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Biomedical subjects

A Pasini

Publications and source records attributed to A Pasini.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1998

Dual effect on the RET receptor of MEN 2 mutations affecting specific extracytoplasmic cysteines.

The RET gene encodes a receptor tyrosine kinase whose function is essential during the development of kidney and the intestinal nervous system. Germline mutations affecting one of five cysteines (Cys609, 611, 618, 620 and 634) located in the juxtamembrane domain of the RET receptor are responsible for the vast majority of two cancer-prone disorders, multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC). These mutations lead to the replacement of a cysteine by an alternate amino acid. Mutations of the RET gene are also the underlying genetic cause of Hirschsprung disease (HSCR), a congenital aganglionosis of the hindgut. In a fraction of kindreds, MEN 2A cosegregate with HSCR and affected individuals carry a single mutation at codons 609, 618 or 620. To examine the consequences of cysteine substitution on RET function, we have introduced a Cys to Arg mutation into the wild-type RET at either codons 609, 618, 620, 630 or 634. We now report that each mutation induces a constitutive catalytic activity due to the aberrant disulfide homodimerization of RET. However, mutations 630 and 634 activate RET more strongly than mutations 609, 618 or 620 as demonstrated by quantitative assays in rodent fibroblasts and pheochromocytoma PC12 cells. Biochemical analysis revealed that mutations 618 and 620, and to a lesser extent mutation 609, result in a marked reduction of the level of RET at the cell surface and as a consequence decrease the amount of RET covalent dimer. These findings provide a molecular basis explaining the range of phenotype engendered by alterations of RET cysteines and suggest a novel mechanism whereby mutations of cysteines 609, 618 and 620 exert both activating and inactivating effects.

3T3 Cells↗
PubMed1998

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↗
PubMed1998

Various mechanisms cause RET-mediated signaling defects in Hirschsprung's disease.

Hirschsprung's disease (HSCR) is a common congenital malformation characterized by the absence of intramural ganglion cells of the hindgut. Recently, mutations of the RET tyrosine kinase receptor have been identified in 50 and 15-20% of familial and sporadic HSCR, respectively. These mutations include deletion, insertion, frameshift, nonsense, and missense mutations dispersed throughout the RET coding sequence. To investigate their effects on RET function, seven HSCR missense mutations were introduced into either a 1114-amino acid wild-type RET isoform (RET51) or a constitutively activated form of RET51 (RET-MEN 2A). Here, we report that one mutation affecting the extracytoplasmic cadherin domain (R231H) and two mutations located in the tyrosine kinase domain (K907E, E921K) impaired the biological activity of RET-MEN 2A when tested in Rat1 fibroblasts and pheochromocytoma PC12 cells. However, the mechanisms resulting in RET inactivation differed since the receptor bearing R231H extracellular mutation resulted in an absent RET protein at the cell surface while the E921K mutation located within the catalytic domain abolished its enzymatic activity. In contrast, three mutations mapping into the intracytoplasmic domain neither modified the transforming capacity of RET-MEN 2A nor stimulated the catalytic activity of RET in our ligand-independent system (S767R, P1039L, M1064T). Finally, the C609W HSCR mutation exerts a dual effect on RET since it leads to a decrease of the receptor at the cell surface and converted RET51 into a constitutively activated kinase due to the formation of disulfide-linked homodimers. Taken together, our data show that allelic heterogeneity at the RET locus in HSCR is associated with various molecular mechanisms responsible for RET dysfunction.

3T3 Cells↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Low growth hormone-binding protein in infants with congenital hypothyroidism.

We evaluated the circulating levels of GH, insulin-like growth factor I (IGF-I), GH-binding protein (GHBP), and IGF-binding protein-3 (IGFBP-3) before L-T4 therapy in 19 infants with congenital hypothyroidism (CH), aged 12-29 days, diagnosed by neonatal screening and in a group of age- and sex-matched control infants. The same parameters were reevaluated after several months of treatment. Serum GHBP was measured by the high performance liquid chromatography-gel filtration method; serum GH, IGF-I, and IGFBP-3 levels were determined by commercial kits. The hypothyroid patients, before beginning therapy, presented significantly lower GHBP values than controls (P < 0.0001); during treatment, these values increased significantly; however, after 6 months they were still significantly lower than control values (P < 0.01). The pretreatment levels of GH were not significantly different from control values; after 1 month of treatment, GH did not show the decrease observed in controls and, therefore, was significantly higher (P < 0.01). The pretreatment levels of IGF-I were not significantly different from control values, but were lower in patients with severe than in those with mild hypothyroidism. They decreased at about 4 months of life and became significantly lower than control values at about 7 months of age (P < 0.05). In conclusion, it may be hypothesized that the condition of CH induces a change in GHBP expression, perhaps beginning in fetal life. The intrauterine production of IGF-I seems to be independent of the levels of GHBP and partially affected by fetal thyroid function.

Carrier Proteins↗
PubMed1997

Oncogenic activation of RET by two distinct FMTC mutations affecting the tyrosine kinase domain.

Multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid carcinoma (FMTC) are two dominantly inherited disorders caused by germline mutations of the RET proto-oncogene. The RET gene codes for a receptor tyrosine kinase. The majority of MEN2A and FMTC mutations are clustered in the extra-cellular cysteine-rich domain and result in constitutive activation of the tyrosine kinase through the formation of disulfide-bonded RET homodimers. Recently, two novel point mutations have been identified in the germline of five distinct FMTC families. Both mutations occur within the catalytic domain of the RET kinase and lead to the substitution of either glutamic acid 768 or valine 804 by an aspartic acid and a leucine respectively. We have introduced each FMTC mutation in two RET isoforms: RET51 the long isoform (1114 aa) and RET9 the short isoform (1072 aa) which differ in the C-terminal region of the protein. The RET51 isoform carrying either E768D or V804L mutation was autophosphorylated, displayed a transforming activity upon expression in Rat1 fibroblasts and induced neuronal differentiation of PC12 cells. However, the transforming capacity of these RET51-FMTC mutants was found to be severalfold less potent compared to the same isoform carrying either the MEN2A mutation (C634R) or the MEN2B mutation (M918T). In contrast, RET9 containing mutations E768D or V804L was not autophosphorylated, exhibited a poor oncogenic potential in fibroblasts and did not promote neuritic outgrowth upon expression in PC12 cells. Overall, these findings demonstrate that mutations E768D and V804L are gain-of-function mutations that confer to the long RET isoform the capacity to exert a biological effect, although these mutations are more weakly activating than the MEN2A and MEN2B mutations. These results may provide a biochemical basis as to why the phenotypic consequences of these mutations are restricted to thyroid C-cells.

3T3 Cells↗
PubMed1997

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↗
PubMed1997

Development of medullary thyroid carcinoma in transgenic mice expressing the RET protooncogene altered by a multiple endocrine neoplasia type 2A mutation.

Multiple endocrine neoplasia type 2 (MEN 2) is a dominantly inherited cancer syndrome that comprises three clinical subtypes: MEN type 2A (MEN-2A), MEN type 2B (MEN-2B), and familial medullary thyroid carcinoma (FMTC). Medullary thyroid carcinoma (MTC), a malignant tumor arising from calcitonin-secreting thyroid C cells, is the cardinal disease feature of this syndrome, and mortality in affected MEN-2 patients is mainly caused by this malignancy. Germ-line mutations of the RET protooncogene, which encodes a receptor tyrosine kinase, are responsible for these three neoplastic-prone disorders. MEN2 mutations convert the RET protooncogene in a dominantly acting oncogene as a consequence of the ligand-independent activation of the tyrosine kinase. The majority of MEN2A and FMTC mutations are located in the extracellular domain and cause the replacement of one of five juxtamembrane cysteines by a different amino acid. To examine whether expression of a MEN2A allele of RET results in transformation of C cells, we have used the transgenic approach. Expression of the RET gene altered by a MEN2A mutation was targeted in C cells by placing the transgene under the control of the calcitonin gene-related peptide/calcitonin promoter. Animals of three independent transgenic mouse lines, which expressed the transgene in the thyroid, displayed overt bilateral C cell hyperplasia as early as 3 weeks of age and subsequently developed multifocal and bilateral MTC. Moreover, these tumors were morphologically and biologically similar to human MTC which afflicts MEN2 individuals. These findings provide evidence that the MEN2A mutant form of RET is oncogenic in parafollicular C cells and suggest that these transgenic mice should prove a valuable animal model for hereditary MTC.

Animals↗
PubMed1997

Distinct biological properties of two RET isoforms activated by MEN 2A and MEN 2B mutations.

Germline mutations of the RET proto-oncogene, which codes for a receptor tyrosine kinase, cause multiple endocrine neoplasia type 2A (MEN 2A) and 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). MEN 2 mutations have been shown to result in RET oncogenic activation. The RET gene encodes several isoforms whose biological properties, when altered by MEN 2 mutations, have not been thoroughly addressed yet. In this study, we have introduced a MEN 2A mutation (Cys634-->Arg) and the unique MEN 2B mutation (Met918-->Thr) in two RET isoforms of 1114 and 1072 amino acids which differ in the carboxy-terminus part. Herein, we report that each RET isoform activated by MEN 2A or MEN 2B mutation was transforming in fibroblasts and induced neuronal differentiation of pheochromocytoma PC12 cells. However, among the different RET-MEN 2 mutants, the long RET isoform activated by the MEN 2B mutation stimulated the most prominent neurite outgrowth in PC12 cells, while the short RET isoform counterpart elicited a very weak differentiation effect in PC12 cells. We further demonstrate that the morphological changes of PC12 cells caused by constitutively activated RET oncoproteins involved the engagement of a Ras-dependent pathway. These findings provide evidence that the biological properties of RET-MEN 2 mutants depend on the interplay between the RET isoforms and the nature of the activating MEN 2 mutation.

Animals↗
PubMed1997

Abnormal insulin response to glucose following treatment for Wilms' tumor in childhood.

UNLABELLED: To determine whether beta-cell function could be impaired by the treatment for Wilms' tumour (WT) in childhood. We investigated the insulin secretion of 44 survivors of WT (22 males) with a median off-treatment follow up of 8.3 years (range 1-19.8). All patients had an intravenous glucose tolerance test (IVGTT) (0.5 gm/kg, max 25 g) to determine the first-phase insulin response (FPIR) (sum of the 1- and 3-min insulin concentrations). Median age at the time of the study was 12.7 years (range 4.2-22.7). Eight subjects (7 males) had a FPIR value below the 3rd percentile, and 7 (3 males) above the 97th centile. Among the 22 patients who received radiotherapy. 7 (6 males) showed a FPIR < 3rd percentile versus only 1 (a male) of the 22 patients who received no radiation (31.8% vs 4.5%; P < 0.05). Analysis of variance showed that the time elapsed since therapy had a significant role on the development of low FPIR only in males. The 7 patients with an insulin release > 97th percentile did not show any significant difference compared to subjects with lower insulin values for weight, age at diagnosis, sex, time elapsed since treatment, radiotherapy and chemotherapy protocol. CONCLUSION: An impaired insulin response is evident in some patients treated for WT in childhood, mainly in male patients who received abdominal radiotherapy and were examined a longer time after therapy. We hypothesize that this decreased insulin release is related to damage due to radiotherapy and therefore a careful follow up is recommended in adulthood in these patients.

Age Factors↗
PubMed1997

Final height of patients treated for isolated GH deficiency: examination of 83 patients.

The aim of the present study was to evaluate retrospectively the influence of various auxological and laboratory parameters on final height in a group of GH-deficient children after replacement therapy and to compare their final height with that of a group of short children with normal GH secretion and hence not treated. The final height was evaluated of 83 patients (51 males and 32 females) affected by idiopathic isolated GH deficiency and treated with recombinant human GH (hGH) for 2-7 years. Inclusion criteria at the start of treatment were short stature (mean height for chronological age in standard deviation score (SDS) -2.21) due to idiopathic isolated GH deficiency (GH peak < 8 micrograms/l after two pharmacological tests and/or mean GH concentration < 3.3 micrograms/l during the night) and treatment with recombinant hGH for at least 2 years at a dose of 15-20 U/m2 per week by s.c. injection for 6 or 7 days/ week. Mean chronological age at diagnosis was 12.2 +/- 1.7 years; 35 were prepubertal and 48 pubertal. The final height of 51 untreated short stature (mean height for chronological age in SDS -2.13 at diagnosis) subjects (42 males and 9 females: 29 prepubertal and 22 pubertal at diagnosis with mean chronological age 11.6 +/- 2.4 years) with normal GH secretion was also evaluated. In the treated subjects final height SDS was higher than that of the untreated group (-1.3 vs -1.7 SDS; P = 0.01). Both treated and untreated subjects showed a final height lower than target height, but 39% of the treated subjects vs only 20% of the untreated group (P = 0.035) had a final height greater than target height. In the treated subjects this percentage was higher in the patients improving their height for bone age in the first years of therapy. While treated females showed a positive correlation only between target and final height (P = 0.0001), in treated males final height correlated with the Bayley-Pinneau prediction at diagnosis, height for chronological age and bone age at diagnosis and target height. Patients who started therapy before puberty also showed these correlations with data calculated at the onset of puberty, together with a correlation with chronological age at the onset of puberty. When considering the influence of GH response at tests on final height, the percentage of subjects exceeding target height increased progressively according to the severity of the GH deficiency. There was no difference in height gain between the patients starting therapy before or during puberty. The height gain, however modest, obtained by our treated patients, the number of patients with final height greater than target height and the favourable comparison with the untreated short-stature subjects represent a promising result, which could be improved by personalizing treatment.

Adolescent↗
PubMed1996

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↗
PubMed1996

The anticonvulsant action of fluoxetine in substantia nigra is dependent upon endogenous serotonin.

Fluoxetine, a serotonin (5-HT) reuptake inhibitor, has been documented to exert a protective action against convulsive seizures in animal models, when administered either systemically, or focally into substantia nigra. It is likely that the mechanism of anticonvulsant action of fluoxetine is due to an enhancement of endogenous 5-HT transmission. To evaluate this possibility in the context of the anticonvulsant action of intranigral fluoxetine, we examined the influence of 5-HT-mediated transmission in substantia nigra on seizure susceptibility in a rat model of focally evoked complex partial seizures. In addition to fluoxetine (3.5 nmol), we found that the directly acting 5-HT receptor agonists, 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP) (10 nmol), 1-(3-chlorophenyl)piperazine (m-CPP) (7.4 nmol), gepirone (70 nmol) and 2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT) (10 nmol), when microinjected bilaterally into substantia nigra, protected rats from limbic motor seizures evoked focally from area tempestas, an epileptogenic site in the deep rostral piriform cortex. This indicates that multiple 5-HT receptor subtypes in substantia nigra may contribute to seizure regulation. Consistent with this, the 5-HT antagonist, metergoline, partially reversed the anticonvulsant action of intranigral fluoxetine. Depletion of endogenous 5-HT, by pretreatment with parachlorophenylalanine (PCPA), completely prevented the anticonvulsant action of intranigral fluoxetine, without modifying the anticonvulsant effect of intranigral TFMPP. These findings support the proposal that the anticonvulsant action of fluoxetine in substantia nigra is due to an enhancement of the synaptic action of endogenous 5-HT in substantia nigra which in turn is mediated via multiple 5-HT receptors. Endogenous 5-HT transmission in substantia nigra is therefore capable of limiting the development and propagation of seizure activity generated in limbic circuits.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

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↗