A. de Castella

Estrogen - a potential treatment for schizophrenia.

Estrogen has been shown in animal studies to modulate both the dopamine and serotonin neurotransmitter systems - the main neurotransmitters implicated in the pathogenesis of schizophrenia. A double blind, 28 day, placebo-controlled study was conducted with three groups of women of child-bearing age (N=12 in each group) who received standardized antipsychotic medication plus 50mcg transdermal estradiol or 100mcg transdermal estradiol or transdermal placebo. Analyses show that women receiving 100mcg of estradiol made greater improvements in the symptoms of schizophrenia than both the 50mcg estradiol and placebo groups. Women receiving 50mcg estradiol had more improvement in their symptoms compared with the placebo group. The 100mcg estradiol group had significantly lower mean lutenizing hormone (LH) and higher mean prolactin levels across the study period compared with both the 50mcg and placebo groups. The addition of 100mcg adjunctive transdermal estrogen significantly enhanced the treatment of acute, severe psychotic symptoms in women with schizophrenia. The differential response of adding 50mcg versus 100mcg estradiol on the types of symptom affected may be related to the estrogen effect on LH and prolactin. The positive impact of estrogen treatment on psychotic symptoms by a direct effect on dopamine and serotonin systems or via an indirect prolactin-mediated effect may be very useful in the overall treatment of women with schizophrenia.

Subject and observer-rated quality of life in schizophrenia

Objective: We aimed to explore the relationship between objectively rated quality of life and subjective measures of social functioning and life satisfaction.

A clinical trial of adjunctive oestrogen treatment in women with schizophrenia.

SummaryA double-blind, 28-day, placebo-controlled study was conducted with three groups of women of child-bearing age (N = 12 in each group) who received standardised antipsychotic medication plus a) 50 μg transdermal estradiol or b) 100 μg transdermal estradiol or c) transdermal placebo. Preliminary analyses show that women receiving 100 μg of estradiol made greater improvements in the symptoms of schizophrenia than either the 50 μg estradiol or placebo groups. The addition of 100 μg adjunctive transdermal oestrogen significantly enhanced treatment responsivity of acute, severe psychotic symptoms in women with schizophrenia. The positive impact of oestrogen treatment on psychotic symptoms via a multiplicity of possible actions (see accompanying articles in this issue) may prove clinically useful in the overall treatment of women with schizophrenia.

Victimization of patients with schizophrenia and related disorders

BACKGROUND Previous research has predominately focused on patients with mental illness as the instigators, rather than the victims, of violence and criminal activity. However, patients with schizophrenia appear to experience a higher degree of victimization compared to general community samples. We aimed to establish the 1-month prevalence of violent and non-violent victimization in a sample of patients with schizophrenia spectrum disorders and to investigate the determinants of victimization. METHOD Reports of violent and non-violent victimization were recorded in 348 patients in Dandenong, an outer metropolitan suburb of Melbourne, Australia along with the subjective perception of patients as to their degree of protection from being robbed or attacked. Patients reporting victimization were compared with those who did not, across a range of clinical and psychosocial variables. RESULTS 11.2% of the sample reported being the victim of non-violent crime and 4.3% the victim of violent crime in the 1-month period. 23.2% reported dissatisfaction with their protection against being attacked or robbed. The major determinant of victimization was the lack of any meaningful daily activity. CONCLUSIONS Patients with schizophrenia spectrum disorders are at increased risk of victimization, both of the violent and non-violent type. Further research is required to understand the pathways through which victimization occurs and to understand whether psychosocial interventions can reduce victimization in this patient population.

A prospective study of the impact of subthreshold mixed states on the 24-month clinical outcomes of bipolar I disorder or schizoaffective disorder.

OBJECTIVES The clinical significance of subthreshold mixed states is unclear. This study investigated the clinical outcomes in participants with bipolar I disorder or schizoaffective disorder, using the Cassidy and Benazzi criteria for manic and depressive mixed states, respectively. METHODS Participants (N=239) in a prospective observational study of treatment and outcomes in bipolar I or schizoaffective disorder, bipolar type, were grouped based on study entry clinical presentation as having pure depression (n=63) if they satisfied DSM-IV-TR criteria for a Major Depressive Episode (MDE), depressive mixed state if they also had at least three concurrent hypomanic symptoms (n=33), or not depressed (n=143) if they did not satisfy the criteria for MDE. Participants were similarly grouped as having pure mania (n=3) if they satisfied DSM-IV criteria for a Manic Episode, manic mixed state if they also had at least two concurrent depressive symptoms (n=33), or not manic (n=203). Clinical data were collected by interview every 3 months over a 24-month period. RESULTS Measures of quality of life, mental and physical health over the 24-month period were significantly worse for participants who were classified as having mixed states at study entry on most outcome measures compared to participants who were not in an illness episode at study entry. A depressive mixed state was predictive of greater manic symptomatology over the 24 months compared to participants with pure depression. CONCLUSION In participants with a current episode of mood disorder, the presence of subthreshold symptoms of opposite polarity was associated with poorer clinical outcomes over a 24-month period.

Quality of life in bipolar and schizoaffective disorder — A naturalistic approach

PURPOSE The aim of this study was to evaluate the health-related quality of life (HRQoL) in bipolar type I (BD I) and schizoaffective (SQA) patients during a 2-year period in a naturalistic study. METHODS This study was based on the data generated by the Bipolar Comprehensive Outcome Study, a prospective, non-interventional, observational study of participants with BD I and SQA disorder. Mixed-Model Repeated Measures Analysis was used to analyze changes in the SF-36 and EQ-5D. RESULTS Participants exhibited low health status at baseline with SF-36 mean scores of 46.7±10.5 and 36.9±12.9 (best imaginable health=100, normal population≈50) for physical and mental components, respectively. No significant differences were found between the ratings of the BD I and SQA patients on HRQoL. The SF-36 SMC improved significantly over 24 months although SPC scores remained consistent across the study. On the whole, the lowest SMC score was observed among the depressed patients (38.20), followed by the patients with a mixed state (39.01) and the manic patients (39.83). LIMITATIONS The observational design may have limited the causal relationships and the generalizability within the current findings. CONCLUSIONS HRQoL was significantly impaired in all stages of BD and SQA when compared to the general population. The impairment of HRQoL was most pronounced in the depressed state, followed by the mixed state and then the manic state. The euthymic patients showed the least impairment. In addition, patients showed a global improvement in their mental health satisfaction over the 2 years follow up period.

Tamoxifen - a potential treatment for women in the manic phase of bipolar affective disorder?

Background: Bipolar affective disorder (BPAD) is an illness with high morbidity and mortality. Lithium and other anticonvulsant drugs are the main treatments for BPAD, despite little being known about their mechanisms of action. Recent attempts to elucidate the biochemical actions of these drugs have focused on the protein kinase C (PKC) pathways. Another PKC inhibitor hypothesized to be effective in the treatment of mania is tamoxifen, a synthetic nonsteroidal antiestrogen. The aim of the current study was to test and compare the effectiveness of two adjunctive antiestrogen agents (tamoxifen or progesterone) in the treatment of acute mania. Methods: A 28-day, three-arm (40 mg/day oral tamoxifen or 20 mg/day oral progesterone or oral placebo), double-blind, placebo-controlled, adjunctive study of 34 women with mania was conducted. All patients also received a mood stabilizer as the baseline treatment. Manic symptoms and psychopathology were measured weekly using the CARS-M and Positive and Negative Syndrome Scale rating scales together with estrogen, progesterone and gonadotropin levels. Cognitive functioning (RBANS) was assessed in a subsample of fi ve participants at baseline and repeated on day 28. Results: Results indicated a decline in the symptoms of mania and psychopathology in the tamoxifen group, and to a lesser extent in the progesterone and control groups. The tamoxifen group also had signifi cant changes in estrogen levels, as well as correlations between estrogen and mania ratings. Conclusion: The results suggest that tamoxifen may be a useful adjunct in the treatment of acute manic symptoms in women with BPAD.

A prospective study of the impact of subthreshold mixed states on the 24-month clinical outcomes of bipolar I disorder or schizoaffective disorder

Introduction: Comorbid psychiatric diagnoses such as panic disorder and drug and alcohol abuse are common in both major depressive disorder (MDD) and bipolar disorder (BD). Although screening instruments such as the Hypomania Checklist (HCL-32) may be useful in distinguishing between bipolar and unipolar patients, very little work has assessed whether comorbidities, for example, substance abuse, may be related to ratings of hypomanic symptoms on such instruments. In this study we assess whether a lifetime diagnosis of comorbid panic disorder, drug abuse, alcohol abuse or alcohol dependence in patients with MDD is associated with increased ratings of hypomanic symptoms on the HCL-32. Methods: 50 patients with MDD (according to DSM-IV) recruited from out-patient psychiatric services were assessed for a range of diagnoses according to the Mini International Neuropsychiatric Interview (MINI). Subjects also completed a detailed structured clinical assessment and the HCL-32 questionnaire. A number of previous reports have found that a score of 14 or more on the HCL-32 is an optimal threshold for the correct identification of bipolar disorder (with a sensitivity of 80% and specificity 51%) so this threshold was applied to our sample of MDD patients. Two groups were identified according to whether they scored above or below 14 on the HCL-32 and were compared on rates on lifetime comorbid diagnosis of panic disorder, drug abuse, alcohol abuse and alcohol dependence. Results: 27 out of 50 MDD patients (54%) scored above the threshold of 14 or more on the HCL-32. There were no significant differences between these subjects and subjects not meeting the threshold on rates of comorbid panic disorder (48.1% versus 47.8%; OR = 1.01, 95%CI 0.60–1.68), drug abuse (7.4% versus 4.3%; OR = 1.25, 95%CI 0.54–2.92) or alcohol abuse (37.0% versus 21.7%; OR = 1.37, 95%CI 0.84–2.25). However, subjects scoring above the threshold had significantly higher rates of comorbid alcohol dependence (18.5% versus 0%; OR = 2.05, 95%CI 1.52–2.76). Discussion: 54% of MDD patients in this sample scored above the threshold of 14 on the HCL-32, suggestive of a bipolar diagnosis. Cormorbid alcohol dependence was significantly associated with scoring above the threshold. In fact, all of the MDD patients in this sample who also had a lifetime history of alcohol dependence scored 14 or more on the HCL-32. Future studies involving screening measures for bipolar disorder, particularly the HCL-32, should carefully consider the role played by comorbidities such as alcohol dependence.

Early age of onset is associated with high rates of anxiety comorbiditity in bipolar I and schizoaffective disorders

Abstract from the XXVI CINP Congress, Munich, Germany, 13-17 July 2008Abstract from the XXVI CINP Congress, Munich, 13-17 July 2008

Time course of illness prior to a diagnosis of bipolar disorder or schizoaffective disorder

248 bipolar disorder are because of a breakdown in communication between neurons and glia, which occurs most potently at the tripartite synapse. Our published data and recent data from our microarray study have now shown that there is a decrease in the expression of specifi c apolipoprotein E receptors in the CNS of subjects with schizophrenia, further supporting our hypotheses of altered neuronal glia communication in psychiatric disease and will be summarized in this presentation.