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Biomedical subjects

G Spalletta

Publications and source records attributed to G Spalletta.

8 recordsLinked to original sources

Concentrations of 3 alpha-reduced neuroactive steroids and their precursors in plasma of patients with major depression and after clinical recovery.

BACKGROUND: There is preclinical and clinical evidence that plasma concentrations of 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-tetrahydroprogesterone; 3 alpha,5 alpha-THP), a neuroactive steroid that is a positive allosteric modulator of the GABAA receptor, are altered in depression and normalize as a result of antidepressant treatment. However, no data are available on the concentrations of 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-tetrahydrodeoxycorticosterone; 3 alpha,5 alpha-THDOC), another GABA ergic neuroactive steroid, in depression. METHODS: We studied nine depressed patients before and after treatment with various antidepressants and compared them to healthy matched control subjects. Blood samples were quantified by means of a highly sensitive combined gas chromatography/mass spectrometry analysis. RESULTS: Compared to control subjects, plasma concentrations of 3 alpha,5 alpha-THDOC and its precursor 5 alpha-dihydrodeoxycorticosterone (5 alpha-DHDOC) were increased in depressed patients and were not significantly influenced by antidepressant treatment. However, 3 alpha,5 alpha-THP plasma concentrations were decreased in depression and clinically effective antidepressant treatment was accompanied by an increase of 3 alpha,5 alpha-THP concentrations in these patients. CONCLUSIONS: Our results provide the first evidence for a differential alteration in the plasma concentrations of the 3 alpha-reduced neuroactive steroids 3 alpha,5 alpha-THDOC and 3 alpha,5 alpha-THP in major depression, which is only partially reversed by successful antidepressant treatment.

Adult

Neuroactive steroid concentrations following metyrapone administration in depressed patients and healthy volunteers.

BACKGROUND: There is evidence that treatment with the 11 beta-hydroxylase inhibitor metyrapone may represent an alternative treatment strategy in major depression. As a consequence of inhibition of cortisol synthesis the overdrive of corticotropin leads to an accumulation of precursor steroids. However, the effects of metyrapone on the concentrations of endogenous neuroactive steroids that modulate ion channels, e.g., the GABAA receptor, have not yet been studied systematically. METHODS: Therefore, we quantified the concentrations of an array of neuroactive steroids following administration of 1.5 g metyrapone before and after pretreatment with 1 mg dexamethasone in 19 patients suffering from severe depression in comparison to 13 healthy controls by means of a highly sensitive gas chromatography/mass spectrometry analysis. RESULTS: The administration of metyrapone induced a pronounced increase in all neuroactive steroids studied both in patients and controls that was prevented by dexamethasone pretreatment. CONCLUSIONS: Thus, the psychotropic properties of endogenous neuroactive steroids may contribute to the antidepressant properties of metyrapone in the treatment of major depression.

Adrenocorticotropic Hormone

Psychiatric symptoms in male cannabis users not using other illicit drugs.

AIM: To assess the prevalence of DSM-III-R axes I and II disorders and the severity of psychiatric symptoms in cannabis users who did not use other illicit drugs. DESIGN: Cross-sectional psychiatric examination of subjects with different patterns of cannabis use: cannabis dependence, abuse and occasional use. PARTICIPANTS: One hundred and thirty-three cannabis users identified through random urine testing of draftees to the Italian army and interviewed after 2-5 days of abstinence from drug use. MEASUREMENTS: The subjects completed the Beck Depression Inventory, the Spielberger State-Trait Anxiety Index and the 20-item revised Toronto Alexithymia Scale and were then interviewed with the Structured Clinical Interview for DSM-III-R. FINDINGS: The prevalence of co-morbid psychiatric disorders varied with the pattern of cannabis use: 83% of subjects with DSM-III-R cannabis dependence, 46% of those with DSM-III-R cannabis abuse and 29% of occasional users received at least one DSM-III-R psychiatric diagnosis. The severity of depressive, anxious and alexithymic symptoms increased progressively with the degree of involvement with cannabis. CONCLUSIONS: In this sample of young men, the risk of associated psychiatric disabilities varied with the pattern of cannabis use. Chronic use of cannabis was associated with a high prevalence of co-morbid psychiatric disorders.

Comorbidity

Non-verbal behaviour deficits in schizophrenia: an ethological study of drug-free patients.

The aims of this study were (i) to define the dimensions of non-verbal behaviour which distinguish between schizophrenic patients and control subjects and (ii) to examine the relationship between patients' non-verbal behaviour and clinical symptoms. The non-verbal behaviour of 28 drug-free patients with schizophrenia according to Research Diagnostic Criteria (RDC) and 25 control subjects was videotaped during interviews and scored according to an ethological scoring system. Patients' symptoms were rated on the Scale for the Assessment of Negative Symptoms, the Scale for the Assessment of Positive Symptoms and the Brief Psychiatric Rating Scale. As a group, schizophrenic patients showed a global restriction of non-verbal expressiveness, as indicated by their lower scores on prosocial behaviour, gesture and conflict. However, some patients had normal ethological profiles. Non-verbal behaviour was largely independent of negative and positive symptoms. Deficits in non-verbal behaviour may play a role in determining or aggravating dysfunctional patterns of relating in schizophrenia. Ethological analysis provides further support for the model that conceptualizes positive symptoms, negative symptoms and disorders of social relationships as three separate dimensions of the schizophrenic syndrome.

Adult

Effects of antidepressant treatment on neuroactive steroids in major depression.

OBJECTIVE: There is evidence from animal studies that fluoxetine may enhance the concentrations of neuroactive steroids. Therefore, the authors investigated whether clinically effective treatment with antidepressants may alter the concentrations of neuroactive steroids in patients suffering from a major depressive episode. METHOD: In the first study, eight drug-naive outpatients with major depression were studied during treatment with fluoxetine. In a complementary study, 11 inpatients with major depression were studied during a severe depressive episode and after recovery following treatment with different antidepressants. Plasma samples were quantified for neuroactive steroids by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis. RESULTS: During depression, there was a significant decrease in 3 alpha, 5 alpha-tetrahydroprogesterone (3 alpha, 5 alpha-THP) and 3 alpha, 5 beta-THP concentrations, both of which are positive modulators of the gamma-aminobutyric acidA receptor, and a concomitant increase in 3 beta, 5 alpha-THP levels. This dysequilibrium of neuroactive steroids could be corrected by treatment with different antidepressants. CONCLUSIONS: These results provide the first clinical evidence of a possible role of neuroactive steroids in successful antidepressant therapy.

Adult

Patients with deficit, nondeficit, and negative symptom schizophrenia: do they differ during episodes of acute psychotic decompensation?

The aims of this study were (1) to test the hypothesis that the clinical profiles of deficit, nondeficit, and negative symptom patients are difficult to distinguish during episodes of acute psychotic decompensation; and (2) to compare these groups of schizophrenic patients in terms of sociodemographic and anamnestic variables. Patients admitted for acute psychotic decompensation were retrospectively diagnosed as having deficit (N = 18) or nondeficit (N = 40) forms of schizophrenia and their symptom profiles were evaluated cross-sectionally by using various rating scales (SAPS, SANS, and PANSS). As a whole, nondeficit patients were clearly differentiated from deficit patients by lower severity of negative symptoms. However, the subgroup (N = 24) of nondeficit patients with prominent negative symptoms that were secondary and/or nonenduring showed a symptom profile largely overlapping with that of deficit patients. Attentional impairment was the only measure distinguishing deficit and negative symptom patients. As for trait variables, deficit patients had lower education than the other two groups and, among male subjects, there was a higher percentage of left-handers in the deficit group than in the negative symptom subgroup. These results confirm the importance of diagnosing the deficit syndrome during periods of clinical stability in order to avoid the risk of misclassifying negative symptom patients into the deficit group.

Adult

Symptom profile, Axis II comorbidity and suicidal behaviour in young males with DSM-III-R depressive illnesses.

We assessed the descriptive validity of DSM-III-R major depression (MDD), dysthymia (DD) and adjustment disorder with depressed mood (ADDM) by comparing the clinical profiles of 176 young male patients. The severity of depression increased progressively across the three diagnostic groups (ADDM < DD < MDD). Symptom presentation did not distinguish clearly between the diagnostic groups, even though somatic symptoms were more frequent among MDD patients. The prevalence of personality disorders was much higher (43%) among DD patients than among MDD (22%) and ADDM (15%) patients. The lifetime prevalence of suicide attempts differed in the three diagnostic groups (MDD 27%, DD 17%, ADDM 4%). Assessment of Axis II comorbidity and suicidal behavior can improve the diagnostic distinction between these DSM-III-R depressive illnesses.

Adjustment Disorders

Marked decrease of plasma neuroactive steroids during alcohol withdrawal.

The neuroactive steroids allopregnanolone (ALLO) and allotet-rahydrodeoxycorticosterone (THDOC) are the most potent endogens positive modulators of gamma-aminobutyric acid (GABA) on GABAA receptors, a receptor system presumably responsible for some behavioral responses to alcohol withdrawal. In a group of nine alcoholic subjects, the levels of plasma ALLO and THDOC were markedly lower than those of control subjects during the early withdrawal phase (day 4 and 5), when anxiety and depression scores were higher. In contrast ALLO and THDOC plasma levels did not differ from those of control subjects during the late withdrawal phase when anxiety and depression scores were low. These results suggest that the decrease of neuroactive steroid biosynthesis may contribute to the withdrawal symptoms.

Adult