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Biomedical subjects

A Bocchetta

Publications and source records attributed to A Bocchetta.

At least 19 recordsLinked to original sources

Suicidal behavior on and off lithium prophylaxis in a group of patients with prior suicide attempts.

One hundred patients who had attempted suicide before commencing lithium prophylaxis were followed up. Outcome was analyzed in terms of attempted or completed suicide after a mean of 10 years since admission to the lithium clinics. Of 10 patients who committed suicide, 9 had discontinued adequate lithium prophylaxis for a period ranging from 2 weeks to 7 years before death. Having discontinued lithium therapy was associated with suicide also in the subgroup of patients for whom lithium had not completely prevented episodes during lithium treatment. Suicide risk was 24 times as high during periods off compared with periods on adequate lithium prophylaxis. Incidence of attempting suicide was similar during the periods before receiving or after discontinuing lithium treatment, whereas it was 5 to 6 times lower during prophylaxis. Continuous and adequate lithium prophylaxis should be considered in the presence of high suicide risk, even if the prophylactic effect on the underlying mood disorder may be incomplete.

Adolescent

Association between dopamine receptor genes and migraine without aura in a Sardinian sample.

BACKGROUND: Migraine seems to be caused by a combination of environmental and genetic factors. Clinical and pharmacologic evidence supports the hypothesis that dopaminergic transmission is involved in the pathogenesis of migraine. OBJECTIVE: The current report concerns a genetic study to test the involvement of genes for dopamine (DA) receptors D2 (DRD2), D3 (DRD3), and D4 (DRD4) in migraine without aura, particularly in a subgroup with enhanced DA sensitivity. METHODS: For the first time, a family-based association method--the Transmission Disequilibrium Test (TDT)--was used to examine an isolated population, such as Sardinians. We studied 50 nuclear families of patients affected by migraine without aura. The subgroup of dopaminergic migraineurs was selected based on the presence of both nausea and yawning immediately before or during the pain phase of migraine. RESULTS: No association was detected using the TDT between DRD3, DRD4, and migraine without aura either in the overall sample or in the subgroup. No difference was observed in DRD2 allelic distribution in the overall sample, although the allelic distribution at the DRD2 locus differed significantly in the subgroup of dopaminergic migraineurs (p = 0.004). Allele 1 of the TG dinucleotide intronic noncoding polymorphism of the DRD2 locus was the individual allele that appeared to be in disequilibrium with migraine without aura (p = 0.02). CONCLUSIONS: Our data suggest that a genetic approach could be useful in providing molecular support to the hypothesis that hypersensitivity of the dopaminergic system may represent the pathophysiologic basis of migraine, at least in a subgroup of patients.

Adolescent

Calcitonin decreases lithium plasma levels in man. Preliminary report.

Lithium kinetics were studied in four manic-depressive women treated with calcitonin for post-menopausal osteoporosis. During calcitonin therapy all patients showed a significant decrease of lithium blood levels, and an increase in lithium renal clearance was observed in two out of two patients. According to these data, lithium therapy needs to be adjusted in patients undergoing concomitant treatment with calcitonin.

Aged

No evidence of association between dopamine D3 receptor gene and bipolar affective disorder.

A recent study reported a possible association between allele 1 of the dopamine D3 receptor gene and bipolar affective disorder using the haplotype relative risk approach. In attempt to replicate these findings, we used similar family-based methods, such as the Haplotype-Based Haplotype Relative Risk method and the Transmission Disequilibrium Test, in a sample of 44 bipolar probands from Sardinia with both parents available. Using the Bal I restriction enzyme site polymorphism of Lannfelt et al. (1992), no differences were found between transmitted and non-transmitted alleles and no evidence of linkage disequilibrium was observed.

Alleles

Value of thyroid echography in the long-term follow-up of lithium-treated patients.

Psychiatric patients on long-term lithium (Li) therapy frequently develop goiter and/or hypothyroidism. It has also been suggested that Li may trigger/exacerbate thyroid autoimmunity. Previous studies provided evidence that underlying thyroid diseases represent important predisposing factors for the development of Li-induced thyroid dysfunction. The aim of the present paper was to assess the value of thyroid ultrasound-a simple and reliable tool to detect subtle thyroid abnormalities-in the longitudinal evaluation of 23 Li-treated psychiatric patients without evidence of biochemical thyroid abnormalities before therapy. For this purpose, thyroid ultrasound was associated with a clinical and laboratory (serum thyroxine, serum triiodothyronine, serum TSH, antithyroglobulin (AbTg), antithyroid microsomal (AbM) and antithyroid peroxidase autoantibodies) evaluation prior to and at 6- to 12-month intervals during Li treatment. On the basis of thyroid ultrasound before Li, patients were subdivided into two groups: group A (n = 15, 7 males, 8 females) with a normal echography and group B (n = 8, 5 males, 3 females) with mild ultrasound abnormalities. In group A the development of a small diffuse goiter was confirmed by physical examination during Li therapy; 2 patients displayed a transient increase of serum TSH concentration and none developed detectable serum antithyroid autoantibodies. Beside the small volumetric increase, no other ultrasound abnormalities were observed during the entire follow-up. In all group B patients a mild diffuse goiter was clinically detected before and on Li administration and no significant volumetric changes were observed during follow-up. Two patients developed high titers of AbM and AbTg 12 and 18 months after the beginning of Li, respectively; in 1 a persistent increase of serum TSH concentration was also observed. Thyroid echography before Li displayed different degrees of scattered or diffuse hypoechogenicity and a further decrease in echogenicity was detected during Li therapy in 2 patients. In conclusion, we provided further evidence that long-term Li administration is not associated with de novo appearance of thyroid autoimmune phenomena in humans, but rather with an exacerbation of underlying thyroid autoimmunity. In addition to thyroid autoantibody and TSH measurements, thyroid echography appears to be a sensitive tool in the identification of patients at risk of developing autoimmune hypothyroidism during long-term Li therapy.

Adult

Heterogeneity of monoaminergic vesicular carriers: pharmacological evidence using MPP+ as a marker.

MPP-production and uptake by dopaminergic terminals are critical steps in MPTP-induced Parkinson-like disorder. We reported evidence for a specific uptake of MPP by synaptic vesicles from mouse striatum. Its regional distribution suggests it as a marker of the dopamine vesicular carrier. We decided to further characterize such an MPP uptake. Tetrabenazine inhibits the dopamine uptake both in the striatum and in the cerebellum with similar Km values suggesting an identify of the vesicular carrier in these areas. On the contrary, 3H-MPP vesicular uptake had in the striatum a t1/2 of 60 sec, but was not detectable at any time in the cerebellum. Moreover, MPP inhibited the uptake of 3H-DA (Ki: 1.6 +/- 0.03 microM) and 3H-NE (Ki 2.6 +/- 0.01 microM) in the striatum but not in the cerebellum, even at molar concentration. These pharmacological data indicate that in nondopaminergic areas the monoamine carrier may be similar but not identical from that located in dopaminergic areas.

1-Methyl-4-phenylpyridinium

Six-year follow-up of thyroid function during lithium treatment.

A cohort of patients at various stages of lithium treatment was followed up for 6 years in order to evaluate the course of thyroid abnormalities. Ultrasonography confirmed that lithium can increase thyroid size, especially in cigarette smokers, and that it can affect the texture of the gland. However, the incidence of clinical hypothyroidism or specific thyroid autoimmunity does not exceed that found in the general population. Repeated determinations of thyrotrophin (TSH) concentrations can prevent clinically relevant consequences. Addition of carbamazepine to lithium can counteract lithium-induced subclinical hypothyroidism, possibly improving prophylactic efficacy in recurrent affective disorders.

Antibodies

A double-blind study of L-sulpiride versus amitriptyline in lithium-maintained bipolar depressives.

A double-blind group comparison study of L-sulpiride and amitriptyline was carried out in 30 bipolar outpatients on maintenance treatment with lithium suffering from a major depressive recurrence. L-sulpiride showed equivalent antidepressant activity to amitriptyline at 4 weeks using the Hamilton Rating Scale for Depression. However, the onset of action was faster in the L-sulpiride group, showing a significant improvement at 1 week in both anxiety-somatization and specific depression items, including depressed mood, feelings of guilt, work & activities and retardation. The incidence of anticholinergic side effects was significantly higher in the amitriptyline treatment group.

Ambulatory Care

The course of thyroid abnormalities during lithium treatment: a two-year follow-up study.

A total of 116 patients on lithium treatment were followed up for 2 years to determine the course and the clinical relevance of thyroid abnormalities. Elevated thyroid-stimulating hormone (TSH) concentrations were transitory in most patients, except those with serum antithyroid antibodies. The patients who initially had microsomal antibodies remained positive, with an increase in titre in two-thirds of cases. Three young patients of both sexes developed thyroid autoimmunity early in the treatment. The risk of developing hypothyroidism was higher in women, especially in the presence of antibodies. TSH concentrations were significantly lower when carbamazepine was combined with lithium.

Adult

Thyroid abnormalities during lithium treatment.

Thyroid function was evaluated in 150 Sardinian outpatients at different stages of lithium treatment. A visible and/or palpable goitre was found in 51% of patients, and there was no apparent correlation with the duration of treatment. No cases of symptomatic hypothyroidism were observed, but subclinical hypothyroidism was present in 19% of patients. The prevalence of specific antithyroid antibodies was positively correlated with age and duration of lithium treatment, and was higher in women. Subclinical hypothyroidism was observed in 53% of antibody-positive lithium-treated patients. Carbamazepine in combination with lithium was associated with significantly lower levels of total T4 and T3 than with lithium alone, and the ratios between total and free hormones were also decreased.

Adult

Familial rates of affective illness in Sardinia with special reference to schizoaffective disorder.

Familial rates of psychiatric disorders were studied in southern Sardinia and showed an increase in relatives of probands with the following research diagnostic criteria (RDC) diagnoses: normal, unipolar depression, schizoaffective depressive, schizoaffective bipolar, bipolar with mania and bipolar with hypomania. A significantly higher risk for bipolar schizoaffective disorder was observed in relatives of bipolar schizoaffectives compared with relatives of normal probands.

Adult

Covalent protein binding of a metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to mouse and monkey brain in vitro and in vivo.

We have recently reported that a reactive metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is formed in rat brain in vitro by type B monoamine oxidase (MAO). In the present study, we further characterize the irreversible binding in vitro using tissues from mice and monkeys, two species more sensitive than rats to MPTP neurotoxicity. We also report the occurrence of irreversible binding of radioactivity after administration of tritiated MPTP in the same species in vivo. Tissue homogenates were incubated at 37 degrees with 1-[methyl-3H]MPTP in in vitro experiments. Animals were injected with labeled MPTP and sacrificed at different times in in vivo experiments. The perchloric acid precipitates of tissue homogenates from either procedure were washed exhaustively with organic solvents and counted for radioactivity. The amount of recovered radioactivity in in vitro experiments was similar using brain homogenates from mice and monkeys, whereas a considerably lower amount was found in mouse liver. MAO-B inhibitors decreased the covalent binding. However, the combined MAO-B/MAO-A inhibitor pargyline had no effect if added after 2 hr of incubation. Sulfhydryl-containing compounds decreased the covalent binding in a concentration-related manner. GSH reduced the rate of the reaction throughout the incubation. The covalent binding slowly increased in time in vivo in mouse brain, not in liver. There was a two-fold variation of covalently bound radioactivity in different brain areas of 3H2-MPTP-treated monkey. This reactive metabolite may play a role in MPTP neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine