G.B. Cassano

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.

Alteration of the platelet serotonin transporter in romantic love

BACKGROUND The evolutionary consequences of love are so important that there must be some long-established biological process regulating it. Recent findings suggest that the serotonin (5-HT) transporter might be linked to both neuroticism and sexual behaviour as well as to obsessive-compulsive disorder (OCD). The similarities between an overvalued idea, such as that typical of subjects in the early phase of a love relationship, and obsession, prompted us to explore the possibility that the two conditions might share alterations at the level of the 5-HT transporter. METHODS Twenty subjects who had recently (within the previous 6 months) fallen in love, 20 unmedicated OCD patients and 20 normal controls, were included in the study. The 5-HT transporter was evaluated with the specific binding of 3H-paroxetine (3H-Par) to platelet membranes. RESULTS The results showed that the density of 3H-Par binding sites was significantly lower in subjects who had recently fallen in love and in OCD patients than in controls. DISCUSSION The main finding of the present study is that subjects who were in the early romantic phase of a love relationship were not different from OCD patients in terms of the density of the platelet 5-HT transporter, which proved to be significantly lower than in the normal controls. This would suggest common neurochemical changes involving the 5-HT system, linked to psychological dimensions shared by the two conditions, perhaps at an ideational level.

Predictors and moderators of time to remission of major depression with interpersonal psychotherapy and SSRI pharmacotherapy.

BACKGROUND Although many studies suggest that, on average, depression-specific psychotherapy and antidepressant pharmacotherapy are efficacious, we know relatively little about which patients are more likely to respond to one versus the other. We sought to determine whether measures of spectrum psychopathology are useful in deciding which patients with unipolar depression should receive pharmacotherapy versus depression-specific psychotherapy. METHOD A total of 318 adult out-patients with major depression were randomly assigned to escitalopram pharmacotherapy or interpersonal psychotherapy (IPT) at academic medical centers at Pittsburgh, Pennsylvania and Pisa, Italy. Our main focus was on predictors and moderators of time to remission on monotherapy at 12 weeks. RESULTS Participants with higher scores on the need for medical reassurance factor of the Panic-Agoraphobic Spectrum Self-Report (PAS-SR) had more rapid remission with IPT and those with lower scores on the psychomotor activation factor of the Mood Spectrum Self-Report (MOODS-SR) experienced more rapid remission with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy. Non-specific predictors of longer time to remission with monotherapy included several panic spectrum and mood spectrum factors and the Social Phobia Spectrum (SHY) total score. Higher baseline scores on the 17- and 25-item Hamilton Depression Rating Scales (HAMD-17 and HAMD-25) and the Work and Social Adjustment Scale (WSAS) also predicted a longer time to remission, whereas being married predicted a shorter time to remission. CONCLUSIONS This exploratory study identified several non-specific predictors but few moderators of psychotherapy versus pharmacotherapy outcome. It offers useful indicators of the characteristics of patients that are generally difficult to treat, but only limited guidance as to who benefits from IPT versus SSRI pharmacotherapy.

Fluvoxamine in the treatment of body dysmorphic disorder (dysmorphophobia).

Fifteen consecutive patients with a DSM-III-R diagnosis of body dysmorphic disorder (BOD) were included in a 10-week open clinical trial of fluvoxamine. Treatment began at 100 mg/day fluvoxamine and was increased to a maximum of 300 mg/day or until intolerable side effects developed or a complete or nearly complete resolution of symptoms occurred. At baseline and at weeks 2, 6 and 10, patients completed the Hopkins Symptoms Check-List (HSCL-90) and a specific rating scale for HDD symptoms (BODSS), and clinicians completed a Clinical Global Improvement Scale. Twelve of the 15 patients completed the trial. Of the three patients who did not complete the study, one improved moderately during the placebo phase, one showed a marked worsening of the depressive symptoms during the wash-out phase and one showed adverse side effects, such as nausea and diarrhoea, after the first week of treatment and was unable to continue the trial. After 10 weeks, of the 12 remaining patients, 10 were considered to be markedly improved, one minimally improved and one unchanged. Several outcome measures showed a significant improvement from baseline to week 10. Our findings suggest flint fluvoxamine may be effective in the treatment of BDD. Double-blind studies will be required to investigate these findings further.

Response to ECT in bipolar I, bipolar II and unipolar depression

OBJECTIVES A significant body of evidence indicates the efficacy of electroconvulsive therapy (ECT) in unipolar depression but mixed results have been reported in bipolar depression. We explored difference of response to ECT in unipolar (UP), bipolar I (BP I) and bipolar II (BP II) depression, in a sample of patients resistant to pharmacological treatment. METHODS One hundred and thirty depressive patients (17 with Major Depression (UP), 67 with bipolar disorder II (BP II) and 46 with bipolar disorder I (BP I) according to DSM-IV criteria) were included in the study and treated with bilateral ECT, on a twice-a-week schedule. The patients were assessed before (baseline) and a week after the ECT course (final score), using the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Improvement (CGI). RESULTS The three groups (UP, BP II, BP I) showed a significant improvement after the ECT course. Global response rate (CGI<2) was 94.1% for UP, 79.1% for BP II and 67.4% for BP I. Concerning depressive symptomatology, the remission rate (HAM-D <8) was respectively 70.5 for UP, 56.7% for BP II and 65.3% for BP I. The best results were achieved by UP patients, while BP I group showed the worst results with a lower remission rate and higher scores in YMRS and BPRS psychotic cluster at the final evaluation. CONCLUSION ECT turns out to be a viable option for the treatment of both unipolar and bipolar depressive patients resistant to pharmacological treatment. Nevertheless, while the UP group showed the best response and clinical outcomes, the BP I patients tended to exhibit residual manic and psychotic symptomatology.

Clomipramine for panic disorder: I. the first 10 weeks of a long-term comparison with imipramine

Clomipramine and imipramine treatments were compared in a sample of 152 panic disorders. Diagnosis was according to the positive criteria of DSM-III-R, but without exclusion of comorbid affective or personality disorders. The 2-year design provides non-blind treatment under typical clinical practice conditions, and it includes random assignment, periodic assessment with standardized measures, and comparable, flexible drug dosages. Findings on six outcome measures in the first 59 cases to complete 10 weeks showed both tricyclics to be markedly and equally effective for blocking panic attacks, alleviating phobic avoidance, and reducing nonspecific aspects of anxiety. Clomipramines predominantly serotonergic action seemed not to determine a different action spectrum. During the first 2 weeks, clomipramine was significantly and unexpectedly superior to imipramine in both antipanic and antiphobic actions. These results require replication under double-blind conditions.

A double-blind study of fluvoxamine and clomipramine in the treatment of obsessive-compulsive disorder

A double-blind trial was carried out to assess the efficacy and safety of fluvoxamine, a selective serotonin reuptake inhibitor, in comparison with clomipramine, a classical tricyclic antidepressant, in the treatment of obsessive-compulsive disorder. A total of 26 individuals with obsessive-compulsive disorder and with no comorbid disorders at baseline were included in the study. The obsessive-compulsive disorder symptom severity was rated using the Yale-Brown Obsessive-Compulsive Scale and the Clinical Global Impression Scale. The primary efficacy measures indicated an equal improvement in the two groups (38% in the patients taking fluvoxamine and 40% in those taking clomipramine, as compared with baseline values), but onset was faster in the clomipramine group. Side effects, in particular anticholinergic side effects, were more prominent in the clomipramine group. The present double-blind trial confirms an equal efficacy of clomipramine and fluvoxamine in obsessive-compulsive patients. Although clomipramine had a faster onset, fluvoxamine was better tolerated, so that it seems more suitable for long-term treatment of obsessive-compulsive patients.

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.

Localization and gene expression of serotonin1A (5HT1A) receptors in human brain postmortem

We investigated the binding parameters, i.e. the maximum binding capacity (Bmax) and the dissociation constant (Kd), of [3H]8-hydroxy-2-(di-N-propylamino)tetralin ([3H]8-OH-DPAT) labeling the serotonin receptor of the 1A type (5HT1A), and the distribution of the mRNA encoding it in some human brain areas obtained from autoptic samples. The results showed that the Bmax was significantly higher in the hippocampus than in the prefrontal cortex and the striatum, while the Kd had the inverse, although not significant, pattern. The expression study revealed that 5HT1A mRNA distribution in the hippocampus and prefrontal cortex was consistent with the data of the [3H]8-OH-DPAT binding. A different result was obtained in the striatum where no 5HT1A mRNA expression was detected, despite the measurement of specific [3H]8-OH-DPAT binding. These findings underline the different nature of [3H]8-OH-DPAT binding sites in different brain areas and the need for further studies on 5HT receptor gene expression in human brain.