H.S. Akiskal

The Semi-Structured Affective Temperament Interview (TEMPS-I) : Reliability and psychometric properties in 1010 14-26-year-old students

BACKGROUND The purpose of this study was to evaluate the reliability and psychometric properties of the Semistructured Affective Temperament Interview, and determine cut-offs for each temperament. METHOD 1010 Italian students aged between 14 and 26 were evaluated by means of the Akiskal and Mallya criteria in a Semistructured Interview for depressive, cyclothymic, hyperthymic, and irritable temperaments. RESULTS This instrument has very good reliability and internal consistency. The percentage of subjects with a z-score higher than the second positive standard deviation ( + 2 SD) on the scales of depressive and cyclothymic temperaments are 3.6% and 6.3% (reaching scores of 7/7 and 9/10), respectively. Hyperthymic traits, on the other hand, are widespread in our sample: most subjects are included within the second positive standard deviation ( + 2 SD), and 8.2% of these reach a 7/7 score; therefore, the problem of defining a cut-off for this temperament is still open. By contrast, the irritable temperament is rare, conforming to a non-gaussian distribution, with 2.2% of cases above the second positive standard deviation ( + 2 SD). LIMITATION The data are based on subject report without collateral information and external validation. CONCLUSION This study contributes to more accurate definition of cut-offs for individual temperament scales. The standardization of the interview thus makes it possible to compare three out of four temperamental scales, showing the dominant temperamental characteristics for each subject. Prospective studies are needed to demonstrate the stability of these traits over time.

Psychopathology, Temperament, and Past Course in Primary Major Depressions. 1. Review of Evidence for a Bipolar Spectrum

In reviewing recent findings on affective conditions in the interface of unipolar and bipolar disorders, we find evidence favoring a partial return to Kraepelins broad concept of manic-depressive illness, which included many recurrent depressives and temperamental variants. This review addresses methodologic, clinical, and familial considerations in the definition and characterization of a proposed spectrum of bipolar disorders which subsumes episodic and chronic forms. Episodic bipolar disorders are subclassified into bipolar schizoaffective, and bipolar I and II, and bipolar III or pseudo-unipolar forms. Chronic bipolar disorders could be either intermittent or persistent, and are subclassified into chronic mania, protracted mixed states, and rapid-cycling forms, as well as the classical temperaments (cyclothymic, hyperthymic, irritable and dysthymic).

Psychopathology, Temperament, and Past Course in Primary Major Depressions. 2. Toward a Redefinition of Bipolarity with a New Semistructured Interview for Depression

We report on the utility of a new instrument to identify subtypes of major depressive episodes with special reference to pseudo-unipolar conditions. By incorporating reliable measures of depressive and hyperthymic temperamental characteristics in subtype definitions, we achieve the sharpest possible demarcation between unipolar and bipolar disorders. The new procedures also reveal that 1 out of 3 primary depressives in a consecutive series of 405 patients belong to the bipolar spectrum. Furthermore, among bipolars, bipolar II disorder (redefined as major depressions with hypomania or hyperthymic temperament) represents the most common variant. We discuss the nosologic, therapeutic, methodologic and theoretical implications of these considerations on the unipolar-bipolar dichotomy. Given that major depression emerges as the final common clinical expression of a heterogeneous group of disorders, it underscores the importance of focusing on temperament and course of illness in subclassification efforts such as attempted here.

Manic-depressive (bipolar) disorder : the course in light of a prospective ten-year follow-up of 131 patients

For a five‐year period, 131 bipolar patients were followed every 6 months; for the next 5 years, they were followed yearly. Each patient was interviewed in a systematic way that gave information about episodes, hospitalizations, cycle lengths and the presence of alcoholism. Women and men were not significantly different in the number of follow‐up manic or depressive episodes or hospitalizations. Chronicity from index episode to the end of the 10‐year follow‐up was uncommon (4%). Alcoholism, which was common in these patients, showed a great diminution at the end of 10 years. Contrary to expectation, cycle lengths showed no systematic decrease in length over the follow‐up. In this naturalistic study, treatment intensity was not related to decreasing episodes or to changes in cycle length. The number of episodes in the first 5 years of follow‐up was not correlated with the number of episodes in the last 5 years. Cycle lengths in the first 5 years of follow‐up were similar in length to the last 5 years of follow‐up. A family history of mania in these bipolar patients was associated with more episodes in follow‐up than if such a family history were absent. The patients whose alcoholism predated the onset of their affective illness were less likely to have episodes in the follow‐up than the patients in whom affective illness predated the onset of the alcoholism.

Long-term prognosis of bipolar I disorder.

This study examined the contribution of demographic. syndromal and longitudinal course variables to the long‐term prognosis of 165 bipolar patients prospectively observed over 10 years as part of the National Institute of Mental Health Collaborative Study of Depression. Although most baseline clinical and demographic variables were not strong prognostic indicators, switching polarity within episodes was. Most episodes among the poor‐prognosis patients were polyphasic, while most episodes among the comparison group with a better prognosis were monophasic. There was no evidence of shortening of cycle lengths over follow‐up for either the poor‐prognosis group or the entire sample. The relevance of these findings to the ‘kindling’ model is discussed.

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.

Role of risperidone in bipolar II: an open 6-month study

BACKGROUND Since treatment approaches thought to be useful for mania are presumably suitable for hypomania as well, little systematic research has been done on the treatment of hypomanic episodes and their long-term outcome. As systematic trials have shown that the atypical antipsychotic risperidone may be effective and safe in the treatment of acute mania, we decided to conduct an open-label study of its effectiveness and tolerability in hypomania associated with bipolar II. METHODS Forty-four DSM-IV bipolar II patients with Young Mania Rating Scale (YMRS) scores above 7 were included and followed-up for 6 months. Efficacy was measured by means of the YMRS and the Clinical Global Impression for Bipolar Disorder (CGI-BD). Treatment-emergent depression was measured by the Hamilton Depression Rating Scale (HDRS-17), and the Udvalg for Kliniske Undersøgelser (UKU) subscale was used for neurological/extrapyramidal side-effects. RESULTS Thirty-four patients completed the trial. The mean dose of risperidone at endpoint was 2.8 mg/day. Last observation-carried-forward analysis showed significant reduction of YMRS scores from the first week of treatment, which continued until the endpoint (P<0.0001). At 6-month follow-up, 60% of patients were assymptomatic according to the CGI. The 32% who received risperidone in monotherapy seemed to respond equally well. Risperidone, as used in this study, appeared to be most protective against hypomanic than depressive recurrences. Nine patients (12%) had a depressive relapse during 6-month follow-up, one patient (2%) had an hypomanic relapse and another (2%) had both. No patients developed tardive dyskinesia during the duration of the study. Although most patients received risperidone in combination with standard mood-stabilizers, only three patients discontinued risperidone because of other side-effects. LIMITATIONS In the absence of a placebo arm, it is uncertain to what extent the foregoing results could be ascribed to spontaneous remission of bipolar II disorder. CONCLUSIONS Risperidone, either in combination with mood-stabilizers or alone was well-tolerated in bipolar II patients, who presented in a hypomanic state, and appeared efficacious. Further controlled research on the role of atypical antipsychotics in the treatment of less-than-manic forms of bipolar illness is warranted.

Dysthymia: clinical and external validity

This paper reviews current evidence in support of dysthymia as a subaffective disorder that precedes major affective episodes, often by more than a decade. In cases beginning in childhood or adolescence, dysthymia is associated with high familial rates of mood disorders, and a recurrent pattern of superimposed major depression. At least two trait‐like markers, sleep electro‐encephalographic and thyroid axis abnormalities — similar to those in major affective disorder — have been reported. These data indicate a common pathophysiological substrate for both dysthymia and major depressive illness. All classes of antidepressants — most recently the serotonin re‐uptake and the reversible MAO inhibitors — have been shown to be effective. Dysthymia was fairly recently included in the US(DSM) and WHO(ICD) classifications of mental disorders, because it characterises a prevalent clinical presentation of depression in both psychiatric and general medical settings. Patients given this diagnosis, instead of presenting with acute or full‐blown episodes, often complain of low‐grade chronic affective malaise for as long as they remember, yet without clinically observable signs of depression. As a result, questions have been raised about its validity, but from fundamentally opposite positions: (i) Is dysthymia better conceptualised as a personality (or neurotic) rather than mood disorder? (ii) Can dysthymia be distinguished from major depressive illness? This paper examines these and related questions along both clinical and external validating strategies, and in particular, the more recent accumulated evidence in support of the utility of the concept of dysthymia.

Dysthymia: clinical picture, extent of overlap with chronic fatigue syndrome, neuropharmacological considerations, and new therapeutic vistas

Dysthymia, as defined in the American Psychiatric Association and International Classification of Mental Disorders, refers to a prevalent form of subthreshold depressive pathology with gloominess, anhedonia, low drive and energy, low self-esteem and pessimistic outlook. Although comorbidity with panic, social phobic, and alcohol use disorders has been described, the most significant association is with major depressive episodes. Family history is loaded with affective, including bipolar, disorders. The latter finding explains why dysthymia, especially when onset is in childhood, can lead to hypomanic switches, both spontaneously and upon pharmacologic challenge in as many as 30%. Indeed, antidepressants from different classes -tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase A (RIMAs), selective serotonin-reuptake inhibitors (SSRIs) and, more recently, amisulpride, and spanning noradrenergic, serotonergic as well as dopaminergic mechanisms of action - have been shown to be effective against dysthymia in an average of 65% of cases. This is a promising development because social and characterologic disturbances so pervasive in dysthymia often, though not always, recede with continued pharmacotherapy beyond acute treatment. Despite symptomatic overlap of dysthymia with chronic fatigue syndrome - especially with respect to the cluster of symptoms consisting of low drive, lethargy, lassitude and poor concentration - neither the psychopathologic status, nor the pharmacologic response profile of the latter syndrome is presently understood. Chronic fatigue today is where dysthymia was two decades ago. We submit that the basic science - clinical paradigm that has proven so successful in dysthymia could, before too long, crack down the conundrum of chronic fatigue as well. At a more practical level, we raise the possibility that a subgroup within the chronic fatigue group represents a variant of dysthymia.

The high prevalence of bipolar II and associated cyclothymic and hyperthymic temperaments in HIV-patients

BACKGROUND Although recent studies have shown high rates of current and lifetime depression in HIV-infected patients, there is little systematic data on the occurrence of bipolarity in these patients. METHOD We compared 46 HIV patients with index major depressive episode (MDE) to an equal number of age- and sex-matched seronegative MDE patients, and systematically examined rates of DSM-III-R bipolar subtypes (enriched in accordance with Akiskals system of classifying soft bipolar disorders). RESULTS Although HIV and psychiatric clinic patients had comparable background in terms of familial affective loading, HIV patients had significantly higher familial rates for alcohol and substance use. The more important finding was the significantly higher proportion of HIV patients with lifetime bipolar II disorder (78%), and associated cyclothymic (52%) and hyperthymic (35%) temperaments; the findings were the same irrespective of HIV risk status (intravenous drug user vs. homosexual and other risk groups combined). LIMITATIONS The major methodologic limitation of our study is that clinicians evaluating temperament were not blind to affective diagnoses and family history. The comparison affective group was a sample of convenience drawn from the same tertiary care university facility. CONCLUSION The finding of a high rate of bipolar II disorder in HIV patients has treatment implications for seropositive patients presenting with depression. More provocatively, we submit that premorbid impulsive risk-taking traits associated with cyclothymic and hyperthymic temperaments may have played an important role in needle-sharing drug use and/or unprotected sexual behavior, leading ultimately to infection with HIV. Given their public health importance, these clinical findings and insights merit further investigation. In particular, systematic case-control studies, as well as other large scale studies with prospective methodology need to be conducted.