Symptom screening scales for detecting major depressive disorder in children and adolescents: A systematic review and meta-analysis of reliability, validity and diagnostic utility.

Depression symptom screening scales are often used to determine a clinical diagnosis of major depressive disorder (MDD) in prevention research. The aim of this review is to systematically examine the reliability, validity and diagnostic utility of commonly used screening scales in depression prevention research among children and adolescents.

A comparison of olanzapine with haloperidol in cannabis-induced psychotic disorder: a double-blind randomized controlled trial

Little controlled data exist on the treatment of substance induced psychotic disorders. In this study, 30 patients meeting DSM-IV criteria for cannabis induced psychotic disorder were randomly allocated to receive either olanzapine or haloperidol in a 4-week double-blind clinical trial. There were no significant outcome differences between the two groups on any of the primary outcome measures, the Brief Psychiatric Rating Scale (haloperidol 25.7; olanzapine 27.1; P = 0.70); Clinical Global Impression (CGI) severity scale (haloperidol 1.8, olanzapine 2.3; P = 0.21) or the CGI improvement scale (haloperidol 1.3, olanzapine 1.7; P = 0.16). The haloperidol group however, developed significantly more extrapyramidal side-effects as measured by the Simpson Angus Scale (haloperidol 11.4, olanzapine 2.5; P = 0.014). Significantly (P = 0.027) more biperidin was used for extrapyramidal side-effects in the haloperidol (7.143 mg) than in the olanzapine (0.357 mg) group. Olanzapine appears to be as effective as haloperidol in the treatment of cannabis induced psychotic disorder, but is associated with a lower rate of extrapyramidal side-effects.

The platelet intracellular calcium response to serotonin and thrombin in patients with panic disorder.

Serotonin is implicated in both the biology of depression and anxiety. The aim of this study was to examine the platelet intracellular calcium response to serotonin and thrombin using spectrofluorometry in 14 patients with DSM-4 panic disorder compared to 14 matched controls. Patients did not show significantly higher baseline platelet intracellular calcium levels and serotonin stimulated levels of intracellular calcium than control subjects. There was a much smaller standard deviation in the control subjects than in the panic patients. The intracellular calcium response to thrombin activation was however greater in panic patients than in control subjects (P<0.001). The failure of this study to find enhanced sensitivity of 5-HT2 receptors in panic disorder is compatible with the findings of previous challenge studies that found no consistent dysregulation of serotonin in panic disorder. The enhanced thrombin sensitivity, nevertheless suggests some receptor mediated second messenger changes independent of serotonin in the disorder.

CNS 14-3-3zeta: changes with sex but not psychiatric diagnoses or psychotropic drug treatment.

mRNA for 14-3-3zeta, an abundant signalling protein in human CNS, is reported as decreased or unchanged in cortex from subjects with schizophrenia. Addressing this dichotomy, using Western blot analyses, we measured levels of 14-3-3zeta proteins in cortex and caudate nucleus from subjects with schizophrenia, bipolar disorder, age/sex matched controls and in analogous CNS regions from rats treated with psychotropic drugs. Anti-14-3-3zeta antibody bound to three proteins (molecular weights: 27, 54 and 70 kDa), in all CNS tissue. Levels of all proteins did not vary with diagnoses (27 kDa: F(2,42.0)=0.35, p=0.71; 54 kDa: F(2,42.1)=0.62, p=0.54; 70 kDa: F(2,41.0)=2.43, p=0.10). By contrast, independent of diagnoses, there were significant increases in the levels of the 27 kDa protein (+32%; p<0.001) and 54 kDa protein (51%; p=0.001) in the caudate nucleus from males compared to females. In addition, there was a trend (-25%; p=0.06) to decreased levels of the 70 kDa protein in BA 9 in males compared to females. Treating with haloperidol, olanzapine, lithium or a combination thereof did not alter 14-3-3zeta levels in rat cortex or striatum. Therefore, this study suggests that 14-3-3zeta proteins are not altered in the cortex or caudate nucleus in schizophrenia, bipolar disorder or in analogous regions in psychotropic drug treated rats. By contrast, our study suggests that levels of 14-3-3zeta in some regions of the human CNS may be modulated by some sex-specific mechanism.

Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and bipolar disorder.

There is evidence that major psychiatric discords such as schizophrenia (SZ) and bipolar disorder (BD) are associated with dysregulation of synaptic plasticity with downstream alterations of neurotrophins. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system (CNS), and performs many biological functions such as promoting the survival, differentiation, and plasticity of neurons. Variants in the BDNF gene increase the risk of SZ and bipolar disorder. Chronic administration of drugs used to treat SZ and BD, such as lithium, valproate, quetiapine, clozapine, and olanzapine, increases BDNF expression in rat brain. To examine serum BDNF, three groups of chronically medicated DSM-IV SZ patients, on treatment with clozapine (n=27), typical (n=14), and other atypical antipsychotics (n=19), 30 euthymic BD patients, and 26 healthy control had 5 ml blood samples collected by venipuncture. Serum BDNF levels were significantly higher in SZ patients (p<0.001) when compared to either controls or euthymic BD patients. Increased BDNF in SZ patients might be related to the course of illness or to treatment variables. Prospective studies are warranted.

Tobacco use in bipolar disorder

Tobacco use in mental health in general and bipolar disorder in particular remains disproportionally common, despite declining smoking rates in the community. Furthermore, interactions between tobacco use and mental health have been shown, indicating the outcomes for those with mental health disorders are impacted by tobacco use. Factors need to be explored and addressed to improve outcomes for those with these disorders and target specific interventions for people with psychiatric illness to cease tobacco smoking. In the context of bipolar disorder, this review explores; the effects of tobacco smoking on symptoms, quality of life, suicidal behavior, the biological interactions between tobacco use and bipolar disorder, the interactions between tobacco smoking and psychiatric medications, rates and factors surrounding tobacco smoking cessation in bipolar disorder and suggests potential directions for research and clinical translation. The importance of this review is to bring together the current understanding of tobacco use in bipolar disorder to highlight the need for specific intervention.

A brief review of exercise, bipolar disorder, and mechanistic pathways.

Despite evidence that exercise has been found to be effective in the treatment of depression, it is unclear whether these data can be extrapolated to bipolar disorder. Available evidence for bipolar disorder is scant, with no existing randomized controlled trials having tested the impact of exercise on depressive, manic or hypomanic symptomatology. Although exercise is often recommended in bipolar disorder, this is based on extrapolation from the unipolar literature, theory and clinical expertise and not empirical evidence. In addition, there are currently no available empirical data on program variables, with practical implications on frequency, intensity and type of exercise derived from unipolar depression studies. The aim of the current paper is to explore the relationship between exercise and bipolar disorder and potential mechanistic pathways. Given the high rate of medical co-morbidities experienced by people with bipolar disorder, it is possible that exercise is a potentially useful and important intervention with regard to general health benefits; however, further research is required to elucidate the impact of exercise on mood symptomology.

Prevalence of psychiatric co-morbidity in treatment-seeking problem gamblers: A systematic review and meta-analysis

OBJECTIVE: The aim of this paper was to systematically review and meta-analyse the prevalence of co-morbid psychiatric disorders (DSM-IV Axis I disorders) among treatment-seeking problem gamblers. METHODS: A systematic search was conducted for peer-reviewed studies that provided prevalence estimates of Axis I psychiatric disorders in individuals seeking psychological or pharmacological treatment for problem gambling (including pathological gambling). Meta-analytic techniques were performed to estimate the weighted mean effect size and heterogeneity across studies. RESULTS: Results from 36 studies identified high rates of co-morbid current (74.8%, 95% CI 36.5-93.9) and lifetime (75.5%, 95% CI 46.5-91.8) Axis I disorders. There were high rates of current mood disorders (23.1%, 95% CI 14.9-34.0), alcohol use disorders (21.2%, 95% CI 15.6-28.1), anxiety disorders (17.6%, 95% CI 10.8-27.3) and substance (non-alcohol) use disorders (7.0%, 95% CI 1.7-24.9). Specifically, the highest mean prevalence of current psychiatric disorders was for nicotine dependence (56.4%, 95% CI 35.7-75.2) and major depressive disorder (29.9%, 95% CI 20.5-41.3), with smaller estimates for alcohol abuse (18.2%, 95% CI 13.4-24.2), alcohol dependence (15.2%, 95% CI 10.2-22.0), social phobia (14.9%, 95% CI 2.0-59.8), generalised anxiety disorder (14.4%, 95% CI 3.9-40.8), panic disorder (13.7%, 95% CI 6.7-26.0), post-traumatic stress disorder (12.3%, 95% CI 3.4-35.7), cannabis use disorder (11.5%, 95% CI 4.8-25.0), attention-deficit hyperactivity disorder (9.3%, 95% CI 4.1-19.6), adjustment disorder (9.2%, 95% CI 4.8-17.2), bipolar disorder (8.8%, 95% CI 4.4-17.1) and obsessive-compulsive disorder (8.2%, 95% CI 3.4-18.6). There were no consistent patterns according to gambling problem severity, type of treatment facility and study jurisdiction. Although these estimates were robust to the inclusion of studies with non-representative sampling biases, they should be interpreted with caution as they were highly variable across studies. CONCLUSIONS: The findings highlight the need for gambling treatment services to undertake routine screening and assessment of psychiatric co-morbidity and provide treatment approaches that adequately manage these co-morbid disorders. Further research is required to explore the reasons for the variability observed in the prevalence estimates.

Physical health comorbidities in women with personality disorder: data from the Geelong osteoporosis study

BACKGROUND: Associations between common psychiatric disorders, psychotic disorders and physical health comorbidities are frequently investigated. The complex relationship between personality disorders (PDs) and physical health is less understood, and findings to date are varied. This study aims to investigate associations between PDs with a number of prevalent physical health conditions. METHODS: This study examined data collected from women (n=765;≥25years) participating in a population-based study located in south-eastern Australia. Lifetime history of psychiatric disorders was assessed using the semi-structured clinical interviews (SCID-I/NP and SCID-II). The presence of physical health conditions (lifetime) were identified via a combination of self-report, medical records, medication use and clinical data. Socioeconomic status, and information regarding medication use, lifestyle behaviors, and sociodemographic information was collected via questionnaires. Logistic regression models were used to investigate associations. RESULTS: After adjustment for sociodemographic variables (age, socioeconomic status) and health-related factors (body mass index, physical activity, smoking, psychotropic medication use), PDs were consistently associated with a range of physical health conditions. Novel associations were observed between Cluster A PDs and gastro-oesophageal reflux disease (GORD); Cluster B PDs with syncope and seizures, as well as arthritis; and Cluster C PDs with GORD and recurrent headaches. CONCLUSIONS: PDs were associated with physical comorbidity. The current data contribute to a growing evidence base demonstrating associations between PDs and a number of physical health conditions independent of psychiatric comorbidity, sociodemographic and lifestyle factors. Longitudinal studies are now required to investigate causal pathways, as are studies determining pathological mechanisms.

Bipolar disorder: a troubled diagnosis

Bipolar disorder is indeed a troubled diagnosis. Conceived from manic-depressive illness, bipolar disorder is a much narrower concept by virtue of the emphasis placed in modern psychiatric taxonomy on polarity rather than recurrence of mood episodes. At first, this "new diagnosis" floundered and received little attention, but once it established itself, it steadily gained interest throughout the "decade of the brain." By the beginning of the new millennium bipolar disorder was perfectly poised for a phenomenal expansion. Its rapid growth led to a proliferation of bipolar subtypes, each of which quickly gained disorder status, wrongly insinuating a disease entity. Prompted by the recent launch of DSM-5 and the imminent arrival of ICD-11, questions are being asked about this complex diagnosis, which has been so problematic, especially in children. This chapter discusses the evolution of bipolar disorder, in the hope that an understanding of its origins will shed light on why it remains such a troublesome diagnosis.

Areas of controversy in neuroprogression in bipolar disorder.

OBJECTIVE: We aimed to review clinical features and biological underpinnings related to neuroprogression in bipolar disorder (BD). Also, we discussed areas of controversy and future research in the field. METHOD: We systematically reviewed the extant literature pertaining to neuroprogression and BD by searching PubMed and EMBASE for articles published up to March 2016. RESULTS: A total of 114 studies were included. Neuroimaging and clinical evidence from cross-sectional and longitudinal studies show that a subset of patients with BD presents a neuroprogressive course with brain changes and unfavorable outcomes. Risk factors associated with these unfavorable outcomes are number of mood episodes, early trauma, and psychiatric and clinical comorbidity. CONCLUSION: Illness trajectories are largely variable, and illness progression is not a general rule in BD. The number of manic episodes seems to be the clinical marker more robustly associated with neuroprogression in BD. However, the majority of the evidence came from cross-sectional studies that are prone to bias. Longitudinal studies may help to identify signatures of neuroprogression and integrate findings from the field of neuroimaging, neurocognition, and biomarkers.

Bipolar disorder

Bipolar disorder is a recurrent chronic disorder characterised by fluctuations in mood state and energy. It affects more than 1% of the world's population irrespective of nationality, ethnic origin, or socioeconomic status. Bipolar disorder is one of the main causes of disability among young people, leading to cognitive and functional impairment and raised mortality, particularly death by suicide. A high prevalence of psychiatric and medical comorbidities is typical in affected individuals. Accurate diagnosis of bipolar disorder is difficult in clinical practice because onset is most commonly a depressive episode and looks similar to unipolar depression. Moreover, there are currently no valid biomarkers for the disorder. Therefore, the role of clinical assessment remains key. Detection of hypomanic periods and longitudinal assessment are crucial to differentiate bipolar disorder from other conditions. Current knowledge of the evolving pharmacological and psychological strategies in bipolar disorder is of utmost importance.

Mitochondrial dysfunction in bipolar disorder: evidence, pathophysiology and translational implications

Bipolar disorder (BD) is a chronic psychiatric illness characterized by severe and biphasic changes in mood. Several pathophysiological mechanisms have been hypothesized to underpin the neurobiology of BD, including the presence of mitochondrial dysfunction. A confluence of evidence points to an underlying dysfunction of mitochondria, including decreases in mitochondrial respiration, high-energy phosphates and pH; changes in mitochondrial morphology; increases in mitochondrial DNA polymorphisms; and downregulation of nuclear mRNA molecules and proteins involved in mitochondrial respiration. Mitochondria play a pivotal role in neuronal cell survival or death as regulators of both energy metabolism and cell survival and death pathways. Thus, in this review, we discuss the genetic and physiological components of mitochondria and the evidence for mitochondrial abnormalities in BD. The final part of this review discusses mitochondria as a potential target of therapeutic interventions in BD.