Mustafa Kula

Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment

Abnormalities in the neurohypophyseal system have been reported in depression. This study aimed to investigate serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment on these levels. Serum oxytocin levels were measured before and after treatment with antidepressant drugs or electroconvulsive therapy (ECT) in 40 inpatients (30 women, 10 men) who met the DSM-IV criteria for major depressive disorder (n=29) or bipolar affective disorder depressive episode (n=11), and in 32 healthy controls (20 women, 12 men). Serum oxytocin levels were decreased both pre-treatment and post-treatment in the patients compared with those in the controls. Serum oxytocin levels were not affected by antidepressant drug treatment or ECT. The female patients had significantly lower oxytocin levels than the control females, whereas no difference was found between the male patients and the male controls. We found no difference in serum levels of oxytocin between the unipolar and bipolar depressive patients. Our result shows reduced oxytocin in depression and a gender difference in oxytocin levels. Furthermore, antidepressant treatments appear to have no effect on serum oxytocin levels.

Androgen levels of preeclamptic patients in the third trimester of pregnancy and six weeks after delivery

Background. The aim of this study was to measure the circulating levels of androgens in the third trimester of pregnancy and six weeks after delivery and to discuss androgen contribution in the pathogenesis of preeclampsia.

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.

The Effects of Electroconvulsive Therapy on GABAergic Function in Major Depressive Patients

Objectives: It has been proposed that major depression is associated with a dysfunction of the &ggr;-aminobutyric acid (GABA) system. This study was planned to investigate whether there are any alterations in GABAergic activities in major depressive patients and, if there are, whether electroconvulsive therapy (ECT) has any effect on these changes. Methods: Twenty-five depressed inpatients who responded to a course of ECT and 23 healthy subjects were included in the study. Serum GABA levels were measured 2 days before and 10 minutes after the first ECT and 3 days after the last ECT, and a baclofen challenge test was performed 2 days before the first ECT and 3 days after the last ECT in the patients. The same tests were carried out only once in the control group. Results: Depressive patients had lower serum GABA levels compared with healthy individuals, and ECT caused a significant increase in these levels. The acute effect of the one-ECT procedure was a huge increase in the baseline GABA levels. Although there was no difference in the maximum alteration in growth hormone with baclofen between the patients and controls before the therapeutic ECT course, it became significantly higher in the depressive patients than in the controls after the treatment. Conclusions: The findings of this study support the GABA deficit hypothesis of major depression because major depressive patients have lower levels of serum GABA that are increased by a completed ECT course. ECT seems to increase brain GABA levels as well as GABAB activity, and these effects may contribute to its mechanism of therapeutic effect.

The regional cerebral blood flow changes in major depressive disorder with and without psychotic features

Depressive patients with psychotic features demonstrate distinct biological abnormalities in the hypothalamic-pituitary-adrenal axis (HPA), dopaminergic activity, electroencephalogram sleep profiles and measures of serotonergic function when compared to nonpsychotic depressive patients. However, very few functional neuroimaging studies were specifically designed for studying the effects of psychotic features on neuroimaging findings in depressed patients. The objective of the present study was to compare brain Single Photon Emission Tomography (SPECT) images in a group of unmedicated depressive patients with and without psychotic features. Twenty-eight patients who fully met DSM-IV criteria for major depressive disorder (MDD, 12 had psychotic features) were included in the study. They were compared with 16 control subjects matched for age, gender and education. Both psychotic and nonpsychotic depressed patients showed significantly lower regional cerebral blood flow (rCBF) values in the left and right superior frontal cortex, and left anterior cingulate cortex compared to those of controls. In comparison with depressive patients without psychotic features (DwoPF), depressive patients with psychotic features (DwPF) showed significantly lower rCBF perfusion ratios in left parietal cortex, left cerebellum but had higher rCBF perfusion ratio in the left inferior frontal cortex and caudate nucleus. The present study showed that DwPF have a different rCBF pattern compared to patients without psychotic features. Abnormalities involving inferior frontal cortex, striatum and cerebellum may play an important role in the generation of psychotic symptoms in depression.

Cerebral blood flow, metabolic, receptor, and transporter changes in bipolar disorder: the role of PET and SPECT studies.

The basic concepts of positron emission tomography (PET) and single photon emission computed tomography (SPECT) scanning are introduced, and the two modalities are compared. Applications to bipolar disorder (BD) are reviewed. Regional cerebral metabolic rate and blood flow, often used as surrogate measures of neuronal synaptic activity, are increased in the frontal lobes in both unipolar and bipolar depression. In mania, metabolism increases in the dorsal cingulate cortex, striatal regions, and the nucleus accumbens, as well as in limbic structures of the temporal lobes, but decreases in dorsolateral prefrontal cortex, possibly reflecting its loss of modulatory control over limbic structures. Specifically targeted PET radioligands are used to investigate neurotransmitter systems. D1 receptor binding potentials are reduced in frontal cortex, but striatal D2 receptor density is normal in all phases of non-psychotic BD. Psychotic BD patients show higher D2 receptor densities in the caudate, which correlate with the degree of psychosis but not mood symptoms. The serotonin transporter shows increased density in the thalamus, dorsal cingulate cortex, medial preftontal cortex, and insula of depressed BD patients. In the dorsal cingulate cortex and insula, it correlates with anxiety (and in the cingulate, with suicide attempts).

Long-term effects of continuous oral and transdermal estrogen replacement therapy on sex hormone binding globulin and free testosterone levels.

OBJECTIVE To determine the long-term effects of estrogen replacement therapy on sex hormone binding globuline (SHBG) and free testosterone (fT) levels in surgical postmenopausal women. STUDY DESIGN Forty patients with surgical menopause were enrolled in this prospective study. The women were randomly divided into two groups. The first group received oral therapy (continuous conjugated equine estrogens (CEE) - 0.625mg per day) and the second group received transdermal therapy (patches delivering continuous 17beta-estradiol (E2)--0.05mg per day). Serum SHBG and fT levels were determined at baseline and after first and second years of treatment. Two-way repeated measures analysis of variance with Bonferroni adjusted post-hoc test and unpaired-t-test were performed for statistical analysis with SPSS program. RESULTS Serum SHBG levels increased significantly with oral CEE after first year of treatment (P<0.05) and remained at this level for the next year. Transdermal therapy did not affect SHBG levels after first and second years (P<0.05). Serum fT levels did not change significantly in either group at the end of the first or second years (P<0.05) although there was a significant difference between the groups after 2 years (P<0.05). CONCLUSION Oral conjugated estrogens increased SHBG levels during therapy. This effect may balance the increased estrogen and androgen stimulation on breast tissue and may be more beneficial to the cardiovascular system in postmenopausal women.

A comparison of the circadian rhythms and the levels of melatonin in patients with diurnal and nocturnal complex partial seizures

The aim of the present work was to assess serum melatonin levels and melatonin circadian rhythm in patients with diurnal and nocturnal complex partial epilepsy. Daily rhythms of melatonin were studied in patients with diurnal complex partial epilepsy (n=10), patients with nocturnal complex partial epilepsy (n=10), and a control group (n=10). All patients were under carbamazepine treatment. Serum melatonin samples were taken at 1000, 2200, 0100, and 0500 hours. We found that melatonin circadian rhythm was normal in all patients when compared with controls. Melatonin levels were low in both patients with nocturnal and patients with diurnal complex partial epilepsy compared with the control group at 1000, 2200, 0100, and 0500 hours; a statistically significant decrease in melatonin levels was observed in the patients with epilepsy at 1000 hours only. These findings suggest that melatonin levels and circadian rhythm of melatonin do not differ between patients with nocturnal and patients with diurnal complex partial epilepsy. Further detailed research is necessary to determine the factors that govern the nocturnal or diurnal occurrence of complex partial seizures.

Effects of 3 Years of Intravenous Pamidronate Treatment on Bone Markers and Bone Mineral Density in a Patient with Osteoporosis-Pseudoglioma Syndrome (OPPG)

We present a 21 year-old woman with osteoporosis-pseudoglioma syndrome (OPPG) suffering from bone pain and frequent long bone fractures (approximately 1 or 2 fractures/year) who was treated with i.v. pamidronate for 3 years. OPPG is a rare autosomal recessive disorder characterized by severe widespread osteoporosis leading to pathological fractures and congenital or early onset blindness. Bone mineral density (BMD) (g/cm2) was determined at lumbar spine and femur neck by dual energy X-ray absorptiometry. BMD studies were also performed in her parents and 18 year-old brother who were phenotypically normal. Within 2 months of the first pamidronate treatment the patient reported considerable decrease in bone pain and improved mobility. During the treatment period no important side effects and no recurrent bone fracture were reported. There were substantial increases in BMD, T score and z-score at both lumbar spine and femoral neck during therapy. Baseline lumbar spine BMD increased from 0.416 to 0.489 g/cm2 and femoral neck BMD increased from 0.455 to 0.532 g/cm2 after 3 years. Although her parents and brother did not have any history of fracture, BMD measurements revealed that her parents were osteopenic and her brother was osteoporotic. We demonstrated that pamidronate therapy seems to be safe and beneficial in both spinal and peripheral skeleton osteoporosis in patients with OPPG. Moreover, the present study clearly indicates that bone density studies and LRPS gene screening for mutations should be performed in phenotypically normal family members of patients with OPPG.