Search

Background Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek information. Methods A 39 question, paper-based, anonymous survey, translated into 12 languages, was completed by 1222 patients in 17 countries as a convenience sample between March 2014 and January 2016. All patients had a diagnosis of bipolar disorder from a psychiatrist. Data were analyzed using descriptive statistics and generalized estimating equations to account for correlated data. Results 976 (81 % of 1212 valid responses) of the patients used the Internet, and of these 750 (77 %) looked for information on bipolar disorder. When looking online for information, 89 % used a computer rather than a smartphone, and 79 % started with a general search engine. The primary reasons for searching were drug side effects (51 %), to learn anonymously (43 %), and for help coping (39 %). About 1/3 rated their search skills as expert, and 2/3 as basic or intermediate. 59 % preferred a website on mental illness and 33 % preferred Wikipedia. Only 20 % read or participated in online support groups. Most patients (62 %) searched a couple times a year. Online information seeking helped about 2/3 to cope (41 % of the entire sample). About 2/3 did not discuss Internet findings with their doctor. Conclusion Online information seeking helps many patients to cope although alternative information sources remain important. Most patients do not discuss Internet findings with their doctor, and concern remains about the quality of online information especially related to prescription drugs. Patients may not rate search skills accurately, and may not understand limitations of online privacy. More patient education about online information searching is needed and physicians should recommend a few high quality websites. Electronic supplementary material The online version of this article (doi:10.1186/s40345-016-0058-0) contains supplementary material, which is available to authorized users.

In many individuals with major neuropsychiatric disorders including depression, bipolar disorder and schizophrenia, their disease characteristics are consistent with a neuroprogressive illness. This includes progressive structural brain changes, cognitive and functional decline, poorer treatment response and an increasing vulnerability to relapse with chronicity. The underlying molecular mechanisms of neuroprogression are thought to include neurotrophins and regulation of neurogenesis and apoptosis, neurotransmitters, inflammatory, oxidative and nitrosative stress, mitochondrial dysfunction, cortisol and the hypothalamic-pituitary-adrenal axis, and epigenetic influences. Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. This paper reviews the potential of the most promising of these agents, including lithium and other known psychotropics, aspirin, minocycline, statins, N-acetylcysteine, leptin and melatonin. These agents are putative neuroprotective agents for schizophrenia and mood disorders.

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 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.

BackgroundCognitive deficits are predictors of functional outcome in patients with psychosis. While conventional antipsychotics are relatively effective on positive symptoms, their impact on negative and cognitive symptoms is limited. Recent studies have established a link between oxidative stress and neurocognitive deficits in psychosis. N-acetylcysteine (NAC), a glutathione precursor with glutamatergic properties, has shown efficacy on negative symptoms and functioning in patients with schizophrenia and bipolar disorder, respectively. However, there are few evidence-based approaches for managing cognitive impairment in psychosis. The present study aims to examine the cognitive effects of adjunctive NAC treatment in a pooled subgroup of participants with psychosis who completed neuropsychological assessment in two trials of both schizophrenia and bipolar disorder.MethodA sample of 58 participants were randomized in a double fashion to receive 2 g/day of NAC (n = 27) or placebo (n = 31) for 24 weeks. Attention, working memory and executive function domains were assessed. Differences between cognitive performance at baseline and end point were examined using Wilcoxon's test. The Mann–Whitney test was used to examine the differences between the NAC and placebo groups at the end point.ResultsParticipants treated with NAC had significantly higher working memory performance at week 24 compared with placebo (U = 98.5, p = 0.027).ConclusionsNAC may have an impact on cognitive performance in psychosis, as a significant improvement in working memory was observed in the NAC-treated group compared with placebo; however, these preliminary data require replication. Glutamatergic compounds such as NAC may constitute a step towards the development of useful therapies for cognitive impairment in psychosis.

Inflammatory processes and neural-immune interactions have been implicated in the pathogenesis of psychiatric conditions, but studies in bipolar disorder are inconclusive so far. We aimed to investigate whether peripheral concentrations of C-reactive protein (CRP), an acute-phase response protein of inflammatory activity, are increased in bipolar disorder across the mood spectrum.In this systematic review and meta-analysis, we searched MEDLINE, the Cochrane Library, Scopus, and Web of Knowledge from database inception to Aug 14, 2016, for studies that measured serum and plasma CRP concentrations in adult patients with bipolar disorder (as defined by DSM-IV-TR) and healthy controls. We extracted data from published reports. We did three between-group meta-analyses comparing CRP concentrations in patients in mania, depression, or euthymia, with those in healthy controls (cross-sectional studies), and two within-group meta-analyses comparing changes in CRP concentrations before and after treatment of an index manic or depressive episode (longitudinal studies). We used Hedges' adjusted g to calculate effect sizes and pooled results using random-effect models. We also did meta-regression analyses by mood state to investigate possible moderators of CRP concentrations.We identified 27 studies representing 2161 patients with bipolar disorder and 81 932 healthy controls. Compared with healthy individuals, CRP concentrations were moderately increased in people with bipolar disorder during depression (g 0·67, 95% CI 0·23 to 1·11; p=0·003) and euthymia (0·65, 0·40 to 0·90; p0·0001) and more substantially increased during mania (0·87, 0·58 to 1·15; p0·0001). The extent of the increases in CRP concentrations in mania and depression was not related to symptom severity (p=0·256 for mania and p=0·626 for depression). CRP concentrations were moderately decreased after resolution of an index manic episode (-0·36, -0·66 to -0·05; p=0·022) and slightly decreased after resolution of an index depressive episode (-0·18, -0·30 to -0·07; p=0·002).CRP concentrations are increased in bipolar disorder regardless of mood state, but are higher during mania than in depression and euthymia, suggesting an increased inflammatory burden in mania.None.

Schizophrenia risk has often been conceptualized using a model which requires two hits in order to generate the clinical phenotype-the first as an early priming in a genetically predisposed individual and the second a likely environmental insult. The aim of this paper was to review the literature and reformulate this binary risk-vulnerability model. We sourced the data for this narrative review from the electronic database PUBMED. Our search terms were not limited by language or date of publication. The development of schizophrenia may be driven by genetic vulnerability interacting with multiple vulnerability factors including lowered prenatal vitamin D exposure, viral infections, smoking intelligence quotient, social cognition cannabis use, social defeat, nutrition and childhood trauma. It is likely that these genetic risks, environmental risks and vulnerability factors are cumulative and interactive with each other and with critical periods of neurodevelopmental vulnerability. The development of schizophrenia is likely to be more complex and nuanced than the binary two hit model originally proposed nearly thirty years ago. Risk appears influenced by a more complex process involving genetic risk interfacing with multiple potentially interacting hits and vulnerability factors occurring at key periods of neurodevelopmental activity, which culminate in the expression of disease state. These risks are common across a number of neuropsychiatric and medical disorders, which might inform common preventive and intervention strategies across non-communicable disorders.

Objective:This study aimed to test the validity of the 21-item Depression Anxiety Stress Scales (DASS-21) as a routine clinical outcome measure in the private in-patient setting. We hypothesized that it would be a suitable routine outcome instrument in this setting.Method:All in-patients treated at a private psychiatric hospital over a period of 24 months were included in the study. Data were collected on demographics, service utilization, diagnosis and a set of four routine measures both at admission and discharge. These measures consisted of the Clinical Global Impressions (CGI) scales, Health of the Nation Outcome Scales (HoNOS), the Mental Health Questionnaire (MHQ-14) and DASS-21. The results of these measures were compared.Results:Of 786 admissions in total, the number of fully completed (ie paired admission and discharge) data sets for the DASS-21 depression, anxiety and stress subscales were 337, 328 and 347, respectively. All subscales showed statistically significant reductions in mean scores from admission to discharge (P< 0.001) and were significantly correlated with all MHQ-14 subscales and significantly related to CGI scale categories. The total DASS-21 and total HoNOS scores were also significantly correlated.Conclusions:The findings from the present study support the validity of DASS-21 as a routine clinical outcome measure in the private in-patient setting.

BACKGROUND: In epidemiological studies, statins appear to benefit mood, and there are now some randomized controlled trials examining the efficacy of statins. However, the role of statins in depression remains uncertain. Thus the aim of this paper was to assess the effect of statins on depressive symptoms by performing a meta-analysis of all double-blind, randomized, placebo controlled clinical trials (RCT) conducted in subjects with depression. METHODS: A systematic search was executed using PubMed and ClinicalTrials.gov in November 30th, 2015 for all double-blind, RCT of statins versus placebo in persons with depressive symptoms. Sixty-seven potential articles were identified through search of electronic databases, of those three met inclusion criteria and were included in the meta-analysis. The outcome measure was change in Hamilton Depression Rating Scale (HDRS) scores associated with statin use. A meta-analysis was conducted and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. GRADE was used to assess study quality. RESULTS: The three articles included provided data on 165 participants with moderate to severe depression. Of these, 82 were randomized to statins as an adjuvant therapy to antidepressant treatment (i.e., citalopram or fluoxetine) and 83 to the placebo arm. All studies were double-blind RCTs, with a follow-up of 6-12 weeks. The statin agents evaluated were lovastatin, atorvastatin, and simvastatin. When compared to placebo, statins, as add-on to treatment as usual, largely improved depressive symptoms as assessed by the HDRS (SMD=-0.73, 95% IC -1.04 to -0.42, p

Additional file 1. Questionnaire: Information seeking in bipolar disorder.

Depression is usually the predominant phase in bipolar disorder, causes the most psychosocial disability, and carries significant risk of suicide. The management of bipolar depression is relatively under-studied and poses significant challenges for clinicians. There is substantial dissent regarding optimal pharmacotherapy for bipolar depression, particularly around the role of antidepressants. Individual and combination pharmacotherapy should be integrated into a personalised psychosocial and lifestyle package of interventions that considers the person's clinical profile and preferences. The relative lack of evidence relating to optimal strategies, especially when bipolar depression occurs with common comorbidities, poses challenges and requires further research. A flexible approach and evidence-based combinations of treatments can provide effective strategies for improving quality of life and reducing morbidity and mortality.

Objective The objective of this study was to investigate the association between pain and mood and anxiety disorders, as well as psychological symptoms, in a population-based sample of women. Methods This study examined the data collected from 1067 women aged 20–93 years (median 51 years) participating in the Geelong Osteoporosis Study. Mood and anxiety disorders were diagnosed using a clinical interview (SCID-I/NP) and psychological symptomatology was assessed using the General Health Questionnaire. Pain was determined using a Visual Analogue Scale (0–100 mm) and deemed present if score ≥ 40 mm. Results Current mood disorders were associated with an increased likelihood of overall (OR = 3.2, 95% CI 2.0–5.1), headache (OR = 2.8, 95% CI 1.6–4.8), back (OR = 4.0, 95% CI 2.5–6.5) and shoulder pain (OR = 2.2, 95% CI 1.2–4.2). In those with current mood disorders, the pain interfered with daily activities (OR = 3.2, 95% CI 1.9–5.5) and was present most of their time awake (OR = 2.5, 95% CI 1.5–4.1). This pattern was similarly observed for those with past mood disorders. Current anxiety disorders were associated with an increased likelihood for overall (OR = 2.2, 95% CI 1.4–3.6), headache (OR = 2.2, 95% CI 1.3–4.0), back (OR = 1.8, 95% CI 1.1–3.0) and shoulder pain (OR = 1.9, 95% CI 1.0–3.5, p = .05). In those with current anxiety disorders, the pain interfered with daily activities (OR = 2.4, 95% CI 1.4–4.1) and was present most of their time awake (OR = 1.9, 95% CI 1.2–3.2). There was no association between pain and past anxiety. Psychological symptomatology was associated with pain at each site (all p Conclusions This study is consistent with studies utilising clinical samples in reporting that mood and anxiety disorders, as well as psychological symptoms, are associated with higher levels of perceived pain.

Bipolar disorder may emerge during several decades of life. Studies from many countries have reported three peaks in the distribution of the age of onset, occurring at about ages 17, 26, and over 40 (1–5). Differences in the distribution of the age of onset were also reported among countries (6), although only limited data are available from some regions of the world. Patients living in North America generally have a younger age of onset than those living in European countries (6–8). In many studies conducted in the USA, about 60% of patients experience the onset of bipolar disorder before the age of 19 (6, 9–12), as compared to a third or less for many studies in European countries (1, 5, 6, 13–16). Diverse factors may contribute to this variation in the age of onset. There is agreement among researchers that both a patient’s genetic makeup and methodological issues in defining onset contribute to the reported differences, and that the variability in the age of onset reflects the genetic heterogeneity underlying bipolar disorder (1–3, 17). A positive family history is one of the strongest predictors of early onset (18). However, in addition to the genetic component, both the broad variability in the age of onset, and the onset peaks occurring after puberty (19) suggest that non-genetic factors may have considerable influence (20). There is limited understanding of how non-genetic factors, such as socioeconomic status and the physical environment, may impact the expression of bipolar disorder (21). In a recent study, a linear association was detected between the age of onset of schizophrenia and latitude, with a much younger onset occurring in individuals living closer to the equator (22). Latitude is often used as a proxy measure of sunlight, such as in studies of seasonal and geographical variation in affective disorders and suicide (23–28). However, more direct measures of the amount of electromagnetic energy striking the surface of the earth are now available, such as solar insolation (29). Sunlight is the primary synchronizer of circadian rhythmicity in most animals, including humans (30), and disruptions in circadian function may contribute to the pathophysiology of bipolar disorder (31). The purpose of this study was to investigate if the age of onset of bipolar I (BP-I) disorder was associated with sunlight at the location of onset, as measured by solar insolation.

BackgroundBipolar disorder (BD) is a psychiatric disorder associated with increased rates of obesity and inflammation. Leptin is an adipokine that is mainly produced by the white adipose tissue in response to insulin. It stimulates the immune system, increasing the production of pro-inflammatory cytokines. There is currently uncertainty regarding possible alterations in peripheral leptin levels across the mood states in BD.MethodsThis study comprises a between-group meta-analysis comparing serum and plasma leptin levels in people with BD in mania, depression or euthymia and healthy controls. We conducted a systematic search for all possibly eligible-English and non-English peer-reviewed articles. We calculated the effect size (ES) utilizing Hedges’ adjusted g using random effects.ResultsEleven studies were included in the meta-analyses, providing data on 1118 participants. Serum and plasma leptin levels were not altered in subjects with BD when compared to healthy controls in mania (g = −0.99, 95% CI −2.43 to 0.43, P = 0.171), in depression (g = 0.17, 95% CI −0.45 to 0.79, P = 0.584), or in euthymia (g = 0.03, 95% CI −0.39 to 0.46, P = 0.882). However, we did observe a stronger association between leptin levels and both age and BMI in patients with BD in euthymia compared to healthy controls, such that the greater the age of the individuals, the greater the difference in leptin levels between BD and controls; and the higher the BMI, the greater the difference in leptin levels between BD and controls.ConclusionsOur meta-analysis provides evidence that leptin levels are not altered in BD across the mood spectrum compared to healthy controls. The disproportionate increase of leptin levels with increase in BMI in BD speaks in favour of a potential inflammatory role of white adipose tissue in BD and a disproportionate increase of leptin levels with increase in age.

INTRODUCTION Both smoking and depression have been associated with increased inflammatory markers. As there are few studies on inflammatory markers that distinguish between depressed and nondepressed smokers, it is unclear if there is a cumulative impact of these mediators of inflammation. The aim of this study was to investigate inflammatory markers in tobacco smokers and compare depressed and nondepressed smokers. METHODS Smokers (n = 155) were recruited from the Cigarette Smoking Cessation Service, Londrina. Mental health status was assessed using the Diagnostic Interview for Research, in accordance with the International Classification of the Disorders-10th (ICD-10). Demographic information was collected by self-report questionnaire, and the Fagerstrom Test for Nicotine Dependence was administered. Blood specimens were simultaneously collected and measured for C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). RESULTS Depressed smokers had significantly higher levels of hs-CRP (p = .05), IL-6 (p = .039), and TNF-α (p = .021) compared with nondepressed smokers. Depressed smokers were also significantly more likely than nondepressed smokers to have been hospitalized in the previous month (p < .032), to suffer from cardiovascular disease (p < .001) and lung disease (p < .003), and to have more work-related disability (p = .001). CONCLUSIONS These findings demonstrate that depressed smokers had higher hs-CRP, IL-6, and TNF-α levels than nondepressed smokers and had worse physical health outcomes and greater work-related disability. This may have important implications in identifying shared risk pathways for depressive and somatic disorders.

Background Evidence is accumulating to support the presence of redox dysregulation in a number of psychiatric disorders, including bipolar disorder. This dysregulation may be amenable to therapeutic intervention. Glutathione is the predominant non-enzymatic intracellular free radical scavenger in the brain, and the most generic of all endogenous antioxidants in terms of action. N-acetylcysteine (NAC) is a glutathione precursor that effectively replenishes brain glutathione. Given the failure of almost all modern trials of antidepressants in bipolar disorder to demonstrate efficacy, and the limited efficacy of mood stabilisers in the depressive phase of the disorder, this is a major unmet need. Method This study reports data on the treatment of 149 individuals with moderate depression during the 2 month open label phase of a randomised placebo controlled clinical trial of the efficacy of 1 g BID of NAC that examined the use of NAC as a maintenance treatment for bipolar disorder. Results In this trial, the estimated mean baseline Bipolar Depression Rating Scale (BDRS) score was 19.7 (SE = 0.8), and the mean BDRS score at the end of the 8 week open label treatment phase was 11.1 (SE = 0.8). This reduction was statistically significant (p

Williams LJ, Pasco JA, Jacka FN, Henry MJ, Dodd S, Nicholson GC, Kotowicz MA, Berk M. Bipolar disorder and adiposity: a study using whole body dual energy X-ray absorptiometry scans.Objective:Previous research has demonstrated a relationship between adiposity and bipolar disorder, although data are derived predominantly from patient samples and use indirect methods of assessing adiposity. This study investigated the association between bipolar disorder and several indices of adiposity, including body fat mass as measured by dual energy X-ray absorptiometry (DXA), in a community-based sample.Methods:In this study, 21 women with bipolar disorder and 523 healthy controls were drawn from an age-stratified, random, community-based sample of women (20–93 years) participating in the Geelong Osteoporosis Study. Bipolar disorder was diagnosed utilising a semi-structured clinical interview. Anthropometric measurements (weight, height, waist and hip circumference) were taken and fat mass was determined from whole body DXA scans (Lunar DPX-L).ResultsThose with bipolar disorder tended to have greater adiposity. Age-adjusted mean (95% CI) values for bipolar versus controls according to adiposity indices were weight 75.6 (68.9–82.3) versus 72.6 (71.3–74.0) kg, waist circumference 89.8 (84.1–95.6) versus 87.3 (86.1–88.5) cm, waist:hip ratio 0.85 (0.82–0.87) versus 0.84 (0.83–0.84), body mass index 27.6 (25.1–30.1) versus 27.5 (27.0–28.0) kg/m2, fat mass 31.4 (26.5–36.3) versus 28.6 (27.5–29.5) kg and %body fat 40.4 (36.9–43.9) versus 38.0 (37.3–38.7)%; allp> 0.05. Further adjustment for height, smoking, alcohol, psychotropic medication, energy intake or physical activity did not influence these patterns.ConclusionAlthough a pattern suggestive of greater adiposity among those with bipolar disorder was observed, no significant differences were detected. We cannot exclude the possibility of a type II error. Further research with a larger sample may produce more conclusive results.

Introduction and Aims Posttraumatic stress disorder (PTSD) is frequently linked with substance abuse. The self-medication hypothesis suggests that some people may use illicit substances in an attempt to self-treat psychiatric symptoms. This study explores the relationship between substance abuse and PTSD symptom clusters in a methadone maintenance population. Design and Methods Clients of a methadone maintenance program at a public Drug and Alcohol Service were invited to complete the PTSD Checklist–Civilian Version, a screening tool for PTSD. Information about their history of substance use was also collected. Results Eighty clients (43 female, 37 male), aged 35 ± 8.0 years (mean ± SD), participated in the study, of which 52.7% screened positive for PTSD. Severity of marijuana use was significantly associated with a number of reexperiencing and hyperarousal symptoms and with overall severity of PTSD symptoms. Opiate, amphetamine, and benzodiazepine use did not appear to be related to PTSD symptoms. Discussion and Conclusions In this sample, marijuana may be used to self-treat certain PTSD symptoms, supporting the self-medication hypothesis. Further research is required to confirm the association between a diagnosis of PTSD and substance use. Given the high prevalence of PTSD in the substance-using population, routine PTSD screening in the substance abuse treatment setting may be justified.

Objective: This paper aims to present an overview of screening and safety considerations for the treatment of clinical depressive disorders and make recommendations for safety monitoring. Method: Data were sourced by a literature search using MEDLINE and a manual search of scientific journals to identify relevant articles. Draft guidelines were prepared and serially revised in an iterative manner until all co-authors gave final approval of content. Results: Screening and monitoring can detect medical causes of depression. Specific adverse effects associated with antidepressant treatments may be reduced or identified earlier by baseline screening and agent-specific monitoring after commencing treatment. Conclusion: The adoption of safety monitoring guidelines when treating clinical depression is likely to improve overall physical health status and treatment outcome. It is important to implement these guidelines in the routine management of clinical depression.

Emerging evidence indicates that early life exposures influence adult health outcomes and there is cause to hypothesise a role for physical activity (PA) in childhood as a protective factor in adult depression. This study aimed to investigate the association between self-reported levels of PA in childhood and self-reported depressive illness. Lifetime depression and levels of physical activity (low/high) in childhood (

Berk M, Brnabic A, Dodd S, Kelin K, Tohen M, Malhi GS, Berk L, Conus P, McGorry PD. Does stage of illness impact treatment response in bipolar disorder? Empirical treatment data and their implication for the staging model and early intervention. Bipolar Disord 2011: 13: 87–98. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objective: The staging model suggests that early stages of bipolar disorder respond better to treatments and have a more favourable prognosis. This study aims to provide empirical support for the model, and the allied construct of early intervention. Methods: Pooled data from mania, depression, and maintenance studies of olanzapine were analyzed. Individuals were categorized as having had 0, 1–5, 6–10, or >10 prior episodes of illness, and data were analyzed across these groups. Results: Response rates for the mania and maintenance studies ranged from 52–69% and 10–50%, respectively, for individuals with 1–5 previous episodes, and from 29–59% and 11–40% for individuals with >5 previous episodes. These rates were significantly higher for the 1–5 group on most measures of response with up to a twofold increase in the chance of responding for those with fewer previous episodes. For the depression studies, response rates were significantly higher for the 1–5 group for two measures only. In the maintenance studies, the chance of relapse to either mania or depression was reduced by 40–60% for those who had experienced 1–5 episodes or 6–10 episodes compared to the >10 episode group, respectively. This trend was statistically significant only for relapse into mania for the 1–5 episode group (p = 0.005). Conclusion: Those individuals at the earliest stages of illness consistently had a more favourable response to treatment. This is consistent with the staging model and underscores the need to support a policy of early intervention.

There is now strong evidence of progressive neuropathological processes in bipolar disorder (BD). On this basis, the current understanding of the neurobiology of BD has shifted from an initial focus on monoamines, subsequently including evidence of changes in intracellular second messenger systems and more recently to, incorporating changes in inflammatory cytokines, corticosteroids, neurotrophins, mitochondrial energy generation, oxidative stress and neurogenesis into a more comprehensive model capable of explaining some of the clinical features of BD. These features include progressive shortening of the inter-episode interval with each recurrence, occurring in consort with reduced probability of treatment response as the illness progresses. To this end, emerging data shows that these biomarkers may differ between early and late stages of BD in parallel with stage-related structural and neurocognitive alterations. This understanding facilitates identification of rational therapeutic targets, and the development of novel treatment classes. Additionally, these pathways provide a cogent explanation for the efficacy of seemingly diverse therapies used in BD, that appear to share common effects on oxidative, inflammatory and neurotrophic pathways.

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.

Autism is a severe, pervasive developmental disorder, the aetiology of which is poorly understood. Current pharmacological treatment options for autism are often focused on addressing comorbid behavioural problems, rather than core features of the disorder. Investigation of a new treatment approach is needed.Recent research has indicated a possible role of abnormalities in oxidative homeostasis in the pathophysiology of autism, based on reports that a range of oxidative biomarkers are significantly altered in people with autism. This article reviews the current findings on oxidative stress in autism, including genetic links to oxidative pathways, changes in antioxidant levels and other oxidative stress markers. We conducted a search of the literature up to June 2010, using Medline, Pubmed, PsycINFO, CINAHL PLUS and BIOSIS Previews.This review provides an overview of the current understanding of the role of oxidative stress in autism. This will assist in highlighting areas of future therapeutic targets and potential underlying pathophysiology of this disorder.Abnormalities in oxidative homeostasis may play a role in the pathophysiology of autism. Antioxidant treatment may form a potential therapeutic pathway for this complex disorder.

Berk M, Dodd S, Dean OM, Kohlmann K, Berk L, Malhi GS. The validity and internal structure of the Bipolar Depression Rating Scale: data from a clinical trial of N-acetylcysteine as adjunctive therapy in bipolar disorder.Background:The phenomenology of unipolar and bipolar disorders differ in a number of ways, such as the presence of mixed states and atypical features. Conventional depression rating instruments are designed to capture the characteristics of unipolar depression and have limitations in capturing the breadth of bipolar disorder.MethodThe Bipolar Depression Rating Scale (BDRS) was administered together with the Montgomery Asberg Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) in a double-blind randomised placebo-controlled clinical trial of N-acetyl cysteine for bipolar disorder (N = 75).Results:A factor analysis showed a two-factor solution: depression and mixed symptom clusters. The BDRS has strong internal consistency (Cronbach's alpha = 0.917), the depression cluster showed robust correlation with the MADRS (r = 0.865) and the mixed subscale correlated with the YMRS (r = 0.750).Conclusion:The BDRS has good internal validity and inter-rater reliability and is sensitive to change in the context of a clinical trial.

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.

Objective: We aimed to report the prevalence, age-of-onset and comorbidity of mood and anxiety disorders in an age-stratified representative sample of Australian women aged 20 years and over. Method: Mood and anxiety disorders were diagnosed utilising a clinical interview (SCID-I/NP). The lifetime and current prevalence of these disorders was determined from the study population (n = 1095) and standardized to 2006 census data for Australia. Results: Approximately one in three women (34.8%) reported a lifetime history of any mood and/or anxiety disorder, with mood disorders (30.0%) being more prevalent than anxiety disorders (13.5%). Of these, major depression (23.4%), panic disorder (5.5%) and specific phobia (3.5%) were the most common. The lifetime prevalence of other disorders was low (≤3%). A total of 14.4% of women were identified as having a current mood and/or anxiety disorder, with similar rates of mood (8.9%) and anxiety disorders (8.0%) observed. The median age-of-onset for mood disorders was 27.0 years and 18.5 years for anxiety disorders. Conclusions: This study reports the lifetime and current prevalence of mood and anxiety disorders in the Australian female population. The findings emphasize the extent of the burden of these disorders in the community.

The term ‘switching’ is often used in bipolar disorder when describing polarity changes in bipolar disorder, but this term is ambiguous and imprecise, and is sometimes used interchangeably with the term ‘cycling’. Furthermore, polarity changes in bipolar disorder can be understood in different ways, because their clinical manifestations range from the emergence of subthreshold symptoms to a full episode of the opposite pole. Besides the need to tighten the meaning of the term ‘switching’, this paper also argues that switching does not adequately describe the complex phenomena that occur with course aggravation of bipolar disorder, such as alteration in episode frequency or amplitude. A more-fine grained approach to course aggravation in bipolar disorder is proposed, which incorporates trans-polar switching, index polarity aggravation, as well as alterations in episodic amplitude, episodic duration, and interepisode length. This approach has the potential to capture a broader, more fine-grained and clinically relevant picture of the process of aggravation of the bipolar cycle.

To review the evidence that supports early intervention in the treatment of bipolar disorder.Bipolar disorder is a pleomorphic condition, with varying manifestations that are determined by a number of complex factors including the "stage" of illness. It is consequently a notoriously difficult illness to diagnose and as a corollary is associated with lengthy delays in recognition and the initiation of suitable treatment.A literature search was conducted using MEDLINE augmented by a manual search.Emerging neuroimaging data suggests that, in contrast to schizophrenia, where at the time of a first-episode of illness there is already discernible volume loss, in bipolar disorder, gross brain structure is relatively preserved, and it is only with recurrences that there is a sequential, but marked loss of brain volume. Recent evidence suggests that both pharmacotherapy and psychotherapy are more effective if instituted early in the course of bipolar disorder, and that with multiple episodes and disease progression there is a noticeable decline in treatment response.Such data supports the notion of clinical staging, and the tailored implementation of treatments according to the stage of illness. The progressive nature of bipolar disorder further supports the concept that the first episode is a period that requires energetic broad-based treatment, with the hope that this could alter the temporal trajectory of the illness. It also raises hope that prompt treatment may be neuroprotective and that this perhaps attenuates or even prevents the neurostructural and neurocognitive changes seen to emerge with chronicity. This highlights the need for early identification at a population level and the necessity of implementing treatments and services at a stage of the illness where prognosis is optimal.

Background: This study aimed to investigate the relationship between depressive and anxiety disorders and indices of adiposity, including body fat mass and percent body fat, as measured by dual energy X-ray absorptiometry. Methods: In this observational study of 979 randomly-selected women aged 20-93 years, psychiatric history was ascertained using a structured clinical interview (SCID-I/NP). Total body fat was assessed using dual-energy X-ray absorptiometry and weight, height and waist circumference were measured. Medication use and lifestyle factors were self-reported. Results: Those with a lifetime history of depression had increased fat mass (+ 7.4%) and percent body fat (+ 4.3%), as well as greater mean weight (+ 3.3%), waist circumference (+ 2.9%) and BMI (+ 3.5%) after adjustment for age, anxiety, alcohol consumption, physical activity and past smoking. Furthermore, those meeting criteria for a lifetime history of depression had a 1.7-fold increased odds of being overweight or obese (BMI ≥ 25), a 2.0-fold increased odds of being obese (BMI ≥ 30) and a 1.8-fold increased odds of having a waist circumference ≥ 80 cm. These patterns persisted after further adjustment for psychotropic medication use, smoking status and energy intake. No differences in any measures of adiposity were observed among those with anxiety disorders compared to controls. Limitations: There is potential for unrecognised confounding, interpretations are limited to women and a temporal relationship could not be inferred. Conclusions: Depression was associated with greater adiposity. The difference in body fat mass was numerically greater than differences in indirect measures of adiposity, suggesting that the latter may underestimate the extent of adiposity in this population.

Objective:To evaluate the effect of N-acetylcysteine (NAC) on substance use in a double-blind, placebo-controlled trial of NAC in bipolar disorder. It is hypothesised that NAC will be superior to placebo for reducing scores on the Clinical Global Impressions scale for Substance Use (CGI-SU).Methods:Participants were randomised to 6-months of treatment with 2 g/day NAC (n = 38) or placebo (n = 37). Substance use was assessed at baseline using the Habits instrument. Change in substance use was assessed at regular study visits using the CGI-SU.Results:Amongst the 75 participants 78.7% drank alcohol (any frequency), 45.3% smoked tobacco and 92% consumer caffeine. Other substances were used by fewer than six participants. Caffeine use was significantly lower for NAC-treated participants compared with placebo at week 2 of treatment but not at other study visits.Conclusion:NAC appeared to have little effect on substance use in this population. A larger study on a substance using population will be necessary to determine if NAC may be a useful treatment for substance use.

N-acetyl cysteine (NAC) is a widely available nutraceutical with a variety of actions. As a precursor of cysteine and glutathione, it has antioxidant properties that may impact on mood and contribute to an effect on impulsivity and obsessive behaviour. Via its additional effect on glutamate via the cystine-glutamate exchange system, NAC has been shown to mediate impulsivity in preclinical models of addiction, reduce craving, and cue extinction. Further, by boosting glutathione, NAC acts as a potent antioxidant and has been shown in two positive, large-scale randomized placebo-controlled trials to affect negative symptoms in schizophrenia and depression in bipolar disorder. We describe three cases in which its actions specifically on nail-biting and associated anxiety may offer a potential treatment. The spontaneous findings are reported as part of an ongoing treatment trial examining the utility of NAC in bipolar disorder. Its actions, if robustly replicated, also point to potential treatment targets in glutathione or glutamate pathways in the brain.

In the absence of clear targets for primary prevention of many psychiatric illnesses, secondary prevention becomes the most feasible therapeutic target, and is best encompassed by the concept of early intervention. This construct encompasses the goals of minimising diagnostic delay and the prompt initiation of clinically appropriate therapy. This paper develops the rationale for early intervention in bipolar disorder. Three interrelated themes are discussed; the clinical data supporting the value of prompt diagnosis and treatment in bipolar disorder, the putative biochemical mechanisms underlying the pathophysiological processes, and the parallel concept of neuroprotection, and the developing neuroimaging data that supports early intervention. Early initiation of appropriate therapy may potentially facilitate improved clinical outcomes, and further might allow the secondary prevention of the sequelae of untreated illness, which include the deleterious impact on family relationships, psychosexual and vocational development, identity and self-concept and self-stigma.

Objective Schizophrenia is a multifaceted illness with positive, negative and cognitive symptom domains. Standard treatments often focus on positive symptoms and may not adequately relieve other symptoms. Previous studies have suggested a role for mirtazapine in schizophrenia, particularly in negative symptoms. This study investigates the efficacy of adding mirtazapine to treatment as usual to alleviate the negative symptoms of schizophrenia. Methods In a 6 week, double-blind clinical trial, participants with a diagnosis of schizophrenia and currently being treated with atypical antipsychotic medication were randomised to adjunctive treatment with mirtazapine (30 mg/day) or placebo. The primary outcome measure was improvement in the Positive and Negative Syndrome Scale (PANSS). Measures of cognition, collected at baseline and week 6 only, were analysed using an Analysis of Covariance (ANCOVA) model. All other outcome measures were analysed using a linear mixed model. Results Forty participants were recruited to the study with equal numbers randomised to each treatment arm. There was no significant difference between mirtazapine and placebo treated participants for improvement in PANSS scores or any of the secondary outcome measures at any stage during the 6-week trial. Conclusions This trial does not confirm previous research supporting the use of mirtazapine adjunctive to atypical antipsychotic treatment for schizophrenia. Copyright © 2009 John Wiley & Sons, Ltd.

Introduction and Aims.To examine client-reported reasons for missed early appointments at a drug and alcohol treatment service and to compare characteristics of those who missed appointments with those who attended. Design and Methods. Clients who missed a first or second appointment between 1 May and 31 August 2007 at a public community-based outpatient treatment facility were invited to participate in a semistructured telephone interview.This consisted of an open-ended question asking the reason(s) for nonattendance, followed by a questionnaire of items for therapeutic alliance and service satisfaction, perceived impact of substance use and previous treatment experience, mostly rated on Likert scales. Database information on demographic and clinical variables was gathered for all clients who were accepted for treatment within the study time frame. Characteristics of those who missed a first or second appointment (n = 66) were compared with those who attended at least their first two appointments (n = 97). Results. Of clients who missed their appointments, 80.6% provided reasons for nonattendance, which included extraneous factors (50.0%), service shortcomings (29.7%), no further need for service (16.2%) and motivational ambivalence (4.1%). They generally had high ratings of therapeutic alliance and service satisfaction and identified their substance use as having a negative impact on their lives. Clients who missed appointments were more likely to be male, unmarried and have a history of polysubstance use. Discussion and Conclusions. Extraneous issues relating to the client may be a dominant obstacle in early treatment engagement. Efforts to overcome these issues may therefore improve early engagement.

Background Acute-mental-health services receive hundreds of admissions every year. Some of these patients will continue to be case-managed by community mental-health teams on discharge from the acute unit while others will not remain in contact with the mental-health service. This study compares the findings of comprehensive interviews conducted with current and past patients of the community mental-health service 3 or more years following case closure from the community ambulatory service. Methods Between 1 July 1999 and 30 June 2001, there were 2245 closed cases identified at Barwon Health. Letters of invitation to participate in a research project were sent to people who had suffered from psychotic illnesses, and had been case-closed by community mental-health services between the above dates and had not been in contact with the Community and Mental Health Service for at least 6 months. A second group of participants was recruited from people who had also been case-closed by community mental-health teams in Barwon Health during the 1999–2001 2-year-time window but whose cases had been re-opened and who were in case management with Barwon Health at the time of the study. All participants were interviewed using the Diagnostic Interview for Psychosis. Results Letter responses were received from 17 men and 18 women, aged 40.7 ± 12.0 (mean ± SD), who were interviewed. A second group of 17 men and 12 women, aged 40.9 ± 9.6 (mean ± SD) of currently case-managed patients was interviewed. All interviewees reported a detailed history of mental illness. Persistent social dysfunction and impaired quality of life were reported in both groups. Conclusion Patients suffering from psychotic disorders who had been case-closed by community mental-health teams and had been discharged to the care of their general practitioners or elsewhere continued to show evidence of significant impairment due to mental illness 3 years after being case-closed.

Background: There are data to suggest low bone mineral density is disproportionately prevalent among those with psychiatric disorders. This paper aims to review the current evidence on the relationship between depression and bone mineral density, and identify potential mechanisms. Methods: Relevant sources were identified from the Pubmed and Web of Science (ISI) databases from the first relevant publication in 1994 to the present, 2007, using a combination of key words and terms including depression, major depressive disorder, osteoporosis, bone mineral density, hypothalamic-pituitary-adrenal axis, cortisol, cytokines, leptin, antidepressants, selective serotonin reuptake inhibitors, smoking, alcohol, physical activity and diet. Reference lists of chosen articles were further reviewed for associated publications. Results: The possible association between psychiatric illness, in particular depression, and osteoporosis has been the subject of a growing body of research yielding various findings, although most identify some effect on bone. In addition to medication-related processes and/or modifiable lifestyle factors associated with mood disturbances, endocrine and immune alteration secondary to depression may play a pathogenetic role in bone metabolism. Conclusions: Additional longitudinal studies, with the advantage of temporal sequencing, remain to be conducted, as well as research into potential mechanisms surrounding the association. Nevertheless, the current findings are of clinical relevance, given the health burden of both depression and osteoporosis.

There is accumulating evidence for oxidative stress mechanisms as common pathophysiological pathways in diverse psychiatric disorders, which offers novel treatment targets in oxidation biology systems. Of these the glutathione system has the most favourable theoretical foundation, given its dominance as the most generic of cellular antioxidants. Clinically, this hypothesis has been supported by several recently published studies that have reported on the efficacy of N-acetylcysteine, a glutathione precursor, in the treatment of various psychiatric disorders. This article outlines the multidimensional evidence that currently exists for oxidative stress mechanisms in psychiatric disorders and specifically discusses glutathione as a promising novel therapeutic target.

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 (HAMD 21 ), 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 HAMD 21 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.

Selective serotonin reuptake inhibitors (SSRIs) are a first-line treatment for depression. They have been reported to regulate serotonin signalling in bone cells and may influence bone metabolism. This study aimed to investigate the effect of SSRIs on bone mineral density (BMD) in a sample of women with a lifetime history of depression. In this community-based study of 607 women, a history of depression was ascertained using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR research version, non-patient edition. BMD was measured at the posterior-anterior (PA) spine, hip, total body and forearm using dual energy absorptiometry, and medication use and lifestyle factors were self-reported. Among 177 women with a lifetime history of depression, current users of bisphosphonates, glucocorticoids, hormone therapy and antidepressants other than SSRIs were excluded. Of the remaining 128 (median age 51.5 years, range 30-74), 26 (20.3%) reported current SSRI use. After controlling for age, weight, height and smoking history, BMD among SSRI users was 5.6% lower at the femoral neck (P=0.03), 6.2% lower at the trochanter (P=0.04) and 4.4% lower at the mid-forearm (P=0.03) than nonusers. No differences in BMD were detected at other sites. Although the mechanism remains unclear, these observations are consistent with a role for the serotonergic system in regulating bone metabolism.

Large disruptions of chronobiological rhythms are documented as destabilizing individuals with bipolar disorder; however, the impact of small phase altering events is unclear. Australian suicide data from 1971 to 2001 were assessed to determine the impact on the number of suicides of a 1-h time shift due to daylight saving. The results confirm that male suicide rates rise in the weeks following the commencement of daylight saving, compared to the weeks following the return to eastern standard time and for the rest of the year. After adjusting for the season, prior to 1986 suicide rates in the weeks following the end of daylight saving remained significantly increased compared to the rest of autumn. This study suggests that small changes in chronobiological rhythms are potentially destabilizing in vulnerable individuals.