses?
    Opbroek A, Delgado PL, Laukes C, McGahuey C, Katsanis J, Moreno FA, Manber R.

    Anecdotal and published case reports suggest that some patients taking selective serotonin reuptake inhibitors (SSRI) experience diminution in emotional responsiveness. This study aims to define the individual components of emotion disturbed in these patients. Fifteen patients reporting SSRI-induced sexual dysfunction completed the Laukes Emotional Intensity Scale (LEIS), a questionnaire about various emotions. Compared to controls, patients reported significantly (p&0.05) less ability to cry, irritation, care about others' feelings, sadness, erotic dreaming, creativity, surprise, anger, expression of their feelings, worry over things or situations, sexual pleasure, and interest in sex. Total score on the LEIS did not correlate with total score on the Hamilton Depression Rating Scale. In our sample, 80% of patients with SSRI-induced sexual dysfunction also describe clinically significant blunting of several emotions. Emotional blunting may be an under-appreciated side-effect of SSRIs that may contribute to treatment non-compliance and/or reduced quality of life.

  • J Clin Psychiatry. 2003 Jun;64(6):698-701. : "Outer-directed irritability": a distinct mood syndrome in explosive youth with a disruptive behavior disorder?
    Donovan SJ, Nunes EV, Stewart JW, Ross D, Quitkin FM, Jensen PS, Klein DF.
    Department of Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.

    OBJECTIVE: To examine whether "outer-directed irritability," a mood construct from the adult literature, characterizes a subgroup of disruptive behavior disordered children and adolescents previously shown to improve on divalproex, a mood stabilizer. METHOD: A sample (N = 20) of disruptive youth (aged 10-18 years) entering a divalproex treatment study of temper and irritable mood swings was compared to normal controls (N = 18) on measures of aggression/irritability directed against others (externalizing symptoms) and on aggression/ irritability against self, anxiety, and depression (internalizing symptoms). All patients met DSM-IV criteria for a disruptive behavior disorder (oppositional defiant disorder of conduct disorder) in addition to research criteria. RESULTS: "Outer-directed irritability" most clearly distinguished patients from controls (effect size 4.1) and did not correlate with other mood measures. Patients and controls showed no to minimal differences on internalizing symptoms. CONCLUSION: Disruptive behavior disordered children and adolescents characterized by outer-directed irritability exist, can be identified, and should be further investigated, especially since they are potentially treatable.

  • Eur Psychiatry. 2003 May;18(3):124-8. : Emotional hyper-reactivity as a fundamental mood characteristic of manic and mixed states.
    Henry C, Swendsen J, Van den Bulke D, Sorbara F, Demotes-Mainard J, Leboyer M.
    Service de Psychiatrie Adulte, Centre Hospitalier Charles Perrens, 121, rue de la Bechade, 33076 Bordeaux, France.
    chantal.henry@bordeaux.inserm.fr

    BACKGROUND: The relationship between depression and mania remains poorly understood and is responsible for much of the confusion about mixed states. The difficulty in conceptualizing opposite states such as euphoric and depressive moods during the same episode may account for the considerable differences in reported frequencies of mixed states, among acutely manic patients. It is possible that the fundamental mood characteristic of mania is not tonality of mood (e.g. euphoric, irritable or depressed mood), but rather the intensity of emotions. METHOD: We interviewed 30 patients hospitalized for a manic episode, asking about their symptoms during the episode, using the list of symptoms for manic and depressive episode of the DSM-IV criteria. Emotional hyper-reactivity, defined as an increase in the intensity of all emotions, was assessed using the Hardy Scale. Manic symptoms were also assessed by a clinician using the Beck-Rafaelsen Mania Scale. RESULTS: This study showed that most of the manic episodes presented many dysphoric symptoms, more particularly depressive mood (33%), irritability (53%), anxiety (76%), and recurrent thoughts of death or suicidal ideation (33%). However, only 10% of our sample met the criteria for mixed state. The other symptoms reported by patients and included in the DSM-IV criteria for depressive mood are common between depressive and manic episodes. All patients (100%) reported that they felt all their emotions with an unusual intensity. CONCLUSION: We suggest that the most appropriate way to define mood in manic states is as a function of intensity, and not as a function of tonality. This definition circumvents the arbitrary dichotomy between mania and mixed state. With this definition, manic episodes can be described as being more or less dysphoric, with the actual characteristics of dysphoria encompassing irritability, anxiety, or depressive affect. This point could be extremely helpful in discriminating mixed state or dysphoric mania from depression.

  • Biol Psychiatry. 2003 Jun 1;53(11):1009-20. : Researching the pathophysiology of pediatric bipolar disorder.
    Leibenluft E, Charney DS, Pine DS.
    Mood and Anxiety Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA

    We suggest that the core feature of bipolar disorder (BPD) is marked state fluctuations. The pathophysiology of switches into depressed, irritable, and extreme positive valence states requires study, with the latter deserving particular focus because it represents a pathognomonic feature of BPD in both adults and children. Hypotheses regarding the pathophysiology of pediatric BPD must account for these marked state fluctuations as well as for specific developmental aspects of the illness. These developmental aspects include marked irritability (in addition to euphoria and depression) and very rapid cycles, along with high rates of attention-deficit/hyperactivity disorder. We review research on neural mechanisms underlying positive valence states and state regulation, focusing on those data relevant to BPD and to development. Researchers are beginning to explore the response of manic patients and control subjects to positive affective stimuli, and considerable research in both nonhuman primates and humans has focused on the cortico-limbic-striatal circuits mediating responses to rewarding stimuli. In control subjects, positive affect affects cognition, and data indicate that prefrontal electroencephalogram asymmetry may differ between control subjects with consistently positive affect and those with more negative affect; however, this latter generalization may not apply to adolescents. With regard to the pathophysiology of state switching in pediatric BPD, data in control subjects indicating that attention regulation plays a role in emotion regulation may be germane. In addition, research detailing physiologic and psychological responses to negative emotional stimuli in bipolar patients and control subjects may increase our understanding of the mechanisms underlying both irritability and rapid cycling seen in children with BPD. Potential foci for research on the pathophysiology of pediatric BPD include reactivity to standardized positive and negative emotional stimuli, and the interaction between emotion regulation and attentional processes.

  • Biol Psychiatry. 2003 Jun 1;53(11):1043-9. : Juvenile bipolar disorder in Brazil. clinical and treatment findings.
    Tramontina S, Schmitz M, Polanczyk G, Rohde LA.
    Federal University of Rio Grande do Sul (ST, MS, GP, LAR), Rio Grande do Sul, Brazil

    Because few studies were conducted to evaluate bipolar disorder in children and adolescents outside North America, this investigation aims to describe clinical features, pattern of comorbidities, and response to pharmacologic treatment in a sample of youths with bipolar disorder (BD) from a pediatric psychopharmacology outpatient clinic in Brazil.We performed a retrospective chart review of all patients under age 15 with BD diagnoses who were evaluated and treated in our clinic from 1998-2001. A comparison sample of subjects with attention-deficit/hyperactivity disorder (ADHD) without BD (n = 362) was also evaluated.The prevalence of juvenile BD in our sample was 7.2% (36/500) (95% confidence interval = 5.2-9.9). Irritable mood was detected in 91.7% of the bipolar patients. The main comorbidity found was ADHD (58.3%). Children with BD had significantly higher rates of abnormally elevated CBCL scores in the externalizing dimension, anxiety and depression, delinquent behavior, and aggressive behavior scales than ADHD subjects (p <.05). Most BD patients (78%) needed combination drug therapy to achieve symptomatic control.Our results replicate clinical and treatment findings from U.S. investigations in a different culture demonstrating that juvenile BD is not a rare disorder in clinical samples.

  • : Am J Psychiatry. 2003 Mar;160(3):430-7.: Defining clinical phenotypes of juvenile mania.
    Leibenluft E, Charney DS, Towbin KE, Bhangoo RK, Pine DS.
    Mood and Anxiety Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1255, USA.
    leibs@mail.nih.gov

    OBJECTIVE: The authors suggest criteria for a range of narrow to broad phenotypes of bipolar disorder in children, differentiated according to the characteristics of the manic or hypomanic episodes, and present methods for validation of the criteria. METHOD: Relevant literature describing bipolar disorder in both children and adults was reviewed critically, and the input of experts was sought. RESULTS: Areas of controversy include whether the diagnosis of bipolar disorder should require clearly demarcated affective episodes and, if so, of what duration, and whether specific hallmark symptoms of mania should be required for the diagnosis. The authors suggest a phenotypic system of juvenile mania consisting of a narrow phenotype, two intermediate phenotypes, and a broad phenotype. The narrow phenotype is exhibited by patients who meet the full DSM-IV diagnostic criteria for hypomania or mania, including the duration criterion, and also have hallmark symptoms of elevated mood or grandiosity. The intermediate phenotypes include 1) hypomania or mania not otherwise specified, in which the patient has clear episodes and hallmark symptoms, but the episodes are between 1 and 3 days in duration, and 2) irritable hypomania or mania, in which the patient has demarcated episodes with irritable, but not elevated, mood. The broad phenotype is exhibited by patients who have a chronic, nonepisodic illness that does not include the hallmark symptoms of mania but shares with the narrower phenotypes the symptoms of severe irritability and hyperarousal. CONCLUSIONS: The presence of distinct episodes and hallmark symptoms can be used to differentiate clinical phenotypes of juvenile mania. The utility and validity of this system can be tested in subsequent research.

  • Encephale. 2003 Jan-Feb;29(1):59-67. : [Criteria defining antimanic drugs (psychopharmacological specificity and/or nonspecificity?)]
    [Article in French]
    Azorin JM.
    SHU de Psychiatrie Adultes, Hopital Sainte-Marguerite, 270, boulevard de Sainte-Marguerite, 13274 Marseille cedex 9, France.

    The question as to whether specific antimanic drugs differ in their action profile from nonspecific drugs is addressed in regard to symptomatic, nosographic, regulatory and physiopathological issues. Results from clinical studies have shown that mood stabilizers and typical neuroleptics differ as regards improvement of manic symptoms: the former appear to act more evenly on all symptoms of mania, showing a more total normalization of affect, ideation and behaviour whereas the latter tend to sedate patients or to cause a psychomotor retardation, leaving the core manic symptoms unaffected. This has been many times underlined, in particular for lithium, notwithstanding the fact that rating scales employed in clinical trials have often been charged to fall far short of being sensitive enough to pick up the qualitative changes in manic psychopathology. Antimanic drugs may also be more or less specific in their capacities to treat all facets of the manic episode (psychotic, depressive, irritable) whatever the bipolar subtype (bipolar I, II, rapid and non-rapid cycling, secondary bipolar disorder) or the disease stage (early and late episodes). In this respect divalproate seems to have a broader spectrum of efficacy than other available agents. Newer antipsychotics such as olanzapine are promising too. From a regulatory point of view, the current European requirements for a specific antimanic drug are more stringent than the US requirements of the Food and Drug Administration (FDA). Efficacy must be demonstrated in short-term studies showing an effect in acute mania; moreover it has to be shown that efficacy is to be maintained during the episode. So far, three armed randomized controlled trials are required, in which the test product is compared both with placebo and with a standard treatment. A possible design is a comparison of test product, placebo and active control for 3 weeks followed by a two-arm phase for the remaining 9 weeks, comparing only test product and active control. In addition, a specific antimanic has to demonstrate that it does not cause switching to depression. As regards physiopathology, integrative models of bipolar disorder, ie kindling and behavioural sensitization, offer an exciting perspective on the specificity issue; agents active in these models initialize a cascade of intracellular signaling that leads to changes in the expression of immediate early genes as well as late effector genes in corticolimbic structures: the former may contribute to acute symptomatology whereas the latter give rise to neuroanatomical reorganization which could underlie more stable changes in mood and cognition. Due to their action on intracellular messaging systems, dopamine D(1) receptors, serotonin 5HT(1a) or 5HT(2a) receptors, especially in orbitofrontal circuit, antimanic agents may exhibit a more specific activity than other drugs. This specificity could concern a whole spectrum of bipolarity which might be characterized by impulsivity.

  • J Affect Disord. 2003 Jan;73(1-2):39-47. : Factor structure of hypomania: interrelationships with cyclothymia and the soft bipolar spectrum
    . Hantouche EG, Angst J, Akiskal HS.
    Psychiatry Department, Mood Center, Pitie-Salpetriere Hospital, Paris, France.

    BACKGROUND: No systematic data exists on the phenomenology and psychometric aspects of hypomania. In this report we focus on the factor structure of hypomania and its relationships with cyclothymic temperament in unipolar (UP) and bipolar II (BP-II) spectrum (soft bipolar) patients. METHOD: The combined sample of UP and BP-II spectrum patients (n=427) derives from the French National multi-center study (EPIDEP). The study involved training 48 psychiatrists at 15 sites in France in a protocol based on DSM-IV phenomenological criteria for major depressive disorder, hypomania, and BP-II, as well as a broadened definition of soft bipolarity. Psychometric measures included Angst's Hypomania Checklist (HCA) and Akiskal's Cyclothymic Temperament (CT) Questionnaires. RESULTS: In the combined sample of the UP and BP-II spectrum, the factor pattern based on the HCA was characterized by the presence of one hypomanic component. In the soft bipolar group (n=191), two components were identified before and after varimax rotation. The first factor (F-1) identified hypomania with positive (driven-euphoric) features, and the second factor (F-2) hypomania with greater irritability and risk-taking. In exploratory analyses, both factors of hypomania tentatively distinguished most soft BP subtypes from UP. However, F-1 was generic across the soft spectrum, whereas F-2 was rather specific for II-1/2 (i.e., BP-II arising from CT). CT, which was found to conform to a single factor among the soft bipolar patients, was significantly correlated only with irritable risk-taking hypomania (F-2). LIMITATION: In a study conducted in a clinical setting, psychiatrists cannot be kept blind of the data revealed in the various clinical evaluations and instruments. However, the systematic collection of all data tended to minimize biases. CONCLUSION: EPIDEP data revealed a dual structure of hypomania with 'classic' driven-euphoric contrasted with irritable risk-taking expressions distributed differentially across the soft bipolar spectrum. Only the latter correlated significantly with cyclothymic temperament, suggesting the hypothesis that repeated brief swings into hypomania tend to destabilize soft bipolar conditions.

  • J Affect Disord. 2003 Jan;73(1-2):7-18. : Proposed multidimensional structure of mania: beyond the euphoric-dysphoric dichotomy.
    Akiskal HS, Azorin JM, Hantouche EG
    . International Mood Center, University of California at San Diego, La Jolla, CA, USA.
    hakiskal@ucsd.edu

    BACKGROUND: Although the construct of depression has been subjected to numerous factor analytic studies and phenomenological subtypes of clinical relevance have been delineated, this is not the case for mania. The few available studies have reported at least two factors, which consist of euphoric versus dysphoric-hostile subtypes. Our objective was to replicate and further enrich this literature. METHODS: In the EPIMAN French National Study we systematically evaluated 104 DSM-IV hospitalized manic patients in four university centers in different regions of France. Psychiatrists completed the Beigel-Murphy Manic State Rating Scale (MSRS), as well as the HAM-D(17), affective temperament scales, and the GAF Axis V from DSM-IV. Categorization of patients into pure versus dysphoric mania was made on the basis of clinical diagnosis, independent from psychometric measures. RESULTS: On principal component analysis of the MSRS, three factors explained the largest variance: a global manic (23.3% variance), paranoid-hostile (14.8% variance), and psychotic (9.1% variance). After varimax rotation, we obtained seven independent factors: F1 Disinhibition-instability, F2 Paranoia-hostility, F3 Deficit, F4 Grandiosity-psychosis, F5 Elation-euphoria, F6 Depression, and F7 (Hyper)sexuality. We could not demonstrate significant correlations between the individual factors and impaired functioning on GAF. However, depressive and, to some extent, cyclothymic temperaments correlated with F6 Depression. Finally, intergroup comparisons between pure versus dysphoric mania diagnosed clinically showed high levels of F3 Deficit and F5 Elation in the pure, and of F6 Depression in dysphoric, mania; F2 Paranoia-hostility did not discriminate these two clinical forms of mania. LIMITATIONS: Although the present analyses on the Beigel-Murphy represent the largest sample studied to date, they are still underpowered and do not guarantee a stable factorial structure. Our findings are cross-sectional and require prospective validation. CONCLUSIONS: Our data suggest that 'dysphoria' as used in the literature to qualify mania is insufficiently precise, and is best further specified as 'depressive' versus 'irritable.' Moreover, our data extend the rich multidimensional phenomenology of mania beyond the existing literature: we submit that disinhibition-instability (a core 'activation' component) can, on the one hand, be associated with distinct emotional presentations (euphoric, depressive, or irritable-hostile), as well as psychotic and deficit symptomatology on the other.

  • 1: J Affect Disord. 2003 Jan;73(1-2):59-64. : The dual factor structure of self-rated MDQ hypomania: energized-activity versus irritable-thought racing.
    Benazzi F, Akiskal HS.
    Department of Psychiatry, National Health Service, Forli, Italy. f.benazzi@fo.nettuno.it

    BACKGROUND: Bipolar II is diagnosed in a clinically depressed patient by documenting history of hypomania. Therefore, it is of great significance for both clinical and research purposes to characterize the factor structure of hypomania. METHODS: Among consecutive depressive outpatients-126 major depressives and 187 bipolar II-diagnosed by the Structured Clinical Interview for DSM-IV (Clinician Version), 181 who had clinically recovered from depression were administered the Mood Disorder Questionnaire (MDQ of. Am. J. Psychiatry 157, 1873). The MDQ is a newly developed, psychometrically validated self-report screening instrument for bipolar spectrum disorders. It screens for lifetime history of manic/hypomanic symptoms by including yes/no items covering all DSM-IV symptoms of mania/hypomania. The MDQ symptom interrelationships were studied by principal component analysis with varimax rotation. RESULTS: Hypomanic symptoms occurring in >50% were racing thoughts, increased energy and social activity, and irritability. Factor analysis revealed two factors: 'Energized-Activity' (eigenvalue=3.1) and 'Irritability-Racing Thoughts' (eigenvalue=1.5). LIMITATIONS: Cross-sectional assessment. CONCLUSIONS: Self-assessment of past hypomanic symptoms by patients, during clinical remission from depression, revealed two independent hypomanic factors, neither of which comprised euphoria. Hypomanic behavior appears to be more fundamental for the diagnosis of hypomania than elated mood accorded priority in DSM-IV; of hypomanic moods, irritability had greater significance than elation. It would appear that self-report of euphoria is less likely when hypomanias are brief (>or=2 vs. >or=4 days). The main implication for busy clinical practice is that energized activity and irritable mood associated with racing thoughts represent the modal experiences of hypomania among bipolar II outpatients; euphoria is neither sensitive, nor pathognomonic, in the diagnosis of these patients. These conclusions accord with recommendations made many years ago for the diagnosis of hypomania among cyclothymic patients [. Am. J. Psychiatry 134, 1227].

  • J Affect Disord. 2003 Jan;73(1-2):49-57. : Bipolar II with and without cyclothymic temperament: "dark" and "sunny" expressions of soft bipolarity.
    Akiskal HS, Hantouche EG, Allilaire JF.
    International Mood Center, UCSD Department of Psychiatry, 9500 Gilman Drive, La Jolla, San Diego, CA 92093-0603, USA.
    hakiskal@ucsd.edu

    BACKGROUND: In the present report deriving from the French national multi-site EPIDEP study, we focus on the characteristics of Bipolar II (BP-II), divided on the basis of cyclothymic temperament (CT). In our companion article (Hantouche et al., this issue), we found that this temperament in its self-rated version correlated significantly with hypomanic behavior of a risk-taking nature. Our aim in the present analyses is to further test the hypothesis that such patients-assigned to CT on the basis of clinical interview-represent a more "unstable" variant of BP-II. METHODS: From a total major depressive population of 537 psychiatric patients, 493 were re-examined on average a month later; after excluding 256 DSM-IV MDD and 41 with history of mania, the remaining 196 were placed in the BP-II spectrum. As mounting international evidence indicates that hypomania associated with antidepressants belongs to this spectrum, such association per se did not constitute a ground for exclusion. CT was assessed by clinicians using a semi-structured interview based on in its French version; as two files did not contain full interview data on CT, the critical clinical variable in the present analyses, this left us with an analysis sample of 194 BP-II. Socio-demographic, psychometric, clinical, familial and historical parameters were compared between BP-II subdivided by CT. Psychometric measures included self-rated CT and hypomania scales, as well as Hamilton and Rosenthal scales for depression. RESULTS: BP-II cases categorically assigned to CT (n=74) versus those without CT (n=120), were differentiated as follows: (1). younger age at onset (P=0.005) and age at seeking help (P=0.05); (2). higher scores on HAM-D (P=0.03) and Rosenthal (atypical depressive) scale (P=0.007); (3). longer delay between onset of illness and recognition of bipolarity (P=0.0002); (4). higher rate of psychiatric comorbidity (P=0.04); (5). different profiles on axis II (i.e., more histrionic, passive-aggressive and less obsessive-compulsive personality disorders). Family history for depressive and bipolar disorders did not significantly distinguish the two groups; however, chronic affective syndromes were significantly higher in BP-II with CT. Finally, cyclothymic BP-II scored significantly much higher on irritable-risk-taking than "classic" driven-euphoric items of hypomania. CONCLUSION: Depressions arising from a cyclothymic temperament-even when meeting full criteria for hypomania-are likely to be misdiagnosed as personality disorders. Their high familial load for affective disorders (including that for bipolar disorder) validate the bipolar nature of these "cyclothymic depressions." Our data support their inclusion as a more "unstable" variant of BP-II, which we have elsewhere termed "BP-II 1/2." These patients can best be characterized as the "darker" expression of the more prototypical "sunny" BP-II phenotype. Coupled with the data from our companion paper (Hantouche et al., 2003, this issue), the present findings indicate that screening for cyclothymia in major depressive patients represents a viable approach for detecting a bipolar subtype that could otherwise be mistaken for an erratic personality disorder. Overall, our findings support recent international consensus in favoring the diagnosis of cyclothymic and bipolar II disorders over erratic and borderline personality disorders when criteria for both sets of disorders are concurrently met.

  • Seishin Shinkeigaku Zasshi. 2003;105(5):533-43. : [Cyclothymia and typus melancholicus: empirical study on personality character of mood disorder]
    [Article in Japanese]
    Akiyama T, Tsuda H, Matsumoto S, Kawamura Y, Miyake Y.
    Department of Psychiatry, Kanto Medical Center NTT, Tokyo, Japan.

    PURPOSE: 1. To investigate whether depressive, cyclothymic, hyperthymic and irritable temperaments as identified by TEMPS-A are characteristic to monopolar or bipolar disorder. 2. To investigate the independency and to discuss the clinical validity of the temperaments. 3. To replicate the previous studies whether Typus Melancholicus is characteristic to monopolar disorder. 4. To investigate the relationship between Typus Melancholicus and mood dysregulation, and the relationship, if any, is characteristically observed with monopolar disorder. 5. To discuss the difference between monopolar and bipolar disorder in terms of personality character. SAMPLE: Monopolar and bipolar groups were recruited consecutively from the patients who received outpatient treatment at Kanto Medical Center between September and November, 2001. The age is between 18 and 60. The exclusion criteria were psychotic disorder, organic disorder, grave physical illness and non-remitted mood symptoms (HRSD > 11 and MRS > 13). Control group was selected from 1391 company employees who participated in TEMPS-A research project between May 2001 and May 2002, matching gender and age with monopolar and bipolar groups. The exclusion criterion was marked depressive symptom (CES-D > 16). STATISTICAL ANALYSIS: The statistical analyses were done with Kruskal-Wallis test and Mann-Whitney U test with Bonferroni's correction regarding the difference among the groups. Spearman coefficients were examined regarding the independency of temperaments. The relationship between Typus Melancholicus and mood dysregulation was examined by mono-regression analysis. RESULT AND DISCUSSION: Depressive and cyclothymic temperaments scores did not differ significantly between monopolar and bipolar. These scores were significantly higher in monopolar and bipolar than in control. Therefore, these temperaments are evidenced to be characteristic with mood disorder. But between monopolar and bipolar there was no significant difference. Irritable temperament score did not differ significantly among the three groups. This score showed a highly significant correlation with cyclothymic and depressive temperaments. Irritable temperament seems closely related with the personality character of mood disorder, however this temperament itself was not characteristic. Hyperthymic temperament score was mildly significantly lower in bipolar than in control. There was no other significant inter-group difference. This temperament hardly showed a correlation with other temperaments. Though hyperthymic temperament may be hypothesized characteristic with manic patients, the result did not support this hypothesis. Typus Melancholicus score did not differ significantly among three groups. This result contradicts with a number of previous studies. It seems that the prevalence of Typus Melancholicus among the groups should be further investigated. Typus Melancholicus showed a mild correlation with depressive temperament in monopolar and with depressive, cyclothymic and irritable and temperaments in bipolar. Regarding mono-regression analysis, no temperament predicted Typus Melancholicus formation in monopolar. Depressive, cyclothymic and irritable temperaments predicted significantly in bipolar. In control group, hyperthymic temperament predicted midly significantly, but the prediction rate was as small as 7%. These results seem to support the theories of Shimoda and Matussek that Typus Melancholicus characters are related with bipolar disorder. Between monopolar and bipolar, there was not much significant difference in terms of personality characteristics. This seems to suggest no marked personality character difference between these groups and supports Akiskal's concept of Bipolar Spectrum. CONCLUSION: 1. Depressive and Cyclothymic temperaments are characteristic with mood disorder. 2. Hyperthymic temperament is independent, but not characteristic with mood disorder. 3. Irritable temperament may be modifying the personality character of mood disorder. 4. Typus Melancholicus was not characteristic to monopolar disorder. 5. Significant relationship between Typus Melancholicus and mood dysregulation was observed in bipolar group. 6. There seems no substantial difference between monopolar and bipolar disorders in terms of personality character.