A prospective study of the impact of smoking on outcomes in bipolar and schizoaffective disorder.

BACKGROUND: Tobacco smoking is more prevalent among people with mental illnesses, including bipolar disorder, than in the general community. Most data are cross-sectional, and there are no prospective trials examining the relationship of smoking to outcome in bipolar disorder. The impact of tobacco smoking on mental health outcomes was investigated in a 24-month, naturalistic, longitudinal study of 240 people with bipolar disorder or schizoaffective disorder. METHOD: Participants were interviewed and data recorded by trained study clinicians at 9 interviews during the study period. RESULTS: Comparisons were made between participants who smoked daily (n = 122) and the remaining study participants (n = 117). During the 24-month study period, the daily smokers had poorer scores on the Clinical Global Impressions-Depression (P = .034) and Clinical Global Impressions-Overall Bipolar (P = .026) scales and had lengthier stays in hospital (P = .012), compared with nonsmokers. LIMITATIONS: Smoking status was determined by self-report. Nicotine dependence was not measured. CONCLUSION: These findings suggest that smoking is associated with poorer mental health outcomes in bipolar and schizoaffective disorder.

The Bipolar Comprehensive Outcomes Study (BCOS): baseline findings of an Australian cohort study.

BACKGROUND: The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, observational study of participants with bipolar I or schizoaffective disorder examining clinical, functional, and economic outcomes associated with naturalistic treatment. METHODS: Participants prescribed mood stabilisers were assessed using various measures, including the Young Mania Rating Scale (YMRS), 21-item Hamilton Depression Rating scale (HAMD21), Clinical Global Impressions-Bipolar Version Severity of Illness scale (CGI-BP), and the EuroQol instrument (EQ-5D). RESULTS: 240 participants were recruited from two sites. On average, participants were 41.8+/-12.7 years of age (mean+/-SD), 58.3% were female, and 73.3% had a diagnosis of bipolar I disorder at study entry. The majority of participants were moderately ill, with an average CGI-BP Overall score of 3.8+/-1.3. Most participants had subthreshold mania and depression symptoms, indicated by HAMD21 Total 13.4+/-8.6, CGI-BP Depression 3.2+/-1.3, YMRS Total 8.2+/-8.5 and CGI-BP Mania 3.0+/-1.6 average scores. For bipolar participants, 94.6% of hospitalisations for psychiatric treatment in the past 3 months were single admissions (vs. 65.2% for schizoaffective participants, p=.002). Bipolar participants rated their overall health state higher (EQ-5D scores: 68.2+/-18.8 vs. 61.6+/-22.7, p=.023), had a higher mean weekly wage ($500-$999, 21.3% vs. 6.3%), lower unemployment (22.2% vs. 48.4%), and higher romantic relationship status (47.1% vs. 26.6%). LIMITATIONS: The observational design and small sample size may have limited the causal relationships and generalisability within the current findings. CONCLUSIONS: Participants were characterised by social and occupational dysfunction at entry, but schizoaffective participants appeared to be more severely affected. Effective treatment is required to address both clinical and functional impairment.

A study of the effects of lorazepam and dextromethorphan on the response to cortical 1 Hz repetitive transcranial magnetic stimulation.

We studied the effects of lorazepam and dextromethorphan on the responses to 1 Hz repetitive transcranial magnetic stimulation applied to the left human motor cortex. Lorazepam, dextromethorphan or placebo was administered to 45 normal controls in a double-blind fashion 2.5 h before the repetitive transcranial magnetic stimulation procedure. Motor cortical excitability was measured with single transcranial magnetic stimulation pulses before and after 15 min of 1 Hz repetitive transcranial magnetic stimulation applied at supra-threshold intensity. 1 Hz repetitive transcranial magnetic stimulation resulted in a decrease in motor cortical excitability in the placebo group but not in the groups taking lorazepam or dextromethorphan. These results suggest that cortical responses to 1 Hz repetitive transcranial magnetic stimulation are dependent on activity at both gamma-aminobutyric acid and N-methyl-D-asparate receptor systems.

A confirmatory factor analytic evaluation of the pentagonal PANSS model.

The positive and negative syndrome scale (PANSS) is widely used in psychiatric research. Reflecting this common use, considerable attention has been applied to the psychometric properties of this instrument. However, despite the publication of numerous studies and analyses, it remains uncertain how best data from the PANSS should be analysed to best model the symptoms of schizophrenia. A resolution to these concerns seemed to be offered following the publication in 1997 of a large multisite factor analysis that produced the 'pentagonal model', which has subsequently been included in the 2000 revision of the PANSS user manual. However, to date, an independent confirmatory analysis of this model has not yet been published. The aim of this study was to test this model in a new independent sample with confirmatory factor analysis (CFA). Independent confirmation of the fit of the model is required to ensure that its implementation is informed by confirmation of its psychometric properties. CFA was performed in a sample of 347 subjects with schizophrenia. The analysis found that the model had inadequate goodness of fit. The use of the pentagonal model has similar difficulties as earlier models and more research is required to ascertain the optimal method for measuring symptom dimensions in research and clinical settings.

A longitudinal study of patient- and observer-rated quality of life in schizophrenia.

Patient-rated life satisfaction and observer-rated quality of life (ORQOL) appear to have different determinants in patients with schizophrenia, although most studies conducted to date have used cross-sectional methods or related clinical dimensions at one time point with quality of life (QOL) measured at another. The aim of this study was to investigate the relationship between changes in patient-rated QOL (PRQOL) and ORQOL over time and changes in clinical variables. Two hundred and thirty-one patients taking part in the Schizophrenia Care Assessment Program (SCAP) study at Dandenong in Australia were included in this analysis. Subjective ratings of several domains of social functioning and life satisfaction were taken from the SCAP instrument and comparisons made with data from the QOL Scale rated by research staff, as well as several psychopathology measures. Changes in these scores over 1 year were correlated to investigate relationships between measures. Weak correlations were seen between changes in PRQOL and ORQOL domains. Patient-rated domains related most closely to depressive symptoms (Montgomery-Asberg Depression Rating Scale scores) whereas observer-rated domains related to both negative symptoms and depressive symptoms. Positive psychotic symptoms had little effect on either domain. Longitudinal data appear to confirm that PRQOL and ORQOL are not closely related and may have differing determinants in patients with schizophrenia. They should be considered as separate and complementary outcome variables and utilized accordingly.

The sick role, illness cognitions and outcomes in bipolar disorder.

OBJECTIVE: In some individuals, recovery from episodes of mental illness may be impeded by maladaptive illness beliefs and behaviors. For individuals with chronic illness, acceptance of its presence and consequences is necessary to seek appropriate treatment, adjust their lifestyle, and adhere to recommended management strategies. Some have difficulty adjusting out of the sick role or develop a degree of illness investment. The Illness Cognitions Scale (ICS) is a 17-item validated scale that measures cognitive factors associated with the sick role. We conducted analyses to test the hypothesis that there may be an association between illness cognitions and clinical and functional measures. METHODS: The ICS was administered to 89 participants at the final study visit of a 24-month observational study involving patients with bipolar I disorder or schizoaffective disorder. RESULTS: Higher scores on the ICS were correlated with more severe depression (p<0.0001), worse general health (p=0.0002), worse functioning (p=0.0001), and worse scores in psychosocial measures including the State Hope Scale (p=0.0082), the Social Provisions Scale (p=0.0054) and the Rosenberg Self-Esteem Scale (p=0.0025). CONCLUSIONS: Illness cognitions and behavior may be a neglected factor that could influence treatment outcomes in bipolar disorder. The ICS might be useful for identifying individuals whose recovery may be facilitated by targeted psychological intervention that addresses these factors.

Psychometric properties of a scale to measure investment in the sick role: the Illness Cognitions Scale.

RATIONALE, AIMS AND OBJECTIVES: A person's beliefs about their illness may contribute to recovery and prognosis. Some degree of acceptance of illness and its impact is necessary to integrate the presence of a chronic disorder into one's lifestyle and adhere to necessary components of illness management; however, some individuals can become 'stuck' and have difficulty adjusting out of the sick role. Inventories exist to measure illness cognitions, attitudes and behaviours as they relate to hypochondria and psychosomatic illness, but there is no extant measure of sick role inertia. We describe the psychometric properties of a new scale, the Illness Cognitions Scale (ICS), a metric of investment in the sick role. METHODS: The ICS was administered to 97 individuals with bipolar or schizoaffective disorder, and the psychometric properties of the scale measured. Dimensionality was assessed using Principal Components Analysis with Oblimin rotation. RESULTS: The scale has a strong internal consistency, with a Cronbach's alpha of 0.858. Results of a factor analysis suggested the presence of one main factor, with three other smaller, related sub-factors, capturing aspects of maladaptive illness beliefs. CONCLUSION: The ICS is a 17-item, internally validated scale measuring difficulty adjusting out of the sick role. The scale predominantly measures a single construct. Further research on external validity of the ICS is required as well as determination of the clinical significance and patient acceptability of the scale.

The impact of age at onset of bipolar I disorder on functioning and clinical presentation.

OBJECTIVES: Recent studies have proposed the existence of three distinct subgroups of bipolar 1 disorder based on age at onset (AAO). The present study aims to investigate potential clinical and functional differences between these subgroups in an Australian sample. METHODS: Participants (n = 239) were enrolled in the Bipolar Comprehensive Outcomes Study (BCOS), a 2-year longitudinal, observational, cross-sectional study. Assessment measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD21), Clinical Global Impressions Scale (CGI-BP), SF-36, SLICE/Life Scale, and the EuroQol (EQ-5D). Participants were also asked about their age at the first major affective episode. RESULTS: Three AAO groups were compared: early (AAO < 20, mean = 15.5 ± 2.72; 44.4% of the participants); intermediate (AAO 20-39, mean = 26.1 ± 4.8; 48.14% of the participants) and late (AAO > 40, mean = 50.6 ± 9.04; 7.4% of the participants). Higher rates of depression, suicidal ideation and binge drinking were reported by the early AAO group. This group also reported poorer quality of life in a number of areas. The early AAO group had a predominant depressive initial polarity and the intermediate group had a manic predominance. CONCLUSION: Early AAO is associated with an adverse outcome.

A functional magnetic resonance imaging study of the effects of low frequency right prefrontal transcranial magnetic stimulation in depression.

The study aimed to explore the biological effects of low-frequency repetitive transcranial magnetic stimulation (LFR-TMS) treatment applied to the right prefrontal cortex, comparing this with the effects of high-frequency left-sided (HFL-TMS) in patients with treatment-resistant depression. Twenty-six patients with treatment-resistant depression were randomized to receive either daily LFR-TMS or HFL-TMS treatment for 3 weeks and underwent functional magnetic resonance imaging during a planning task before and after treatment. Patients responded clinically to both forms of treatment with no difference in the degree of response (F1,24 = 0.65;P > 0.05). Low-frequency repetitive transcranial magnetic stimulation resulted in no overall change in task-related activation. However, responders to LFR-TMS demonstrated a bilateral decrease in activity in middle frontal gyrus. In contrast, HFL-TMS produced an increase in activation in left precuneus with responders showing increased activation in several additional regions. Response to LFR-TMS is associated with a bilateral reduction in frontal activation that does not seem to be a nonspecific effect of treatment and differs from the response to HFL-TMS.

Australian Schizophrenia Care and Assessment Programme: real-world schizophrenia: economics.

OBJECTIVE: The treatment of patients with schizophrenia consumes a considerable proportion of health service budgets, yet there have been few attempts to prospectively analyse the costs associated with this condition. Amid the current debate about where to invest scarce treatment resources to achieve optimal outcomes, real-world studies, such as the Schizophrenia Care and Assessment Programme (SCAP) contrast with hypothetically based models and provide comprehensive and broad-ranging data. METHOD: Direct health-care costs were prospectively studied in a cohort of 347 patients with schizophrenia in Dandenong, Australia over 3 years. Indirect costs were estimated from patient self-reported information. RESULTS: The average annual societal cost was AU $32,160 per participant in the first year of the study, AU $27,190 in the second year and AU $29,181 in the third year. Indirect costs accounted for 46% of the total costs in the first year, 52% of the total costs in the second year and 50% of the total costs in the third year. The most expensive component of treatment was inpatient hospital care, which accounted for 42%, 34% and 36% of the total costs in the first, second and third year, respectively. CONCLUSIONS: Considerable resources are required for the provision of treatment for patients with schizophrenia. But for the majority of people in this cohort, funding assertive treatment programmes and measures to reduce hospitalization was accompanied with enhanced functioning and quality of life, as well as a reduction in long-term societal and government costs. The distribution of health-care costs is highly skewed, with a relatively small proportion of patients (39%) consuming the majority of resources (80%). Improving rates of employment for this patient group could hold substantial benefits in reducing the overall economic and personal impact of this disorder.

Australian Schizophrenia Care and Assessment Programme: real-world schizophrenia: outcomes.

OBJECTIVE: It has been increasingly recognized that there is need to assess patient outcomes in schizophrenia across a broad range of dimensions. But few studies have attempted to do this in clinical populations and no systematic study has broadly assessed outcomes in schizophrenia in Australia using a longitudinal design. Thus, a real-world study, the Schizophrenia Care and Assessment Programme (SCAP), was structured to collect comprehensive information over time to inform policy debate and extend current knowledge about the course of schizophrenia in an Australian context. METHODS: A cohort of 347 patients with schizophrenia was followed up over 3 years. Clinical outcomes, occupational and psychosocial functioning and quality of life were assessed at 6 monthly intervals, and resource utilization and costing data were collected continuously from internal and external databases as well as from participants directly. RESULTS: The participants as a group experienced an overall decline in positive and negative symptoms of schizophrenia, a reduction in general psychopathology and a reduction in severity of depression. There was an improvement in functioning, a reduction in mental health-related disability and an improvement in patient- and observer-rated quality of life. Change of severity within the variously assessed domains over time appeared to be relatively independent. CONCLUSIONS: In the present sample of schizophrenia patients treatment was associated with positive health outcomes; but outcomes across assessment domains did not closely correlate across time. The scrutiny of a broad range of patient outcomes will assist with the assessment of new treatment modalities and with service planning.

Naturalistic study of the use of transcranial magnetic stimulation in the treatment of depressive relapse.

BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression has been assessed in a number of acute treatment trials during the last 10 years. Little is known about the long-term impact of the treatment on the disorder and its effectiveness when applied for repeated relapses of depression over time. METHOD: Nineteen patients who had previously responded to rTMS in clinical trials received treatment with rTMS for a total of 30 episodes of depressive relapse. RESULTS: Approximately 10 months elapsed between treatment episodes. The majority of patients achieved a significant improvement in each treatment course with significant improvements achieved in patients treated with both low-frequency right-sided rTMS and high-frequency left-sided rTMS. CONCLUSIONS: The study suggests that rTMS may have value in the treatment of episodes of depressive relapse with little reduction in efficacy over time.

The relationship of changes in leptin, neuropeptide Y and reproductive hormones to antipsychotic induced weight gain.

OBJECTIVES: Weight gain is an important side effect of antipsychotic (AP) treatment. Weight is regulated by multiple systems, including leptin, neuropeptide Y (NPY) and gonadal steroids. The aim was to investigate whether AP-induced weight gain was related to leptin and NPY abnormalities and whether these were associated with a disruption of gonadal steroid production. METHODS: Twenty two female patients with schizophrenia receiving standard AP treatment were studied over a 3-month period. Plasma leptin, NPY, gonadal steroids and their regulators were measured along with weight and BMI. RESULTS: Weight, leptin and testosterone levels increased over time. There were significant relationships between a change in oestrogen levels and both a change in NPY levels and a change in BMI. Change in BMI, weight and leptin all correlated strongly with a change in the testosterone/luteinizing hormone ratio. CONCLUSIONS: AP treatment results in increase in weight over time and this increase is accompanied by increased leptin levels. AP-induced weight gain is also associated with disruption of the hypothalamic-pituitary-gonadal axis. Altered regulation of NPY, either through abnormal leptin control or serotonin blockade, is a possible explanation for the effects of AP medication on both weight and gonadal steroid levels.