Seher Sofuoglu

Effects of antidepressant treatment and of gender on serum leptin levels in patients with major depression.

Leptin is a product of the obese gene and plays an important role in the regulation of body weight and food intake. Weight and appetite are frequently altered in depression. So far, inconsistent results have been reported in terms of leptin levels in depression. Therefore, the authors investigated serum leptin levels in patients with depression and in healthy controls, and whether there was any alteration throughout antidepressant treatment. Female patients showed significantly higher leptin levels than those of the control females both before and after the response to antidepressant treatment, whereas no difference was found between the male patients and the male controls. The improvement from depression with antidepressant treatment caused a further elevation on the leptin levels, in both female and male patients. These findings confirm an increase in leptin levels in depressive patients and presence of a sexual dimorphism. Moreover, clinical response to antidepressant treatment seems to have an additional increasing effect on leptin levels.

A Tc-99m HMPAO SPECT study of regional cerebral blood flow in drug-free schizophrenic patients with deficit and non-deficit syndrome

Twenty-nine patients with DSM-IV diagnoses of schizophrenia were categorized into deficit syndrome (n=14) and non-deficit syndrome (n=15) subgroups on the basis of the Schedule for the Deficit Syndrome. The patients, who had all been free of antipsychotic medication for at least 3 weeks, and 17 sex- and age-matched normal controls were studied with single-photon emission computed tomography with Tc-99m HMPAO. Age at onset, Brief Psychiatric Rating Scale (BPRS) total scores, BPRS positive symptom subscores and duration of illness were similar between the two schizophrenic subgroups. As expected, the deficit patients had more negative symptoms than the non-deficit patients. There were no statistically significant correlations between clinical parameters and regional cerebral blood flow (rCBF) values. The deficit syndrome subgroup showed diminished rCBF in the frontal regions bilaterally, right parietal regions and right superior temporal region compared with the control groups. Deficit patients showed significantly lower rCBF perfusion ratios in the right superior and inferior frontal cortex than did the non-deficit patients. No differences were detected between the controls and the non-deficit schizophrenic patients in terms of rCBF perfusion indices. The results of the present study confirm previous reports of different patterns of rCBF in deficit vs. non-deficit schizophrenic subgroups.

Changes in regional cerebral blood flow demonstrated by single photon emission computed tomography in depressive disorders: comparison of unipolar vs. bipolar subtypes

Single photon emission tomography (SPECT) with 99mTc-HMPAO was used to compare regional cerebral blood flow (rCBF) in patients with unipolar and bipolar depression. The study group consisted of 10 unipolar depressed patients and seven bipolar depressed patients who met the DSM-III-R criteria for major depressive disorder (MDD). Nine physically and mentally healthy volunteers served as control subjects. SPECT images were obtained in the patients at two time points: (1) during the major depressive episode before patients had received medication; and (2) at the beginning of the remitted state while patients were receiving antidepressant medication. During the depressive episode, unmedicated unipolar depressed patients showed relatively increased left frontal rCBF compared both with the control subjects and the bipolar patients (P < 0.05). No significant differences in rCBF emerged between the bipolar patients and the control subjects. The data suggest that unipolar depressed patients, unlike bipolar patients, have relatively increased rCBF in the left frontal lobes during the depressive episode, but these differences tend to disappear during the period of remission.

Effects of short and long-term lithium treatment on serum prolactin levels in patients with bipolar affective disorder

1. In this study, the authors sought to test the hypothesis that Li (lithium) treatment can induce alterations in PRL (prolactin) secretion in euthymic bipolar patients compared to controls and that short and long-term administration can lead to prolactin changes different from each other. 2. Twenty euthymic bipolar male patients on long-term lithium carbonate treatment for more than 6 months and 15 euthymic male bipolar patients on short-term Li treatment for shorter than 6 months who met DSM-IV criteria for bipolar affective disorder were included in the study. Seventeen age-matched healthy control males were chosen among the hospital staff. The mean +/- SD duration of Li use was 68.93+/-46.31 months in the long-term lithium-treated group and 4+/-3.42 months in the short-term lithium-treated group. 3. Serum PRL values in the long-term Li-treated group were significantly lower than those of the control group, while there was no significant difference in PRL values between the short-term Li-treated group and the control group. 4. Our study documents that short-term (<6 months) Li treatment does not induce any significant changes in PRL release in bipolar patients compared to normal control subjects while long-term Li treatment (>6 months) leads to lower PRL release compared to the controls. Furthermore, PRL has wide intra-interindividual and circadian variations Li-PRL relationship seems to be very complex and probably depends on various interactions among dopamine, serotonin and PRL. Therefore, further studies are needed to confirm the data.

Effects of short- and long-term lithium treatment on kidney functioning in patients with bipolar mood disorder

Lithium (Li) carbonate has been reported to be able to cause some reversible functional changes in the kidney. In this study, the authors aimed to investigate whether the duration of Li treatment is the primary determinant of the changes in renal functioning due to the Li treatment. For this purpose, 10 Li-naïve (mean age+/-S.D.: 34.50+/-4.85), 10 short-term (mean age+/-S.D.: 31.77+/-7.61) and 10 long-term (mean age+/-S.D.: 36.60+/-10.15) Li-treated bipolar patients were included in the study. Serum blood urea nitrogen (BUN) and creatinine, urine creatinine levels, creatinine clearance, urine osmolality before and after 8-h water deprivation and urine osmolality after desmopressin injection were measured in all patients. Serum BUN and creatinine levels were within the normal limits and not statistically different among the groups. Creatinine clearance of the long-term Li-treated group was significantly lower than both that of the Li-naïve group and that of the short-term Li-treated group. After 8-h water deprivation and also after desmopressin injection, no difference was found among the groups in terms of urine osmolality. However, when each patient was evaluated individually in terms of their renal concentrating ability, partial nephrogenic diabetes insipidus was diagnosed in four patients on long-term and in two patients on short-term Li treatment. To our surprise, hypothalamic diabetes insipidus was also diagnosed in other two patients on long-term Li treatment. These results demonstrate that long-term Li treatment may cause impairment in renal concentrating ability, some of which may originate from the effects of Li on vasopressin on hypothalamic level, and a decrease in glomerular filtration rate (GFR). In the light of these data, we can conclude that long-term administration of Li may be a risk factor for Li-induced renal impairment, which is a progressive effect in nature.

Lithium-induced hematologic changes in patients with bipolar affective disorder

We planned this study to examine the effects of short-term (10-day) and long-term (6 months) administration of lithium in patients with bipolar affective disorder, those who may be given lithium in nontoxic prophylactic doses

Tc-99 HMPAO SPECT study of regional cerebral blood flow in olanzapine-treated schizophrenic patients

Abstract. Dopamine D2 blocking typical antipsychotic drugs are known to change the cerebral perfusion patterns of schizophrenic patients, especially in the frontal cortex and basal ganglia. In recent years atypical antipsychotics such as olanzapine, which have high serotonin 5-HT2A/dopamine D2 occupation ratios, have been shown to be more effective in the treatment of schizophrenia symptoms. The aim of this study was to evaluate the regional cerebral blood flow (rCBF) of the schizophrenic patients treated with olanzapine in a within-subject design. Twenty-four patients with schizophrenia participated as subjects in the study. Each subject was scanned in a medication-free state and after 6 weeks of 10 mg/day fixed dose olanzapine treatment. Despite the clinical improvement seen in the patients, repeated-measures analysis of variance showed that olanzapine produced no significant changes in cortical rCBF after the six-week treatment. This finding indicates that unlike typical antipsychotics olanzapine has no negative effect on cortical cerebral perfusion patterns of schizophrenic patients.

Effects of olanzapine and haloperidol on serum prolactin levels in male schizophrenic patients

It has been proposed that new atypical antipsychotics cause minimal prolactin (PRL) elevation compared to traditional antipsychotic agents because they spare dopamine blockade within the brain’s tuberoinfundibular tract. The aim of this study was to compare the effects of olanzapine and haloperidol on PRL secretion in male schizophrenic patients. Twenty-nine male schizophrenic inpatients were included in the study. Fifteen of them were given olanzapine in a fixed dose of 10 mg/day PO and 14 of them were given haloperidol in a fixed dose of 10 mg/day PO for 6 weeks after a 2-week drug washout period. Fifteen age-matched healthy control subjects were used as control group. PRL levels were measured both before and after the 6-week treatment period in the patients. At the end of the 6th week, the PRL values observed with olanzapine treatment were significantly less than those observed with haloperidol, but not different from those of the controls. There was a significant positive correlation between the PRL values and the severity of extrapyramidal side effects in only the haloperidol group after the six week’s treatment period. Our data indicate that short-term olanzapine treatment at doses of 10 mg/day PO causes minimal elevations in PRL secretion in male schizophrenic patients in contrast to haloperidol. This finding is consistent with the previous reports and may be attributed to olanzapine’s differential effects on dopamine neurotransmission.  2001 Elsevier Science Ltd. All rights reserved.

Effects of antidepressant treatment on thyrotropin-releasing hormone stimulation, growth hormone response to L-DOPA, and dexamethasone suppression tests in major depressive patients

Dexamethasone suppression (DST), thyroid-stimulating hormone (TSH) and prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) and growth hormone (GH) response to L-DOPA tests were evaluated in 19 depressed inpatients before the commencement of the antidepressant treatment and after the clinical response to examine: (i) the functional relationships among the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axis and dopaminergic system in depression, (ii) any alterations in these hormonal functions with the antidepressant treatment. TSH responses to TRH showed a tendency to increase from pre- to posttreatment period, while TRH-induced PRL and L-DOPA-induced GH responses did not change with treatment in depressed patients who responded to the treatment. Females showed significantly higher TSH and PRL responses to TRH compared to males. No interconnections were found among the responses in DST, TRH stimulation test and L-DOPA-induced GH test in the patients. The results do not support the interrelations between the abnormalities in the HPT and HPA axes and central dopaminergic activity in depression.

A technetium-99m hexamethylpropylene amine oxime brain single-photon emission tomography study in adolescent patients with major depressive disorder

Abstract. We have not encountered any brain single-photon emission tomography (SPET) study performed in adolescent depressed patients in the literature. Therefore, we used technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) brain SPET in adolescent patients with major depressive disorder (MDD) to examine the possible changes in cerebral perfusion and the possible association between perfusion indices and clinical variables. Fourteen adolescent out-patients (nine females, five males; mean±SD age: 13.11±1.43 years; range: 11–15 years) fulfilling the DSM-IV criteria for MDD and 11 age-matched healthy control subjects (six females, five males; mean±SD age: 13.80±1.60 years; range: 12–15 years) were included in the study. 99Tc-HMPAO brain SPET was performed twice in the patient group and once in the control group. The first SPET investigation was performed under non-medicated conditions and the second was performed after depressive symptoms had subsided. A relative perfusion index (PI) was calculated as the ratio of regional cortical activity to the whole brain activity. We found significant differences between the PI values of the untreated depressed patients and those of the controls, indicating relatively reduced perfusion in the left anterofrontal and left temporal cortical areas. No significant differences in regional PI values were found between the remitted depressed patients and the controls. Our study suggests that adolescent patients with MDD may have regional cerebral blood flow deficits in frontal regions and a greater anterofrontal right-left perfusion asymmetry compared with normal subjects. The fact that these abnormalities in perfusion indices have a trend toward normal values with symptomatic improvement suggests that they may be state-dependent markers for adolescent MDD.