The prevalence of premenstrual dysphoric disorder: Systematic review and meta-analysis.

BACKGROUND: Premenstrual dysphoric disorder is characterised by symptoms confined to the premenstrual phase of the menstrual cycle. Confirmed diagnosis requires prospective monitoring of symptoms over two cycles, otherwise the diagnosis is provisional. We aimed to measure the point prevalence of premenstrual dysphoric disorder. METHODS: We searched for studies of prevalence using MEDLINE, EMBASE, PsycINFO and PubMed. For each study, the total sample size and number of cases were extracted. The prevalence across studies was calculated using random effects meta-analysis with a generalised linear mixed model. Potential sources of heterogeneity were explored by meta-regression and subgroup analyses. Pre-registration was with PROSPERO (CRD42021249249). RESULTS: 44 studies with 48 independent samples met inclusion criteria, consisting of 50,659 participants. The pooled prevalence was 3.2 % (95 % confidence intervals: 1.7 %-5.9 %) for confirmed and 7.7 % (95 % confidence intervals: 5.3 %-11.0 %) for provisional diagnosis. There was high heterogeneity across all studies (I2 = 99 %). Sources of heterogeneity identified by meta-regression were continent of sample (p < 0.0001), type of sample (community-based, university, high school) (p = 0.007), risk of bias (p = 0.009), and method of diagnosis (p = 0.017). Restricting the analysis to community-based samples using confirmed diagnosis resulted in a prevalence of 1.6 % (95 % confidence intervals: 1.0 %-2.5 %), with low heterogeneity (I2 = 26 %). LIMITATIONS: A small number of included studies used full DSM criteria in community settings. CONCLUSIONS: The point prevalence of premenstrual dysphoric disorder using confirmed diagnosis is lower compared with provisional diagnosis. Studies relying on provisional diagnosis are likely to produce artificially high prevalence rates.

Systematic review of the association between adverse life events and the onset and relapse of postpartum psychosis.

Postpartum psychosis is defined as a psychotic episode occurring within 4 to 6 weeks of childbirth. While there is robust evidence that adverse life events are associated with the onset and relapse of psychosis outside the postpartum period, the extent to which these contribute to postpartum psychosis is less clear. This systematic review examined whether adverse life events are associated with an increased likelihood of developing postpartum psychosis or subsequent relapse in women diagnosed with postpartum psychosis. The following databases were searched from inception to June 2021: MEDLINE, EMBASE, PsycInfo. Study level data were extracted including setting, number of participants, type of adverse event, and differences between groups. A modified version of the Newcastle-Ottawa Quality Assessments Scale was used to assess risk of bias. In total, 1933 records were identified, of which 17 met the inclusion criteria, comprising nine case-control studies and eight cohort studies. Most studies (16/17) examined the association between adverse life events and the onset of postpartum psychosis, with only in which the outcome was relapse of psychosis. Overall, there were 63 different measures of adversity examined (most of which were examined in a single study only) and 87 associations between these measures and postpartum psychosis tested across the studies. In terms of statistically significant associations with onset/relapse of postpartum psychosis, 15 (17%) were positive (i.e., the adverse event increased the risk of onset/relapse), 4 (5%) were negative, and 68 (78%) were not statistically significant. Our review highlights the diversity of risk factors examined in this field, with few attempts at replication, hence limiting the ability to conclude that any single risk factor is robustly associated with the onset of postpartum psychosis. Further large-scale studies, that attempt to replicate earlier studies, are urgently needed to determine whether adverse life events play a role in the onset and exacerbation of postpartum psychosis. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=260592], identifier [CRD42021260592].

Point of care assay for blood aripiprazole concentrations: development, validation and utility.

BACKGROUND: The antipsychotic aripiprazole is often used in the treatment of first-episode psychosis. Measuring aripiprazole blood levels provides an objective measure of treatment adherence, but this currently involves taking a venous blood sample and sending to a laboratory for analysis. AIMS: To detail the development, validation and utility of a new point of care (POC) test for finger-stick capillary blood concentrations of aripiprazole. METHOD: Analytical performance (sensitivity, precision, recovery and linearity) of the assay were established using spiked whole blood and control samples of varying aripiprazole concentration. Assay validation was performed over a 14-month period starting in July 2021. Eligible patients were asked to provide a finger-stick capillary sample in addition to their usual venous blood sample. Capillary blood samples were tested by the MyCare™ Insite POC analyser, which provided measurement of aripiprazole concentration in 6 min, and the venous blood sample was tested by the standard laboratory method. RESULTS: A total of 101 patients agreed to measurements by the two methods. Venous blood aripiprazole concentrations as assessed by the laboratory method ranged from 17 to 909 ng/mL, and from 1 to 791 ng/mL using POC testing. The correlation coefficient between the two methods (r) was 0.96 and there was minimal bias (slope 0.91, intercept 4 ng/ml). CONCLUSIONS: The MyCare Insite POC analyser is sufficiently accurate and reliable for clinical use. The availability of this technology will improve the assessment of adherence to aripiprazole and the optimising of aripiprazole dosing.

A case series of premenstrual disorders presenting to the UK's National Female Hormone Clinic.

AIMS AND METHOD: We aimed to describe the clinical characteristics of female patients presenting with premenstrual disorders to a tertiary service in the UK. We conducted a retrospective case-note review of referrals to the National Female Hormone Clinic from April 2014 to August 2020. Based on clinical assessment, we determined whether the patient met criteria for premenstrual dysphoric disorder or premenstrual exacerbation of an underlying psychiatric disorder. RESULTS: Of 146 patients seen in clinic for premenstrual disorders, an ICD-10 psychiatric diagnosis was made in 130 (89.0%); a minority 16 (11.0%) did not have a psychiatric diagnosis. Following assessment, 94 patients (64.4%) met criteria for premenstrual dysphoric disorder and 67 (45.6%) had exacerbation of a psychiatric disorder. CLINICAL IMPLICATIONS: Patients presenting to this specialist service had complex psychiatric comorbidity; almost half presented with exacerbation of a psychiatric disorder.

Intermittent selective serotonin reuptake inhibitors for premenstrual syndromes: A systematic review and meta-analysis of randomised trials.

BACKGROUND: Intermittent (luteal phase) dosing of selective serotonin reuptake inhibitors is one treatment strategy for premenstrual syndromes such as premenstrual dysphoric disorder. This avoids the risk of the antidepressant withdrawal syndrome associated with long-term continuous dosing. AIMS: To compare intermittent dosing to continuous dosing in terms of efficacy and acceptability. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, PubMed and CINAHL for randomised trials of intermittent compared with continuous dosing of selective serotonin reuptake inhibitors in premenstrual syndromes. We extracted response rates, dropout rates and changes in symptom scores. We used random effects meta-analyses to pool study-level data and calculated odds ratio for dichotomous data and standardised mean difference for continuous data. Risk of bias was assessed using the Cochrane risk-of-bias tool. The study was registered with PROSPERO (CRD42020224176). RESULTS: A total of 1841 references were identified, with eight studies being eligible for analysis, consisting of a total of 460 participants. All included studies provided response rates, six provided dropout rates and five provided symptom scores. There was no statistically significant differences between intermittent and continuous dosing in terms of response rate (odds ratio: 1.0, 95% confidence interval (CI): 0.23-4.31, I2 = 71%), dropout rate (odds ratio 1.26, 95% CI: 0.39-4.09, I2 = 33%) or symptom change (standardised mean difference: 0.04, 95% CI: -0.27 to 0.35, I2 = 39%). All studies had a moderate or high risk of bias. CONCLUSION: Since intermittent dosing avoids the potential for withdrawal symptoms, it should be considered more commonly in this patient population.

Serum NOX1 and Raftlin as New Potential Biomarkers of Interest in Schizophrenia: A Preliminary Study.

Introduction: There is increasing evidence that oxidative stress (OS) and neuroinflammation play a role in the neuroprogression of schizophrenia (SCZ). Promising novel candidates which have been proposed in the search for biomarkers of psychotic illness include NADPH oxidase 1,2 (NOX1,2) and raftlin. NOX1 from the NOX family is the main source of physiological reactive oxygen species (ROS) and raftlin, the main lipid raft protein, is associated with inflammatory processes. The aim of the present study was to evaluate serum NOX1 and raftlin levels in chronic stable patients with SCZ. Methods: We measured serum NOX1 and raftlin levels from 45 clinically stable patients with SCZ and 45 healthy controls (HCs) matched for age, sex, and body-mass index. The Positive and Negative Syndrome Scale was applied to the patient group to evaluate the severity of psychotic symptoms. Results: NOX1 and raftlin levels in the patients were statistically significantly higher than the HCs (NOX1 p<0.001, raftlin p<0.001). Both parameters showed very good diagnostic performance (NOX1 AUC = 0.931, raftlin AUC = 0.915). We obtained positive and significant correlations between serum levels of both biomarkers and symptom severity. Discussion: This preliminary study indicating elevations in serum NOX1 and raftlin levels in patients with SCZ supports the importance of OS and inflammatory processes in the etiopathogenesis of the illness.

Exacerbation of Psychosis During the Perimenstrual Phase of the Menstrual Cycle: Systematic Review and Meta-analysis.

Psychotic disorders can be exacerbated by the hormonal changes associated with childbirth, but the extent to which exacerbations occur with the menstrual cycle is unclear. We addressed this issue by conducting a systematic review. Embase, Medline, and PsychINFO databases were searched for studies that measured exacerbations of psychotic disorders in relation to the menstrual cycle. We extracted exacerbation measure, definition of menstrual cycle phase, and measurement of menstrual cycle phase. Standard incidence ratios were calculated for the perimenstrual phase based on the observed admissions during this phase divided by the expected number of admissions if the menstrual cycle had no effect. Random effects models were used to examine pooled rates of psychiatric admission in the perimenstrual phase. Nineteen studies, comprising 1193 participants were eligible for inclusion. Eleven studies examined psychiatric admission rates, 5 examined symptoms scores, 2 examined self-reported exacerbation, and 1 examined both admission rates and symptom scores. A random effects model demonstrated the rate of admissions during the perimenstrual phase was 1.48 times higher than expected (95% CI: 1.31-1.67), with no significant heterogeneity detected. Four of six symptom score studies reported perimenstrual worsening, but lack of consistency in timepoints precluded meta-analysis. Two studies examining self-reported menstrual exacerbations reported prevalences ranging from 20% to 32.4%. Psychiatric admission rates are significantly higher than expected during the perimenstrual phase. There is some evidence that a worsening of psychotic symptoms also occurs during this phase, but further research with more precise measurement of the menstrual cycle and symptomatology is required.

What Causes the Onset of Psychosis in Individuals at Clinical High Risk? A Meta-analysis of Risk and Protective Factors.

Twenty percent of individuals at clinical high risk for psychosis (CHR-P) develop the disorder within 2 years. Extensive research has explored the factors that differentiate those who develop psychosis and those who do not, but the results are conflicting. The current systematic review and meta-analysis comprehensively addresses the consistency and magnitude of evidence for non-purely genetic risk and protective factors associated with the risk of developing psychosis in CHR-P individuals. Random effects meta-analyses, standardized mean difference (SMD) and odds ratio (OR) were used, in combination with an established stratification of evidence that assesses the association of each factor and the onset of psychotic disorders (from class I, convincing evidence to class IV weak evidence), while controlling for several types of biases. A total of 128 original controlled studies relating to 26 factors were retrieved. No factors showed class I-convincing evidence. Two further factors were associated with class II-highly suggestive evidence: attenuated positive psychotic symptoms (SMD = 0.348, 95% CI: 0.280, 0.415) and global functioning (SMD = -0.291, 95% CI: -0.370, -0.211). There was class III-suggestive evidence for negative psychotic symptoms (SMD = 0.393, 95% CI: 0.317, 0.469). There was either class IV-weak or no evidence for all other factors. Our findings suggest that despite the large number of putative risk factors investigated in the literature, only attenuated positive psychotic symptoms, global functioning, and negative psychotic symptoms show suggestive evidence or greater for association with transition to psychosis. The current findings may inform the refinement of clinical prediction models and precision medicine in this field.

Gamma band oscillations in the early phase of psychosis: A systematic review.

Abnormal gamma oscillations, measured by electroencephalography (EEG), have been associated with chronic psychotic disorders, but their prevalence in the early phase of psychosis is less clear. We sought to address this by systematically reviewing the relevant literature. We searched for EEG studies of gamma band oscillations in subjects at high risk for psychosis and in patients with first episode psychosis. The following measures of gamma oscillations were extracted: resting power, evoked power, induced power, connectivity and peak frequency. Forty-five studies with a total of 3099 participants were included. There were potential sources of bias in the study designs and potential artefacts. Although there were few consistent findings, several studies reported decreased evoked or induced power in both high risk subjects and first episode patients. Studies using larger samples with serial EEG measurements, and designs that minimise artefacts that occur at the gamma frequency may advance work in this area.

Neuroleptic malignant syndrome following catatonia: Vigilance is the price of antipsychotic prescription.

OBJECTIVES: To describe a case of neuroleptic malignant syndrome following antipsychotic treatment of catatonia, highlighting the potentially serious complications of this rare adverse drug reaction. METHODS: We present a case report of a patient who developed this syndrome with various sequelae. RESULTS: The patient developed neuroleptic after being treated with lorazepam and olanzapine for catatonia. He subsequently developed the complications of rhabdomyolysis, acute kidney injury, pulmonary embolism, urinary retention and ileus. He received high-dose lorazepam, anticoagulation and intravenous fluids. Antipsychotic medication in the form of haloperidol was reinstated with no adverse effect, and he went on to make a full recovery. CONCLUSIONS: This case illustrates the potential life-threatening complications of neuroleptic malignant syndrome and the need for a low index of clinical suspicion. It also highlights the lack of evidence for treatment of catatonia, including the use of antipsychotics.

Crystal structure and tartrate inhibition of Legionella pneumophila histidine acid phosphatase.

Histidine acid phosphatases (HAPs) utilize a nucleophilic histidine residue to catalyze the transfer of a phosphoryl group from phosphomonoesters to water. HAPs function as protein phosphatases and pain suppressors in mammals, are essential for Giardia lamblia excystation, and contribute to virulence of the category A pathogen Francisella tularensis. Herein we report the first crystal structure and steady-state kinetics measurements of the HAP from Legionella pneumophila (LpHAP), also known as Legionella major acid phosphatase. The structure of LpHAP complexed with the inhibitor l(+)-tartrate was determined at 2.0 Å resolution. Kinetics assays show that l(+)-tartrate is a 50-fold more potent inhibitor of LpHAP than of other HAPs. Electrostatic potential calculations provide insight into the basis for the enhanced tartrate potency: the tartrate pocket of LpHAP is more positive than other HAPs because of the absence of an ion pair partner for the second Arg of the conserved RHGXRXP HAP signature sequence. The structure also reveals that LpHAP has an atypically expansive active site entrance and lacks the nucleotide substrate base clamp found in other HAPs. These features imply that nucleoside monophosphates may not be preferred substrates. Kinetics measurements confirm that AMP is a relatively inefficient in vitro substrate of LpHAP.

Inactivation of protein tyrosine phosphatases by dietary isothiocyanates.

Isothiocyanates are bioactive dietary phytochemicals that react readily with protein thiol groups. We find that isothiocyanates are time-dependent inactivators of cysteine-dependent protein tyrosine phosphatases (PTPs). Rate constants for the inactivation of PTP1B and SHP-2 by allyl isothiocyanate and sulforaphane range from 2 to 16 M(-1)s(-1). Results in the context of PTP1B are consistent with a mechanism involving covalent, yet reversible, modification of the enzyme's active site cysteine residue.

The neurology-psychiatry divide: a thought experiment.

Diseases of the brain are generally classified as either neurological or psychiatric. However, these two groups of illnesses cannot be readily separated on the basis of pathophysiology or symptomatology. It is difficult to rationally explain to someone with no prior frame of reference why we have the split between neurological and psychiatric illness. This demonstrates that the division is untenable, which has implications for training in both psychiatry and neurology.

Psychometric properties of the 16-item Quick Inventory of Depressive Symptomatology: a systematic review and meta-analysis.

Effective management of depression is predicated upon reliable assessment. The Quick Inventory of Depressive Symptomatology (QIDS) is a depression severity scale with both self-rated (QIDS-SR16) and clinician-rated (QIDS-C16) versions. Although widely used in research, the psychometric properties of the QIDS16 have not been systematically reviewed. We performed a systematic review of studies of the psychometric properties (factor structure, internal consistency, convergent validity, discriminant validity, test-retest reliability and responsiveness to change) of the QIDS-SR16 or QIDS-C16. Six databases were searched: MEDLINE, EMBASE, PsycINFO, CinAHL, Web of Science and the Cochrane Central Register of Controlled Trials. Findings were summarised, bias assessed and correlations with reference standards were pooled. 37 studies (17,118 participants) were included in the review. Both versions of the QIDS16 were unidimensional. Cronbach's alpha ranged from 0.69 to 0.89 for the QIDS-SR16 and 0.65 to 0.87 for the QIDS-C16. The QIDS-SR16 correlated moderately to highly with several depression severity scales. Seven studies were pooled where QIDS-SR16 was correlated with the HRSD-17 (r = 0.76, CI 0.69, 0.81) in patients diagnosed with depression. Four studies examined convergent validity with the QIDS-C16. Four studies examined discriminant validity, for the QIDS-SR16 alone. Eighteen studies had at least one author who was a co-author of the original QIDS16 study. Most studies were conducted in the USA (n = 26). The QIDS-SR16 and the QIDS-C16 are unidimensional rating scales with acceptable internal consistency. To justify the use of the QIDS16 scale in clinical practice, more research is needed on convergent and discriminant validity, and in populations outside the USA.

Isolation of Aureimonas altamirensis, a Brucella canis-like bacterium, from an edematous canine testicle.

Microbiological and histological analysis of a sample from a swollen testicle of a 2-year-old Border Collie dog revealed a mixed infection of the fungus Blastomyces dermatitidis and the Gram-negative bacterium Aureimonas altamirensis. When subjected to an automated microbial identification system, the latter isolate was provisionally identified as Psychrobacter phenylpyruvicus, but the organism shared several biochemical features with Brucella canis and exhibited agglutination, albeit weakly, with anti-B. canis antiserum. Unequivocal identification of the organism was only achieved by 16S ribosomal RNA gene sequencing, ultimately establishing the identity as A. altamirensis. Since its first description in 2006, this organism has been isolated infrequently from human clinical samples, but, to the authors' knowledge, has not been reported from a veterinary clinical sample. While of unknown clinical significance with respect to the pathology observed for the polymicrobial infection described herein, it highlights the critical importance to unambiguously identify the microbe for diagnostic, epidemiological, infection control, and public health purposes.

Genome Sequence of Actinobacillus suis Type Strain ATCC 33415T.

The assembled and annotated genome of Actinobacillus suis ATCC 33415(T) is reported here. The 2,501,598-bp genome encodes 2,246 open reading frames (ORFs) with strain variable incursion of an integrative conjugative element into a tRNA locus. Comparative analysis of the deduced gene set should inform our understanding of pathogenesis, genomic plasticity, and serotype variation.

The relative frequencies of causes of widespread ground-glass opacity: a retrospective cohort.

PURPOSE: The purpose of our study was to determine the relative frequencies of causes of widespread ground-glass opacity (GGO) in an unselected, consecutive patient population and to identify any associated imaging findings that can narrow or reorganize the differential. MATERIALS AND METHODS: The study was approved by the center's IRB and is HIPPA compliant. Cases with widespread GGO in the radiology report were identified by searching the Radiology Information System. Medical records and CT scan examinations were reviewed for the causes of widespread GGO. Associations between a less dominant imaging finding and a particular diagnosis were analyzed with the chi square test. Our study group consisted of 234 examinations with 124 women and 110 men and a mean age of 53.7 years. RESULTS: A cause was established in 204 (87.2%) cases. Hydrostatic pulmonary edema was most common with 131 cases (56%). Interstitial lung diseases (ILD) were the next most common, most often hypersensitivity pneumonitis (HP) (n=12, 5%) and connective tissue disease related ILD (n=7, 3%). Infection accounted for 5% (12 cases). A few miscellaneous diseases accounted for 5 cases (2.1%). The combination of septal thickening and pleural effusions had a specificity of 0.91 for hydrostatic pulmonary edema (P<.001) while centrilobular nodules and air trapping had a specificity of 1.0 for HP. In 24 (10.2%) patients, increased opacification from expiration was incorrectly interpreted as representing widespread ground glass opacity. The relative frequency of disease dramatically changed according to the setting. In the inpatient setting, diffuse alveolar disease and diffuse infection accounted for all of the known diagnoses. Pulmonary edema accounted for 75% of the diagnoses and diffuse infection accounted for approximately 7%. In the outpatient setting, interstitial lung disease was the most common cause, accounting for 26 of 53 cases (49%). Regarding immunocompromised patients, hydrostatic pulmonary edema was still the most common cause (46%) with diffuse infection (24%) the next most likely diagnosis. For patients with bone marrow suppression, 80% of the cases were due to opportunistic viral infection. CONCLUSION: Widespread GGO is most commonly a manifestation of hydrostatic pulmonary edema. Outpatients will most often have HP or connective tissue disease related ILD. Associated findings are helpful for the diagnosis of hydrostatic pulmonary edema and HP.

Draft Genome Sequence of Moraxella bovoculi Strain 237T (ATCC BAA-1259T) Isolated from a Calf with Infectious Bovine Keratoconjunctivitis.

Moraxella bovoculi is a recently identified species, recovered from the bovine eye, which is under investigation as an etiological agent of infectious bovine keratoconjunctivitis. A draft genome sequence of the Moraxella bovoculi type strain 237(T) has been determined to identify features that may be important during host colonization.