The distance of ∼2.49 Å separating the carboxylic OH oxygen from the water oxygen atom in the α-polymorph of crystalline oxalic acid dihydrate is by ∼0.1 Å shorter than the average distance in ...carboxylic acid monohydrates. It is also by ∼0.2 Å shorter than the corresponding distance presently calculated for the heterotrimer consisting of one acid and two water molecules. The large difference between R O···O in the heterotrimer and in the crystal is attributed to the cooperative effect in the latter; this is supported by calculations carried out on clusters constituted of an increasing number of acid and water molecules. The present DFT calculations with geometry optimization include seven isolated model clusters, the largest of which contains five acid and eight water molecules. The R O···O of the short hydrogen bond shortens progressively with increasing the number of cluster constituents; in the largest cluster, it reaches 2.50 Å. This is remarkably close to both the experimental distance as well as to the distance obtained by the periodic DFT calculation. The electronic effects were studied by Natural Bond Orbital analysis, revealing an enhancement of hydrogen bonding on extending the network by increased polarization of the carbonyl group and by the increased delocalization interaction between the lone electron pair on the acceptor oxygen atom and the OH antibond orbital. The formation of circular motifs appears to be the most important factor in the cooperative shortening of the hydrogen bonds. In agreement with the measured hydrogen bond distances, inspection of the electron density reveals a notable difference in hydrogen bond shrinking tendency between the two known polymorphs of the title system.
Low temperature Raman spectra of oxalic acid dihydrate (8–300 K) for both the polycrystalline and single crystal phase show strong variation with temperature in the interval from 1200 to 2000 cm–1. ...Previous low temperature diffraction studies all confirmed the stability of the crystal P21/n phase with no indications of any phase transition, reporting the existence of a strong hydrogen bond between the oxalic acid and a water molecule. A new group of Raman bands in the 1200–1300 cm–1 interval below 90 K is observed, caused by possible loss of the center of inversion. This in turn could originate either due to disorder in hydroxyl proton positions or due to proton transfer from carboxylic group to water molecule. The hypothesis of proton transfer is further supported by the emergence of new bands centered at 1600 and 1813 cm–1, which can be explained with vibrations of H3O+ ions. The broad band at 1600 cm–1 looses intensity, while the band at 1813 cm–1 gains intensity on cooling. The agreement between quantum calculations of vibrational spectra and experimentally observed Raman bands of hydronium ions in oxalic acid sesquihydrate crystal corroborates this hypothesis.
Objective: To examine whether patients with bipolar disorder (BD) have subtle neuropsychological deficits that manifest clinically as cognitive and functional compromise, and this study attempted to ...determine the pattern of such cognitive deficits and their functional impact across all three phases of BD. We hypothesised that euthymia does not equate with normal neuropsychological function and that each phase has a characteristic pattern of deficits, with disturbance in attention and memory being common across all phases of the illness: (i) bipolar depression – psychomotor slowing and impairment of memory; (ii) hypomania by frontal‐executive deficits and (iii) euthymia – a mild disturbance of attention, memory and executive function.
Methods: Twenty‐five patients with a diagnosis of bipolar I disorder underwent neuropsychological testing over a period of 30 months in the natural course of their illness while hypomanic and/or depressed and/or euthymic. The results from these assessments were compared with findings from neuropsychological tests conducted on 25 healthy controls matched for age, sex, education and handedness.
Results: Initial analyses revealed modest impairment in executive functioning, memory and attention in both hypomanic and depressed bipolar patients, with additional fine motor skills impairment in the latter. Memory deficits, also noted in euthymic patients, were non‐significant after controlling for confounding variables, although bipolar depressed patients remained significantly impaired on tests of verbal recall. Bipolar depressed and hypomanic patients differed with respect to the nature of their memory impairment. Depressed patients were more impaired as compared with euthymic patients on tests of verbal recall and fine motor skills. Psychosocial functioning was impaired across all three patient groups, but only in depressed and hypomanic patients did this correlate significantly with neuropsychological performance.
Conclusions: The mood‐state‐related cognitive deficits in both bipolar depression and hypomania compromise psychosocial function when patients are unwell. In euthymic patients, subtle impairments in attention and memory suggest that an absence of symptoms does not necessarily equate to ‘recovery’. The possibility of persistent cognitive deficits in BD is an issue of profound clinical and research interest that warrants further investigation; however, future research needs to adopt more sophisticated neuropsychological probes that are able to better define state and trait deficits and determine their functional impact.
Bipolar disorder (BD) is associated with a 20–30‐fold increased suicide risk compared to the general population. First‐degree relatives of BD patients show inflated rates of psychopathology including ...suicidal behaviors. As reliable biomarkers of suicide attempts (SA) are lacking, we examined associations between suicide‐related polygenic risk scores (PRSs)—a quantitative index of genomic risk—and variability in brain structures implicated in SA. Participants (n = 206; aged 12–30 years) were unrelated individuals of European ancestry and comprised three groups: 41 BD cases, 96 BD relatives (“high risk”), and 69 controls. Genotyping employed PsychArray, followed by imputation. Three PRSs were computed using genome‐wide association data for SA in BD (SA‐in‐BD), SA in major depressive disorder (SA‐in‐MDD) (Mullins et al., 2019, The American Journal of Psychiatry, 176(8), 651–660), and risky behavior (Karlsson Linnér et al., 2019, Nature Genetics, 51(2), 245–257). Structural magnetic resonance imaging processing employed FreeSurfer v5.3.0. General linear models were constructed using 32 regions‐of‐interest identified from suicide neuroimaging literature, with false‐discovery‐rate correction. SA‐in‐MDD and SA‐in‐BD PRSs negatively predicted parahippocampal thickness, with the latter association modified by group membership. SA‐in‐BD and Risky Behavior PRSs inversely predicted rostral and caudal anterior cingulate structure, respectively, with the latter effect driven by the “high risk” group. SA‐in‐MDD and SA‐in‐BD PRSs positively predicted cuneus structure, irrespective of group. This study demonstrated associations between PRSs for suicide‐related phenotypes and structural variability in brain regions implicated in SA. Future exploration of extended PRSs, in conjunction with a range of biological, phenotypic, environmental, and experiential data in high risk populations, may inform predictive models for suicidal behaviors.
A precise X-ray crystal structure determination of systems that exist in a polycrystalline form often poses a challenge due to several factors that limit the resolution of the diffraction ...measurement. The location of atoms is usually determined at significantly lower precision than the unit cell parameters, rendering the complete characterization of the structure difficult. This is particularly pronounced when precise location of hydrogen atoms is required, for instance in ionizable biomolecules or in hydrogen bonds. In such cases periodic quantum (DFT) calculations may crucially assist structure determination, because they can reliably predict the location of atoms, provided that the unit cell parameters, the space group and tentative atomic positions are known. In this work we present DFT-assisted structure determination of pentadecafluorooctanoic acid hydrate, a benchmark system featuring short hydrogen bonds (R.sub.O...O approximately equal to 2.5 Angstrom) between acid and water molecules. While Rietveld refinement based solely on powder diffraction data cannot reliably resolve the location of crystal water molecules and even less so the position of hydrogen atoms in the network of hydrogen bonds, periodic DFT optimization yields several minimum energy structures suitable for further refinement. Due to the low experimental resolution and similarity, comparison between model and experimental powder diffraction pattern can barely distinguish between certain structure candidates provided by DFT calculations, but it can rule out those featuring larger misfits. The proposed structure solution is delivered from a tandem application of structure determination from powder diffraction data and DFT optimization, the former providing the unit cell parameters and estimated atomic positions that are finely tuned by DFT. The present strategy can in principle be generalized to other examples of structure determination at relatively low resolution, such as is often the case with biological macromolecules. Keywords: powder diffraction, structure determination, periodic DFT calculations, hydrogen bonding.
The benefits of self-monitoring on symptom severity, coping, and quality of life have been amply demonstrated. However, paper and pencil self-monitoring can be cumbersome and subject to biases ...associated with retrospective recall, while computer-based monitoring can be inconvenient in that it relies on users being at their computer at scheduled monitoring times. As a result, nonadherence in self-monitoring is common. Mobile phones offer an alternative. Their take-up has reached saturation point in most developed countries and is increasing in developing countries; they are carried on the person, they are usually turned on, and functionality is continually improving. Currently, however, public conceptions of mobile phones focus on their use as tools for communication and social identity. Community attitudes toward using mobile phones for mental health monitoring and self-management are not known.
The objective was to explore community attitudes toward the appropriation of mobile phones for mental health monitoring and management.
We held community consultations in Australia consisting of an online survey (n = 525), focus group discussions (n = 47), and interviews (n = 20).
Respondents used their mobile phones daily and predominantly for communication purposes. Of those who completed the online survey, the majority (399/525 or 76%) reported that they would be interested in using their mobile phone for mental health monitoring and self-management if the service were free. Of the 455 participants who owned a mobile phone or PDA, there were no significant differences between those who expressed interest in the use of mobile phones for this purpose and those who did not by gender (χ2(1), = 0.98, P = .32, phi = .05), age group (χ2(4), = 1.95, P = .75, phi = .06), employment status (χ2(2), = 2.74, P = .25, phi = .08) or marital status (χ2(4), = 4.62, P = .33, phi = .10). However, the presence of current symptoms of depression, anxiety, or stress affected interest in such a program in that those with symptoms were more interested (χ(2) (1), = 16.67, P < .001, phi = .19). Reasons given for interest in using a mobile phone program were that it would be convenient, counteract isolation, and help identify triggers to mood states. Reasons given for lack of interest included not liking to use a mobile phone or technology, concerns that it would be too intrusive or that privacy would be lacking, and not seeing the need. Design features considered to be key by participants were enhanced privacy and security functions including user name and password, ease of use, the provision of reminders, and the availability of clear feedback.
Community attitudes toward the appropriation of mobile phones for the monitoring and self-management of depression, anxiety, and stress appear to be positive as long as privacy and security provisions are assured, the program is intuitive and easy to use, and the feedback is clear.
Although genetic epidemiological studies have confirmed increased rates of major depressive disorder among the relatives of people with bipolar affective disorder, no report has compared the clinical ...characteristics of depression between these two groups.
To compare clinical features of depressive episodes across participants with major depressive disorder and bipolar disorder from within bipolar disorder pedigrees, and assess the utility of a recently proposed probabilistic approach to distinguishing bipolar from unipolar depression. A secondary aim was to identify subgroups within the relatives with major depression potentially indicative of 'genetic' and 'sporadic' subgroups.
Patients with bipolar disorder types 1 and 2 (n = 246) and patients with major depressive disorder from bipolar pedigrees (n = 120) were assessed using the Diagnostic Interview for Genetic Studies. Logistic regression was used to identify distinguishing clinical features and assess the utility of the probabilistic approach. Hierarchical cluster analysis was used to identify subgroups within the major depressive disorder sample.
Bipolar depression was characterised by significantly higher rates of psychomotor retardation, difficulty thinking, early morning awakening, morning worsening and psychotic features. Depending on the threshold employed, the probabilistic approach yielded a positive predictive value ranging from 74% to 82%. Two clusters within the major depressive disorder sample were found, one of which demonstrated features characteristic of bipolar depression, suggesting a possible 'genetic' subgroup.
A number of previously identified clinical differences between unipolar and bipolar depression were confirmed among participants from within bipolar disorder pedigrees. Preliminary validation of the probabilistic approach in differentiating between unipolar and bipolar depression is consistent with dimensional distinctions between the two disorders and offers clinical utility in identifying patients who may warrant further assessment for bipolarity. The major depressive disorder clusters potentially reflect genetic and sporadic subgroups which, if replicated independently, might enable an improved phenotypic definition of underlying bipolarity in genetic analyses.
Infrared, Raman and INS spectra of picolinic acid N-oxide (PANO) were recorded and examined for the location of the hydronic modes, particularly O−H stretching and COH bending. PANO is representative ...of strong chelate hydrogen bonds (H-bonds) with its short O···O distance (2.425 Å). H-bonding is possibly well-characterized by diffraction, NMR and NQR data and calculated potential energy functions. The analysis of the spectra is assisted by DFT frequency calculations both in the gas phase and in the solid state. The Car−Parrinello quantum mechanical solid-state method is also used for the proton dynamics simulation; it shows the hydron to be located about 99% of time in the energy minimum near the carboxylic oxygen; jumps to the N−O acceptor are rare. The infrared spectrum excels by an extended absorption (Zundel's continuum) interrupted by numerous Evans transmissions. The model proton potential functions on which the theories of continuum formation are based do not correspond to the experimental and computed characteristics of the hydrogen bond in PANO, therefore a novel approach has been developed; it is based on crystal dynamics driven hydronium potential fluctuation. The envelope of one hundred 0 → 1 OH stretching transitions generated by molecular dynamics simulation exhibits a maximum at 1400 cm-1 and a minor hump at ∼1600 cm-1. These positions square well with ones predicted for the COH bending and OH stretching frequencies derived from various one- and two-dimensional model potentials. The coincidences with experimental features have to be considered with caution because the CPMD transition envelope is based solely on the OH stretching coordinate while the observed infrared bands correspond to heavily mixed modes as was previously shown by the normal coordinate analysis of the IR spectrum of argon matrix isolated PANO, the present CPMD frequency calculation and the empirical analysis of spectra. The experimental infrared spectra show some unusual characteristics such as large temperature effects on the intensity of some bands, thus presenting a challenge for theoretical band shape treatments. Our calculations clearly show that the present system is characterized by an asymmetric single well potential with no large amplitudes in the hydronium motion, which extends the existence of Zundel-type spectra beyond the established set of hydrogen bonds with large hydronic vibrational amplitudes.
Gender-based violence (GBV) represents a major cause of psychological morbidity worldwide, and particularly in low- and middle-income countries (LMICs). Although there are effective treatments for ...common mental disorders associated with GBV, they typically require lengthy treatment programs that may limit scaling up in LMICs. The aim of this study was to test the effectiveness of a new 5-session behavioural treatment called Problem Management Plus (PM+) that lay community workers can be taught to deliver.
In this single-blind, parallel, randomised controlled trial, adult women who had experienced GBV were identified through community screening for psychological distress and impaired functioning in Nairobi, Kenya. Participants were randomly allocated in a 1:1 ratio either to PM+ delivered in the community by lay community health workers provided with 8 days of training or to facility-based enhanced usual care (EUC) provided by community nurses. Participants were aware of treatment allocation, but research assessors were blinded. The primary outcome was psychological distress as measured by the total score on the 12-item General Health Questionnaire (GHQ-12) assessed at 3 months after treatment. Secondary outcomes were impaired functioning (measured by the WHO Disability Adjustment Schedule WHODAS), symptoms of posttraumatic stress (measured by the Posttraumatic Stress Disorder Checklist PCL), personally identified problems (measured by Psychological Outcome Profiles PSYCHLOPS), stressful life events (measured by the Life Events Checklist LEC), and health service utilisation. Between 15 April 2015 and 20 August 2015, 1,393 women were screened for eligibility on the basis of psychological distress and impaired functioning. Of these, 518 women (37%) screened positive, of whom 421 (81%) were women who had experienced GBV. Of these 421 women, 209 were assigned to PM+ and 212 to EUC. Follow-up assessments were completed on 16 January 2016. The primary analysis was intention to treat and included 53 women in PM+ (25%) and 49 women in EUC (23%) lost to follow-up. The difference between PM+ and EUC in the change from baseline to 3 months on the GHQ-12 was 3.33 (95% CI 1.86-4.79, P = 0.001) in favour of PM+. In terms of secondary outcomes, for WHODAS the difference between PM+ and EUC in the change from baseline to 3-month follow-up was 1.96 (95% CI 0.21-3.71, P = 0.03), for PCL it was 3.95 (95% CI 0.06-7.83, P = 0.05), and for PSYCHLOPS it was 2.15 (95% CI 0.98-3.32, P = 0.001), all in favour of PM+. These estimated differences correspond to moderate effect sizes in favour of PM+ for GHQ-12 score (0.57, 95% CI 0.32-0.83) and PSYCHLOPS (0.67, 95% CI 0.31-1.03), and small effect sizes for WHODAS (0.26, 95% CI 0.02-0.50) and PCL (0.21, 95% CI 0.00-0.41). Twelve adverse events were reported, all of which were suicidal risks detected during screening. No adverse events were attributable to the interventions or the trial. Limitations of the study include no long-term follow-up, reliance on self-report rather than structured interview data, and lack of an attention control condition.
Among a community sample of women in urban Kenya with a history of GBV, a brief, lay-administered behavioural intervention, compared with EUC, resulted in moderate reductions in psychological distress at 3-month follow-up.
Australian New Zealand Clinical Trials Registry ACTRN12614001291673.
The difference between the calculated metric parameters that are characteristic of the hydrogen bond (H-bond) in the isolated title compound and ones obtained from diffractions on crystals are ...unusually large (∼0.1 Å) even if high levels of theory are used. The probable origin of this discrepancy lies in strong intermolecular interactions that are investigated here using two models. The first one is the periodic density functional theory (DFT) with plane-wave basis sets and relativistic pseudopotentials (Car−Parrinello molecular dynamics, CPMD 3.5 program). An isolated molecule was also treated by this approach to facilitate the comparison with the local basis set model. The metric parameters calculated by the periodic model are in acceptable agreement with diffraction data, except for the O−H bond length. However, accounting for the quantum nature of the proton brought further improvement. The second model consisted of clusters of n molecules up to n = 3. With increase in the cluster size, the calculated geometry approached the experimental one. One-dimensional proton potential functions were calculated with the cluster and the periodic models. The effects of aggregation are markedly reflected in the shapes of the respective functions in that the increasing number of aggregated molecules tends to flatten the potential. The O−H stretching frequencies calculated from the potentials move to lower values with increasing aggregation. The frequency calculated for the crystal phase (1407 cm-1) is in accord with the estimated center of the broad absorption appearing in the crystal spectrum. To obtain insight into the origin of the effects of molecular aggregation, we applied the natural bond orbital analysis Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. Rev. 1988, 88, 899−926. The results suggest that the energy of association that is in the range of 3−5 kcal/mol originates in mutually induced charges.
PDF
