May oxytocin be a trait marker for bipolar disorder?

There is evidence to suggest that oxytocin is effective in stabilizing mood in humans. Lower plasma oxytocin levels have been reported in patients with major depression. The objective of this study was to investigate serum oxytocin levels during manic and depressive episodes and in the remission period in patients with bipolar disorder. Twenty-two patients in manic episode, 21 in depressive episode, and 24 in remission at the initial phase, ranging from 18 to 65 years of age, who were diagnosed with BD Type I and 24 healthy individuals were included in this study. Blood samples were collected from subjects in the morning at the beginning of the study. A second blood sampling was obtained from manic and depressive patients after response to treatment. MANCOVA was performed to compare the oxytocin values of the groups. The serum oxytocin levels of patients in manic episode were statistically significantly higher than those of the depressive episode and remission groups and of the healthy subjects. The serum oxytocin levels of patients in the depressive episode group and in the remission group were statistically significantly higher than those of the control group. The serum oxytocin levels of the manic episode and depressive episode patients after response to treatment were statistically significantly higher than those of the control group, and there was no statistically significant difference between the patient groups in serum oxytocin levels. The higher oxytocin levels observed in patient groups, compared to the controls, before and after response to treatment suggest that oxytocin may be a trait marker in BD.

Association between depression, nutritional status, and inflammatory markers in peritoneal dialysis patients.

BACKGROUND: To investigate the relationship between depression, nutritional status, and inflammatory markers in patients on peritoneal dialysis (PD). PATIENTS AND METHODS: This prospective study included 40 PD patients and 20 healthy people. The severity of depressive symptoms was assessed using the Beck depression inventory, the Hamilton depression rating scale, and the Hamilton anxiety rating scale. The depressive patients received antidepressant drug for 8 weeks. Blood samples were taken before and after antidepressant treatment for the high-sensitive C-reactive protein (hs-CRP), interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α) levels. RESULTS: Ten (25%) of the 40 PD patients had depression. No significant difference was determined between depressive patients and nondepressive patients. The mean erythrocyte sedimentation rate was higher in depressive patients. There was no significant difference for other inflammation parameters, including hs-CRP, TNF-α, IL-1, and IL-6, between depressive patients and nondepressive patients. In the depressive patients, we did not observe any significant change in nutritional parameters after antidepressant treatment. When we evaluated inflammation parameters of the depressive patients before and after antidepressant treatment, only IL-1 and IL-6 levels were significantly increased after antidepressant treatment. CONCLUSION: The depressive disorder in PD patients is a common psychopathology and has no significant effects on nutritional status and inflammation.

Relationship between depression and proinflammatory cytokine levels in hemodialysis patients.

AIM: To evaluate the presence of the relationship between depression and proinflammatory cytokine levels in hemodialysis (HD) patients. METHODS: The study included 40 HD patients and 20 healthy controls. All participants were evaluated for the presence of depression using the structured clinical interview based on criteria defined by Diagnostic and statistical manual mental disorders (Fourth Edition, Text Revision) Axis I disorders. The severity of depressive symptoms was assessed using the Beck Depression Inventory, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale. The depressive patients received antidepressants for 8 weeks. Blood samples were taken at baseline and after 8 weeks of antidepressant treatment for interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) levels. RESULTS: A total of 9 (22.5%) of the 40 HD patients had depression. IL-1, IL-6, and TNF-α levels were significantly higher in HD patients compared with that in the control group, but were not significantly different between HD patients with and without depression. In the depressive patients, we observed no significant difference in proinflammatory cytokine levels after antidepressant treatment. The psychometric measurements in depressive patients decreased significantly after antidepressant treatment. CONCLUSION: We observed that depression is a common psychiatric disorder and has no significant effect on proinflammatory cytokine levels in HD patients; no important improvement in cytokine levels was observed after antidepressant therapy.

Ultrasonically determined thyroid volume and thyroid functions in lithium-naïve and lithium-treated patients with bipolar disorder: a cross-sectional and longitudinal study.

OBJECTIVE: This study investigated thyroid volume, hormone levels and antibodies in long-term lithium-treated and lithium-naïve bipolar patients, some of whom underwent prospective follow-up evaluations. METHODS: Fourteen lithium-naïve patients, 13 long-term lithium-treated patients diagnosed with bipolar disorder and 12 healthy controls were included. Seven lithium-naïve patients were followed-up during their lithium receiving period (range 6-9 months). Thyroid volume and serum levels of thyroid hormones and antibodies were measured once in the long-term lithium-treated patients and controls, and twice in the lithium-naïve patients, i.e. before and after lithium treatment. RESULTS: Mean thyroid volumes in the lithium-naïve patients were significantly higher than those in the controls. Long-term lithium-treated patients had significantly higher total thyroid volume than the lithium-naïve patients and the controls. Total thyroid volume in the patients after the lithium treatment was significantly higher than that before. Serum free thyroxine (fT4) levels in the long-term lithium-treated patients were lower than those in the lithium-naïve patients and the controls. In the lithium-naïve patients, after lithium treatment, free triiodothyronine (fT3) levels were lower, and thyroid stimulating hormone (TSH) levels were higher compared to those before lithium treatment. CONCLUSIONS: The results suggest that thyroid enlargement and some alterations in thyroid hormones in bipolar patients may present even before lithium treatment and increase further with lithium treatment.

Manic episode associated with mega cisterna magna.

Mega cisterna magna is a part of "Dandy-Walker Complex" and it is characterized by the enlargement of the cisterna magna, morphologically intact vermis and cerebellar hemispheres. We report a case of manic attack in a 23-year-old man with mega cisterna magna. The patient was treated with quetiapine 1,000 mg/day and sodium valproate 1,500 mg/day and the symptoms were ameliorated within 2.5 months. In this case, mega cisterna magna and manic symptoms may be found together coincidentally or any cerebellar dysfunction due to mega cisterna magna may cause or contribute to the appearance of affective symptoms. To our knowledge, this is the first case reporting manic attack with psychotic symptoms associated with mega cisterna magna. This report suggests that any lesion in the cerebellum might contribute to the occurrences of some affective and psychotic symptoms seen in bipolar disorder.

The effects of galantamine hydrobromide treatment on dehydroepiandrosterone sulfate and cortisol levels in patients with chronic fatigue syndrome.

OBJECTIVE: Mental fatigue, cognitive disorders, and sleep disturbances seen in chronic fatigue syndrome (CFS) may be attributed to cholinergic deficit. A functional deficiency of cholinergic neurotransmission may cause the hypothalamic-pituitary-adrenal axis hypoactivity seen in CFS. Therefore, we investigated the alterations in stress hormones such as cortisol and dehydroepiandrosterone sulfate (DHEAS) in CFS patients before and after 4-week administration of galantamine hydrobromide, a selective acetylcholinesterase inhibitor, and aimed to investigate whether there are any relationships between the probable hormonal changes and cholinergic treatment. METHODS: Basal levels of cortisol and DHEAS were measured in 29 untreated CFS patients who were diagnosed according to Centers for Disease Control (CDC) criteria and in 20 healthy controls. In the patient group, four weeks after 8 mg/d galantamine hydrobromide treatment, cortisol and DHEAS levels were measured again. After the treatment 22 patients who stayed in study were divided into two subgroups as responders and nonresponders according to the reduction in their Newcastle Research Group ME/CFS Score Card (NRG) scores. RESULTS: Important findings of this study are lower pre-and post-treatment cortisol levels and in all CFS patients compared to controls (F=4.129, p=0.049; F=4.803, p=0.035, respectively); higher basal DHEAS values and higher DHEAS/cortisol molar ratios which were normalized following four weeks' treatment with 8 mg/d galantamine hydrobromide in the treatment-respondent group (F=5.382, p=0.029; F=5.722, p=0.025, respectively). CONCLUSION: The findings of the decrease in basal DHEAS levels and DHEAS/cortisol molar ratios normalizing with galantamine treatment may give some support to the cholinergic deficit hypothesis in CFS.

[Acute and chronic effects of electroconvulsive therapy on neuroactive steroids in patients with major depressive disorder]. / Major depresif bozuklugu olan hastalarda elektrokonvulsif tedavinin nöroaktif steroidler üzerine akut ve uzun süreli etkisi.

OBJECTIVE: Baseline serum levels of neuroactive steroids such as dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), testosterone, and cortisol were measured, and the acute and long-term effects of electroconvulsive therapy (ECT) on these hormones and the effect of gender on alterations in steroid hormones were investigated in patients with major depressive disorder (MDD). METHODS: The study included 25 inpatients (11 male, 14 female) diagnosed with MDD that responded to ECT, and 37 healthy controls (17 male, 20 female). Serum levels of cortisol, DHEAS, 17-OHP, and testosterone were measured 2 days before and 10 min after the first ECT, and 3 days after the last ECT in the patients. These measurements were obtained only once in the controls. RESULTS: Basal DHEAS increased, testosterone and 17-OHP decreased, and cortisol levels remained unchanged in MDD patients as compared to the controls. After completion of the therapeutic course of ECT, DHEAS levels in the patients were higher than they were before the treatment. After ECT treatment, cortisol and 17-OHP levels in the patients were lower than those in the controls; however, testosterone levels did not differ between the groups. In the MDD patients, increases in DHEAS and decreases in testosterone were only observed in men, while decreases in 17-OHP were only seen in women. CONCLUSIONS: Alterations were observed in some neuroactive steroids in MDD patients and it appears that ECT affected these hormones. It is not clear whether the observed alterations in neuroactive steroids are associated with the pathophysiology of depression or whether they play a role in the therapeutic effects of ECT.

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 gamma-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.

Growth hormone response to the GABA-B agonist baclofen in 3-week abstinent alcoholics.

Gamma-aminobutyric acid (GABA) dysfunction is a known feature of alcoholism. We investigated GABA-B receptor activity in 3-week abstinent alcoholics using the growth hormone (GH) response to baclofen, a GABA-B receptor agonist. The study aimed to investigate the relationship between GABA-B receptor activity and alcohol withdrawal. GH response to baclofen was measured in alcohol-dependent males without depression (n = 22) who were on day 21 of alcohol abstinence and in healthy control male subjects (n = 23). After 20mg baclofen was given orally to the subjects, blood samples for GH assay were obtained every 30 min for the subsequent 150 min. The patients were divided into two subgroups (continuing withdrawal and recovered withdrawal subgroups) according to their withdrawal symptom severity scores on day 21 of alcohol cessation. Baclofen administration significantly altered GH secretion in the controls, but not in the patients. When GH response to baclofen was assessed as DeltaGH, it was lower in the patients with continuing withdrawal symptoms than in the controls and in the recovered withdrawal group. Impaired GH response to baclofen in all patients mainly pertained to the patients whose withdrawal symptoms partly continued. Our results suggest that reduced GABA-B receptor activity might be associated with longer-term alcohol withdrawal symptoms in alcoholic patients.

A 12-month study of the efficacy of rivastigmine in patients with advanced moderate Alzheimer's disease.

The efficacy of a centrally active cholinesterase inhibitor, rivastigmine tartrate (ENA 713), in patients with advanced moderate Alzheimer's disease (AD) was evaluated in a 12-month placebo-controlled study. We aimed to investigate whether there was any evidence for the benefits of rivastigmine in patients with severe disease. These patients were compared with matched controls. In this study, 24 patients with advanced moderate AD received rivastigmine for 12 months. Another 20 patients received placebo. Mean daily doses of rivastigmine in the higher-dose group at 3, 6, 9, and 12 months were 6.1 +/- 1.0, 8.3 +/- 1.2, 8.9 +/- 1.3, and 10.7 +/- 1.6 mg/day, respectively. Cognitive abilities were assessed using the 11-item cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). Forty-five percent of placebo-treated patients declined by at least 4 points on the ADAS-cog. Conversely, only 18.3% of patients treated with rivastigmine declined by 4 or more points. Functional disabilities, as assessed using the Disability Assessment for Dementia Scale, remained significantly superior in rivastigmine-treated patients compared with placebo-treated patients. Patients benefited from high-dose rivastigmine treatment on all outcome measures, including the Mini-Mental State Examination, Progressive Deterioration Scale, as well as the Global Deterioration Scale. Patients receiving rivastigmine for 12 months significantly improved compared with placebo-treated patients (p < 0.001). By 52 weeks, patients originally treated with 6-12 mg/day rivastigmine had a significantly better cognitive function than patients originally treated with placebo. Long-term rivastigmine treatment appeared to be well tolerated in patients with advanced moderate AD and significantly benefits the cognitive and functional symptoms of AD.

Effects of electroconvulsive therapy on the thyrotropin-releasing hormone test in patients with depression.

We investigated the acute and lasting effects of electroconvulsive therapy (ECT) on the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in patients with depression. The TRH stimulation test was conducted (1) under basal conditions, after a first ECT, and at the end of a therapeutic course of 7 ECTs in 20 inpatients with depression; (2) before the initiation of antidepressant therapy and after the therapeutic response in 16 other inpatients with depression who responded to antidepressant drug treatment; and (3) in 20 healthy control subjects. Baseline TSH levels were lower in patients with depression, especially in those with more severe depression who were considered appropriate for ECT. Before the treatment, TSH response to TRH did not differ between the patients with depression and controls; however, more blunted TSH responses to TRH were observed in these patients compared with the controls. TSH response to TRH changed neither with one ECT nor throughout consecutive ECT sessions in patients with depression. Drug treatment also was found to have no impact on this response. These findings suggest that the therapeutic action of ECT in depression is not directly related to its effects on the hypothalamic-pituitary-thyroid axis. However, possible delayed effects of ECT on the HPT axis function should not be overlooked.

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.

Effects of electroconvulsive therapy on hypothalamic-pituitary-thyroid axis activity in depressed patients.

In this study, the authors aimed to test the hypothesis that electroconvulsive therapy (ECT) may cause some alterations in hypothalamic-pituitary-thyroid (HPT) axis hormones and these responses may change throughout respective ECT sessions. Nineteen depressed inpatients (8 males, 11 females; mean age+/-S.D.: 44.77+/-10.59 years) considered suitable for ECT were included in the study. Each patient was exposed to 7 ECT sessions with general anaesthesia. The blood samples for measurements of thyroid-stimulating hormone (TSH), free thyroiodothyronine (fT3) and free thyroxine (fT4) were drawn before (baseline) and after propofol, immediately after ECT, and 30 and 60 min after ECT during the first and last (seventh) ECTs. In both the first and seventh ECTs, there was a significant increase in TSH levels 30 min after ECT compared to the pre-ECT values. Additionally, a significant decrease in post-ECT fT4 values compared to the baseline values was found only during the seventh ECT. No difference was detected in the TSH, fT3 and fT4 responses to ECT between males and females, and between bipolar and unipolar depressive patients. These results show that ECT may have some effects on the HPT system. However, whether there is a relationship between these neuroendocrine responses and the therapeutic effect of ECT is not clear.

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.

Auditory event-related potentials in panic and generalised anxiety disorders.

In this study, we aimed to investigate event-related potential (ERP) changes in panic disorder (PD) and generalised anxiety disorder (GAD) and to determine whether two disorders are different from each other in terms of endogenous potentials. A total of 35 outpatients who fully met DSM-III-R criteria for PD (8 males and 27 females) were included in this study as the PD group. The GAD group consisted of 30 subjects (5 males and 25 females) who met DSM-III-R GAD criteria. The control group consisted of 29 healthy age and sex-matched volunteers (5 males and 24 females) having no history of psychiatric or neurological illness. ERPs were recorded by using auditory "odd-ball two-tone discrimination task" method. It was found that there was significant prolongation in P3 latency in the PD group compared to the GAD and control groups. Our study suggests that there are some disturbances in early information processing in patients with PD but not with GAD.