Eugenia Daskalopoulou

Association between the GABAA receptor α5 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 GABAA receptor α5 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. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:73–80, 1998.

Self-esteem, social adjustment and suicidality in affective disorders

Self-esteem (SE) and social adjustment (SA) are often impaired during the course of affective disorders; this impairment is associated with suicidal behaviour. The aim of the present study was to investigate SE and SA in unipolar or bipolar patients in relation to demographic and clinical characteristics, especially the presence of suicidality (ideation and/or attempt). Forty-four patients, 28 bipolar and 16 unipolar, in remission for at least 3 months, and 50 healthy individuals were examined through a structured clinical interview. SE and SA were assessed by the Rosenberg self-esteem scale and the social adjustment scale, respectively. The results have shown that bipolar patients did not differ from controls in terms of SE, while unipolar patients had lower SE than bipolars and controls. No significant differences in the mean SA scores were found between the three groups. Suicidality during depression was associated only in bipolar patients with lower SE at remission; similar but not as pronounced was the association of suicidality with SA. It is concluded that low SE lasting into remission seems to be related to the expression of suicidality during depressive episodes of bipolar patients, while no similar pattern is evident in unipolar patients.

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 (GABRA5) and schizophrenia. Genotyping of the GABRA5 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.

Changes in central serotonergic function as a correlate of duration of illness in paranoid schizophrenia

There is evidence that the duration of untreated psychosis may affect both the course and outcome of treatment in schizophrenic patients. In the present study, we used neuroendocrine probes to test the hypothesis that untreated psychosis may induce time-dependent changes in central serotonergic and dopaminergic neurotransmission. Prolactin responses to the administration of clomipramine (i.v.) and haloperidol (i.m.) were measured in healthy control subjects and in 16 never-treated male patients with DSM-IV diagnoses of schizophreniform or schizophrenic disorders of paranoid subtype, both before and after 5 weeks of treatment with haloperidol. In the drug-free state, schizophrenic patients exhibited significantly increased prolactin responses to clomipramine administration compared with both the healthy control subjects and the schizophreniform patients. Maximum prolactin responses to clomipramine in the total group of patients were positively correlated with the duration of psychotic illness and negatively correlated with changes in Positive and Negative Syndrome Scale (PANSS) total, negative symptoms and general psychopathology scores after 5 weeks of treatment with haloperidol. Prolactin responses to haloperidol challenge in the drug-free state were lower in the schizophreniform group than in the control and the schizophrenic groups, but the differences did not reach statistical significance. The results provide evidence that the persistence of psychotic psychopathology induces secondary neuroadaptive effects, which seem to involve changes in central serotonergic function.

Convulsive status epilepticus following abrupt high-dose benzodiazepine discontinuation

The misuse of benzodiazepines (BNZ)s may result in serious side effects. Three cases of convulsive status epilepticus (CSE) following abrupt discontinuation of long-term use of 25 mg of lorazepam in one patient and more than 20 mg of flunitrazepam in two patients are presented; they were non-epileptics and free of other high-risk factors for seizures. A favorable outcome for all three cases was noted. They remain free of seizures without antiepileptic treatment. Nevertheless, because of the extensive use of benzodiazepines, such rare high-risk side effects must be emphasized.

Neuroendocrine responsivity to clomipramine challenge test in neuroleptic naive psychotic patients before and after treatment with haloperidol

Abstract The prolactin, cortisol and growth hormone (GH) responses to intravenous administration of 25 mg clomipramine (CMI) were studied in young male psychotic patients who had never received neuroleptics and suffered from schizophrenia (13 patients), delusional disorder (three patients) or schizoaffective disorder (one patient). The test was repeated after 1 month in 16 patients who were hospitalized and treated with haloperidol in doses appropriate for best clinical response (range: 7.5–40 mg daily). Symptomatology was assessed by the Brief Psychiatric Rating Scale (BPRS). There was no association of the side effects caused by the administration of CMI (nausea and emesis) to the GH responses. The side effects appeared significantly less in the after treatment trials. Treatment with haloperidol did not influence the response patterns of the three hormones. An indication that high haloperidol doses may inhibit the prolactin response to CMI was obtained when the data were compared between low (7.5–10 mg/day, mean 9.7) and high (15–40 mg/day, mean 22.0) dose subgroups. Significant positive correlations were found between the prolactin and cortisol responses to CMI in the drug-free state, and the scores in the positive symptoms subscale of the BPRS. The degree of improvement did not correlate to any of the hormonal data.

P.2.075 Neuroendocrine responsivity to clomipramine challenge test in neuroleptic naive psychotic patients before and after treatment with haloperidol

The prolactin, cortisol and growth hormone (GH) responses to intravenous administration of 25 mg clomipramine (CMI) were studied in young male psychotic patients who had never received neuroleptics and suffered from schizophrenia (13 patients), delusional disorder (three patients) or schizoaffective disorder (one patient). The test was repeated after 1 month in 16 patients who were hospitalized and treated with haloperidol in doses appropriate for best clinical response (range: 7.5-40 mg daily). Symptomatology was assessed by the Brief Psychiatric Rating Scale (BPRS). There was no association of the side effects caused by the administration of CMI (nausea and emesis) to the GH responses. The side effects appeared significantly less in the after treatment trials. Treatment with haloperidol did not influence the response patterns of the three hormones. An indication that high haloperidol doses may inhibit the prolactin response to CMI was obtained when the data were compared between low (7.5-10 mg/day, mean 9.7) and high (15-40 mg/day, mean 22.0) dose subgroups. Significant positive correlations were found between the prolactin and cortisol responses to CMI in the drug-free state, and the scores in the positive symptoms subscale of the BPRS. The degree of improvement did not correlate to any of the hormonal data.