Biomedical subjects

Hagop S Akiskal

Publications and source records attributed to Hagop S Akiskal.

At least 19 recordsLinked to original sources

PubMed2006

Special issue on circular insanity and beyond: historic contributions of French psychiatry to contemporary concepts and research on bipolar disorder.

The original contribution of French psychiatry to what today we call bipolar disorder has its roots in 1854 in two papers that were presented in the French National Academy of Medicine by Falret and Baillarger. This event was celebrated in the same Academy in Paris in February, 2004 at its 150th anniversary. Because nearly all of the contributions of French alienists to the field of mood disorders have not been translated into English, their pioneering contributions are not as well known to the Anglophone world as those of Kraepelin, who in 1899 integrated French and other German work into his systematic treatise. To the best of our knowledge, the present special issue is the first monograph in English devoted to the pioneering French contributions in the field of mood disorders as well as contemporary research on bipolar disorder in France, Italy and the United States which supports and extends them.

Bipolar Disorder↗

PubMed2006

Validity of the assessment of bipolar spectrum disorders in the WHO CIDI 3.0.

OBJECTIVE: Although growing interest exists in the bipolar spectrum, fully structured diagnostic interviews might not accurately assess bipolar spectrum disorders. A validity study was carried out for diagnoses of threshold and sub-threshold bipolar disorders (BPD) based on the WHO Composite International Diagnostic Interview (CIDI) in the National Comorbidity Survey Replication (NCS-R). CIDI BPD screening scales were also evaluated. METHOD: The NCS-R is a nationally representative US household population survey (n=9282 using CIDI to assess DSM-IV disorders. CIDI diagnoses were evaluated in blinded clinical reappraisal interviews using the non-patient version of the Structured Clinical Interview for DSM-IV (SCID). RESULTS: Excellent CIDI-SCID concordance was found for lifetime BP-I (AUC=.99 kappa=.88, PPV=.79, NPV=1.0), either BP-II or sub-threshold BPD (AUC=.96, kappa=.88, PPV=.85, NPV=.99), and overall bipolar spectrum disorders (i.e., BP-I/II or sub-threshold BPD; AUC=.99, kappa=.94, PPV=.88, NPV=1.0). Concordance was lower for BP-II (AUC=.83, kappa=.50, PPV=.41, NPV=.99) and sub-threshold BPD (AUC=.73, kappa=.51, PPV=.58, NPV=.99). The CIDI was unbiased compared to the SCID, yielding a lifetime bipolar spectrum disorders prevalence estimate of 4.4%. Brief CIDI-based screening scales detected 67-96% of true cases with positive predictive value of 31-52%. LIMITATION: CIDI prevalence estimates are still probably conservative, though, but might be improved with future CIDI revisions based on new methodological studies with a clinical assessment more sensitive than the SCID to sub-threshold BPD. CONCLUSIONS: Bipolar spectrum disorders are much more prevalent than previously realized. The CIDI is capable of generating conservative diagnoses of both threshold and sub-threshold BPD. Short CIDI-based scales are useful screens for BPD.

Bipolar Disorder↗

PubMed2006

Bipolar II and anxious reactive "comorbidity": toward better phenotypic characterization suitable for genotyping.

OBJECTIVE: In DSM-IV, bipolar II (BP-II) disorder is defined by depression and hypomania. There is little appreciation of affective instability, often associated with anxiety-particularly panic disorder and agoraphobia (PDA)-comorbidity. This association has genetic-familial implications, which we believe must be incorporated in refining the BP-II phenotype suitable for genotyping purposes. METHOD: We examined in a semi-structured format 107 consecutive patients who met DSM-IV criteria for major depressive episode with atypical features and separated them into two subgroups according to the co-occurring criteria for PDA. They were further evaluated on the basis of the Atypical Depression Diagnostic Scale (ADDS), the Hopkins Symptoms Check-list (HSCL 90), and the Hamilton Rating Scale for Depression (HRSD), coupled with its modified form for reverse vegetative features, as well as Axis I and II comorbidity and temperamental dispositions, particularly cyclothymic instability. RESULTS: Fifty (46.7%) of our patients met the DSM-IV criteria for PDA. In terms of significant results, PDA+ was more frequently female, had higher number of hypomanic episodes, and stressors; they were also more often BP-II, and cyclothymic. Ratings of reactivity, somatization, OCD and phobic anxiety too were significantly higher among the PDA+. In related analyses, most AD (75.7%) met criteria for BP-II; the BP-II subgroup was characterized by PDA, as well as borderline personality features and cyclothymic and hyperthymic temperaments. LIMITATIONS: Correlational clinical study in which clinicians could not be kept entirely blind to the variables under investigation. CONCLUSIONS: In line with the description by the French psychiatrist Pierre Kahn a century earlier, cyclothymic reactivity and neurotic features (i.e., atypicality and panic attacks) appear relevant to the definition of what today we consider BP-II disorder. These data, which are in line with current familial-genetic models of this disorder, suggest that the DSM-IV characterization of BP-II must be enriched by greater emphasis on temperamentally based mood and anxious reactivity. Such phenotypic characterization is likely to assist in better genotyping. Previous work by us further suggests the relevance of bulimic and addictive tendencies, as well as "borderline personality" diagnosis in the proband and/or the family. We submit that these conditions, rather than being "comorbid," constitute, along with BP-II, a spectrum of overlapping underlying genetic diatheses.

Adolescent↗

PubMed2006

Suitability of the TEMPS-A for population-based studies: ease of administration and stability of affective temperaments in its Lebanese version.

BACKGROUND: The Temperament Evaluation of Memphis Pisa Paris and San Diego Auto-questionnaire (TEMPS-A) has been translated and validated into several languages, and used in different subgroups (e.g. clinical, students, company, employees and those with different educational levels). METHODS: Lebanon is the only country that has validated the TEMPS-A in a national cohort, as part of the Lebanese Evaluation of the Burden of Ailments and Needs Of the Nation (LEBANON). In this paper, we test the suitability of the TEMPS-A for large scale epidemiologic population-based studies. RESULTS: 82.1% of the respondents found the TEMPS-A to be easy to understand. The global reports of the Lebanese of their own temperaments paralleled those of the formal sub-scores on the five affective temperament subscales. The majority of respondents (90.3%) felt that their answers on the Lebanese-Arabic TEMPS-A scale represented them throughout their adulthood; the minority who did not were more likely to be older, and to have scored higher on the cyclothymic, and lower on the hyperthymic subscales. LIMITATION: Although the TEMPS-A has been designed for self-administration (auto-questionnaire), this was not practical in all subjects. We nonetheless feel that the interview format is viable as it introduces flexibility with certain subjects in population studies. CONCLUSIONS: The TEMPS-A appears to be suitable for use in epidemiologic surveys and research.

Arabs↗

PubMed2006

Dose-response relationship between number of comorbid anxiety disorders in adolescent bipolar/unipolar disorders, and psychosis, suicidality, substance abuse and familiality.

OBJECTIVES: To ascertain rates of panic, obsessive-compulsive (OCD) and social phobic disorders among adolescents with bipolar disorder (BP), unipolar major depressive disorder (MDD) and psychiatric comparison patients, to assess their relationships to suicidality, psychosis, comorbidity patterns and familiality. METHODS: The first author (SCD) interviewed 313 Latino adolescents using a structured interview based on the SCID. Family history was ascertained by live interview or interview by proxy. Patients were classified as BP, MDD, or non-affectively ill comparison controls (CC). Data regarding suicidality and psychosis were collected. Regression analysis was used to test associations and control for confounding effects. Positive likelihood ratios were used to measure the dose-response relationships between number of anxiety disorders and measures of severity of illness and familial loading for affective illness. RESULTS: Of the total sample, 36.7% were BP, 44.7% MDD and 18.5% CC. In BP vs. MDD the odds of panic disorder were 4.4, of OCD 5.1, and of social phobia 3.3. MDD, in turn, were more likely to have these disorders than CC. BP (but not MDD) with panic disorder and social phobia, were more likely to have suicidal ideation; among the anxiety disorders, only social phobia was associated with having greater odds of suicide attempts. Among BP and MDD, patients with all three anxiety disorders were more likely to be psychotic. Presence of any mood disorder among first-degree relatives substantially increased the odds of having panic disorder and social phobia. The presence of one comorbid anxiety disorder increased the odds of having another. Finally, there were dose-response relationships between number of anxiety disorders and measures of severity of illness and familial loading for affective illness. LIMITATIONS: Single interviewer using the SCID; cross sectional exploratory study. CONCLUSIONS: BP adolescents have a greater anxiety disorder burden than their MDD counterparts. The results are compatible with the hypothesis that heavy familial-genetic loading for affective illness in juveniles is associated with bipolarity, cumulative anxiety disorder comorbidity, suicidality and psychosis. These observations are in line with pioneering psychopathologic observation in the early 1900s by two French psychiatrists, Gilbert Ballet and Pierre Kahn, who saw common ground between what until then had been considered the distinct categories of the neuroses and cyclothymic (circular) psychoses. This perspective has much in common with current complex genetic models of anxious diatheses in bipolar disorder.

Adolescent↗

PubMed2006

Validating the bipolar spectrum in the French National EPIDEP Study: overview of the phenomenology and relative prevalence of its clinical prototypes.

BACKGROUND: Few studies have been undertaken to ascertain the feasibility of using the bipolar (BP) spectrum in clinical practice. The only systematic national study is the French EPIDEP Study of consecutive inpatients and outpatients presenting with major depressive episodes (MDE). The protocol was developed in 1994 and implemented in 1995; publication of its first data began in 1998. This report provides the complete data set of the EPIDEP. METHODS: Forty-eight psychiatrists, practicing in 15 sites in four regions of France (Paris, Besançon, Bordeaux and Marseille), were all trained on a common protocol based on DSM-IV criteria for MDE (n=537) subdivided into BP-I (history of mania), BP-II (history of hypomania), as well as extended definitions of the "softer spectrum" beyond BP-I and BP-II. Measures tapping into this spectrum included the Hypomania Checklist (HCA), the cyclothymic (CT), depressive (DT) and hyperthymic (HT) temperament scales. These measures and course permitted post-hoc assignment of MDE in the bipolar spectrum, based in part on the Akiskal, H.S., Pinto, O., 1999. [The evolving bipolar spectrum: Prototypes I, II, III, IV. Psychiatr. Clin. North Am. 22, 517-534] proposal: depression with history of spontaneous hypomanic episodes (DSM-IV, BP-II), cyclothymic depressions (BP-II(1/2)), antidepressant-associated hypomania (BP-III) and hyperthymic depressions (BP-IV). < > was thereby limited to an exclusion diagnosis for the remainder of MDE. LIMITATION: In the clinical setting, psychiatrists cannot be entirely blind to the observations in the various clinical evaluations and instruments. However, the systematic multisite collection of such data tended to minimize any such biases. RESULTS: After excluding patients lost to follow-up, among 493 presenting with MDE with complete data files, the BP-II rate was estimated at index at 20%; 1 month later, systematic probing for hypomania doubled the rate of BP-II to 39%. The comparison between BP-II and UP showed differential phenomenology, such as hypersomnia, increased psychomotor activation, guilt feelings and suicidal thoughts in BP-II. Related data demonstrated the importance of CT in further qualifying of MDE to define a distinct, more severe ("darker") BP-II(1/2) variant of BP-II. Moreover, BP-III, arising from DT and associated with antidepressants, emerged as a valid soft bipolar variant on the basis of the phenomenology of hypomania and bipolar family history. Finally, we found preliminary evidence for the inclusion of BP-IV into the bipolar spectrum, its total hypomania score falling intermediate between BP-II and strict UP. Using this broader diagnostic framework, the bipolar spectrum (the combined "hard" BP-I phenotype, BP-II and the soft spectrum) accounted for 65% of MDE. CONCLUSION: The EPIDEP study achieved its objectives by demonstrating the feasibility of identifying the bipolar spectrum at a national level, and refining its phenomenology through rigorous clinical characterization and validation of bipolar spectrum subtypes, including MDE with brief hypomanias, cyclothymia and hyperthymia. The spectrum accounted for two out of three MDE, making "strict UP" less prevalent than BP as redefined herein. Our findings were anticipated by Falret, who in 1854 had predicted that many melancholic patients in the community would 1 day be classified in his circular group. We also confirmed Baillarger's observation in the same year that episodes (in this study, hypomanic episodes) could last as short as 2 days. Our findings deriving from a systematic French national database a century and a half later invite major shifts in clinical and public health services, as well as in the future conduct of psychopharmacologic trials. In this respect, the systematic training of clinicians in four regions of France represents a national resource for affective disorders and can serve as a model to effect change in diagnostic practice in other countries.

Adolescent↗

PubMed2006

Does the FDA proposed list of possible correlates of suicidality associated with antidepressants apply to an adult private practice population?

BACKGROUND: In issuing an advisory about a relationship of suicidality emerging during antidepressant use in mood and other psychiatric disorders in juvenile and, possibly patients of all ages, the FDA listed such warning symptomatologic correlates as psychomotor agitation, panic, insomnia, irritability, aggressiveness, and impulsivity, and additionally urged screening for personal and family history for bipolar disorder. It must be recalled that the FDA warning was based on post hoc examination of antidepressant trial data pertaining largely to emergent suicidal ideation rather than attempts. In this report we examine the relevance of the "FDA list" for adults. METHODS: Consecutive 650 outpatients presenting with a major depressive episode (MDE) in the second author's (FB) private practice were interviewed using the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen. The threshold for a bipolar II (BP-II) diagnosis was broadened by bypassing the stem-A probes on hypomanic mood, lowering the duration of hypomanic episodes to as short as 2 days and, most importantly, eliciting hypomanic intrusions into depressive episodes. Beyond the FDA proposed list and in line with previous work by us, we considered symptoms of depressive mixed state (DMX, an MDE plus 3 or more DSM-IV intradepressive non-euphoric hypomanic symptoms) as possible substrates for suicidality. RESULTS: Suicidal ideation was present in 49.3% of the sample, and significantly greater in BP-II versus MDD (OR=1.46). Odds ratio for patients with suicidal ideas, versus those without suicidal ideas in univariate analyses were as follows: irritability (1.32), psychomotor agitation (1.48) and racing/crowded thoughts (2.0). In DMX, irritability was present in 76.4% and in non-DMX in 23.8% (OR=10.3), psychomotor agitation in 51.3% versus 4.4%, (OR=22.6), and racing/crowded thoughts in 89.2% versus 45.3% (OR=9.9). Insomnia and family history for bipolarity were not associated with suicidal ideation. Racing/crowded thoughts emerged as the only significant independent predictor in multiple logistic regression. LIMITATION: Panic was not specifically tested, because it was not systematically entered into our clinical database. Furthermore, we studied a population which was not taking antidepressants. Our operating hypothesis was that the FDA listed correlates of suicidality are pre-existing baseline substrates that might be potentially further activated by antidepressants. CONCLUSION: Going beyond previous work by us, the present data further refine the "FDA list" under scrutiny. While not designed to test whether antidepressants induce suicidality, the present report shows that the type of depression associated with suicidal ideas is an agitated, irritable, and especially mentally overactive syndrome (i.e. a DMX). Bipolarity falling short of the DSM-IV schema (represented by BP-II with brief hypomania and DMX) appears to represent the main diagnostic substrate for the occurrence of suicidality. Although controlled trials of antidepressants in adults have not been specifically conducted in DMX patients, it would be clinically prudent to avoid the prescription of antidepressant monotherapy to such patients to avert any potential iatrogenic aggravation of their condition.

Adult↗

PubMed2006

Toward an integrative model of the spectrum of mood, behavioral and personality disorders based on fear and anger traits: I. Clinical implications.

Current formal psychiatric approaches to nosology are plagued by an unwieldy degree of heterogeneity with insufficient appreciation of the commonalities of emotional, personality, behavioral, and addictive disorders. We address this challenge by building a spectrum model that integrates the advantages of Cloninger's and Akiskalian approaches to personality and temperament while avoiding some of their limitations. We specifically propose that "fear" and "anger" traits--used in a broader connotation than in the conventional literature--provide an optimum basis for understanding how the spectra of anxiety, depressive, bipolar, ADHD, alcohol, substance use and other impulse-control, as well as cluster B and C personality disorders arise and relate to one another. By erecting a bidimensional approach, we attempt to resolve the paradox that apparently polar conditions (e.g. depression and mania, compulsivity and impulsivity, internalizing and externalizing disorders) can coexist without cancelling one another. The combination of excessive or deficient fear and anger traits produces 4 main quadrants corresponding to the main temperament types of hyperthymic, depressive, cyclothymic and labile individuals, which roughly correspond to bipolar I, unipolar depression, bipolar II and ADHD, respectively. Other affective temperaments resulting from excess or deficiency of only fear or anger include irritable, anxious, apathetic and hyperactive. Our model does not consider schizophrenia. We propose that "healthy" or euthymic individuals would have average or moderate fear and anger traits. We further propose that family history, course and comorbidity patterns can also be understood based on fear and anger traits. We finally discuss the implications of the new derived model for clinical diagnosis of the common psychiatric disorders, and for subtyping depression and anxiety as well as cognitive and behavioral styles. We submit this proposed schema represented herein as a heuristic attempt to build bridges between basic and clinical science.

Alcoholism↗

PubMed2006

Toward an integrative model of the spectrum of mood, behavioral and personality disorders based on fear and anger traits: II. Implications for neurobiology, genetics and psychopharmacological treatment.

Current psychiatry relies on a purely categorical paradigm for diagnosis of mental disorders that profoundly impacts research and clinical practice. However, high comorbidity rates and relative non-specificity of family history for psychiatric disorders suggests that this categorical approach fails to identify the underlying diathesis. As an attempt to overcome such limitations, we developed a bidimensional model based on fear and anger traits or temperaments which does not preclude the use of a categorical approach. As a result, it is hypothesized that mood, behavioral and personality disorders share a neurobiological substrate according to combinations of fear and anger traits. Both fear and anger, when excessive or deficient, lead to increased risk for mental disorders and should be considered in genetic, neurobiological and neuroimaging studies. Fear traits are much influenced by the amygdala and the serotonergic, noradrenergic and GABAergic systems, whereas anger seems to be mostly regulated by the nucleus accumbens and the dopaminergic and glutamatergic systems. Pharmacological treatments with antidepressants and anxiolytics can be considered as essentially restraint on fear, whereas lithium and alpha2 noradrenergic agonists would attenuate fear deficiency. Dopaminergic antidepressants and psychostimulants are anger enhancers and antipsychotics and mood stabilizers, such as divalproate and carbamazepine, may share antianger effects. Drugs effective for manic and depressive phases probably have both antianger and antifear effects. This framework may lead to a better understanding of the neurobiological basis of mental health and disease, providing an integrative approach for future research.

Anger↗

PubMed2006

Toward a unitary perspective on the bipolar spectrum and substance abuse: opiate addiction as a paradigm.

Bipolar spectrum disorders and addiction often co-occur and constitute reciprocal risk factors that the authors believe are best considered under a unitary perspective. In particular, we submit that patients whose disorders fall under the bipolar spectrum - and its hyperthymic and cyclothymic temperamental substrates are at increased risk for substance use, possibly moving towards addiction through exposure to intrinsically dependence-producing substances. In our experience, the contribution of bipolar spectrum disorders to the addictive process is often clinically missed, because attenuated and subclinical expressions of such mood disorders as bipolar II and cyclothymia are not adequately appreciated by our current formal diagnostic system (e.g. DSM-IV, as well as research and clinical practice based on it). The use of agonist treatment in dual diagnosis heroin addicts has allowed us to gather valuable knowledge about the intrinsic, and historically and clinically documented mood-regulating effects of opiates. From the therapeutic point of view, the challenge of double diagnosis requires double competence from clinicians. The combination of opiate agonists and mood stabilizers often produces results difficult to obtain with the use of the two types of drugs separately. We therefore submit that the present conceptualization of the link between bipolar spectrum and addictive disorders has not only heuristic and scientific values, but also an important message for the clinician.

Alcoholism↗

PubMed2006

The distinct temperament profiles of bipolar I, bipolar II and unipolar patients.

BACKGROUND: Despite a plethora of studies, controversies abound on whether the long-term traits of unipolar and bipolar patients could be differentiated by temperament and whether these traits, in turn, could be distinguished from subthreshold affective symptomatology. METHODS: 98 bipolar I (BP-I), 64 bipolar II (BP-II), and 251 unipolar major depressive disorder (UP-MDD) patients all when recovered from discrete affective episodes) and 617 relatives, spouses or acquaintances without lifetime RDC diagnoses (the comparison group, CG) were administered a battery of 17 self-rated personality scales chosen for theoretical relevance to mood disorders. Subsamples of each of the four groups also received the General Behavior Inventory (GBI). RESULTS: Of the 436 personality items, 103 that significantly distinguished the three patient groups were subjected to principal components analysis, yielding four factors which reflect the temperamental dimensions of "Mood Lability", "Energy-Assertiveness," "Sensitivity-Brooding," and "Social Anxiety." Most BP-I described themselves as near normal in emotional stability and extroversion; BP-II emerged as labile in mood, energetic and assertive, yet sensitive and brooding; MDD were socially timid, sensitive and brooding. Gender and age did not have marked influence on these overall profiles. Within the MDD group, those with baseline dysthymia were the most pathological (i.e., high in neuroticism, insecurity and introversion). Selected GBI items measuring hypomania and biphasic mood changes were endorsed significantly more often by BP-II. Finally, it is relevant to highlight a methodologic finding about the precision these derived temperament factors brought to the UP-BP differentiation. Unlike BP-I who were low on neuroticism, both BP-II and UP scored high on this measure: yet, in the case of BP-II high neuroticism was largely due to mood lability, in UP it reflected subdepressive traits. LIMITATION: We used self-rated personality measures, a possible limitation generic to the paper-and-pencil personality literature. It is therefore likely that BP-I may have over-rated their "sanguinity"; or should one consider such self-report as a reliable reflection of one's temperament? One can raise similar unanswerable questions about "depressiveness" and "mood lability." CONCLUSION: As contrasted to CG and published norms, the postmorbid self-described "usual" personality is 1) sanguine among many, but not all, BP-I; 2) labile or cyclothymic among BP-II; and 3) subanxious and subdepressive among UP. It is further noteworthy that with the exception of BP-II, the temperament scores of BP-I and MDD were within one SD from published norms. Rather than being pathological, these attributes are best conceived as subclinical temperamental variants of the normal, thereby supporting the notion of continuity between interepisodic and episodic phases of affective disorders. These findings overall are in line with Kraepelin's views and contrary to the DSM-IV formulation of axis-II constructs as being pathological and sharply demarcated from affective episodes.

Adult↗

PubMed2006

The DSM-IV and ICD-10 categories of recurrent [major] depressive and bipolar II disorders: evidence that they lie on a dimensional spectrum.

BACKGROUND: Presently it is a hotly debated issue whether unipolar and bipolar disorders are categorically distinct or lie on a spectrum. We used the ongoing Ravenna-San Diego Collaboration database to examine this question with respect to major depressive disorder (MDD) and bipolar II (BP-II). METHODS: The study population in FB's Italian private practice setting comprised consecutive 650 outpatients presenting with major depressive episode (MDE) and ascertained by a modified version of the Structured Clinical Interview for DSM-IV. Differential assignment of patients into MDD versus BP-II was made on the basis of discrete hypomanic episodes outside the timeframe of an MDE. In addition, hypomanic signs and symptoms during MDE (intra-MDE hypomania) were systematically assessed and graded by the Hypomania Interview Guide (HIG). The frequency distributions of the HIG total scores in each of the MDD, BP-II and the combined entire sample were plotted using the kernel density estimate. Finally, bipolar family history (BFH) was investigated by structured interview (the Family History Screen). RESULTS: There were 261 MDD and 389 BP-II. As in the previous smaller samples, categorically defined BP-II compared with MDD had significantly earlier age at onset, higher rates of familial bipolarity (mostly BP-II), history of MDE recurrences (>or=5), and atypical features. However, examining hypomania scores dimensionally, whether we examined the MDD, BP-II, or the combined sample, kernel density estimate distribution of these scores had a normal-like shape (i.e., no bimodality). Also, in the combined sample of MDE, we found a dose-response relationship between BFH loading and intra-MDE hypomania measured by HIG scores. LIMITATIONS: Although the interviewer (FB) could not be blind to the diagnostic status of his private patients, the systematic rigorous interview process in a very large clinical population minimized any unintended biases. CONCLUSIONS: Unlike previous studies that have examined the number of DSM-IV hypomanic signs and symptoms both outside and during MDE, the present analyses relied on the more precise hypomania scores as measured by the HIG. The finding of a dose-response relationship between BFH and HIG scores in the sample at large strongly suggests a continuity between BP-II and MDD. Our data indicate that even in those clinically depressed patients without past hypomanic episodes (so-called "unipolar" MDD), such scores are normally rather than bimodally distributed during MDE. Moreover, the absence of a 'zone of rarity' in the distribution of hypomanic scores in the combined total, MDD and BP-II MDE samples, indicates that MDD and BP-II exist on a dimensional spectrum. From a nosologic perspective, our data are contrary to what one would expect from a categorical unipolar-bipolar distinction. In practical terms, intra-MDE hypomania and BFH, especially in recurrent MDD, represent strong indicators of bipolarity.

Adult↗

PubMed2006

The clinical phenotypes of juvenile bipolar disorder: toward a validation of the episodic-chronic-distinction.

BACKGROUND: Recent research has addressed the issue of subtyping juvenile bipolar disorder (JBD). Accordingly, we set out to find out, in a naturalistic sample of bipolar children and adolescents with mania and mixed mania, whether the most useful subtyping should be based on clinical features (elated vs. irritable) or course (episodic vs. chronic). METHODS: We studied 136 patients, 81 male patients (59.6%) and 55 female patients (40.4%), mean age 13.5 +/- 2.9 years, meeting the DSM-IV diagnosis of bipolar disorder, assessed by a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version [K-SADS-PL]). RESULTS: Regarding course, 77 patients (56.6%) had an episodic course and 59 patients (43.4%) had a chronic course. Patients with chronic course were significantly younger, had an earlier onset of JBD, and presented a more frequent comorbidity with disruptive behavior disorders. According to the prevalent mood disturbance, 75 patients (55.1%) showed an elated and 61 patients (44.9%) showed an irritable mood. Elated mood was more frequent in patients with episodic course, whereas irritable mood was more frequent in the patients with chronic course. CONCLUSIONS: These findings suggest that chronic versus episodic course may be a putative differential feature. Further validation of such a distinction would require prospective studies, temperament evaluation, gender and neurobiologic approaches, and differential psychopharmacologic assignment and response.

Adolescent↗

PubMed2006

The 5HTTLPR polymorphism of the serotonin transporter gene is associated with affective temperaments as measured by TEMPS-A.

BACKGROUND: Increasing evidence supports the notion of a continuum between affective temperaments and major mood disorders, suggesting that these temperament types represent the subclinical manifestations of affective disorders and often present an increased vulnerability for these diseases. METHODS: The Hungarian rendition of the full-scale 110-item version of the TEMPS-A questionnaire and 5HTTLPR genotype was investigated in a sample of 139 unrelated Caucasian females with no current or lifetime Axis I psychiatric disorders. RESULTS: A significant association was found between the s allele and the TEMPS scores of the depressive, anxious, irritable, and particularly the cyclothymic temperaments; no such association emerged with respect to the hyperthymic temperament. LIMITATION: The database is entirely female. Given that the hyperthymic type predominates in males, our results could have been different if men were included in our sample. CONCLUSIONS: Our results are in good agreement with earlier studies reporting a strong association between the s allele of the 5HTTLPR and major as well as subthreshold forms of depression, and extend this association to the normative temperament level. Indeed, these temperaments might best be regarded as proximate behavioural endophenotypes. Our data raise the provocative possibility that the genetic potential for mood episodes lies in these temperaments. Further studies are needed to delineate the role of gender in the associations under consideration, as well as to investigate the genetic background of the hyperthymia-mania part of the affective spectrum. Given that affective temperaments are widely distributed in the general population, the strategy employed by us is of potential public health significance in terms of detecting individuals in the community at risk for affective spectrum disorders.

Adolescent↗

PubMed2006

Bulimia nervosa in atypical depression: the mediating role of cyclothymic temperament.

OBJECTIVE: Recent data indicate significant clinical, biological, and treatment response overlap between eating and bipolar disorders, especially when soft symptoms of either spectrum disorders are considered. The aim of the present analyses is to evaluate the lifetime prevalence of bulimia nervosa (BN) in patients with atypical depression (AD) and to delineate any demographic, clinical, personality or temperamental factors that may characterize this subgroup. METHOD: We examined in a semi-structured format 107 consecutive patients who met DSM-IV criteria for major depressive episode with atypical features and we separated them into two groups according to the co-occurring criteria for BN. They were further evaluated on the basis of the Atypical Depression Diagnostic Scale (ADDS), the Hopkins Symptoms Check-list (HSCL 90), and the Hamilton Rating Scale for Depression (HRSD), coupled with its modified form for reverse vegetative features, as well as Axis I and II comorbidity and temperamental dispositions. RESULTS: Seventeen (17.8%) percent of AD met the DSM-IV criteria for Bulimia Nervosa (BN+). These patients, compared with those who did not meet criteria for BN (BN-), were indistinguishable on all demographic and most psychopathologic and clinical features (including bipolar I and II), but were significantly higher in lifetime comorbidity for Narcissistic, Histrionic, Borderline and Dependent personality disorders as well as that for Cyclothymic temperament. BN+ also scored higher on the ADDS items of reactivity of mood and interpersonal sensitivity. LIMITATIONS: Correlational clinical study in which doctors could not be entirely blind to the variables under investigation. CONCLUSIONS: Cyclothymic temperament and related mood reactivity and interpersonal sensitivity may account for much of the relationship between AD and BN. Narcissistic, histrionic and borderline traits, too, seem to be related to the presence of a cyclothymic disposition. The data overall, in particular the cyclothymic reactivity in the absence of differences in BP-I and II, all support the hypothesis that places BN in the "ultra-soft" bipolar realm.

Adolescent↗

PubMed2006

Biphasic course in bipolar II outpatients: prevalence and clinical correlates of a cyclic pattern described by Baillarger and Falret in hospitalised patients in 1854.

BACKGROUND: Biphasic course refers to a mood episode immediately followed by one of opposite polarity and then usually by a free interval. It was described under the rubric of folie à double forme among psychiatric inpatients by the French psychiatrist Baillarger 150 years ago. A rapid cycling form (folie circulaire) was also described in the same year by his compatriot Falret. These patients would probably have today met the criteria for bipolar I. Our aim was to find the prevalence and clinical correlates of biphasic course in bipolar II (BP II) in contemporary ambulatory patients. METHODS: Consecutive 206 BP II outpatients were interviewed in the first author's private practice, using a modified Structured Clinical Interview for DSM-IV. To assign a patient to biphasic episode, it must have occurred at least once when not on an antidepressant. RESULTS: Frequency of biphasic course was 80%. Biphasic vs. non-biphasic course was significantly higher in polyepisodic major depressive episode (MDE) and those with antidepressant-associated hypomania; the same was true for index melancholic subtype, where index of Global Assessment of Functioning scale (GAF) score was lower. Female gender, age at onset, mixed depressive episodes and bipolar family history were not significantly different between the two groups. LIMITATIONS: Patients were not observed on a prospective basis. We cannot report on the relative proportion of MDE preceded vs. followed by hypomania, because such distinction was not part of FB's naturalistic database. CONCLUSIONS: Strikingly in line with Baillarger's observation 150 years ago, biphasic course represented the typical pattern in this outpatient private practice sample of BP II. That antidepressant-associated hypomania was significantly more common in the biphasic course variety suggests that when MDE preceded hypomania-in such patients, antidepressants might have simply accentuated the natural cycle rather than causing it. Switching in the clinical setting then seems to depend on a biphasic cyclic baseline aggravated by antidepressant use. The fact that mixed states were equally prevalent in both course patterns suggests that the mechanisms involved in switching and mixity may be distinct. The significantly higher number of melancholic episodes with lower GAF scores indicates that-in line with Falret's description-overall, the biphasic course represents a relatively unfavorable outcome pattern.

Adult↗

PubMed2006

Cyclothymia and labile personality: is all folie circulaire?

BACKGROUND: Historically, cyclothymia has been used broadly to refer either to a temperament (Kretschmer) or the entire range of bipolar disorders. Within this spectrum, it is uncertain whether it characterizes the "hard" (or manic-depressive) forms (as Kurt Schneider argued) or its "soft" expressions (bipolar II and highly recurrent depressions); the latter perspective is in line with Falret's view that the melancholic expressions of his folie circulaire (circular insanity) were highly prevalent in the community. METHODS: Eight hundred forty-three outpatients were interviewed with the Schedule for Affective Disorders and Schizophrenia without regard to hierarchical exclusionary rules. RESULTS: Compared to 630 psychiatrically interviewed outpatients who did not have cyclothymia, 163 cyclothymics were significantly more likely to have most of the disorders listed in the SADS in univariate analyses. Discriminant analyses limited the significant associations to labile personality, bipolar II, intermittent depression, secondary depression, hypomanic disorder and schizoaffective mania. LIMITATION: The RDC construct of cyclothymia is rather broad. CONCLUSIONS: Despite such operational breadth, cyclothymia was nonetheless largely limited to the soft end of the bipolar spectrum where labile moods and depressive recurrence predominate. In this sense, it is natural to place it on the border of manic-depressive psychosis. Although Kurt Schneider was the first to describe the "labile psychopath" [personality], he believed it was unrelated to his narrow concept of cyclothymia, which he used synonymously with manic-depressive psychosis. Our data do not support his position. Instead, they support both Kretchmer's and Falret's views.

Bipolar Disorder↗

PubMed2006

Prevalence and effects of mood disorders on work performance in a nationally representative sample of U.S. workers.

OBJECTIVE: Research on the workplace costs of mood disorders has focused largely on major depressive episodes. Bipolar disorder has been overlooked both because of the failure to distinguish between major depressive disorder and bipolar disorder and by the failure to evaluate the workplace costs of mania/hypomania. METHOD: The National Comorbidity Survey Replication assessed major depressive disorder and bipolar disorder with the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) and work impairment with the WHO Health and Work Performance Questionnaire. A regression analysis of major depressive disorder and bipolar disorder predicting Health and Work Performance Questionnaire scores among 3,378 workers was used to estimate the workplace costs of mood disorders. RESULTS: A total of 1.1% of the workers met CIDI criteria for 12-month bipolar disorder (I or II), and 6.4% meet criteria for 12-month major depressive disorder. Bipolar disorder was associated with 65.5 and major depressive disorder with 27.2 lost workdays per ill worker per year. Subgroup analysis showed that the higher work loss associated with bipolar disorder than with major depressive disorder was due to more severe and persistent depressive episodes in those with bipolar disorder than in those with major depressive disorder rather than to stronger effects of mania/hypomania than depression. CONCLUSIONS: Employer interest in workplace costs of mood disorders should be broadened beyond major depressive disorder to include bipolar disorder. Effectiveness trials are needed to study the return on employer investment of coordinated programs for workplace screening and treatment of bipolar disorder and major depressive disorder.

Absenteeism↗