Simavi Vahip

Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients

Researchers have reported that serum brain–derived neurotrophic factor (sBDNF) of drug–free depressed patients are lower than those of healthy controls and proposed that low sBDNF levels might reflect failure of neuronal plasticity in depression. In this study, we compared sBDNF levels of depressed patients (n = 28) before and after 8 weeks of antidepressant treatment, with those of healthy controls (n = 18) to test the hypothesis that initially low sBDNF levels of drug–free depressed patients will increase parallel with their clinical response to antidepressant treatment. The severity of depression and response to treatment were assessed with Hamilton Rating Scale for Depression (HAM–D). sBDNF was assayed with the sandwich ELISA method. Baseline sBDNF levels of patients (mean, 20.8 ng/ml; [S.D., 6.7]) were significantly lower than those of controls (mean, 26.8 ng/ml; [S.D., 9.3]; p = 0.015), and were negatively correlated with HAM–D scores (r = –0.49, p = 0.007). After 8 weeks of treatment, sBDNF levels of patients had increased significantly (mean, 33.3 ng/ml; [S.D., 9.9]; p < 0.001) and no longer differed from those of controls. These results support the hypothesis that BDNF might play a critical role in the pathophysiology of major depressive disorder and successful antidepressant treatment increases the attenuated BDNF levels in depressed patients.

Evidence for theory of mind deficits in euthymic patients with bipolar disorder

Objective:  i) To investigate the subtle ToM (theory of mind) deficits in euthymic patients with bipolar disorder. ii) To investigate the impact of non‐ToM cognitive deficits on ToM abilities.

Executive and verbal working memory dysfunction in first-degree relatives of patients with bipolar disorder

The authors aimed to investigate cognitive performance of first-degree relatives of probands with bipolar disorder (BD). They hypothesized that the relatives of BD patients would have impaired performance on cognitive tests of frontal-executive functions. A neuropsychological battery was administered to 34 first-degree relatives of BD probands and 25 control subjects. Relatives showed significant impairment in verbal working memory and executive function. Verbal memory and psychomotor performances of relatives were not different from control subjects. One particular component of executive function, cognitive flexibility, was associated with family history of mood episodes with psychotic features. Verbal working memory and executive function deficits may be useful endophenotypic markers of genetic vulnerability to BD.

Valproate-associated reproductive and metabolic abnormalities: are epileptic women at greater risk than bipolar women?

OBJECTIVE Evidence indicates that valproate (VPA) may have an adverse impact on reproductive endocrine and metabolic functions in women with epilepsy. This study explores whether the association of VPA with reproductive endocrine abnormalities is applicable to women with bipolar disorder (BD) or is unique to women with epilepsy. METHODS Thirty female patients aged 18-40 years with a DSM-IV diagnosis of BD (15 on lithium monotherapy and 15 on VPA monotherapy or VPA in combination with lithium therapy) and 15 with idiopathic generalized epilepsy (IGE) on VPA monotherapy were evaluated for reproductive endocrine functioning and metabolic parameters. RESULTS The menarche age, mean length of menstrual cycle and mean length of menses were not significantly different between groups. None of the bipolar patients on lithium, three (20%) of the bipolar patients on VPA and seven (47%) of the epileptic patients on VPA reported menstrual disturbances. Hirsutism scores of the epilepsy group were significantly higher than those bipolar women, regardless of treatment. Serum total testosterone levels were significantly higher in patients (both with BD and with IGE) treated with VPA than in those treated with lithium. Serum FSH levels were significantly lower and LH-to-FSH ratio was significantly higher in patients with epilepsy than in patients with BD, regardless of treatment. The weight parameters and lipid values investigated did not differ significantly between the groups. CONCLUSION The study supports the conclusion that VPA may be associated with menstrual abnormalities and increased total testosterone levels in both bipolar and epileptic patients although women with BD did not show clinical features of hyperandrogenism (menstrual abnormalities, hirsutism and truncal obesity) as did frequently as women with epilepsy.

Executive dysfunction and cognitive subgroups in a large sample of euthymic patients with bipolar disorder

Bipolar disorder (BP), at the group level, is associated with significant but modest cognitive deficits, including executive dysfunction. Among executive functions, response inhibition deficits have been suggested to be particularly relevant to BP. However, BP is associated with significant heterogeneity in neurocognitive performance and level of functioning. Very few studies have investigated neurocognitive subgroups in BP with data-driven methods rather than arbitrarily defined criteria. Other than having relatively small sample sizes, previous studies have not taken into consideration the neurocognitive variability in healthy subjects. Five-hundred-fifty-six euthymic patients with BP and 416 healthy controls were assessed using a battery of cognitive tests and clinical measures. Neurocognitive subgroups were investigated using latent class analysis, based on executive functions. Four neurocognitive subgroups, including a good performance cluster, two moderately low-performance groups, which differ in response inhibition and reasoning abilities, and a severe impairment cluster were found. In comparison to healthy controls, BP patients were overrepresented in severe impairment cluster (27% vs 5.3%) and underrepresented in good performance cluster. BP patients with lower educational attainment and older age were significantly more likely to be members of cognitively impaired subgroups. Antipsychotic use was less common in good performance cluster. These results suggest that there is a considerable overlap of cognitive functions between BP and healthy controls. Neurocognitive differences between BP and healthy controls are driven by a subgroup of patients who have severe and global, rather than selective, cognitive deficits.

Risk Factors Associated with Childbearing-Related Episodes in Women with Bipolar Disorder

Objective: For the onset of illness and possible recurrence during the childbearing period, women with bipolar disorder (BD) are at a higher risk. The aim of this study was to evaluate the impact of clinical and psychosocial factors associated with pregnancy and the postpartum period on the course of BD. Methods: The childbearing and illness history of 72 women with BD were assessed to determine mood episodes related to the childbearing period. Data was analyzed to evaluate the risk factors (clinical, obstetric and psychosocial factors) related with mood episodes during pregnancy and the postpartum period. Results: Data of 252 pregnancies and childbirths of 72 women with BD were included in the analysis. Twenty-three (32%) women with BD reported at least one mood episode during pregnancy or within 1 month after childbirth (childbearing-related episode, CBRE). Subjects with CBREs mean age at onset of illness and mean age at the time of assessment were significantly younger than subjects with N-CBRE. A lower number of women who experienced a postpartum episode after the birth of the first child chose to have the second one. Psychosocial factors during pregnancy and the postpartum period and method of delivery did not predict the first postpartum episode. Onset of illness at an early age, experiencing episode during the first pregnancy and experiencing physical problems during pregnancy predicted a mood episode during the first postpartum period. Conclusions: Interpretation of the results of the study is limited with the retrospective nature of data collection. Within the limitations, we may suggest that psychosocial factors do not play a significant role in the genesis of CBREs in women with BD.

Renal side-effects of long-term lithium treatment.

The beta 2-Mg (beta 2-microglobulin) and GAG (glycosaminogyclan) excretions in 107 patients with bipolar disorder who had been on lithium treatment for 1-15 years were compared with 29 matched psychiatric control patients. 24-h urine volume, urine beta 2-Mg, GAG values were significantly higher, and maximal urinary osmolality was significantly lower in patients on lithium than in controls. No relationship was found between creatinine clearances and duration of illness, duration of lithium treatment and daily lithium dosages. Duration of lithium treatment was not related to the concentrating capacity. The beta 2-Mg excretion rates were significantly higher in patients with manifest polyuria and with severe concentration defect.

Selective serotonin reuptake inhibitors combined with venlafaxine in depressed patients who had partial response to venlafaxine: four cases

One third of depressive patients show partial or no response to antidepressant treatment. With partial or nonresponders, treatment strategies are as follows: switching to another antidepressant, augmenting with other psychotropic agents, or combining antidepressants. There are no data in the literature about the positive effect of combining venlafaxine with selective serotonin reuptake inhibitors (SSRIs). In this report, the presented cases had been on at least two different classes of antidepressant medication (or combination of antidepressants) for an adequate time and dose. They showed only a partial response to high dose of venlafaxine but improved after the addition of an SSRI (sertraline, citalopram, or paroxetine) to venlafaxine. The combination treatment was well tolerated in all of the cases.