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C Stefanis

Publications and source records attributed to C Stefanis.

At least 19 recordsLinked to original sources

Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: a multicenter association study.

BACKGROUND: Being the rate-limiting enzyme in the biosynthesis of serotonin, the tryptophan hydroxylase gene (TPH) has been considered a possible candidate gene in bipolar and unipolar affective disorders (BPAD and UPAD). Several studies have investigated the possible role of TPH polymorphisms in affective disorders and suicidal behavior. METHODS: The TPH A218C polymorphism has been investigated in 927 patients (527 BPAD and 400 UPAD) and their matched healthy control subjects collected within the European Collaborative Project on Affective Disorders. RESULTS: No difference of genotype distribution or allele distribution was found in BPAD or UPAD. No statistically significant difference was observed for allele frequency and genotypes counts. In a genotype per genotype analysis in UPAD patients with a personal history of suicide attempt, the frequency of the C-C genotype (homozygosity for the short allele) was lower in UPAD patients (24%) than in control subjects (43%) (chi(2) = 4.67, p =.03). There was no difference in allele or genotype frequency between patients presenting violent suicidal behavior (n = 48) and their matched control subjects. CONCLUSIONS: We failed to detect an association between the A218C polymorphism of the TPH gene and BPAD and UPAD in a large European sample. Homozygosity for the short allele is significantly less frequent in a subgroup of UPAD patients with a history of suicide attempt than in control subjects.

Alleles↗

Melatonin response to clonidine administration in depression: indication of presynaptic alpha2-adrenoceptor dysfunction.

BACKGROUND: The aim of this study was to investigate alpha2-adrenoceptor sensitivity in depression, by using melatonin response to clonidine administration as an index of alpha2-adrenoceptor functioning. METHOD: 35 depressed subjects and 41 healthy controls were assessed for overnight urinary melatonin pre- and post-administration of oral clonidine. RESULTS: Administration of clonidine significantly reduced melatonin concentrations in depressed patients but not in control subjects. LIMITATION: A single oral dose (0.15 mg) of clonidine was administered. CONCLUSIONS: Further indication is provided for presynaptic alpha2-adrenoceptor dysfunction in depression with the application of an alternative pharmacological challenge method.

Adult↗

Association between GABA-A receptor alpha 5 subunit gene locus and schizophrenia of a later age of onset.

Heritability is considered to be a major etiologic factor for schizophrenia. Among the genes considered as candidates for the disease, are those related to GABAergic neurotransmission. Our aim was to test for a genetic association between GABA-A receptor alpha 5 subunit gene locus (GABRA(5)) and schizophrenia. Genotyping of the GABRA(5) locus was performed by the use of a dinucleotide (CA) repeat marker in 46 schizophrenic patients and 50 healthy individuals, all unrelated Greeks. Eight alleles were identified, 276-290 bp long. A nonsignificant excess of the 282-bp allele, which was found in a previous study in a Greek population to be associated with bipolar affective disorder, was observed in schizophrenic patients (33.8 vs. 23.9% in the controls). The frequency of this allele was 43.3% among patients with a later age of onset (over 25 years), differing at a statistically significant level from the controls (p < 0.05). These results suggest that common pathophysiological mechanisms may possibly underlie affective disorders and schizophrenia, at least in a subgroup of patients.

Adult↗

Substance use among high school students in Greece: outburst of illicit drug use in a society under change.

Trends in self-reported substance use in surveys of Greek adolescent students show that regular tobacco smoking increased in 1998 (20.8%) after having fallen between 1984 (22%) and 1993 (14.6%). Frequent alcohol consumption decreased in 1998 to 12.1%, from around 15% in both previous surveys. A sharp increase was observed in illicit drug use from 6% in 1993 to 13.7% in 1998. Unprescribed use of psychoactive medicines continued to decrease steadily from 53.8% in 1984 to 31.8% in 1998. Perceived availability and risks of cannabis parallel trends in use. Policy measures and recent sociocultural changes seem to influence illicit use.

Adolescent↗

The effect of family intervention on chronic schizophrenics under individual psychosocial treatment: a 3-year study.

BACKGROUND: The effectiveness of family intervention in schizophrenia has mainly been tested by controlled trials which recruited patients after hospital discharge. Less is known about its effectiveness when chronic schizophrenics displaying negative rather than positive symptoms are engaged in treatment. This study was conducted in two community-based rehabilitation units for chronic psychiatric patients and was planned to test: (1) whether family intervention combined with individual psychosocial treatment is more effective than individual psychosocial treatment in improving the clinical and social prognosis of schizophrenic patients belonging to high expressed emotion (high-EE) families, and (2) whether family intervention exerts its effect on the patients through the reduction of EE in their families. METHODS: Forty patients from high-EE families, all under neuroleptic medication and in remission at intake, were evenly assigned to individual psychosocial treatment or to psychoeducational family intervention plus individual psychosocial treatment. Individual treatment consisted of vocational and social skills training; family intervention mainly comprised 13 group sessions with relatives. Patients were treated for 12 months and were followed-up for the next 2 years. Measures of clinical outcome comprised relapse, hospitalization and clinical exacerbation. Measures of social outcome included social functioning and role performance. Re-employment served as an additional measure at the follow-up assessments. RESULTS: The experimentals were free of relapses and hospitalizations during the 1st year of follow-up. The difference in relapse rates between experimentals and controls over the same period was statistically significant (P = 0.05), especially if drop-outs were included in the statistical analysis. The difference in hospitalization rates did not yield any statistical significance. All differences declined in the 2nd year of follow-up. Family intervention was found to be positively, but not significantly, associated with higher reversal rates from high to low EE, especially among full attenders of relatives' group sessions. High EE was identified as a predictor of relapse, but not of hospitalization, over the 2-year follow-up period. CONCLUSION: Results support the importance of encompassing family members in the community care and tertiary prevention of schizophrenia.

Adult↗

Five-factor model of schizophrenic psychopathology: how valid is it?

Aim of the study was to examine the consistency of the five-factor model of schizophrenic symptoms, assess its validity and evaluate its dimensional factor structure using confirmatory factor (CFA) analysis. A sample of 258 randomly assigned DSM-III R patients with schizophrenic disorders were studied by means of the structured clinical interview for the Greek validated Positive and Negative Syndrome Scale (PANSS) and were rated on its 30 items. Patients' scores were subjected to principal component analysis (PCA) with varimax rotation. Internal consistency for each of the components was determined by the use of Cronbach's alpha. External validity of the model derived was investigated by searching for possible relationships between the components and sociodemographic characteristics with the aid of canonical correlation analysis. Confirmatory factor analysis (CFA) was also performed. Using the scree plot criterion PCA revealed a five-factor model. These factors were interpreted as representing--in a decreasing order of relative importance--the following dimensions of schizophrenic psychopathology: negative, excitement, depression, positive and cognitive impairment. The model was comparable with six previous factor analytic studies. Internal consistency was quite satisfactory whereas external validity was found to be not so powerful. CFA did not show that the proposed model yields an adequate factor structure.

Adult↗

Simulated generation of evoked potentials components using networks with distinct excitatory and inhibitory neurons.

Long latency evoked potentials (EP's) are electrical potentials related to brain information processing mechanisms. In this paper, three-layered neurophysiologically based artificial neural network model is presented whose neurons obey to Dale's law. The first two layers of the network can memorize and recall sparsely coded patterns, oscillating at biologically plausible frequencies. Excitatory low-pass filtering synapses, from the second to the third layer, create evoked current dipoles, when the network retrieves memories related to stimuli. Based on psychophysiological indications, simulated intracranial dipoles are straightforwardly transformed into long latency EP components such as N100 and P300 that match laboratory-measured scalp EP's.

Biomedical Engineering↗

Sharp increase in illicit drug use in Greece: trends from a general population survey on licit and illicit drug use.

The study aims to follow trends in the prevalence of licit and illicit substance use between 1984 and 1998 in the Greek general population. Data are drawn from two nationwide cross-sectional household surveys. Probability samples consisted of 4,297 (1984) and 3,759 (1998) 12- to 64-year-old respondents. Regular tobacco smoking in the total sample increased in women and decreased in men while alcohol consumption remained at similar levels. The use of illicit drugs showed a 3-fold increase since 1984 reaching a lifetime prevalence of 19% in males and 6% in females. In contrast, a significant decrease was noted in the unprescribed use of psychoactive medicines, especially among women. Trends in licit and illicit substance use can be explained by sociocultural and policy changes in Greece in the last 15 years.

Adolescent↗

Geographical variation in mental hospital discharges in Greece and socioeconomic correlates: a nationwide study (1978-1993).

BACKGROUND: In this paper the geographical distribution of discharge rates of psychiatric patients in Greece, nationwide, is shown. METHOD: Utilization rates are estimated by the number of discharged patients from all public and private mental hospitals for the period 1978-1993. RESULTS: During this period six prefectures were repeatedly found to exhibit the highest discharge rates for both sexes. Five out of those six areas are mountainous, socially isolated and of a lower level of socioeconomic development, lacking mental health services. The correlation coefficients for the annual mean age-standardized discharge rates of psychiatric patients and the corresponding General Index of Development score of each area were found to be statistically significant for all diagnoses, and for schizophrenic psychoses taken separately, in each prefecture for each of those years (1978-1993). CONCLUSIONS: It seems that the higher the hospital treated psychiatric morbidity is, the lower is the level of general socioeconomic development of the area. It is possible that families from socially disadvantaged areas, with limited support resources, are unable to avoid the hospitalization of their mentally ill members.

Epidemiologic Studies↗

Blunted TSH response to TRH and seizure duration in ECT.

The relationship between the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) and the duration of seizures induced by electroconvulsive therapy (ECT) in depressed patients was investigated. In a balanced-order cross-over design, 16 depressed women were given 0.4 mg TRH or placebo intravenously, 20 min before ECT in the first two sessions. In the third ECT session TRH was given just prior to ECT. Thyrotropin (TSH) levels at various sampling times, as well as the duration of seizures, were measured. There was a significant inverse correlation between plasma TSH concentrations 20 min after TRH administration (deltaTSH) and seizure duration. Furthermore, when patients were categorized according to their TSH response to TRH, the group with blunted responses (deltaTSH <6 microIU/ mL, n = 7) had a longer seizure time during ECT than the group with non-blunted responses (deltaTSH > 6 microIU/mL, n = 9). Finally, the seizure duration in the group with blunted TSH responses was reduced significantly when TRH was co-administered, while it remained unchanged in the group with non-blunted TSH responses. It is concluded that a blunted TSH response to TRH might indicate a seizure susceptibility as measured by the duration of seizures induced by ECT. The fact that TRH pre-administration had a reducing effect suggests that this substance might be involved in the pathophysiology of ECT-induced seizures.

Adult↗

A survey of bloodborne viruses and associated risk behaviours in Greek prisons.

AIMS: To determine HIV and hepatitis infection prevalence and correlates with risk behaviour. DESIGN: Cross-sectional study: voluntary, anonymous HIV, hepatitis (HCV, HBV and HDV) surveillance and questionnaire on risk factors. SETTING: Korydallos Prison, Athens and Ag. Stefanos Prison, Patra, Greece. PARTICIPANTS: Of 544 drug users imprisoned for drug related offences, all completed the questionnaire and 533 blood samples were collected. MEASUREMENTS: HIV (by anti-HIV-1), HCV (by anti-HCV), HBV (by anti-HBc, HBsAg) and HDV (by anti-HDV) prevalence. Data on demography, legal status, drug use, sharing of injecting equipment. FINDINGS: Of the 544 drug users, 375 (68.9%) had injected drugs (IDUs) at some time, 35% of whom had injected whilst in that prison. Of the 533 blood samples tested, one was positive for anti-HIV-1 (0.19%), 310 for anti-HCV (58.2%), 306/531 (57.6%) for anti-HBc, 34/527 (6.5%) for HBsAg and 12/527 (2.3%) for anti-HDV. Prevalence rates for IDUs only were 0.27% for HIV-1, 80.6% for hepatitis C, 62.7% for hepatitis B and 3.3% for hepatitis D. Ninety-two per cent of IDUs injecting in prison shared needles, indicating that IDUs inject less but share more during incarceration. Multiple logistic regression revealed needle-sharing as the most important risk factor for HCV infection in IDUs. Prior knowledge of a positive hepatitis result did not appear to inhibit IDUs from practising risky behaviours in prison. CONCLUSIONS: The epidemic of hepatitis B and C among imprisoned IDUs identified by this study constitutes a major public health problem. Prevention programmes, such as counselling, HBV vaccination, community-based methadone maintenance treatment and syringe exchange schemes, are necessary in order to prevent a further spread.

Adult↗

Prolactin and TSH responses to TRH and to ECT in pre- and postmenopausal women with major depression.

The patterns of prolactin and thyrotropin (TSH) release after thyrotropin-releasing hormone (TRH) (0.4 mg i.v.) and during the first session of a course of electroconvulsive treatment (ECT) were studied in women with major depression, 16 in pre- and 29 in postmenopausal status. The prolactin responses to both stimuli were lower in postmenopausal women, whereas the TSH responses were not different. The known correlation between the maximal prolactin response to ECT and the maximal response to TRH was significantly stronger in the group of premenopausal women (r = .8648, versus .4249 in the postmenopausal group, p < .02). A common underlying mechanism promoting prolactin release for both stimuli can be suggested, which diminishes after menopause, probably an influence of estradiol on the affinity of dopaminergic and serotonergic receptors. That mechanism does not interfere with the TSH release either by ECT or by TRH.

Adult↗

Effects of thyrotropin-releasing hormone administration on the electroconvulsive therapy induced prolactin responses and seizure time.

The effects of thyrotropin-releasing hormone (TRH) administration on electroconvulsive therapy (ECT)-induced prolactin (PRL) secretion and the duration of the seizure were studied in 14 depressed women. In a balanced order crossover design the patients were given 0.4 mg TRH or placebo intravenously 20 min before ECT during the first two sessions. In the third ECT session TRH was given just prior to ECT. ECT elicited the expected PRL response when given alone and when given 20 min after TRH when PRL plasma levels were high. During the coadministration design (third ECT session) PRL levels were raised not as a sum of the two stimuli but even significantly more. TRH failed to modify the duration of the seizure induced by ECT. Therefore, if TRH is involved in seizure modulation during ECT, our findings suggest a postictal rather than ictal role for TRH.

Adult↗

Differential responsiveness of late passage C-6 glial cells and advanced passages of astrocytes derived from aged mouse cerebral hemispheres to cytokines and growth factors: glutamine synthetase activity.

In this study, we were interested to compare the responsiveness to growth factors, NGF, b-FGF and EGF and cytokines, IL1 beta, and TNF-alpha, in late passages (74-79) C6 glial cells committed astrocytes and astrocytes of advanced passages (26-28) in cultures derived from aged mouse cerebral hemispheres (MACH). Cultures were grown in either DMEM or chemically defined medium (CDM/TIPS) in order to test the effects of growth factors or cytokines. The activity of glutamine synthetase (GS), a marker for astrocytes, was used as a test parameter. We found that treatment with growth factors increased GS activity in both glial cell culture systems with the exception of EGF in C-6 glial cells. Treatment with cytokines markedly decreased GS activity in the late passage C6 glial cells whereas only TNF-alpha had a similar effect on MACH astrocytes. In view of the generally opposite effects of growth factors and cytokines on GS activity, we speculate that these molecules which are also endogenously present in glial cells may play a role in the maintenance of cellular homeostasis.

Animals↗

Stimulation of glutamine synthetase activity by excitatory amino acids in astrocyte cultures derived from aged mouse cerebral hemispheres may be associated with non-N-methyl-D-aspartate receptor activation.

We have been using glial cells derived from aged mouse cerebral hemispheres (MACH) at several passages to study the responsiveness of astrocytes to microenvironmental signals in culture. In the present study, we examined the effects of excitatory amino acids on the activity of glutamine synthetase, a marker for astrocytes. MACH glia cell passages 25 to 29 were used. Culture groups were Dulbecco's modified Eagle's medium +10% fetal bovine serum (control); glutamate 100 microM; gamma-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid (AMPA) 50 microM; kainic acid 10 microM; N-methyl-D-aspartate (NMDA) 10 microM. In all treated groups glutamine synthetase activity was significantly higher than in controls. We speculate that this increase represents an enhanced differentiation of immature astrocytes. In a second series, we examined the effects of glutamate receptor antagonists on glutamine synthetase activity as follows. MACH cultures were treated with glutamate 100 microM in combinations with either L(+)-2-amino-3-phosphonopropionic acid (L-AP3; 50 microM); D(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 50 microM) or 6,7-dinitroquinoxaline-2,3-dione (DNQX, 50 microM). The increase in GS activity produced by glutamate was inhibited by the non-selective NMDA receptor antagonist, DNQX, but not by the metabotropic receptor antagonist, L-AP3 or a selective NMDA receptor antagonist, D-AP5. We also found that in cultures treated with glutamate, a number of astrocytes resembled "reactive astrocytes" morphologically. These astrocytes were absent in cultures treated with glutamate+DNQX. The findings provide supportive evidence that astrocytes from aged mouse cerebral hemispheres respond to excitatory amino acids and that this response is mediated by non-NMDA receptor activation.

2-Amino-5-phosphonovalerate↗

GHQ-28 as an aid to detect mental disorders in neurological inpatients.

The prevalence of mental disorders (DSM-IIIR criteria) among 107 neurological inpatients was estimated, as well as the extent to which disorders were detected by neurologists. The validity of the scaled version of the General Health Questionnaire (GHQ-28) was evaluated using Receiver Operating Characteristic (ROC) analysis and DSM-IIIR as external criteria. Of the 107 patients who submitted to a structured psychiatric interview (SCID-R), 56 (52.3%) showed evidence of a mental disorder. Major depressive episode (n = 16), generalized anxiety disorders (n = 13) and dysthymia (n = 12) were the most frequent diagnoses. The neurologists recognized only 13/107 cases (12.1%). Significantly more women than men exhibited some form of mental disorder. The validation of GHQ-28 in the series of 107 neurological inpatients indicated that the best trade-off between sensitivity and specificity was the cut-off score of 5/6. The high occurrence of mental disorder, in association with the low rate of detection by the neurologists, points to the need for special attention to be paid to this problem by staff and experts.

Adjustment Disorders↗

Acute tolerance to the excitatory effects of opioids in the rat hippocampus.

Prolonged iontophoretic administrations of delta- and mu-selective opioid receptor agonists were conducted in the hippocampus of rats, in order to study the possible development of acute tolerance to the excitatory effects of the opioids. Acute tolerance (AT) to the excitatory effects of the delta-selective opioid receptor agonist Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET) was observed when the drug was applied locally for 3-5 min in the CA1 hippocampal pyramidal neurons. The acute tolerance was expressed as a decrease in the commissurally evoked spike responsiveness during peptide's administration and led to a long-lasting potentiation of the population spike (PS) upon its withdrawal. In all cases, where AT and spike potentiation were evident, the population excitatory postsynaptic potential (pEPSP) remained unaltered. Pharmacological studies of AT and long-lasting spike potentiation showed the following: (1) the nonselective opioid receptor antagonist, naloxone, while effective in blocking the excitatory effects of DSLET when applied prior and during the application of the latter, failed to exhibit any effect on the long-lasting potentiating effect of the opioid; and (2) during the spike potentiation phase, administration of DSLET exhibited a depressant effect towards baseline values. This depressant effect of the opioid was evident 2-3 min from the beginning of the application and was completely antagonized by naloxone. The above results show that the development of acute tolerance to the excitatory effects of the DSLET led to long-lasting spike potentiation, which manifests a withdrawal phenomenon.

Analgesics↗

Association of biogenic amine metabolites with symptomatology in delusional (psychotic) and nondelusional depressed patients.

1. The levels of the main norepinephrine, serotonin, and dopamine metabolite excretion in the urine, MHPG, 5HIAA and HVA respectively, were measured in 84 patients with major depressive disorder, 34 delusional (psychotic) and 50 nondelusional (DSM-III-R criteria). 2. Associations with the 17 items of the HDRS were evaluated using the multiple regression analysis model. In the delusional group, MHPG excretion was positively related to the scores in the items of depressed mood (p = 0.04), middle insomnia (p = 0.008) and genital symptoms (p = 0.001). 5HIAA excretion was negatively associated with late insomnia (p = 0.02), work and interests (p = 0.001) and genital symptoms (p = 0.007). HVA was positively related to agitation (p = 0.043). In the nondelusional group the only association found was between agitation and HVA excretion (p = 0.03).

Adult↗