Biomedical subjects

G Faedda

Publications and source records attributed to G Faedda.

6 recordsLinked to original sources

PubMed1998

Reliability and validity of depressive personality disorder.

OBJECTIVE: Depressive personality disorder was introduced into DSM-IV's appendix amid controversy. While that disorder appears to be a reliable and valid one, the authors offer new data about its relationship to major depression, dysthymic disorder, and other personality disorders. METHOD: The authors assessed 54 subjects with early-onset, long-standing mild depressive features for depressive personality disorder, axis I and axis II disorders, family history, and treatment history; they conducted follow-up interviews 1 year after the baseline assessment. Subjects with (N=30) and without (N=24) depressive personality disorder were characterized and compared in terms of those variables. RESULTS: Although depressive personality disorder and dysthymia co-occurred in some subjects, 63% of subjects with depressive personality disorder did not have dysthymia, and 60% did not have current major depression. Although subjects with depressive personality disorder were more likely than the mood disorder comparison group to have another personality disorder, 40% had no such disorder. Contrary to study hypotheses, mood disorder was not more common in first-degree relatives of subjects with depressive personality disorder than in relatives of the comparison group. Subjects with and without depressive personality disorder had similar rates of past treatment with medication and psychotherapy; however, the duration of psychotherapy was significantly longer for subjects with than for those without depressive personality. The depressive personality diagnosis was relatively stable over the 1-year follow-up period. CONCLUSIONS: Depressive personality disorder appears to be a relatively stable condition with incomplete overlap with axis I mood disorders and personality disorders. Further studies are needed to better characterize its treatment response and relationship to axis I mood disorders.

Adult↗

PubMed1996

Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome.

Velo-cardio-facial-syndrome (VCFS) is a common congenital disorder associated with typical facial appearance, cleft palate, cardiac defects, and learning disabilities. The majority of patients have an interstitial deletion on chromosome 22q11. In addition to physical abnormalities, a variety of psychiatric illnesses have been reported in patients with VCFS, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. The psychiatric manifestations of VCFS could be due to haploin-sufficiency of a gene(s) within 22q11. One candidate that has been mapped to this region is catechol-O-methyltransferase (COMT). We recently identified a polymorphism in the COMT gene that leads to a valine-->methionine substitution at amino acid 158 of the membrane-bound form of the enzyme. Homozygosity for COMT158met leads to a 3-4-fold reduction in enzymatic activity, compared with homozygotes for COMT158val. We now report that in a population of patients with VCFS, there is an apparent association between the low-activity allele, COMT158met, and the development of bipolar spectrum disorder, and in particular, a rapid-cycling form.

Abnormalities, Multiple↗

PubMed1992

[Mixed depressive syndrome].

For a period of six months (april to october 1990) 361 manic-depressive in-patients or out-patients were examined and treated. 178 patients (119 females and 69 males) were suffering from depression at examination time. Among them, 34 women and 11 men had mixed mood disorders with a symptomatology near that of typical depression (major depression, according to the DSM III-R criteria) but not of mixed bipolar disorder. The main symptoms were: dysphoric mood with irritability; internal tension, psychic and sometimes physical agitation; emotional lability; head crowded with thoughouts or thoughts that vanish too quickly; sleep disorders with initial insomnia or with frequent night awakenings; suicidal thoughts or attempted suicide with impulsiveness. These patients sustained severe suffering. They were in no way slow-minded but rather talkative and expressive. Antidepressant drugs increased agitation and insomnia, and in some cases, suicidal impulses. BZDs had limited efficacy but neuroleptics given in small doses, anticonvulsants and lithium gave very effective results. A limited number of electroshocks provided rapid improvement. In many respects, depression with delirium seems a more severe form of the above-described combined depressive syndrome and responds to the same treatments. We think that this mood disorder includes excitement as an important component, although this was not clearly evident. However, it is not easy to conceive this syndrome as a mixture of depressive and manic symptoms; it should rather be regarded as another specific mood condition, either permanent or transient, situated between the two other conditions.

Antidepressive Agents↗

PubMed1990

Dopamine D1 receptor development depends on endogenous dopamine.

Profound depletion of forebrain dopamine by 6-hydroxydopamine in neonatal rats (day 3) was associated with up to 82% loss of D1 receptor sites labeled with [3H]SCH-23390 at day 21. Administration of the selective D1 agonist SKF-38393 (days 6-18) abolished the correlation between D1 receptor density and DA concentrations, even with greater than 99% depletion of DA. In intact control animals, there was an inverse correlation between spontaneous variation in levels of DA and D1 receptor site density in forebrain tissue (r = -0.79) which also was abolished by treatment with the D1 agonist. Thus, D1 receptor density may be regulated by reciprocal regulatory processes during normal development, but may fail to develop in the absence of an adequate level of stimulation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Postnatal development of dopamine D1 and D2 receptor sites in rat striatum.

Tissue was obtained from corpus striatum of maturing rats at representative postnatal ages of 8-120 days for evaluation of D1 and D2 dopamine (DA) receptor sites in radioreceptor assays based on use of 0.05-2.5 nM concentrations of [3H]SCH-23390 or [3H]domperidone, respectively. Pharmacologic selectivity was verified by high rank-correlations (rs greater than 0.90) of Ki values for representative test agents in both assays (vs 0.3 nM ligand), using striatal tissue obtained at ages 20 and 120 days. Data from repeated (3-5x) six-concentration isotherm experiments involving a wide range of D1 or D2 radioligand concentrations were analyzed by linear regression of specific binding (B) vs free ligand concentration (F) in linearized form (B/F vs B) for each replicate assay and for pooled values, as well as by curve-fitting all available raw data (B vs F) using the LIGAND program adapted to microcomputer. Values for apparent ligand affinity (Kd = 0.15-0.35 nM) failed to show a consistent change with age, while values for apparent receptor site density (Bmax) followed a similar developmental course with both methods of analysis (between methods: r = 0.99 and 0.89 for D1 and D2 assays, respectively, across all ages tested).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1989

Pharmacology of binding of 3H-SCH-23390 to D-1 dopaminergic receptor sites in rat striatal tissue.

3H-SCH-23390, a selective antagonist of D-1 dopamine (DA) receptors, was used in a radioreceptor assay with rat brain striatal tissue, optimized biochemically, and extensively characterized pharmacologically with striatal membranes. Nonspecific binding, defined with excess cis(Z)-flupenthixol (300 nM), averaged 20-25% of total counts bound. Specific binding was linearly dependent on the amount of original striatal tissue (0-4 mg) or protein (0-250 micrograms), temperature dependent, saturable and reversible, and appeared to involve a single site at ligand concentrations limited to less than 10 nM. Binding in rat brain regions ranked as: striatum greater than accumbens greater than prefrontal cortex greater than posterior cerebral cortex greater than cerebellum. Association was virtually complete within 30 min at 30 degrees, and the rate of dissociation at 30 degrees was 0.0377 min-1 (half-time = 18.4 min). Affinity (Ka or Kd) determined from association and dissociation rate constants and from concentration isotherms averaged 0.349 and 0.340 nM respectively. Including Na+ at 150 mM increased apparent maximum specific binding (Bmax) by 19%, with a 29% increase in affinity; other monovalent cations alone had small effects on specific binding; Ca2+ and Mg2+ reduced binding by 42%. Agents (N = 85) were tested for potency (Ki or IC50) in competition with the ligand (at 0.30 nM). Those known to have selective effects at D-1 receptors, generally, were most potent and stereoselective. Na+ (150 mM) had little effect on the affinity of cis-thioxanthenes but decreased that of most other agents tested with high D-1 affinity. For antipsychotic agents, the correlation of typical clinical daily doses versus Ki at D-1 sites (r = 0.06) was much lower than at D-2 sites (r = 0.94). (-)Thioridazine was discovered to be D-1 selective, whereas the (+) enantiomer was selective for D-2 sites labeled with 3H-spiperone. Relatively sedating antidepressants had greater D-1 affinity than their less-sedating, secondary amine congeners.

Animals↗