Refined diagnostic criteria for the bipolar disorders: phase two of the AREDOC project.

OBJECTIVE: As limitations exist across DSM criteria sets for defining and differentiating the bipolar disorders generally and their component bipolar I (BP-1) and bipolar II (BP-II) sub-types, we sought to generate empirically based criteria. METHOD: We formed an international Task Force (TF) comprising members with bipolar disorder expertise, and who recruited 74 patients with a TF-diagnosed bipolar I and 104 with a bipolar II condition (with patients responding to definitional queries and symptom questionnaires), while 33 unipolar depressed patients recruited by the first author also completed the symptom questionnaire. A factor analysis sought to determine granular hypo/manic constructs. RESULTS: The bipolar disorder subjects strongly affirmed a new general definition of a bipolar disorder (capturing both manic and hypomanic episodes). While DSM-5 requires impaired functioning, we established that a high percentage of individuals with a BP-I or a BP-II disorder reported improved functioning and therefore modified this criterion. Analyses identified syptoms with differential high rates in individuals with bipolar disorder and its sub-types (and thus not simply capturing happiness), while a factor analysis generated seven symptom constructs both linked with and differing from DSM-5 bipolar symptom criteria. CONCLUSION: This second-stage report details a new set of criteria for differentiating the bipolar disorders from unipolar depressive conditions, while arguing for BP-I and BP-II disorders being differentiated principally by the respective presence or absence of psychotic features. Future studies will evaluate whether further modifications are required and examine for differential treatment benefits for those with a BP-I versus a BP-II condition.

Evaluation of Self-Perceived Changes in Gastrointestinal Symptoms During Ramadan Fasting.

Little is known regarding the effects of Ramadan fasting on common gastrointestinal symptoms. The aim of this study was to assess the alterations of these symptoms in a healthy Iranian adult population during Ramadan. In a cross-sectional study, self-administered questionnaires were used to evaluate the alterations in seven groups of gastrointestinal symptoms (esophageal symptoms, dyspeptic symptoms, bloating and abdominal distension, constipation, diarrhea, abdominal pain, and nausea) after Ramadan. A total of 900 individuals participated in the study. Almost 87 % of participants reported to fast for at least 2 weeks during Ramadan. After adjusting for potential confounders, we found no relationship between alteration in frequency of gastrointestinal symptoms and Ramadan fasting, except for constipation which increased significantly after Ramadan fasting (odds ratio 1.99, 95 % confidence interval 1.05-3.80, P < 0.05). In addition, those who fasted for at least 2 weeks reported to experience severe or very severe constipation-related symptoms three times more in comparison with those who fasted for less than 2 weeks (P < 0.05). There was no relationship between severity of other gastrointestinal symptoms and Ramadan fasting. We found that Ramadan fasting does not increase frequency and severity of common gastrointestinal symptoms in the general population except for constipation that may be experienced more frequently and severely among those who fast for 2 weeks or more.

Floral diversity and pollination strategies of three rheophytic Schismatoglottideae (Araceae).

Homoplastic evolution of 'unique' morphological characteristics in the Schismatoglottideae - many previously used to define genera - prompted this study to compare morphology and function in connection with pollination biology for Aridarum nicolsonii, Phymatarum borneense and Schottarum sarikeense. Aridarum nicolsonii and P. borneense extrude pollen through a pair of horned thecae while S. sarikeense sheds pollen through a pair of pores on the thecae. Floral traits of spathe constriction, presence and movement of sterile structures on the spadix, the comparable role of horned thecae and thecae pores, the presence of stamen-associated calcium oxalate packages, and the timing of odour emission are discussed in the context of their roles in pollinator management. Pollinators for all investigated species were determined to be species of Colocasiomyia (Diptera: Drosophilidae).

Antenatal depression: an artefact of sleep disturbance?

Research indicates that poor sleep quality is linked to and may precede depressive symptomatology in pregnancy, complicating screening for either condition. Pregnancy onset may also contribute to the development of sleep-disordered breathing (SDB). For the first time, the link between SDB and depression was examined in pregnancy. A total of 189 pregnant women completed the Edinburgh Postnatal Depression Scale (EPDS), Pittsburgh Sleep Quality Index (PSQI) for sleep quality and the Berlin Questionnaire for SDB. Women were also asked what they felt was the cause of their symptoms. PSQI-assessed poor sleep quality and self-perceived depression were strongly associated with EPDS scores of probable depression (X (2) 13.39; p < 0.001). Berlin-assessed risk of SDB was also associated with probable depression (X (2) 9.20 p < 0.01), though this was attenuated following multivariate analysis. There was a significant relationship between total PSQI score and the tendency for participants to attribute 'sleep-related causes' to their low mood (X (2) 20.78; p < 0.001). This study confirms the link between PSQI-assessed poor sleep quality and depressive symptoms in pregnancy, suggesting the two questionnaires assess the same or overlapping conditions. Although there was a relationship between probable depression and high risk SDB, the effect was attenuated after accounting for other depression risk factors, including body mass index (BMI).

Manipulating melatonin in managing mood.

OBJECTIVE: Disturbances in circadian rhythms have been associated with major depression and may be an underlying mechanism for the disorder. Resynchronisation of circadian rhythms may provide a new approach to treatment, especially by manipulating melatonin secretion. Melatonin is secreted at night and is a stable marker of circadian rhythms. The timing of its secretion can be changed by exogenous melatonin, agonism of specific melatonin receptors in the suprachiasmatic nucleus, its suppression by light and by sleep deprivation. METHOD: As part of a series of papers ['Chronobiology of mood disorders' Malhi & Kuiper. Acta Psychiatr Scand 2013;128 (Suppl. 444): 2-15; and 'Getting depression clinical practice guidelines right: time for change?' Kuiper et al. Acta Psychiatr Scand 2013;128 (Suppl. 444): 24-30.] addressing chronobiology, in this article, we conducted a selective review of studies that have examined the antidepressant effects of exogenous melatonin, light therapy, sleep deprivation and melatonin receptor agonists. RESULTS: Antidepressant effects were identified for bright light therapy, especially for seasonal affective disorder; sleep deprivation, although its antidepressant effect is time limited; and for the novel antidepressant agomelatine with agonistic properties for the MT1 and MT2 receptors and antagonism of 5HT2c receptor. The role of melatonin as an antidepressant has yet to be demonstrated. CONCLUSION: Shifting the circadian secretion of melatonin using the strategies reviewed offers a new approach to treating depression.

Pharmacological management of unipolar depression.

OBJECTIVE: To be used in conjunction with 'Psychological management of unipolar depression' [Lampe et al. Acta Psychiatr Scand 2013;127(Suppl. 443):24-37] and 'Lifestyle management of unipolar depression' [Berk et al. Acta Psychiatr Scand 2013;127(Suppl. 443):38-54]. To provide clinically relevant recommendations for the use of pharmacological treatments in depression derived from a literature review. METHOD: Using our previous Clinical Practice Guidelines [Malhi et al. Clinical practice recommendations for bipolar disorder. Acta Psychiatr Scand 2009;119(Suppl. 439):27-46] as a foundation, these clinician guidelines target key practical considerations when prescribing pharmacotherapy. A comprehensive review of the literature was conducted using electronic database searches (PubMed, MEDLINE), and the findings have been synthesized and integrated alongside clinical experience. RESULTS: The pharmacotherapy of depression is an iterative process that often results in partial and non-response. Beyond the initiation of antidepressants, the options within widely used strategies, such as combining agents and switching between agents, are difficult to prescribe because of the paucity of pertinent research. However, there is some evidence for second-line strategies, and a non-prescriptive algorithm can be derived that is based broadly on principles rather than specific steps. CONCLUSION: Depression is by its very nature a heterogeneous illness that is consequently difficult to treat. Invariably, situation-specific factors often play a significant role and must be considered, especially in the case of partial and non-response. Consulting with colleagues and trialling alternate treatment paradigms are essential strategies in the management of depression.

The role of computed tomography in terminal ballistic analysis.

Terminal ballistics concerns the science of projectile behaviour within a target and includes wound ballistics that considers what happens when a projectile strikes a living being. A number of soft tissue ballistic simulants have been used to assess the damage to tissue caused by projectiles. Standard assessment of these materials, such as ballistic soap or ordnance gelatine, requires the block to be opened or that a mould to be made to visualize the wound track. This is time consuming and may affect the accuracy of the findings especially if the block dries and alters shape during the process. Therefore, accurate numerical analysis of the permanent or temporary cavity is limited. Computed tomography (CT) potentially offers a quicker non-invasive analysis tool for this task. Four commercially purchased ballistic glycerine soap blocks were used. Each had a single firearm discharged into it from a distance of approximately 15 cm using both gunshot and shotgun projectiles. After discharge, each block was imaged by a modern 16 slice multi-detector CT scanner and analysed using 3-D reconstruction software. Using the anterior-posterior and lateral scout views and the multi-plane reconstructed images, it was possible to visualize the temporary cavity, as well as the fragmentation and dispersal pattern of the projectiles, the distance travelled and angle of dispersal within the block of each projectile or fragment. A virtual cast of the temporary cavity can be also be made. Multi-detector CT with 3-D analysis software is shown to create a reliable permanent record of the projectile path allowing rapid analysis of different firearms and projectiles.

Putting sexuality (back) into HIV/AIDS: issues, theory and practice.

After more than twenty years of programming and activism aimed at stemming the sexual transmission of HIV (and addressing the needs of those most vulnerable to infection) the HIV/AIDS epidemic continues to grow worldwide. Taking up this concern, this paper argues that one of the reasons why HIV prevention has had limited success is because of inadequate conceptualization of human sexuality in such work. Giving sexuality a more prominent position in responses to the epidemic raises a range of issues, including theorization of gender, understanding of sexual subjectivity, the significance of pleasure (or lack of pleasure) in sexual decision-making, and conceptualization of sexual behaviour and culture. Taking these themes forward entails asking significant questions about the underlying paradigmatic and methodological commitments of mainstream HIV/AIDS research, especially the tendency to reproduce accounts of human sexuality as if it were a measurable form of conduct only. Advocating new approaches that take the meaning and symbolic value of sexualities into account complicates established orthodoxies in the field whilst offering potential for more effective HIV prevention strategies.

PIK3CA mutations in head and neck squamous cell carcinoma.

PURPOSE: Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic alpha (PIK3CA) gene in several human solid tumors. Although gene amplifications of PIK3CA have been reported in head and neck squamous cell carcinoma (HNSCC), small mutation of the gene has not been evaluated in HNSCC previously. In this study, we examined the mutation frequency of PIK3CA in HNSCC. EXPERIMENTAL DESIGN: More than 75% of the somatic mutations of PIK3CA are clustered in the helical (exon 9) and kinase domains (exon 20). To investigate the possible role of PIK3CA in HNSCC tumorigenesis, exons 1, 4, 5, 6, 7, 9, and 20 of the gene were analyzed by direct genomic DNA sequencing in 38 HNSCC specimens. RESULTS: We identified four missense mutations in the seven exons of PIK3CA from 38 HNSCC specimens (11%). Three of the four mutations (i.e., H1047R, E542K, and E545K) have been previously reported as hotspot mutations. The remaining novel mutation, Y343C, is identified at exon 4 nucleotide 1028 A --> G. Three of the four mutations were shown to be somatic, whereas the fourth mutation (H1047R) was identified in a cell line. Interestingly, three of the four mutations identified were in pharyngeal cancer samples. CONCLUSIONS: These data provide evidence that oncogenic properties of PIK3CA contribute to the carcinogenesis of human head and neck cancers, especially in pharyngeal cancer. A specific kinase inhibitor to PIK3CA may potentially be an effective therapeutic reagent against HNSCC or pharyngeal cancer in particular.

Epidemiology of the functional gastrointestinal disorders diagnosed according to Rome II criteria: an Australian population-based study.

BACKGROUND: Population-based studies of the prevalence of all functional gastrointestinal disorders (FGID) using the Rome II criteria are lacking. It is also not certain whether subjects who meet the Rome II criteria for an FGID are different in terms of demographic and psychological characteristics from those subjects meeting exclusively the more restrictive Rome I criteria. AIM: To determine whether using the more restrictive Rome I criteria would result in a more biologically determined group of FGID than when the Rome II is applied. METHODS: Subjects included individuals aged 18 years and older (n = 1,225) from the Penrith population who were initially surveyed with the Penrith District Health Survey in 1997. Subjects were sent a self-report questionnaire that contained items on gastrointestinal symptoms applying the Rome II criteria. Subjects were also assessed on psychological and personality factors and on physical and mental functioning. RESULTS: A total of 36.1% (n = 275) of respondents was diagnosed with an FGID according to Rome II criteria. The five most prevalent FGID were functional heartburn (10.4%), irritable bowel syndrome (8.9%), functional incontinence (7.6%), proctalgia fugax (6.5%) and functional chest pain (5.1%). Subjects meeting Rome II only criteria for FGID scored significantly higher on measures of psychological caseness and emotionality than Rome I only subjects, and these were independently associated with meeting Rome I only versus Rome II only criteria for FGID. CONCLUSION: The Rome II criteria FGID are common and do not appear to identify a vastly different group of FGID sufferers compared with the earlier Rome I criteria.

-308GA and TNFB polymorphisms in acute respiratory distress syndrome.

The -308GA and TNFB1/2 polymorphisms of the tumour necrosis factor genes have been associated with increased susceptibility to, and mortality in sepsis, although, prior studies are not consistent. Their role in acute respiratory distress syndrome (ARDS) has not been evaluated. The current authors hypothesised that the -308A allele and TNFB22 genotype would be associated with increased susceptibility to, and mortality in ARDS. The above hypothesis was investigated in a nested case-control study of 441 Caucasian controls and 212 cases admitted to an intensive care unit with sepsis, trauma, aspiration or hyper-transfusions. The -308A and TNFB1 alleles were in linkage disequilibrium. These polymorphisms were not associated with ARDS susceptibility on crude analysis. On subgroup analyses, they were associated with either increased or decreased odds of developing ARDS depending on whether the clinical risk for ARDS results in direct or indirect pulmonary injury. The -308A allele was associated with increased 60-day mortality in ARDS, with the strongest association found among younger patients. There was no association between the TNFB polymorphism and ARDS mortality. The -308GA, but not the TNFB12, polymorphism was associated with increased mortality in acute respiratory distress syndrome, but their association with acute respiratory distress syndrome susceptibility depended on the site of injury predisposing to acute respiratory distress syndrome.

Neonatal depletion of cortical dopamine: effects on dopamine turnover and motor behavior in juvenile and adult rats.

Abnormal development of mesoprefrontal dopamine (DA) neurons may contribute to the pathophysiology of schizophrenia. Consistent with this hypothesis, DA nerve terminal density is decreased in the cortex of schizophrenic subjects [M. Akil, J.N. Pierri, R.E. Whitehead, C.L. Edgar, C. Mohila, A.R. Sampson, and D.A. Lewis, Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects, Am. J. Psychiatry, 156 (1999) 1580-1589]. This abnormality may be present early in development, giving rise to dysfunction as an individual matures. The present studies examined the effects of early partial loss of medial prefrontal cortex (mPFC) DA on DA turnover and locomotor behavior in juvenile, pubertal, and adult rats (30, 45, and 60 days of age, respectively). Local infusions of 6-hydroxydopamine on postnatal day (PN) 12-14 produced persistent decreases in basal tissue DA concentrations and increases in 3,4-dihydroxyphenylacetic acid (DOPAC):DA ratios in the mPFC. In the nucleus accumbens of lesioned rats, basal DA concentrations were decreased and DOPAC:DA ratios were increased on PN30, but not PN45 or 60. Footshock (30 min at 0.6 mA) increased DOPAC and DOPAC:DA ratios in the mPFC of PN30 and 60 control rats. These effects were attenuated in age-matched rats previously sustaining approximately 50% loss of mPFC DA on PN12-14. Footshock did not affect DOPAC:DA ratios in the nucleus accumbens of control or lesioned rats. The lesion also failed to alter basal or stress-evoked motor activity. The present data suggest that a decreased density of mPFC DA nerve terminals occurring early in development results in persistent alterations in basal and stress-evoked activity of mesoprefrontal DA neurons, but not mesoaccumbens DA neurons.

Exposure to welding fumes is associated with acute systemic inflammatory responses.

AIMS: To investigate the acute systemic inflammatory response to welding fume exposure. METHODS: Twenty four welders (42% smokers) and 13 non-exposed controls (23% smokers) were monitored at a welding school. Exposure to fine particulate matter (PM2.5) was assessed using cyclone samplers. Markers of systemic inflammation, including C-reactive protein (CRP), fibrinogen, and white blood cell (WBC) levels, were determined in peripheral blood samples collected at baseline and after 5.3 (SD 1.0) hours of exposure. RESULTS: The median PM2.5 concentration for welders was 1.66 mg/m3, which was significantly greater than that for controls (0.04 mg/m3). Compared to non-smokers, smokers had a significantly higher baseline WBC count, but comparable levels of CRP and fibrinogen. In non-smokers, welding fume exposure was associated with a significant increase in WBC and neutrophil counts immediately following exposure (+0.8x10(3)/mul, 95% CI 0.1 to 1.6, and +1.0x10(3)/mul, 95% CI 0.4 to 1.7, respectively). A significant decrease in fibrinogen levels was observed in non-smokers (-32 mg/dl, 95% CI -63 to -1). No significant changes in WBC, neutrophil, and fibrinogen levels were found in smokers. Sixteen hours after welding exposure, CRP levels were found to be significantly increased in both non-smokers and smokers (0.90 mg/l, 95% CI 0.17 to 1.64). PM2.5 concentrations were found to be significantly associated with absolute neutrophil counts in non-smokers, and CRP levels in both non-smokers and smokers. CONCLUSIONS: High levels of welding fume exposure induce acute systemic inflammation in a relatively young, healthy working population. These results also suggest that smoking may modify the effect of welding fume exposure on specific inflammatory markers.

Further psychometric testing of a brief personality scale to measure vulnerability to postpartum depression.

The Vulnerability Personality Style Questionaire (VPSQ), a 9-item self-report personality scale, was developed to identify women at-risk for postpartum depression due to personality vulnerability. Preliminary research with this scale suggests it has satisfactory psychometric properties. The purpose of this methodological study was to further examine the psychometric properties of the VPSQ in a sample of Canadian women. As part of a longitudinal study, women completed postal questionnaires at 1, 4, and 8 weeks postpartum that included the VPSQ, Edinburgh Postnatal Depression Scale, Rosenburg Self-Esteem Scale, and Perceived Stress Scale. Five hundred and ninety-four women returned questionnaires suitable for analysis. The Cronbach's alpha coefficient for the VPSQ was 0.67 and significant correlations between the VPSQ and self-esteem (r = 0.58) and perceived stress (r = 0.55) scales were found, providing evidence for construct validity. In a logistic regression analysis, VPSQ was predictive of developing depressive symptomatology 1, 4 and 8 weeks postpartum; an increase of one point on the VPSQ increased the risk of developing postpartum depression 1.3 fold. The results from this study support the overall utility of the VPSQ. As such, this brief instrument is ready to assist in the identification of women at-risk of developing postpartum depression such that appropriate secondary preventive or treatment interventions may be initiated.

Risk factors for postnatal depression: a review and risk factors in Australian populations.

Postnatal depression affects up to 15% of women in the six months following childbirth. Risk factors for this disorder are predominantly psychosocial. An overview of sociodemographic, early life experiences, external environment, internal environment and obstetric and infant variables are presented in the introduction. Two studies that recruited women shortly after they had given birth and followed up to six months postpartum are used to demonstrate the salience of such risk factors. The importance of clarifying risk factors to postnatal depression are discussed especially in relation to improving our understanding of the mechanisms of postnatal depression, how they may assist in developing preventative strategies and how they can help in planning treatment.

Attitudes toward psychiatry among students entering medical school.

OBJECTIVE: To survey the attitudes of Australian medical students to determine their views about the relative attractiveness of psychiatry as a career compared with other specialties, and against findings from a North American study. METHOD: We surveyed 655 first-year medical students attending six Australian Universities. RESULTS: Responses indicated that Australian medical students view psychiatry as distinctly less 'attractive' than other career options, as reported in the North American sample. In comparison with other disciplines, psychiatry was regarded as more interesting and intellectually challenging, but also as lacking a scientific foundation, not being enjoyable and failing to draw on training experiences. CONCLUSION: Our findings suggest that psychiatry has an image problem that is widespread, reflecting community perceptions and the specialist interests of medical students on recruitment. If psychiatry is to improve its 'attractiveness' as a career option, identified image problems need to be corrected and medical student selection processes re-considered.

Predictors of conventional and alternative health care seeking for irritable bowel syndrome and functional dyspepsia.

BACKGROUND: The drivers of conventional and, especially, alternative health care use for irritable bowel syndrome and functional dyspepsia are not clear. AIM: To determine the predictors of conventional and alternative health care use for irritable bowel syndrome and functional dyspepsia. METHODS: Two hundred and seven subjects with irritable bowel syndrome or functional dyspepsia, identified from a previous population survey, were included in the study. Individuals with irritable bowel syndrome/functional dyspepsia were defined as consulters (n = 103) if they had visited their doctor for gastrointestinal symptoms more than once in the past year. Controls (n = 100) did not report having any abdominal pain. Subjects were given structured interviews to assess the Diagnostic and Statistical Manual - version IV (DSM-IV) and International Classification of Disorders - version 10 (ICD-10) psychiatric diagnosis for anxiety, depression, somatization or any psychiatric diagnosis, aspects of health care use and symptom factors. RESULTS: About one-half (n = 103, 49.8%) of community subjects with irritable bowel syndrome/functional dyspepsia had sought conventional care for gastrointestinal symptoms in the past 12 months. Lifetime rates for alternative health care use for gastrointestinal symptoms were 20.8% (n = 43). Independent predictors of conventional health care use were more frequent abdominal pain, greater interference of gastrointestinal symptoms with work and activities and a greater satisfaction with the physician-patient relationship. Being female independently predicted alternative health care use. CONCLUSIONS: Psychological morbidity did not predict conventional or alternative health care use for gastrointestinal symptoms. Other factors were more important.