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.

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.

Low light level detectors for astronomy.

There is an almost bewildering variety of detectors being used for ground-based astronomical observations. Many of the detectors have advantages for particular projects. One-dimensional detectors are simple, yet suitable for spectroscopy. Other detectors offer high photometric precision and dimensional stability. Some are designed for observing only faint objects and some for bright ones. Sometimes the necessity of having a high quantum efficiency at a particular wavelength dictates the choice of detector. In reality the situation is even more chaotic. This review has not covered some of the exotic detectors that have been developed for x-ray and far-ultraviolet imaging from spacecraft. These detectors use devices such as resistive plates, multianode or crossed-wire microchannel plates, and so on. These devices have not yet seen extensive use in ground-based applications, and their future as visible light detectors remains uncertain. The reasons for the development of such a wide variety of detectors are clear. Commercially available devices are simply not capable of meeting the low light level and photometric performance capabilities needed for astronomical observations. The driving forces are the commercial and military applications for detectors, and with few exceptions there has not been sufficient funding available to mount a detector development program for astronomy. Therefore, astronomers have sought to adapt existing commercial devices to the particular problem at hand. The large number of individual efforts summarized in this review is the result. In the future, I expect the variety to diminish as one or two really good detectors become capable of performing well under the wide variety of observational conditions encountered in astronomy. Many people have proclaimed the ultimate detector to be just around the corner. This is yet to happen. However, I venture to speculate that low-noise, high-performance CCD detectors with a format of 500 by 500 or larger will emerge as the preferred astronomical detector within the next few years. I also expect photographic plates will continue to be used for the many applications requiring wide fields up to 10,000 pixels on a side. Finally, as the detectors approach the ultimate quantum limit, attention will shift away from them and toward development of the system necessary to manipulate, display, and extract the information from the 250,000 numbers that make up a 500 by 500 digital image.

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.

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).

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.

Effects of light on melatonin production.

A study was carried out to determine the intensity of light necessary to suppress melatonin. Ten normal subjects were exposed to four light intensities of 1000, 1500, 2000, and 2500 lux for 2 hr on different occasions, and melatonin levels were measured during exposure. All light intensities suppressed melatonin significantly, but none do daytime levels, with 2500 lux appearing to be the most "potent."

Depressive psychomotor disturbance, cortisol, and dexamethasone.

We examine the dexamethasone suppression test as a biological correlate of melancholia as defined by the CORE system, a scale for rating objective signs of psychomotor disturbance. Postdexamethasone cortisol concentrations and rates of nonsuppression were higher in CORE, Newcastle, and DSM-III-R defined melancholic groups. These differences, however, were no longer significant after partialling out the combined effects of age, dexamethasone, and basal cortisol concentrations. There was a significant correlation between the CORE (but not the Newcastle) scale and 8:00 AM postdexamethasone cortisol levels, which persisted after partialling out those same three covariates. Dexamethasone concentrations themselves were lower in CORE- and Newcastle-defined melancholics, though these were no longer significant after covarying for cortisol concentrations. Dexamethasone levels were also significantly inversely correlated with CORE and Newcastle scales. A significant correlation between CORE (but not Newcastle) scores and dexamethasone levels at 4:00 PM persisted after partialling out the effects of age and cortisol. These findings indicate an intriguing relationship between the CORE system as a dimensional construct for rating psychomotor disturbance, and both postdexamethasone cortisol and dexamethasone concentrations.

RNA 4 sequences from cucumber mosaic virus subgroups I and II.

The complete sequences of RNA 4 from cucumber mosaic virus (CMV) strains Ny (subgroup I) and Sn (subgroup II) have been determined and compared to all other known complete CMV RNA 4 sequences. The identification of a unique EcoRI site, present only in subgroup-II RNA 4 sequences, provides the basis for a simple method of classifying CMV isolates.

6-Sulphatoxy melatonin in melancholia.

The daytime and nighttime levels of 6-sulphatoxy melatonin, a metabolite of melatonin, were measured in eight melancholic patients. Three patients did not show a marked nocturnal increase in 6-sulphatoxy melatonin excretion. The author discusses the relationship between melatonin and melancholia.

Seasonal affective disorder in the southern hemisphere.

To determine whether seasonal affective disorder exists in the southern hemisphere and whether there is any seasonal specificity in phenomenology, the authors compared 23 subjects who reported a winter/autumn affective disorder, consistent with earlier definitions of the syndrome, with 22 subjects who reported a spring/summer affective disorder. The subjects with winter/autumn onset were characterized by increased appetite, carbohydrate craving, and increased sleep; those with spring/summer onset reported decreased sleep and decreased appetite. Hypotheses concerning the etiology of seasonal affective disorder are discussed.

Personality differences between patients with remitted melancholic and nonmelancholic depression.

Seventy-five patients with remitted depression were categorized as having melancholic-endogenous or non-melancholic-nonendogenous depression according to DSM-III criteria, Research Diagnostic Criteria, and the Newcastle endogeneity scale. The patients' scores on four personality scales--the Eysenck Personality Inventory, the Interpersonal Dependency Inventory, locus of control, and the Interpersonal Sensitivity Measure--were then compared. Patients with nonmelancholic-nonendogenous depression were generally rated as having more vulnerable personality styles, but the differences were dependent on the particular diagnostic system used. A principal components analysis isolated three underlying personality constructs--dependency, introversion, and timidity. Patients with nonmelancholic-nonendogenous depression scored as significantly more dependent.

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.

Carbamazepine for treatment-resistant melancholia.

BACKGROUND: There have only been a few studies of the role of carbamazepine in the management of treatment-resistant depression. METHOD: The response to carbamazepine of 16 melancholic patients, who had been depressed for an extended period despite a number of standard treatments, was studied retrospectively. RESULTS: Seven patients (44%) had a moderate or marked improvement. The responders included both psychotic and nonpsychotic depressives, and patients with concurrent organic brain disease. There was, however, a high rate of complications, with 5 of these 7 responders (71%) having to discontinue carbamazepine because of adverse effects. This high rate of complications may have reflected the older age of our sample. CONCLUSION: These findings suggest the efficacy of carbamazepine in melancholic patients who have not responded to conventional treatments, but indicate that the high rate of significant side effects may limit its long-term usefulness.

Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole.

OBJECTIVE: To investigate the effects of the immune modulators levamisole and loxoribine in a rat model of endometriosis. DESIGN: Prospective, placebo-controlled study. SETTING: Hospital-based research facility. ANIMAL(S): Nineteen rats with experimentally induced endometriosis. INTERVENTION(S): Rats were treated with three weekly intraperitoneal injections of levamisole (2 mg per rat; n = 6), loxoribine (1 mg per rat; n = 6), or saline (control; n = 7) and killed 8 weeks after treatment. MAIN OUTCOME MEASURE(S): Histologic and immunohistochemical analysis of endometriotic explants. RESULT(S): The loxoribine-treated group showed marked regression of both epithelial and stromal components. Epithelial regression was noted in the control group, but the epithelium was strikingly preserved in the levamisole group. There were significantly greater numbers of dendritic cells in the explants of animals treated with loxoribine and levamisole. The number of natural killer cells was significantly reduced in loxoribine-treated explants. CONCLUSION(S): Loxoribine, a potent immunomodulatory drug, appeared to cause regression in both stromal and epithelium components in a rat model of endometriosis. Further, specific cell-mediated immune responses in this model of endometriosis were elucidated.