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Biomedical subjects

George N Christodoulou

Publications and source records attributed to George N Christodoulou.

At least 19 recordsLinked to original sources
PubMed2006

Risperidone augmentation of clozapine: a critical review.

OBJECTIVE: Atypical antipsychotics are frequently used as augmentation agents in clozapine-resistant schizophrenic patients. Risperidone (RIS) is the one most studied as a clozapine (CLZ) adjunct. The aim of this study is to critically review all published studies regarding the efficacy and safety of RIS as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients. METHODS: A MEDLINE search from January 1988 to June 2005 was conducted. Identified papers were examined against several clinical, pharmacological and methodological parameters. RESULTS: A total of 15 studies were found (2 randomized controlled trials, 3 open-label trials (OTs) and 8 case-studies (CSs)) comprising 86 schizophrenic or schizoaffective patients (mean age 38.4 years). Mean CLZ dosage during the combined treatment was 474.2 mg/day. Plasma CLZ levels were assessed in 62 patients (72.1%). RIS was added at a mean dosage of 4.6 mg/day for a mean of 7.9 weeks. Significant improvement in psychopathology was reported for 37 patients (43%). A lower RIS dosage and a longer duration of the trial seemed to be associated with a better outcome. Main side effects reported were: extrapyramidal symptoms or akathisia (9.3%), sedation (7%) and hypersalivation (5.8%). CONCLUSIONS: Existing evidence encourages the use of RIS as an adjunctive agent in CLZ-resistant schizophrenic or schizoaffective patients.

Antipsychotic Agents↗
PubMed2006

Early post-traumatic stress disorder in relation to acute stress reaction: an ICD-10 study among help seekers following an earthquake.

Disaster research related to earthquakes has almost exclusively dealt with their long-term psychosocial impact; besides, diagnoses were previously based only on DSM criteria. Therefore, it is pertinent to assess stress-related reactions of earthquake victims during the early post-disaster period through the application of ICD-10 criteria. For the first 3 weeks following an earthquake, 102 help-seekers were assessed based on a checklist of sociodemographic variables and a semi-structured interview for the detection of acute stress reaction (ASR) and posttraumatic stress disorder (PTSD) according to ICD-10. Forty-four subjects (43%) fulfilled the ICD-10 criteria for PTSD; all but one of them had suffered ASR. Moreover, among a series of potential predictors for PTSD, ASR was found to be the only significant one; this indicates a definite association between ASR and early development of PTSD. Logistic regression to predict group membership (PTSD/no PTSD) based on specific ASR symptoms showed that accelerated heart rate and feelings of derealization were the only significant predictors for early PTSD. Individuals who fulfill the ICD-10 diagnostic criteria for ASR following an earthquake are at high risk for subsequent occurrence of early PTSD. Increased heart rate and feelings of derealization within the first 48 h after the traumatic event appear to be the principal factors associated with the development of early PTSD. In addition to their potential value for timely prevention and treatment, these findings raise important nosological issues pertaining to the current diagnostic classification of stress-related disorders (ICD-10 versus DSM-IV).

Adolescent↗
PubMed2006

Physical anhedonia in the acute phase of schizophrenia.

BACKGROUND: The aim of the current study is to investigate the relationship between physical anhedonia and psychopathological parameters, pharmacological parameters or motor side-effects in a sample of inpatients with schizophrenia in an acute episode of their illness. METHOD: Eighty one patients with schizophrenia, consecutively admitted, with an acute episode of their illness, at the Eginition Hospital, Department of Psychiatry, University of Athens, during a one-year period were investigated regarding possible relationships between physical anhedonia, social-demographic data and clinical parameters as well as motor side-effects, induced by antipsychotic agents. All patients were assessed using the Chapman Revised Physical Anhedonia Scale (RPAS), the Positive and Negative Syndrome Scale (PANSS), the Rating Scale for Extrapyramidal Side-Effects (EPSE), the Barnes Akathisia Rating Scale (BARS) and the Abnormal Involuntary Movement Scale (AIMS). Simple cross tabulations were initially employed. Subsequently, multiple regression analysis was performed. RESULTS: Both positive and negative symptoms were associated with physical anhedonia. A positive association between physical anhedonia and the non-paranoid sub-category of schizophrenia was also proved. CONCLUSION: According to these results, it seems that in the acute phase of schizophrenia, physical anhedonia may be a contributing factor to patient's psychopathology.

Journal Article↗
PubMed2005

Psychophysiological differences in schizophrenics with and without delusional misidentification syndromes: a P300 study.

There is a debate on whether delusional misidentification syndromes (DMSs) and schizophrenia are distinct disorders. Information-processing deficits have been found in both. Since the P300 component of event-related potentials (ERPs) reflects attention and working memory (WM) mechanisms, the P300 elicited during a WM test was studied in schizophrenic patients with DMS in comparison to schizophrenic patients without DMS and controls. Nine schizophrenic patients with DMS, 11 without DMS and 11 healthy controls were tested with a computerized version of the digit span test of the Wechsler batteries. Auditory ERPs were measured during the anticipatory period of the test. P300 amplitude in prefrontal areas was found to be significantly reduced in schizophrenics without DMS and markedly less in DMS patients compared to controls. P300 latency in the central midline brain region was significantly prolonged in DMS patients compared to the other groups. Memory performance was significantly reduced in both patient groups as compared to healthy controls. The results may indicate abnormalities in both allocation of attentional resources and automatic orienting in schizophrenic patients with DSM. In contrast, even though schizophrenic patients without DMS exhibit partial similarities with patients suffering from DMS, they show excessive reduction of P300 amplitude located at the left frontal area. Future studies might clarify these issues.

Acoustic Stimulation↗
PubMed2005

Rapid cycling bipolar disorder: biology and pathogenesis.

The rapid cycling (RC) pattern of a mood disorder is characterized by at least four affective episodes (manic, hypomanic or major depressive) during the last year; different episodes must be demarcated by a switch to an episode of opposite polarity or by a period of remission of at least 2 months. RC is very rare in unipolar patients; its prevalence, however, in bipolar patients is 10-30% with the majority being women (70-90%). Patients with RC usually suffer from bipolar II disorder with onset with a depressive episode. Genetic studies have not convincingly shown that the condition is genetically determined. Major abnormalities of thyroid function have not been shown to be related to RC, but recent studies propose that latent subclinical hypothyroidism might play a role in the acceleration of cycles. Perturbations of the circadian biological and social rhythms might influence the expression of RC. No major effect of the menstrual cycle has been found. Despite the absence of firm empirical data, the possible contribution of the kindling phenomenon on the acceleration of cycles cannot be excluded. Finally, there is evidence that RC can be induced by the use of antidepressant drugs, especially for women.

Antimanic Agents↗
PubMed2004

Cytokine production in bipolar affective disorder patients under lithium treatment.

BACKGROUND: Our knowledge concerning immune functioning in bipolar affective disorder (BAD) is limited, while lithium's immunomodulatory effects seem multiple and conflicting. Our aim was to evaluate cytokine production and lithium's effect on it in BAD patients, using ELISPOT technique as a sensitive tool. METHODS: Cytokine (IL-2, IL-6, IL-10 and IFN-gamma) production from isolated peripheral blood lymphocytes (PBLs) was evaluated (ELISPOT technique) in 40 euthymic BAD patients under chronic lithium treatment, in 20 healthy volunteers, and in 10 never medicated BAD patients before and after the introduction of lithium therapy. In all cases, cytokine plasma levels were also measured using ELISA. RESULTS: BAD patients under chronic lithium treatment had significantly lower numbers of IL-2, IL-6, IL-10 and IFN-gamma secreting cells compared to healthy volunteers. The number of cytokine secreting cells decreased in never medicated patients after 3 months of lithium treatment. In vitro stimulation of PBLs with lithium did not affect the number of cytokine secreting cells either in the patients or in the healthy volunteers. CONCLUSIONS: The significantly lower number of PBLs producing cytokines (IL-2, IL-6, IL-10 and IFN-gamma) in euthymic BAD patients under chronic lithium treatment result from the long-term (over 3 months) lithium administration. In vitro stimulation of PBLs with lithium did not change the number of cytokine producing cells. Our findings may be useful in elucidating possible downregulatory effects of lithium in humans.

Adult↗
PubMed2004

Sex hormones and biogenic amine turnover of sex offenders in relation to their temperament and character dimensions.

Relationships between Cloninger's temperament and character dimensions and plasma sex hormone levels and biogenic amine turnover were studied in male prison inmates convicted of rape (n=61) or child molestation (n=24) and normal male controls (n=25). The participants completed the Temperament and Character Inventory (TCI), which includes the temperament dimensions Novelty Seeking, Harm Avoidance, Reward Dependence and Persistence as well as the character dimensions Self-Directedness, Cooperativeness and Self-Transcendence. Plasma levels of testosterone, dihydrotestosterone, sex hormone binding globulin, luteinizing hormone (LH) and follicle-stimulating hormone were estimated in plasma samples and 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine samples. Both sex offender groups had higher Novelty, Seeking and lower Reward Dependence, Self-Directedness and Cooperativeness scores compared with the controls. Plasma levels of testosterone and dihydrotestosterone were significantly higher in rapists than in controls. Novelty Seeking scores were positively correlated with LH levels in rapists, and with testosterone levels in child molesters. Harm Avoidance scores were negatively correlated with 5-HIAA levels in rapists and with HVA levels in child molesters. In rapists, the calculated free androgen index showed a negative correlation with 5-HIAA. For the sex offender sample as a whole, the subgroup with high testosterone levels had higher Harm Avoidance scores, the subgroup with low HVA levels had lower Cooperativeness scores, and the subgroups with high 5HIAA or MHPG levels had lower Persistence scores. The results indicate that Novelty Seeking behavior in the group of rapists is associated with a hyperactive hypothalamic-pituitary-gonadal axis. In addition, low serotonin turnover and low dopamine turnover seem to be associated with a passive-avoidant behavioral style in rapists and child molesters, respectively.

Adult↗
PubMed2004

Obsessive-compulsive symptoms with olanzapine.

The emergence or exacerbation of obsessive-compulsive (OC) symptoms during treatment with atypical antipsychotics, mostly clozapine, has been documented by numerous case reports (reviewed by Lykouras et al., 2003). In six recent reports involving nine cases, (Jonkers and de Haan, 2002; Lykouras et al., 2003) olanzapine was found either to cause de novo emergence or to exacerbate OC symptoms. In six of these cases olanzapine caused exacerbation and in three cases caused de novo emergence of OC symptoms.

Adult↗
PubMed2004

P300 alterations in schizophrenic patients experiencing auditory hallucinations.

RATIONALE: Attentional deficits have been implicated in the pathophysiology of auditory hallucinations in schizophrenia. Since the latency of the P300 component of event-related potentials (ERPs) is considered to be a sensitive measure of stimulus classification speed, while its amplitude-a measure of attentional resource allocation when memory updating is engaged, the present study focuses on the comparison of P300 between healthy subjects and schizophrenic patients experiencing auditory hallucinations and treated with clozapine and olanzapine. METHODS: The auditory P300 was assessed during the anticipatory period of a short memory test, in 16 male hallucinated schizophrenic patients and 13 male normal subjects matched for age and educational level. The patients were reexamined under identical conditions when their hallucinations had resolved following treatment with clozapine (8 patients) and olanzapine (8 patients). RESULTS: The patients with hallucinations exhibited significantly reduced P300 amplitude at leads Fp1, F3, (C3-T5)/2, F4, Cz and Fz, when compared to the normal controls and at leads Fp1, F3, F4, (C4-T6)/2, C4, P4, Cz and Fz when compared to themselves during the remission phase. However logistic regression models revealed that the most important leads, differentiating the patient group before treatment either with the healthy controls, or with itself after treatment, were that at the left temporoparietal and at the left prefrontal area. Memory performance of the patient group, even after treatment and in spite of its significant improvement, remained significantly less than that of healthy controls. both antipsychotic agents had similar effects on the p300 amplitude and memory performance. CONCLUSIONS: These findings indicate that auditory hallucinations in schizophrenia manifest abnormal aspects of attention, mediated by a distributed network involving or affecting the left temporoparietal and left prefrontal area. Additionally, the present study points to an improvement of attentional function in schizophrenic patients experiencing auditory hallucinations, both in the clozapine group but also in the olanzapine group.

Adult↗
PubMed2004

Pituitary volume in psychosis.

BACKGROUND: Patients with psychosis have activation of the hypothalamic-pituitary-adrenal (HPA) axis during the acute phase of the psychosis. Whether this has any morphological consequences for the pituitary gland is currently unknown. AIMS: To examine pituitary volume variation in people at different stages of psychotic disorder. METHOD: Pituitary volume was measured using 1.5 mm, coronal magnetic resonance images in 24 people with first-episode psychosis, 51 with established schizophrenia and 59 healthy controls. RESULTS: Compared with the control group, the people with first-episode psychosis had pituitary volumes that were 10% larger, whereas those with established schizophrenia had pituitary volumes that were 17% smaller. In both of the groups with psychosis, there was no difference in pituitary volume between those receiving typical antipsychotic drugs and those receiving atypical antipsychotics. CONCLUSIONS: The first episode of a psychosis is associated with a larger pituitary volume, which we suggest is due to activation of the HPA axis. The smaller pituitary volume in the group with established schizophrenia could be the consequence of repeated episodes of HPA axis hyperactivity.

Acute Disease↗
PubMed2003

Olanzapine-associated neuroleptic malignant syndrome: Is there an overlap with the serotonin syndrome?

BACKGROUND: The neuroleptic malignant syndrome is a rare but serious condition mainly associated with antipsychotic medication. There are controversies as to whether "classical" forms of neuroleptic malignant syndrome can occur in patients given atypical antipsychotics. The serotonin syndrome is caused by drug-induced excess of intrasynaptic 5-hydroxytryptamine. The possible relationship between neuroleptic malignant syndrome and serotonin syndrome is at present in the focus of scientific interest. METHODS: This retrospective phenomenological study aims to examine the seventeen reported olanzapine - induced neuroleptic malignant syndrome cases under the light of possible overlap between neuroleptic malignant syndrome and serotonin syndrome clinical features. RESULTS: The serotonin syndrome clinical features most often reported in cases initially diagnosed as neuroleptic malignant syndrome are: fever (82%), mental status changes (82%) and diaphoresis (47%). Three out of the ten classical serotonin syndrome clinical features were concurrently observed in eleven (65%) patients and four clinical features were observed in seven (41%) patients. CONCLUSION: The results of this study show that the clinical symptoms of olanzapine-induced neuroleptic malignant syndrome and serotonin syndrome are overlapping suggesting similarities in underlying pathophysiological mechanisms.

Journal Article↗
PubMed2003

Treatment of severe neuroleptic-induced tardive torticollis.

BACKGROUND: The aim of this paper is to describe a case of severe neuroleptic-induced tardive torticollis successfully treated with a combination of clozapine, clonazepam and botulinum toxin-A. CASE REPORT: The patient, a 30-year old man with a seven-year history of delusional disorder experienced severe right torticollis with painful tightness of the neck and elevation of the shoulder. At this time he was receiving haloperidol 20 mg, trifluoperazine 5 mg, zuclopenthixol 20 mg and biperidine 4 mg daily. The combination therapy with clozapine and clonazepam and the long-term use of botulinum toxin-A resulted in a complete remission of dystonic movements. CONCLUSIONS: The present observations provide evidence indicating that this combination therapy may be of benefit in patients with severe neuroleptic-induced tardive torticollis.

Journal Article↗
PubMed2003

Do atypical antipsychotics fail to exert cognitive sparing effects?

The aim of the study was to investigate patterns of the P600 component of event-related potentials (ERPs) elicited during a working memory test in 16 male schizophrenic patients experiencing auditory hallucinations before and after treatment with clozapine and olanzapine, and 13 male normal subjects matched for age and educational level. Before treatment, patients showed significantly reduced P600 amplitudes on the right parietal region compared with controls, and when in remission also showed significantly reduced P600 amplitudes located on the right parietal and temporofrontal areas, compared both to themselves before treatment and to normal controls. The patient's memory performance before and after treatment remained significantly lower than that of healthy controls. These findings may indicate that auditory hallucinations in schizophrenia are associated with impaired synchronization of the processes related to target detection, as reflected by the P600. The present study also casts doubts regarding the cognitive sparing effect of atypical antipsychotics, despite the fact that they mediate symptom improvement.

Adult↗
PubMed2003

Psychophysiological evidence for altered information processing in delusional misidentification syndromes.

Recent research provides evidence that delusional misidentification syndromes (DMS) are associated with cognitive deficits. However, the underlying mechanisms of these deficits are not known. Since the P300 component of event-related potentials (ERPs) is related to fundamental aspects of working memory (WM), the present study is focused on P300 elicited during a WM test in DMS patients, as compared to those of healthy controls. Nine patients with DMS and 11 healthy controls, matched for age, sex and educational level were tested with a computerized version of the digit span test of the Wechsler batteries. Auditory ERPs were measured during the anticipatory period of the test. DMS patients showed significant reductions in P300 amplitude at the right frontal region compared to healthy controls. P300 latency in the central midline brain region was significantly prolonged in the DMS group. Each of these measures classified correctly 90% of the two groups. Moreover, the memory performance of the patient group was significantly lower, relatively to healthy controls. These findings provide evidence supporting the suggestion that DMS is associated with psychophysiological alterations occurring at the right frontal region, which mediates automatic processes, as well as with an irregular allocation of attentional resources, involving the interhemispheric circuitry, possibly due to gray matter degeneration. Finally, present work points to a need for further research investigating the characteristics, causes, course and treatment of severe cognitive deficits associated with DMS.

Adult↗
PubMed2003

Induction of mania by rTMS: report of two cases.

There is some evidence that repetitive transcranial magnetic stimulation (rTMS) may be effective in treating depression. Using an intensive methodology of rTMS in two drug-resistant patients, we observed a good antidepressant effect, but also, induction of manic symptoms.

Antidepressive Agents↗