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Biomedical subjects

C N Stefanis

Publications and source records attributed to C N Stefanis.

At least 19 recordsLinked to original sources

Association between the GABA(A) receptor alpha5 subunit gene locus (GABRA5) and bipolar affective disorder.

Genetic factors seem to play an important role in the pathogenesis of affective disorder. The candidate gene strategies are being used, among others, to identify the genes conferring vulnerability to the disease. The genes coding for the receptors of gamma-aminobutyric acid (GABA) have been proposed as candidates for affective disorder, since the GABA neurotransmitter system has been implicated in the pathogenesis of the illness. We examined the possible genetic association between the GABA(A) receptor alpha5 subunit gene locus (GABRA5) on chromosome 15 and affective disorder, in 48 bipolar patients (BP), 40 unipolar patients (UP), and 50 healthy individuals, age- and sex-matched to the patients. All patients and controls were unrelated Greeks. Diagnoses were made after direct interviews according to the DSM-IV and ICD-10 criteria. For the genotyping, a dinucleotide (CA) repeat marker was used. The polymerase chain reaction (PCR) products found were nine alleles with lengths between 272 and 290 base pairs (bp). The distribution of allelic frequencies of the GABRA5 locus differed significantly between BP patients and controls with the 282-bp allele found to be associated with BP affective disorder, while no such difference was observed between the groups of UP patients and controls nor between the two patient groups. The presence or absence of the 282-bp allele in the genotype of BP patients was not shown to influence the age of onset and the overall clinical severity, but was found to be associated with a preponderance of manic over depressive episodes in the course of the illness.

Adult

Growth hormone secretion during sleep in male depressed patients.

1. Growth hormone (GH) secretion during sleep was studied in ten male patients with major depression according to DSM III and eight normal controls. 2. Samples were collected through a continuous blood withdrawal pump while sleep was recorded in the laboratory. 3. The results showed a marked decrease in the GH secretion mainly during the first three hours of sleep in depressed patients as compared to normal controls. DST and TRH tests were also administered to the same patients but no correlation was observed between a positive test and a blunted GH secretion, suggesting that the various neuroendocrinological disturbances do not coexist in all depressed patients. 4. This disturbance in GH secretion during sleep, along with reduced slow wave sleep (SWS), gives support to the theory that GHRH is the common stimulus of SWS and GH release and that the ratio of GHRH and its counterpart CRH plays a major role in the pathophysiology of disturbed endocrine activity during sleep in depression.

Aged

Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21.

Schizophrenia is a common disorder characterized by psychotic symptoms; diagnostic criteria have been established. Family, twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (heritability is approximately 71%; ref. 2), however, little is known about the aetiology of schizophrenia. Clinical and family studies suggest aetiological heterogeneity. Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated with susceptibility to schizophrenia, and collaborations provided some support for regions on chromosomes 8 and 22 (refs 9-13). We present here a genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite markers on 54 multiplex pedigrees. Non-parametric linkage (NPL) analysis provided significant evidence for an SSL on chromosome 13q32 (NPL score=4.18; P=0.00002), and suggestive evidence for another SSL on chromosome 8p21-22 (NPL=3.64; P=0.0001). Parametric linkage analysis provided additional support for these SSL. Linkage evidence at chromosome 8 is weaker than that at chromosome 13, so it is more probable that chromosome 8 may be a false positive linkage. Additional putative SSL were noted on chromosomes 14q13 (NPL=2.57; P=0.005), 7q11 (NPL=2.50, P=0.007) and 22q11 (NPL=2.42, P=0.009). Verification of suggestive SSL on chromosomes 13q and 8p was attempted in a follow-up sample of 51 multiplex pedigrees. This analysis confirmed the SSL in 13q14-q33 (NPL=2.36, P=0.007) and supported the SSL in 8p22-p21 (NPL=1.95, P=0.023).

Adult

A meta-analysis and transmission disequilibrium study of association between the dopamine D3 receptor gene and schizophrenia.

We performed a meta-analysis of over 30 case-control studies of association between schizophrenia and a bi-allelic, Bali polymorphism in exon 1 of the dopamine D3 receptor gene. We observed a significant excess of both forms of homozygote in patients (P = 0.0009, odds ratio (OR) = 1.21, 95% Confidence Interval (CI) = 1.07-1.35) in the combined sample of 5351 individuals. No significant heterogeneity was detected between samples and the effects did not appear to be the product of publishing bias. In addition we undertook an independent, family-based association study of this polymorphism in 57 parent/proband trios, taken from unrelated European multiplex families segregating schizophrenia. A transmission disequilibrium test (TDT) showed a significant excess of homozygotes in schizophrenic patients (P = 0.004, odds ratio (OR) = 2.7, 95% CI = 1.35-5.86). Although no significant allelic association was observed, a significant association was detected with the 1-1 genotype alone (P = 0.02, OR = 2.32, 95% CI = 1.13-4.99). In addition when the results of the family-based association study were included in the meta-analysis, the homozygosity effect increased in significance (P = 0.0002, OR = 1.23, 95% CI = 1.09-1.38). The results of the meta-analysis and family-based association study provide independent support for a relationship between schizophrenia and homozygosity at the Bali polymorphism of the D3 receptor gene, or between a locus in linkage disequilibrium with it.

Alleles

Discriminating borderline from antisocial personality disorder in male patients based on psychopathology patterns and type of hostility.

Dimensions of psychopathology and patterns of hostility, as well as the relationship of hostility to psychopathology, were studied in 85 male young adults: 41 with borderline personality disorder (BPD) and 44 with antisocial personality disorder (APD). Diagnoses were based on DSM-III. The following instruments were also used: Brief Psychiatric Rating Scale, Hamilton Depression Rating scale, State-Trait Anxiety Inventory, and Hostility and Direction of Hostility Questionnaire. BPD patients compared with APD patients showed higher levels of overall psychopathology and depression, whereas both groups had equally high anxiety. Total hostility was quite high in both groups. However, BPD patients had more introverted hostility and APD patients had more extroverted hostility. In BPD patients, introverted hostility was related to overall psychopathology, depression, and trait anxiety, whereas in APD patients, no significant relationship of any type of hostility to various dimensions of psychopathology was observed. In conclusion, when comprehensively assessed, BPD patients can be discriminated from APD patients based on certain dimensions of psychopathology and differences in the direction of their hostility. Moreover, the relationship between psychopathology and hostility patterns suggests that the direction of patients' hostility plays an important role in the development of disorder-specific symptomatology.

Adult

Seasonal pattern of melatonin excretion in humans: relationship to daylength variation rate and geomagnetic field fluctuations.

In order to investigate the influence of various environmental parameters on melatonin excretion, the night-time urinary melatonin excretion of 16 healthy volunteers was measured in samples collected monthly over a period of one year. No significant interindividual differences were detected in the monthly rate of change of melatonin excretion. A seasonal bimodal pattern did, however, emerge. Peak values were observed in June and November. In these months a combination of high daylength stability and low values of the vertical component of the geomagnetic field was recorded. Trough values were found in April and August-October when low daylength stability was combined with high values of the vertical component of the geomagnetic field. We propose that the daylength variation rate, and the fluctuations of the vertical component of the geomagnetic field, interact to induce the changes in melatonin secretion which signalize the different seasons in humans.

Adult

Formal clinical characteristics of delusional beliefs.

We studied 13 formal clinical characteristics of delusions by means of observer-rated ordinal scales in a sample of 74 psychiatric inpatients with mainly schizophrenic or schizophreniform disorders. The interrater reliability of the scales was found to be satisfactory. High levels of conviction about their truth and to a lower extent lack of dismissibility and lack of resistance against them were found to be the hallmarks of delusional beliefs. The lack of strong intercorrelations among the scales items supports the hypothesis that the concept of delusions represents various aspects of delusional experience which are relatively independent of one another.

Adolescent

Effects of methysergide and ritanserin on the prolactin and thyrotropin responses to TRH in depressed patients.

Despite extensive study of the effects of various pharmacological agents on the thyrotropin (TSH) and prolactin (PRL) responses to TRH challenge, the effect of serotoninergic agents remains inconclusive. We studied the effect of the serotonin antagonists methysergide (non-selective 5-HT1/5-HT2 blocker with dopaminergic properties) and ritanserin (selective 5-HT2 blocker) on the TSH and PRL responses to TRH stimulation in two groups of medication-free female depressed patients in a double-blind, within-subject design. Methysergide was found to decrease significantly the PRL response to TRH, while ritanserin had no effect. Neither compound influenced the TSH response. Results suggest that 5-HT2 mechanisms do not mediate the PRL and TSH responses to TRH challenge in depression. The reduction in PRL observed after methysergide is probably due to either 5-HT1 or dopaminergic mechanisms.

Aged

Clinical characteristics of auditory hallucinations.

We studied 25 clinical characteristics of auditory hallucinations by means of 3-point observer-rated scales in a sample of 60 inpatients with mainly schizophrenic or schizophreniform disorders. The interrater reliability of the scales was found to be satisfactory. High levels of conviction about the reality of the sensory stimuli, clarity of content, location of their source of origin and lack of volitional control were found to be the hallmarks of verbal hallucinations. This finding supports the hypothesis that the concept of auditory hallucinations represents many aspects of patients' hallucinatory experiences, which are relatively independent of one another.

Adolescent

Factors affecting illicit and licit drug use among adolescents and young adults in Greece.

A cross-sectional survey on psychosocial issues, drug use, alcohol and health was carried out in Greece, with a nationwide probability sample of 2448 respondents aged 12-17 and 18-24. Factors potentially associated with illicit and unprescribed licit drug use were tested by logistic regression analysis. Several predictors were revealed. Sex and age were related to a higher lifetime use of illicit drugs, the male young adults reported a higher lifetime use of illicit drugs than the females. Positive attitudes toward hashish use, systematic smoking and use of drugs by close friends were more closely related to illicit than to unprescribed licit drug use. In addition "low self-esteem, family members using tobacco and alcohol" and "problematic drinking" were found only to predict illicit drug use. Other variables, "family members using drugs with or without a doctor's prescription", "being dissatisfied with social life" and "suffering from anxiety, depression and depersonalization symptoms" were found to be significantly associated with licit but unprescribed drug use.

Adolescent

Low and high melatonin excretors among healthy individuals.

To meet the need of establishing firm normative data regarding the secretion/excretion of human melatonin, nighttime urinary melatonin of 16 healthy volunteers was measured in samples collected monthly over a period of 1 year. Low melatonin excretors (N = 8) were distinguished from high melatonin excretors (N = 8), based on a cut-off mean melatonin value of 0.25 nmol/l. There was no overlap in any of the monthly melatonin values between the two groups, while their annual rhythms of melatonin excretion were not different in shape. Since no obvious factors (age, sex, height, weight, etc.) were responsible for the observed differences, the distinction between low and high nocturnal excretion and by inference secretion of melatonin most likely reflects genetically determined variable levels of the noradrenergic secretory drive and/or variable N-acetyltransferase/hydroxyindole-O-methyltransferase enzymatic activity during the night.

Adult

Suicide and violence risk. I. Relationship to coping styles.

Thirty suicidal psychiatric inpatients were compared with 30 nonsuicidal psychiatric inpatients. A battery of self-report tests was administered measuring suicide risk, violence risk and coping styles. The suicidal patients scored higher on both the suicide risk and violence risk. They also used almost all coping styles less frequently than the nonsuicidal patients. Among suicidal patients, suicide risk was negatively correlated with the coping styles of minimization, replacement and blame. Further, suicide risk and violence risk in suicidal patients were shown to be predicted by coping styles. These data indicate that suicidal patients have inadequate mental resources to deal with life problems. Besides their significance for assessing suicide risk, the findings may have possible clinical implications for case detection and early intervention with potential preventive value.

Adaptation, Psychological

Symptoms of depression, suicidal behaviour and use of substances in Greece: a nationwide general population survey.

This study aimed at investigating the relationship between the use of unprescribed licit and illicit drugs and problematic drinking with reported depressive symptoms and suicidal behaviour in a nationwide general population sample of 4291 respondents aged 12 to 64. Depressive symptoms were detected by the use of the Center for Epidemiological Studies Depression Scale (CES-D). A higher proportion of respondents who have reported illicit drug use in their lifetime were found to be depressed with a > 16 score in the CES-D in all age groups and both sexes, than of the other categories of substance use. A multiple range test revealed 3 groups of substance users. The more frequent illicit drug users together with the problematic drinkers exhibited the higher average depressive symptoms scores. The 12-month prevalence of suicidal ideation and suicide attempts was found to be in accordance with the severity and frequency of substance consumption.

Adolescent

Drinking practices of illicit and licit drug users in the general population across Greece.

This article presents the results on the patterns of alcohol consumption among illicit and licit drug users in a Greek nationwide sample of general population with 4,290 respondents aged 12 to 64. The type of survey was cross sectional and the respondents were interviewed in their homes with a multidimensional structured questionnaire. The illicit drug users of all age groups reported a higher frequency of alcohol consumption in their lifetime, past year, month, and week prior to interview than the unprescribed licit drug users and the nonusers. The majority of illicit drug users of all ages reported their reason for drinking "to feel better or to get high." Illicit drug users of all age groups had a higher frequency of episodes of drunkenness than the other categories. Finally, the higher the frequency (> or = 3 times) of illicit drug use, the more excessive drinking reported during the past year and month. Forty percent of this category of illicit drug users reported that they had two or more serious alcohol-related problems.

Adolescent