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Biomedical subjects

G B Cassano

Publications and source records attributed to G B Cassano.

At least 19 recordsLinked to original sources

The importance of measures of affective temperaments in genetic studies of mood disorders.

Collaboration between the University of Pisa, Italy, and the University of Tennessee, Memphis, U.S.A., on patients presenting with major depressive episodes (in the absence of nonaffective psychiatric illness) focused on the detection of depressive and hyperthymic temperaments. From our data on symptomatology, family history and course of 538 such patients, several findings emerge of cardinal relevance to genetic studies. Hyperthymic temperament, observed more commonly in men, appears as one pole of an attenuated form of manic-depressive illness. Thus, major depressives with this temperament have high rates of bipolar family history, even in the absence of hypomanic and manic episodes. The depressive temperament, more prevalent in women, is correlated with earlier onset and higher number of depressive episodes, greater severity of the Hamilton Rating Scale for Depression (HAM-D), as well as higher familial loading for mood disorders, compared with major depressives without this temperament. Building on Akiskal's latest model on the multifactorial origin of mood disorders, we submit that these temperamental dysregulations constitute the intermediate step between predisposing familial-genetic factors in affective illness and gender-related clinical expressions of mood disorders. The authors recommend that future high-risk prospective studies and genetic investigations should include measures of affective temperament.

Adult

Proposed subtypes of bipolar II and related disorders: with hypomanic episodes (or cyclothymia) and with hyperthymic temperament.

In an attempt to improve the classification of Bipolar II disorders, we have examined a consecutive series of 687 primary major depressives: 5.1% gave a past history of mania (Bipolar I), 13.7% met our operational criteria for hypomania (Bipolar II), and the remaining 81.2% were provisionally categorized as 'unipolar.' Although Bipolar II was in some respects intermediate between Bipolar I and Unipolar, gender, familial bipolar history, age at onset and course characteristics generally supported its closer kinship to bipolar illness. Seventy one of the unipolars (10.3% of the total series) further met our operational criteria for hyperthymic temperament (U-HT), leaving behind a purer unipolar group of 487 major depressives. With respect to the proportion having male gender and bipolar family history, U-HT was similar to Bipolar I and II, and all three differed significantly from pure unipolar; as for age at onset, number of episodes and related indices of course, BI and BII were similar, and U-HT was closer to pure unipolar. These findings suggest that major depressive episodes arising from a hyperthymic temperament (constituting 12.4% of the 'unipolar' universe by conventional definition) are 'genotypically' closer to Bipolar II defined by hypomania, and course-wise similar to other unipolars.

Bipolar Disorder

Peripheral markers of serotonin and dopamine function in obsessive-compulsive disorder.

In an attempt to clarify the possible role of a serotonergic and dopaminergic dysfunction in obsessive-compulsive disorder (OCD), we measured platelet 3H-imipramine (3H-IMI) binding, serotonin uptake, and platelet sulfotransferase activity in 17 drug-free OCD patients and an equal number of healthy controls. Serotonin uptake and 3H-IMI binding sites in platelets have been shown to constitute peripheral markers of those present in presynaptic serotonergic neurons. Sulfotransferase, an enzyme involved in the catabolism of phenolic compounds and of cathecholamines such as dopamine, has similar kinetic characteristics in brain and platelets. Our results showed a lower number of 3H-IMI binding sites and a higher level of sulfotransferase activity in OCD patients compared with those in controls. These preliminary results suggest involvement of both the serotonin and dopamine systems in OCD.

Adult

Immune cell imbalance in major depressive and panic disorders.

We investigated subsets of peripheral immunologic cells in 12 drug-free patients affected by major depression according to DSM-III-R criteria, and who had recent evidence of somatic diseases. They were compared with 10 drug-free depressives, with 10 patients with panic disorder, and with 12 healthy volunteers, all without somatic disease. The immune subsets were measured by flow cytometry. The results showed that both groups of depressives had the same abnormalities in immune cells compared with the healthy volunteers or the panic disorder patients; in particular they presented a lower number of CD3+, CD8+ and HLA-DR+. The patients with panic attacks did not differ from healthy controls, except for CD4+ cells which were significantly lowered, even in comparison with the depressive groups. These data, although preliminary and in a small sample, suggest that some immune parameters may be influenced by the presence of a major psychiatric disorder.

Adolescent

Psychotic symptom patterns and the diagnosis of schizophrenia.

In comparing 101 psychotic patients subtyped by DSM-III criteria into paranoia, schizophrenia, schizoaffective, and affective disorders, we failed to distinguish them on the basis of delusional and hallucinatory experiences. These 'productive', 'positive' or 'irritative' symptoms--which the literature tends to link with temporolimbic dysfunction--did not appear specifically linked to schizophrenia. By contrast, 'negative' or 'deficit' symptoms--which the literature tends to relate to frontal lobe dysfunction--appeared more specific--especially for the disorganized subtype of schizophrenia. Although these data tend to support Bleulerian over Schneiderian conceptualization of schizophrenia, the heterogeneity of neuropsychological deficits implied in the negative symptom complexes limits the nosologic utility of the rubric of schizophrenia so defined.

Adolescent

Diagnosis and clinical use of bromperidol in HIV-related psychoses in a sample of seropositive patients with brain damage.

We evaluated in an open trial the safety and effectiveness of a high-potency neuroleptic (bromperidol) for the treatment of AIDS-related organic mental syndromes. Eleven (nine men and two women) seropositive patients with psychotic features were included; six were intravenous drug users (IVDU) and five were not IVDU (NON-IVDU). On the basis of the achievement of a CGI score of 1 or 2 (much improved or very much improved) at the fourth week, nine patients were considered responders, one was a partial responder and one was a non-responder. From a clinical point of view, "positive" psychotic symptoms had a significant remission, while the "negative" ones seemed to be less sensitive or insensitive to bromperidol treatment.

AIDS Dementia Complex

Major depressive episode: unipolar and bipolar II.

Major Depressive Episod (MDE) delimits a wide range of heterogeneous disorders. Nowadays, both for research and for therapeutic aims, precise characteristization of MDE subtypes are needed, different subtypes of MDE requiring individualized short, long-term and preventive treatments. As patients mainly seek for physician help during the full-blown depressive phase, we focused our study on patients presenting a major depression as the index episode. In order to attempt to isolate subtypes of the disorder relatively to the mood spectrum disease and to obtain a better clinical characterization of each, we have considered the role of soft indicators of bipolarity or of milder mood disregulations in distinguishing among subtypes of MDE; special attention was devoted to detect spontaneous or drug-induced hypomania, as well as to assess the hyperthymic or cyclothymic temperament, and family history for mood disorders. Data on prior course, characteristics of index episode, and familial aggregation of patients with Bipolar II Disorder support the autonomy of this condition. Differently from our previous analyses we considered Bipolar II with hypomanic episodes separately from U-HT unipolar with only hyperthymic temperament. The comparison between these two subgroups showed a higher percentage of males in the hyperthymics, longer duration of illness and a greater number of depressive episodes and hospitalizations in bipolar II with hypomania. Data from our analyses are exposed and discussed.

Adult

[Benzodiazepine withdrawal syndrome. Problems of differential diagnosis against depression, panic attacks and generalized anxiety].

Anxiety and mood disorders are among the psychic afflictions which tend to lead to prolonged benzodiazepine intake. This is also one of the reasons why doctors are faced with a difficult task when having to differentiate between these phenomena and the anxiolytic withdrawal syndrome. Since preexisting psychiatric pathology may modify withdrawal symptoms, thus making differential diagnosis between withdrawal syndrome and recrudescence of the previous disorder even more difficult, it is necessary carefully to assess clinical phenomenology both in relation to its course and to its variability with possible emergence of new symptoms. In addition to drawing attention to the diagnostic elements that can be most useful for identifying the withdrawal syndrome in mood disturbances and panic attack disorder, the authors also report the data of an experimental study of benzodiazepine withdrawal in patients suffering from generalized anxiety.

Anxiety

[Benzodiazepine withdrawal syndrome].

Benzodiazepines (BDZ) are widely prescribed in clinical practice for many pathological conditions, because of their anxiolytic, sedative, myorelaxant and anticonvulsant properties. The effectiveness, specificity and rapidity of action, the few side effects and the virtual absence of toxicity, have contributed to the widespread use of these compounds. In the last decade, however, the attitude towards BDZ has greatly changed, due to growing awareness and concern about dependence liability, withdrawal phenomena, and long-term side effects. Withdrawal symptoms have been singled out and specified in the contest of a well-defined syndrome with foreseeable onset, duration and remission. Psychic and physical symptoms and disorders of sensory perception can be observed. These manifestations can be suppressed by resuming treatment. The symptomatic and developmental aspects of BDZ withdrawal syndrome are discussed, according to the available literature, with particular reference to clinical features of patients suffering from anxiety and mood disorders.

Anti-Anxiety Agents

[Omega benzodiazepine receptor subtypes and new ligands].

Pharmacological and biochemical studies indicate that for many receptors, distinct subtypes exist; the multiplicity and diversity of signal reception proteins increase the information-handling capacity of neurons, thus contributing to neural plasticity. This is also the case for the allosteric modulatory-centre omega of the GABA-A receptor. Binding studies suggest the presence of at least two pharmacologically distinct omega receptors in the human brain; furthermore, molecular biological studies have confirmed the existence of genes encoding different omega subtypes. As omega receptors are the site of action of benzodiazepines and other anxiolytic compounds, this knowledge may be useful for developing new subtype-specific drugs, with more selective therapeutic effects.

Anti-Anxiety Agents

The manic-depressive mixed state: familial, temperamental and psychopathologic characteristics in 108 female inpatients.

Data on 108 hospitalized bipolar I women were analyzed to characterize those whose course was marked with at least one mixed episode (i.e. an episode with concomitant manic and depressed features) on the basis of various anamnestic and cross-sectional clinical features in comparison with those without mixed episodes. Our data revealed a later age of appearance of the first mixed episode in the course of bipolar illness with a tendency to recur true to type; greater prevalence of mood incongruent psychotic features; lower frequency of hyperthymic temperament; and familial depressive, rather than bipolar, disorders. These characteristics tend to identify the mixed state as a distinct longitudinal pattern of manic-depressive illness.

Adult

Serotoninergic dysfunction in bipolar disorder.

The recent discovery of peripheral markers of central neurotransmitter systems has broadened the scope of biological research in psychiatry. Human platelets resemble presynaptic serotoninergic neurons and permit us to investigate the involvement of the serotonin system in the pathophysiology of mood disorders. In particular, platelets show an active uptake of serotonin and the related 3H-imipramine (3H-IMI), similar to cerebral binding sites. We evaluated 3H-IMI binding in a group of 30 bipolar patients as compared with healthy controls. In 20 patients, platelet 14C-5HT uptake was also measured. The results showed no difference in IMI binding parameters between bipolar patients and healthy controls. However, the patients showed a lower Vmax of 14C-5HT uptake than the controls. These findings suggest that bipolarity influences one of the main components of the 5HT transporter complex in platelets.

Adult

Decreased platelet serotonin uptake in bipolar I patients.

The 5HT transporter complex in platelets is similar to that in the brain and thus widely used in biological psychiatry as a peripheral marker of the 5HT system. Our study aim was to measure 14C-5HT uptake parameters (Vmax and Km) in platelets from 12 patients affected by bipolar disorder, as compared with 12 healthy controls. The uptake assay was performed according to the method of Arora and Meltzer (1981). The results showed that the Vmax was significantly lower in bipolar patients than in healthy controls, with no modification of the Km. These preliminary data would indicate therefore that the mechanism of 5HT transport is altered in platelets of bipolar patients.

Adult

Analgesia by nefopam: does it act through serotonin?

In an attempt to clarify the possible mode of action of nefopam, a new analgesic compound, the authors tested its effects on imipramine (IMI) binding to platelet membranes. The results showed that nefopam exerted a concentration-dependent inhibition of IMI binding, with a potency comparable to that of tricyclic antidepressants. This finding suggests a possible intervention of serotonergic mechanisms in nefopam-related analgesia.

Analgesia