Cengiz Tuglu

Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder.

RationaleOver the last 15 years, an increasing body of evidence has suggested a causal relationship between depression and the immunological activation and hypersecretion of pro-inflammatory cytokines, such as interleukin-1, interleukin-6 and tumor necrosis factor-alpha (TNF-α). However, little is known about the probable relationship of serum TNF-α with major depressive disorder (MDD).ObjectiveTo assess whether serum TNF-α levels could be associated with the clinical course of MDD.Subjects and methodsTNF-α and C-reactive protein (CRP) serum concentrations, erythrocyte sedimentation rate, and leukocyte count were measured in 26 MDD patients and in 17 controls. The measurements were repeated following 6 weeks of antidepressant treatment with selective serotonin re-uptake inhibitors. Psychopathological improvement and the severity of depression were evaluated with the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI).ResultsOn admission, serum TNF-α and leukocyte count were significantly higher in MDD patients compared to controls (P<0.001 and P=0.005, respectively). With the antidepressant treatment, both HAMD and BDI scores decreased significantly (P<0.001 for both). Comparison of pre- and post-treatment measurements revealed that TNF-α, CRP, and leukocyte count decreased to levels comparable with those of the control subjects (P<0.001, P=0.01, and P=0.01, respectively).ConclusionsThe results emphasized that some immunological parameters, such as CRP, leukocyte count and TNF-α, are significantly involved in the clinical course and treatment response in MDD. TNF-α in particular could be considered as a potential state marker in MDD.

Assessment of cytokine levels and hs-CRP in bipolar I disorder before and after treatment

We aimed to assess the relationship between cytokine levels and the severity of the manic period in medication free patients. 30 Medication free patients and 28 healthy subjects (HS) were recruited. Plasma levels of pro-inflammatory, anti-inflammatory, inflammatory cytokines, and hs-CRP levels were investigated upon hospital admission, after six weeks follow up in bipolar disease manic episode and the results were compared to HS. The severity of the manic episodes was assessed according to the Young mania rating scale. TNF-α, INF-γ, IL-6 and hs-CRP levels were significantly higher in patients with manic episode of bipolar I disorder before treatment than HS. After treatment the levels of TNF-α, INF-γ, IL-6 and hs-CRP were observed to be significantly decreased. There was no difference between the levels of anti-inflammatory cytokines in patients before or after treatment of bipolar disorder and HS. hs-CRP was observed to be the only parameter correlated with clinical response. The most significant outcome of this study is the correlation between clinical outcome and hs-CRP levels in treatment naive manic episode bipolar type I patients. hs-CRP is the most consistent indicator according to pro-inflammatory, inflammatory and anti-inflammatory cytokines, in predicting treatment outcomes.

Post‐stroke mania in late life due to right temporoparietal infarction

Depressive syndromes following stroke are a wellknown phenomenon, but a few clear-cut cases of secondary mania have been reported. 1 Post-stroke mania has been strongly associated with right hemispheric strokes involving limbic or limbic-related cortical ‘orbitofrontal/basotemporal’ or subcortical ‘caudate nucleus or thalamus’ regions. 2 Mania after brain pathology is relatively rare. It occurs in less than 1% of all strokes. 3 We report a case of secondary mania late in life with lesions in the dominant hemisphere and discuss the clinical course and response to treatment in the light of the current literature. We also aim to illustrate clinical points in the evaluation of post-stroke mania. A 69-year-old right-handed woman with hypertension, hypercholesterolemia, and type II diabetes mellitus but no personal or family history of psychiatric disorder was initially admitted to the emergency room because of disorganized speech, laughing and visual hallucinations (moving animals such as birds over the wall), the sudden onset of left-sided arm and leg weakness and focal motor seizure. Her relatives reported a 2 day history of sudden change in behavior. She had an elevated mood, rapid speech, inappropriate laughing and did not want to sleep at night. When the patient was examined in the emergency room, she showed pressured speech, flight of ideas, grandiosity, and pyschomotor agitation. Neurological examination revealed a visual and motor neglect to the left side of the body, and left-sided hemiparesia with hyperactive reflexes. Electrocardiography demonstrated atrial fibrillation and the patient was on digitalis and diltiazem treatment. After initiating oral anticoagulant and carbamazepine, the patient was hospitalized. Physical examination was normal. The patient responded to simple and complex verbal commands. The patient’s formal thinking was characterized by loosened associations and rhyming. There was no aphasia. Memory and cognitive functions were normal. There was no amnestic period. Examination of left upper and lower limbs revealed normal tone, 4/5 graded power, minimally increased reflexes in comparison with the right side. The plantar reflexes were extensor on the left side. Laboratory tests including full blood count, kidney, liver and thyroid functions, electrolytes, and urine analysis were within normal limits. Electroencephalography was normal. The cranial magnetic resonance imaging revealed age-related cortical atrophy and right temporoparietal cortical infarction. Atherosclerotic changes were observed with Doppler ultrasound of the carotid artery. Because the patient’s mood and sleep disturbances continued at the end of the first week, we asked for psychiatric consultation, and it became obvious that the patient was suffering from a mood disorder characterized by severe manic episode with mood-congruent psychotic symptoms. The ongoing 800 mg/day carbamazepine treatment was titrated up to 1200 mg/day. Over a 3 week period her elevated mood settled to a hyperthymic level. Her disorganized behavior gradually improved. The patient was reassessed on 6 month follow-up visit: the scores of the Young–Mania Rating Scale and Hamilton Depression Scale were under the threshold but the patient was still talkative and had characteristics of hyperthymic temperament with unimpairment in social functioning. Premorbidly the patient was a euthymic person with introvert characteristic features. Mania is a rare complication of cerebral ischemia, its frequency is less than 1% of all strokes. 3 Dunne et al . diagnosed only three cases of post-stroke mania among 661 stroke patients, 4 and similarly Starkstein et al . identified three cases in their clinical sample of 700 consecutive stroke patients. 5 Mania was not diagnosed among 157 patients following their first stroke, who were consecutively admitted to a rehabilitation unit in Hong Kong. 6 Most of the reported patients had lesions in the non-dominant hemisphere, similarly to this patient. 7

Delirium and extrapyramidal symptoms due to a lithium-olanzapine combination therapy: a case report.

We report an elderly patient who developed severe delirium and extrapyramidal signs after initiation of lithium-olanzapine combination. On hospital admission, serum levels of lithium were found to be 3.0 mM/L which were far above toxic level. Immediate discontinuation of both drugs resulted in complete resolution of most of the symptoms except for perioral dyskinesia which persisted for three more months. We critically discussed the differential diagnosis of lithium intoxication and assessed confounding factors which induce delirium and extrapyramidal signs related with combination therapy of lithium and olanzapine.

The Role of Serum Cytokines in the Pathogenesis of Hepatic Osteodystrophy in Male Cirrhotic Patients

Objective. In this study, we aimed to investigate the possible role of serum cytokines in the development of hepatic osteodystrophy. Matherial and Methods. 44 consecutive male cirrhotic patients (17 alcoholic, 20 hepatitis B, 7 hepatitis C), 15 age- and sex-matched chronic alcoholics without liver disease, and 17 age- and sex-matched healthy controls were included in the study during one year period. Bone mineral density was measured by dual X-ray absorptiometry in the lumbar vertebrate and femoral neck. Serum interleukin levels were measured by ELISA method. Results. Although osteopenia frequency between our cirrhotic patients was 20%, there was no difference in T-scores among the controls and other groups. Serum interleukin-1, interleukin-8, and tumor necrosis factor-alpha levels were not different between all groups. Serum interleukin-2 and interleukin-6 levels were higher in the cirrhotics than controls (P < 0.001). However, there were no significant difference between osteopenic and nonosteopenic cirrhotics. Conclusion. According to the results of the study in this small population of 44 male cirrhotic patients, frequency of hepatic osteopenia is small and serum interleukins 1, 2, 6, 8, and tumor necrosis factor-alpha may not play a role in the pathogenesis of hepatic osteodystrophy. Further studies in which large number of patients involved are necessary in this field.

Aortic aneurysm and electroconvulsive therapy in elderly depressive patient.

We report the case of a 67-year-old single man with aortic aneurysm whose depression was successfully treated with electroconvulsive therapy. Metoprolol succinate was used for blood pressure control, and there were no cardiovascular side effects and no significant increase in blood pressure detected.