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Objective Studies indicate that serotoninergic and noradrenergic pathophysiological mechanisms may underlie both alcohol abuse/dependence and depressive disorder. The purpose of this study was to evaluate and compare the effectiveness and tolerability of two serotonergic and noradrenergic antidepressant drugs-mirtazapine and amitriptyline, for the treatment of patients with alcohol dependence co-morbid with depressive disorder in a randomized, double-blind treatment setting. Methods Forty-four patients were included in the study. Twenty-four patients were randomized to mirtazapine and twenty to amitriptylinegroups. Thirty-six of them completed the study. The 17-item Hamilton Depression Rating Scale (HDRS), the Spielberger State-Trait Anxiety Inventory (STAI) and alcohol craving questionnaire were used at baseline and, at days 7, 14, 28, 42, and 56 to estimate the effectiveness of the antidepressant treatment. Michigan Alcoholism Screening Test (MAST) was used in the assessment of alcohol dependence. The tolerability was assessed with the Udvalg for Kliniske Undersogelser Side Effect Rating Scale (UKU). Results There was significant improvement in HDRS and alcohol craving scores with both the drugs. However there were no statistical differences between treatment groups. Mirtazapine was tolerated better than amitriptyline treatment. Conclusions The treatment with either mirtazapine or amitriptyline resulted with the reduction of HDRS and craving scores. The side-effect profile of mirtazapine was relatively favorable in our study. Copyright # 2008 John Wiley & Sons, Ltd. key words—alcohol dependence; depressive disorder; mirtazapine; amitriptyline; co-morbidity

The medial frontal cortex has been shown to modulate emotional behavior and stress responses, suggesting that the dysfunction of this region may be involved in the pathogenesis of depressive symptoms. The present study was performed to determine whether there was any effect of antidepressant treatment on the metabolite levels in the left medial frontal cortex as measured by proton magnetic resonance spectroscopy in depressed patients. Twenty patients diagnosed as having major depressive disorder according to DSM-IV and 18 healthy volunteer subjects were included in the study. Twelve of patients had their first episode and were drug-naïve. Other depressed patients were drug-free for at least 4 weeks. The severity of depression was assessed by HAM-D and Clinical Global Impression Scale-Severity (CGI-S). Single voxel, 8 cm(3), 1H MR spectra of left medial frontal cortex was acquired both before and following antidepressant treatment. The concentrations and ratios of N-acetyl aspartate (NAA), Creatine+Phosphocreatine (Cr+PCr) and Choline (Cho) were measured. Pretreatment NAA/Cr values of patients were lower than those of healthy controls, but this difference did not reach to statistically significant levels (t=1.83, df=36, p=0.07). However, antidepressant treatment had significant effect on NAA/Cr ratios (groupxtreatment interaction: F=9.93 df=1,36, p=0.03). After the treatment, NAA/Cr values of patients increased significantly compared to pretreatment values (t=3.32, df=19, p=0.004). No significant difference was observed between the post-treatment NAA/Cr values of patients and those of controls (t=1.64, df=36, p=0.19). Correlation analysis detected negative correlation between pretreatment CGI-S scores and NAA/Cr ratios (r=-0.51, p=0.02). This preliminary result suggests that there might be a possible defect in the neuronal integrity in the left medial frontal cortex (mainly left anterior cingulate cortex) of depressed patients. Antidepressant treatment with its neurotrophic effects might play a positive role in restoring the neuronal integrity. Further studies are needed to support these initial findings.

Background: The aims of this study were to identify the dominant affective temperamental characteristics of patients with bipolar disorder (BP) and their clinically well first-degree relatives and to compare the prevalence rates of these temperaments with those in healthy control subjects. Methods: One hundred bipolar I probands and their 219 unaffected first-degree relatives were enrolled in the study. The control group consisted of healthy subjects without any personal or family history of bipolar disorder, matched with the age and gender of the probands and first-degree relatives. To identify the dominant affective temperaments, the Turkish version of TEMPS-A scale was used. Results: At least one dominant temperament was found in 26% of the proband group, in 21.9% of the relative group, and 6.0% and 10.0% of the control groups, respectively. The most noteworthy finding was that both the probands and their relatives had significantly higher frequency of hyperthymic temperament than the controls. Limitations: Temperament had not been assessed premorbidly in the probands with bipolar disorder. Conclusions: The study supports the familial, possibly genetic, basis for the hyperthymic temperament in the genesis of bipolar I dosorder. That the cyclothymic temperament was not similarly represented, may be due to the higher specificity of the cyclothymic temperament to the bipolar II sybtype (which we did not study). More research is needed on the relevance of cyclothymic and other temperaments to the genetics of bipolar disorders selected by rigorous subtyping along the clinical spectrum of bipolarity.

Background Recently it was proposed that nitric oxide metabolites (NO) may have a role in the pathophysiology of schizophrenia and major depressive disorders. The present study was performed to assess changes in serum nitric oxide metabolite levels in schizophrenic patients compared with healthy controls. Our secondary aim was to further evaluate the impact of psychopharmacologic treatment on circulating NO levels not assessed previously. Methods Serum NO levels of patients with schizophrenia (n = 20) before and after 6 weeks of treatment were compared with those of healthy controls (n = 20). Severity of schizophrenia and response to treatment were assessed with positive and negative symptoms of schizophrenia. NO levels were estimated by Griess method in serum samples. Results In patients with schizophrenia, pre-treatment serum NO levels were higher than those of control subjects (39.15 ± 18.24 vs. 25.40 ± 5.83 μmol/L, p = 0.036) and also of post-treatment values (34.41 ± 16.35 vs. 25.40 ± 5.83 μmol/L, p = 0.049), respectively. However, no significant difference was found between serum NO levels in pre- and post-treatment values. Conclusions Our findings of increased serum NO levels in schizophrenic patients confirmed the role of NO in the pathophysiology of schizophrenia. However, we found that antipsychotic drugs do not reveal significant effects on serum levels of NO in schizophrenia in a 6-week treatment regimen. Further studies with longer therapy periods may suggest some new clues for novel treatment strategies employing antioxidants and NOS inhibitors in schizophrenia.

Background: Although several studies have documented the existence of psychopathology in obese adolescents, disagreement remains regarding the extent and nature of this psychopathology. The aim of the present study was to explore the type and frequency of psychopathology in a clinical as well as a non-clinical sample of obese adolescents, and in a normal weight control group. Methods: The study sample consisted of a clinical study group of 30 obese adolescents, a non-clinical obese group of 30 obese adolescents, and a control group of 30 normal weight adolescents. Psychological assessment was performed using a non-structured psychiatric interview, the Child Behavior Checklist (CBCL), Children Depression Inventory (CDI), Rosenberg Self-esteem scale (SES) and the Eating Attitude Test (EAT). Results: More than half of the clinical obese adolescents (16/30) had a DSM-IV diagnosis, often involving major depressive disorder (n = 10). The mean scores of anxiety-depression, social problems, social withdrawal and total problem in the CBCL scale of the clinical obese group were significantly higher than the non-clinical obese group and the normal weight control group. The mean total scores of the SES and the CDI of the clinical obese group were higher than the normal weight control group. The mean total score of EAT of the clinical obese group was significantly higher than the normal weight control group, and the mean score of EAT of the non-clinical obese group was significantly higher than the normal weight control group. Conclusions: The results support previously published reports which show a higher ratio of psychopathology (depression, behavioral problems, low-esteem) among clinical obese adolescents than among non-clinical obese adolescents. Findings provided evidence for a psychosocial at-risk population in a subgroup of obese adolescents.

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.

Significant sex differences have been described for mental disorders in terms of prevalence, symptom presentation and prescription of psychotropic medication. Most of the published studies and reviews emphasize the impact of female-specific reproductive events on the course of the mental illness or sex difference of the adverse effects of psychotropic medication or the concerns about treatment of female patients during the perinatal period. Different from other reviews, we will summarize the effects of current mental disorder/psychotropic medication on the female-specific reproduction-related events (such as menstrual regularity, pregnancy, postpartum period and menopause).A number of recent studies have highlighted the adverse effects of psychotropic agents on the female reproductive system, especially on the regularity of the menstrual cycle or on the female gonadal hormones. Without any medication, disturbances of the female gonadal system are observed especially among severely mentally ill female patients. In the studies, the prevalence of female-specific gonadal abnormalities and their mechanism of action, prevention and recommendations are given in detail.The field of reproductive psychiatry is rapidly evolving. There is increasing evidence that clinicians should be aware of female medical health while treating severely mentally ill female patients. Analyzing the present data will further advance our understanding of treatment safety and impact of untreated mental illness in women.

The prevalence of bipolar disorder (BD) in males and females is almost equal. The onset of BD in females typically occurs during the reproductive years, complicating its treatment. Although it was once believed that pregnancy prevents recurrence, studies have shown that recurrence is common and severe during pregnancy. On the other hand, the effects of pharmacological treatment on obstetrical outcome are not well known and some of these agents are considered teratogenic. Thus, the decision to treat pregnant patients with psychotropic agents requires solving an ethical dilemma. Risk-benefit decisions should be made while considering both the risk of relapse of BD and its morbidity, and the risk of fetal exposure to psychotropic medications. Moreover, the risk of recurrence increases dramatically in the postpartum period. It is well known that all of the psychotropic medications studied enter the breast milk. Thus, their effects on infants should be considered while prescribing for a breastfeeding mother. The aim of this review was to discuss the safety profiles of the treatment options for pregnant and breastfeeding BD patients. Firstly, each medication's effects on organ dysgenesis, neonatal toxicity, and neurobehavioral development, and their associated adverse events during pregnancy and the postpartum period are discussed, with a focus on the emerging literature. Given this background, practical suggestions on tailoring treatment in BD patients, from preconception to breastfeeding are highlighted.

Valproate is an antiepileptic commonly used in the treatment of psychiatric and neurologic diseases. Some of the most frequently seen side effects affect the gastrointestinal, neurological, and hematological systems. Its side effects on reproductive functions have not been sufficiently studied. The use of valproate by females with bipolar disorder and epilepsy may cause menstrual cycle abnormalities, polycystic ovary syndrome, and hyperandrogenism. The effects on male reproductive functions have been researched only in epileptic patients and animals, and the results have been conflicting, because reproductive function abnormalities may be independent of the use of valproate and may be due to epilepsy itself. In the first part of this review reproductive function abnormalities due to epilepsy will be discussed, independent of the use of valproate or any other antiepileptic. Then, the results of research on valproate's effects on male reproductive functions (hormonal levels and sperm parameters) will be presented, including the possible underlying mechanisms of these effects, the effect of the duration of valproate use, and whether or not the effects are reversible. In the second section we review the results of animal research, which could be beneficial in assessing the effects of valproate and epilepsy.

Despite a wide range of various drugs, a significant proportion of depressed bipolar patients fail to respond to the treatment strategies. Novel theraupetics for bipolar depression are needed. Preliminary studies suggest that pramipexole a dopaminergic agent that has been used in the treatment of Parkinson's disease and restless leg syndrome may have antidepressant properties in unipolar and bipolar depressed patients as well as neurotrophic properties. The optimal antidepressant daily dose of pramipexole is not known. It has been suggested to be used between 0.125 to 9.0 mg/day. In double blind placebo controlled bipolar depression treatment studies, the average daily dose of pramipexole was 1.7 mg. Manic switches have been reported with depressive subjects and with subjects without any mental disorders. We report two cases of treatment resistant bipolar depression. Despite different treatment strategies and treatment adherence, the patients did not give optimal response to the treatments and continue to experience depressive relapses. They have been treated with low dose (0.5-0.75 mg/day) pramipexole augmentation successfully. The severity and the duration of the depressive episodes were decreased. No serious adverse event has been reported with pramipexole during the maintenance treatment.

The genetic phenomenon of anticipation is a pattern of inheritance that includes earlier age at onset and increased severity of symptoms in succeeding generations, and is a feature of some neurodegenerative diseases. This phenomenon is suggested to occur in bipolar disorder (BP) as well.Anticipation in children with BP type 1 (s2) (n = 31) and their parents (s1) (n = 31) not-consecutive generations-was assessed by analyzing clinical characteristics and prognoses.Age at onset of BP type 1 in s2 (mean: 19.3 +/- 4.2 years) occurred earlier than in s1 (mean: 29.5 +/- 10.2 years) (u = 345, P0.001). There was a direct negative correlation between the s1 and s2 cases (r = -0.554, P0.001). The total number of episodes in s1 (13.9 +/- 12.3) was greater than in s2 (8.7 +/- 7), which had a higher frequency of episodes (0.6 +/- 0.3 and 1.5 +/- 1.2) (u = 357, P0.001). There was a direct correlation between total episodes and the frequency of manic episodes between s1 and s2 (r = 0.312, P0.001 and r = 0.365, P0.001, respectively). We observed that 72.7% of BP type 1 parents that had episodes with psychotic features had offspring that had episodes with psychotic features.Results of this study show that age at onset was earlier and the frequency of episodes was greater in s2 BP type 1 cases. In addition, episodes with psychotic features might be a marker for genetic anticipation.

Objectives: Cognitive dysfunctions in several domains were proposed to be trait markers of bipolar patients. The aim of this study was to evaluate the effect of previous psychotic features on neuropsychological measures, including sustained attention, in remitted bipolar patients. Methods: The study participants were 40 euthymic psychotic, 25 non-psychotic bipolar I patients and 30 healthy control subjects. Participants were assessed with a battery of neuropsychological tests targeting attention, executive functions, psychomotor speed, verbal learning and memory. Results: Euthymic psychotic bipolar patients performed worse than controls on most of the measures, after controlling for the confounding effects of education, age and residual symptoms. Non-psychotic patients were also impaired on tasks of attention, fluency and psychomotor speed. ‘Number of Wisconsin Card Sorting Test (WCST) categories’ achieved was the only measure on which psychotic patients performed significantly worse compared to non-psychotic patients. Differences among patient groups were not explained by illness severity measures. The duration of illness was related to slowness in psychomotor speed tasks. Verbal memory deficits may be related to serum lithium levels and age of onset of disease. Conclusions: Deficits in cognitive flexibility may be a candidate for being a trait marker of psychotic features among bipolar patients. However, verbal fluency, psychomotor speed and sustained attention deficits may be candidates for vulnerability indicators of bipolar disorder in general.

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. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

This paper will present a review of the literature on the relationship between the menstrual cycle and mood disorders.We performed a MEDLINE search of the Turkish and English language literature for the years 1955-2005 using the following terms: depression, bipolar disorder, premenstrual syndrome, premenstrual exacerbation, premenstrual dysphoric disorder, menstrual cycle, and suicide. Earlier reports had shown higher psychiatric admission during premenstrual period of the menstrual cycle and higher prevalence of suicide attempts during specific phase of the menstrual cycle.Women of reproductive age with mental disorders may experience a fluctuating course of illness over the menstrual cycle. Some data suggest that for a subset of women there is a relationship between phases of the menstrual cycle and increased vulnerability for an exacerbation of ongoing mood disorders (especially major depressive episode) or the development of a new episode. The question of whether the direction of mood shifts in the course of bipolar disorder is associated with specific cycle phase has been raised, albeit with limited and inconsistent data.There are a limited number of studies to elucidate these relationships and most of them lack prospective assessments, include the small number of patients and use unreliable methods of determining menstrual-cycle phases. Additionally, many reports do not specify whether the exacerbations reflect an aggravation of the underlying mood disorder or a new subset of symptoms that occur only during certain phases of the menstrual cycle. Further studies should provide more information about the contribution of premenstrual fluctuation or worsening to increased illness severity of mood disorder and treatment resistance.

Sustained attention deficits are proposed to be both state and trait indicators of bipolar disorder. The nature of these deficits and their association with medication and symptoms is not clear yet. The aim of this study was to investigate the impairments in various components of sustained attention task in euthymic and manic patients and was to investigate the relationship between the deficits in the manic state and medication effects. The performances of 37 manic patients, 34 euthymic patients with bipolar disorder and 34 control subjects on eight scores from Conners' CPT II, reflecting three different dimensions of sustained attention were compared. Similar to some recent findings, euthymic patients had decreased target sensitivity (omission errors) and response time inconsistency. The increased false responding (commission errors), perseveration and vigilance deficits were prominent in the manic patients. These state dependent impairments could not be explained by the impact of medication. In contrast, the exacerbation of seemingly trait-related impairments in the manic state can be at least partly explained by the impact of pharmacological therapy. (c) 2006 Elsevier Inc. All rights reserved.

The aim of the present study was to investigate the relationship between affective temperaments and clinical features in bipolar disorder. Testing the relationships between phenomenological features, course, severity of episodes, overall severity of illness and comorbid conditions would clarify the reliability and validity of affective temperamental descriptions.One hundred patients with bipolar I disorder were recruited from consecutive admissions and evaluated when euthymic. Affective temperaments were assessed with TEMPS-A Turkish version. Information about the characteristics of each patient's illness was obtained from three main sources; interview with patient (SCID-I), interview with at least one close relative and patient records. We compared the clinical features of patients with and without a specific affective temperament.Similar rates of cyclothymic, hyperthymic and irritable temperaments were observed in bipolar patients. Five important findings of the present study were (1) hyperthymic temperament was more frequent in males than females; (2) manic switches were more frequent among bipolar patients with hyperthymic temperament; (3) psychotic features were more common in the irritable temperament group; (4) comorbid conditions, (mostly alcohol use disorders) were more common among bipolar patients with cyclothymic temperament; and (5) bipolar patients with irritable temperament were more likely to have a manic episode at the onset of illness.These findings suggest that affective temperaments have significant clinical implications in bipolar disorder, beyond the genetic basis and predisposing factors. There were significant differences between patients with different affective temperaments in terms of gender, type of first episode, psychotic symptoms, switch and comorbidity.

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. Method: Forty-three euthymic patients with bipolar disorder and 30 healthy control subjects were involved in this study. ToM was assessed by the Eyes test and the Hinting task. Both groups were also evaluated with a comprehensive neuropsychological battery including tasks for basic emotion and face recognition. Results: The patient group was impaired on both of the ToM tasks. The patient group also showed impairment in many cognitive tasks including tasks related to sustained attention. Conclusion: Even euthymic patients with bipolar disorder may be impaired in advanced ToM tasks. Executive dysfunction and some other cognitives deficits such as basic emotion recognition may be at least partly responsible for this result.

The aim of this study is to investigate whether depressive (DT), hyper thymic (HT), cyclothymic (CT), irritable and anxious temperaments as identified by Turkish version of Temperament Evaluation of Memphis, Pisa, Paris and San Diego Auto questionnaire (TEMPS-A) are characteristic to depressive or bipolar disorder (BD) and to compare underlying affective temperamental differences.68 patients with recurrent major depression (MD-R), 50 patients with single episode major depressive disorder (MD-S), 84 euthymic bipolar patients and 100 healthy controls were included in the study and evaluated with TEMPS-A.There was a gender difference between patient groups. The females were more dominant in the MD-R group. The mean age of onset of illness of bipolar patients was lower than the depressive patients and the mean duration of illness of bipolar patients was longer than those of the MD-R patients. The prevalence of the rate of any dominant affective temperament was significantly higher in the MD-R group than other study groups. The prevalence rate and scores of DT were significantly higher both in MD-R and MD-S groups (25.0% and 12.0% respectively) than the BD group (2.4%) and control subjects (3.0%). The prevalence rate and scores of CT were higher among the patients groups than the controls. None of the subjects except BD patients had HT.With the limitations of the study, it is thus reasonable to speculate that affective temperament, to a degree, determine the nature and the existence of the mood disorders.

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.

Brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the etiology of schizophrenia. There is a line of evidence that disruption of neurotrophins could play a role in the etiology of schizophrenia, and antipsychotics show their effect by altering levels of neurotrophins. The aim of this study was to evaluate the effect of antipsychotics on serum BDNF levels and their relationship with the symptoms in patients with schizophrenia. Twenty-two schizophrenia patients were enrolled in the study. The control group consisted of 22 age- and sex-matched physically and mentally healthy volunteers (7 male, 15 female). Serum BDNF levels and the positive and negative syndrome scale (PANSS) scores were recorded at baseline and after 6 weeks of treatment. Serum BDNF levels were also recorded in the control group. Schizophrenia patients who failed to meet 30% improvement in PANSS score were excluded from the study. The baseline serum BDNF levels of schizophrenia patients were lower than those of controls (t = 4.56; df = 21; p0.001). There was no correlation between serum BDNF levels and PANSS scores in patients with schizophrenia (p0.05). Although PANSS (for positive symptoms p0.001, for negative symptoms p0.001) and general psychopathology (t = 20.9; df = 22; p0.001) scores improved significantly after 6 weeks of antipsychotic treatment; there was no change in BDNF levels in patients' serum (p0.05). Our results support the view that BDNF would be associated with schizophrenia. However, we could not conclude that treatment with antipsychotics alters serum BDNF levels in patients with schizophrenia.

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.

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.