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Atypical and melancholic subtypes of depression based on the Diagnostic and Statistical Manual (DSM) IV are important concepts, especially for biological psychiatry. The aim of this study was to determine whether the symptoms used for the diagnoses of atypical and melancholic depression can distinguish these subtypes during pregnancy.
A modified version of the Structured Clinical Interview for DSM IV (SCID interview) was used that allowed assessment of all DSM IV symptoms of melancholic and atypical depression with depressed and non depressed women in pregnancy. A Swiss cohort of 449 women was interviewed. Four diagnostic groups were compared: women with melancholic, atypical, or non specified depression, and those without depression.
Seventeen per cent of the cohort met SCID criteria for a depressive episode of depression at least once in pregnancy, with melancholic depression 2.4%, atypical depression 4.4%, and non specified depression 10.2%. Many of the symptoms used to distinguish atypical and melancholic depression did not discriminate between these groups during pregnancy. However some, such as mood reactivity, distinct quality of mood and sleep pattern, did discriminate.
Differential diagnosis between melancholic and atypical depression in pregnancy needs to be based on pregnancy specific definitions. The possible therapeutic consequences and the neurobiological basis for these findings warrant further research.
There is now good evidence from several prospective studies that antenatal maternal stress, anxiety or depression can have long term consequences for the development of the fetus and the child. There can be a wide range of effects and both behavioural and cognitive outcomes can be altered. Such fetal programming is independent of the postnatal environment, although the nature of maternal care may have a modifying influence. The effects are clinically significant; about 15% of behavioural problems such as attention deficit/hyperactivity disorder may be attributable to prenatal stress. Not all children are affected, and those that are can be affected in different ways. Presumably there is an interaction with the genetic predisposition, but this has not yet been studied. There is little agreement about the gestational windows of vulnerability, which are probably different for different outcomes. Also we do not know the nature of the stress which is most harmful, although there is some evidence that stress due to a bad relationship with the partner is damaging, and anxiety has greater influence than depression.
In animal models there is good evidence for the mediating effects of the HPA axis in both mother and fetus. In humans the evidence is less clear. Several studies have found little or no association between anxiety or depression and maternal cortisol in later pregnancy. However we have found an inverse association between amniotic fluid cortisol and child cognitive ability at 17 months, which is only apparent in insecurely attached children.
This study investigated the diurnal output of saliva cortisol and saliva amylase in women with symptoms of depression postnatally.
Twenty one depressed and 30 non depressed women at 7.5 weeks postpartum, and 21 non perinatal controls, collected saliva at waking, 30 minutes, and three and twelve hours post waking.
Women who were not depressed postnatally showed a pattern of cortisol secretion over the day similar to non perinatal controls. There was a significant difference in diurnal pattern between postnatally depressed and postnatally non depressed women, due to a difference in the first two time points (waking and +30 mins): compared to the other two groups who each had a significant increase in cortisol levels from waking to +30 minutes, the depressed women had significantly higher cortisol levels at waking and no increase at +30 minutes. Analyses of amylase are underway and will be presented.
The lack of a morning rise in the depressed women is similar to that reported for Post-traumatic Stress Disorder and chronic fatigue syndrome and may reflect a response, in vulnerable women, to the marked cortisol withdrawal that occurs after delivery. Alternatively it could be a trait marker for women at risk of developing postnatal depression.
The physiological changes in peripartum may affect symptoms of depression and impact diagnostic judgments in the peripartum. The sharp fall in cortisol and CRH after childbirth suggests that the HPA axis characteristics of postpartum depression are different from melancholic depression, the latter being characterized by high cortisol levels.
A modified version of the SCID was used to assess symptoms of depression and melancholic and atypical subtypes in pregnancy and the postpartum period. Secondly, we investigated the diurnal output of saliva cortisol in women with and without symptoms of depression at 7.5 weeks postpartum, and non perinatal controls.
The antenatal symptom pattern (n = 892 women) was different from the postnatal. The sensitivity of the symptoms ranged from 0.7% to 51.6%, and specificity from 61.3% to 99.1%. The best discriminating symptoms were motor retardation/agitation and concentration antenatally, and motor retardation/agitation, concentration and fatigue postnatally. In a subgroup of this sample (n = 449) 17% of the cohort met SCID criteria for a depression at least once in pregnancy: melancholic depression (2.4%), atypical depression (4.4%), and non specified depression (10.2%). Mood reactivity, distinct quality of mood and sleep pattern discriminated between the two groups. There was no increase in cortisol over the day, however a significant difference in diurnal pattern of cortisol between postnatally depressed and non-depressed women.
These findings suggest that perinatal depression has different associated symptoms from depression at other times. The cortisol pattern in the postnatally depressed women is similar to that reported for PTSD and atypical depression.
Pregnancy may cause somatic alterations and possible transformation in women's behaviour, emotions and cognition.
To analyse monthly somatic and cognitive changes in pregnancy.
To examine the pattern of cognitive (depressed mood, lack of self-esteem, guilt, lack of concentration, sensitivity to criticism, thoughts of death) and somatic (decreased energy, feelings of heavy limbs and feeling worse in the morning) symptoms throughout the 9 months of pregnancy.
N=374 women were interviewed once (6 weeks postnatal) using a modified version of the Structured Clinical Interview for DSM IV. Women were asked whether they had experienced each symptom at any time during pregnancy and if they said yes, the monthly symptom occurrence was assessed. Repeated measures General Linear Model analysis was used.
There were both linear (a) and quadratic (b) significant changes over time for sensitivity to criticism (Fa=20.9(1), Fb=7.02(1), pa,b=0.00), lack of concentration (Fa=37.0(1); Fb=10.3(1); pa,b=0.00), decreased energy (Fa=13.4(1), Fb=62.6(1); pa,b=0.00) and feelings of heavy limbs(Fa=92.9(1), Fb=67.7(1) pa,b=0.00). Guilt (F=0.00(1); p=0.93) showed no change over pregnancy, lack of self-esteem (F=10.15(1); p= 0.00) showed linear significance while depressed mood (F=5.15(1); p= 0.02) showed quadratic significance. After controlling for covariates, no significant interactions between them and all symptoms were found.
Cognitive symptoms changed throughout pregnancy as much as somatic symptoms. Most symptoms showed a different pattern from depressed mood (Figure 1). Sensitivity to criticism, lack of concentration, feelings of heavy limbs and decreased energy were especially high during late pregnancy.
Anxiety symptoms are frequent during pregnancy, and they adversely affect pregnancy outcomes and offspring development. The underlying biological mechanisms are not known, but may in part be explained by alterations in certain maternal metabolic pathways. No metabolomic studies have investigated possible metabolic alterations in anxious pregnant women.
This pilot study compared the metabolic profiles of anxious and non-anxious pregnant women using a mass spectrometry-based quantitative metabolomics system.
Cases were 20 participants of the Kuopio birth cohort study (www.kubico.fi) with first and third trimester symptoms of anxiety (Edinburgh postnatal depression scale, anxiety subscale – EPDS-3A ≥ 4), but no depression (EPDS ≤ 12). Controls were 20 participants with low anxiety (EPDS–3A ≤ 3) and depression (total EPDS ≤ 9) in both the first and third trimester. Maternal metabolic profiles were analyzed from serum samples drawn when the mothers arrived at the delivery hospital.
Metabolic pathway analyses revealed significant enrichment in the glycine, serine and threonine metabolism (P = 0.046), as well as in the betaine (P = 0.048) metabolism pathways. Homocysteine was the only metabolite to significantly differentiate between cases and controls (VIP score 3.3), with lower concentrations in cases (P = 0.003) even when excluding non-users of folic acid supplementation (n = 5; P = 0.002), C-sections (n = 5; P = 0.013), or samples taken immediately postpartum (n = 2; P = 0.004). No other metabolites significantly differed between the groups.
Physiological adaptation induced by pregnancy, which may have homogenized the study populations, could explain the only minor metabolic differences between the two groups. Further research in larger samples, comparing metabolic alterations in umbilical cord blood and maternal blood is warranted.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Effective treatment of maternal antenatal depression may ameliorate adverse neurodevelopmental outcomes in offspring. We performed two follow-up rounds of children at age 2 and age 5 whose mothers had received either specialized cognitive-behavioural therapy or routine care for depression while pregnant. Of the original cohort of 54 women, renewed consent was given by 28 women for 2-year follow-up and by 24 women for 5-year follow-up. Child assessments at the 2-year follow-up included the Parenting Stress Index (PSI), Bayley Scales of Infant Development (BSID-III) and the Child Behaviour Checklist (CBCL). The 5-year follow-up included the Wechsler Preschool and Primary Scales of Intelligence (WPPSI-III) and again the CBCL. Treatment during pregnancy showed significant benefits for children’s development at age 2, but not at age 5. At 2 years, intervention effects were found with lower scores on the PSI Total score, Parent Domain and Child domain (d=1.44, 1.47, 0.96 respectively). A non-significant trend favoured the intervention group on most subscales of the CBCL and the BSID-III (most notably motor development: d =0.52). In contrast, at 5-year follow-up, no intervention effects were found. Also, irrespective of treatment allocation, higher depression or anxiety during pregnancy was associated with higher CBCL and lower WPPSI-III scores at 5 years. This is one of the first controlled studies to evaluate the long-term effect of antenatal depression treatment on infant neurodevelopmental outcomes, showing some benefit. Nevertheless, caution should be taken interpreting the results because of a small sample size, and larger studies are warranted.
Recent findings highlight that there are prenatal risks for affective disorders that are mediated by glucocorticoid mechanisms, and may be specific to females. There is also evidence of sex differences in prenatal programming mechanisms and developmental psychopathology, whereby effects are in opposite directions in males and females. As birth weight is a risk for affective disorders, we sought to investigate whether maternal prenatal cortisol may have sex-specific effects on fetal growth. Participants were 241 mothers selected from the Wirral Child Health and Development Study (WCHADS) cohort (n=1233) using a psychosocial risk stratifier, so that responses could be weighted back to the general population. Mothers provided saliva samples, which were assayed for cortisol, at home over 2 days at 32 weeks gestation (on waking, 30-min post-waking and during the evening). Measures of infant birth weight (corrected for gestational age) were taken from hospital records. General population estimates of associations between variables were obtained using inverse probability weights. Maternal log of the area under the curve cortisol predicted infant birth weight in a sex-dependent manner (interaction term P=0.029). There was a positive and statistically significant association between prenatal cortisol in males, and a negative association in females that was not statistically significant. A sex interaction in the same direction was evident when using the waking (P=0.015), and 30-min post-waking (P=0.013) cortisol, but not the evening measure. There was no interaction between prenatal cortisol and sex to predict gestational age. Our findings add to an emerging literature that suggests that there may be sex-specific mechanisms that underpin fetal programming.
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
Maternal prenatal stress during pregnancy is associated with fetal growth restriction and adverse neurodevelopmental outcomes, which may be mediated by impaired placental function. Imprinted genes control fetal growth, placental development, adult behaviour (including maternal behaviour) and placental lactogen production. This study examined whether maternal prenatal depression was associated with aberrant placental expression of the imprinted genes paternally expressed gene 3 (PEG3), paternally expressed gene 10 (PEG10), pleckstrin homology-like domain family a member 2 (PHLDA2) and cyclin-dependent kinase inhibitor 1C (CDKN1C), and resulting impaired placental human placental lactogen (hPL) expression.
A diagnosis of depression during pregnancy was recorded from Manchester cohort participants’ medical notes (n = 75). Queen Charlotte's (n = 40) and My Baby and Me study (MBAM) (n = 81) cohort participants completed the Edinburgh Postnatal Depression Scale self-rating psychometric questionnaire. Villous trophoblast tissue samples were analysed for gene expression.
In a pilot study, diagnosed depression during pregnancy was associated with a significant reduction in placental PEG3 expression (41%, p = 0.02). In two further independent cohorts, the Queen Charlotte's and MBAM cohorts, placental PEG3 expression was also inversely associated with maternal depression scores, an association that was significant in male but not female placentas. Finally, hPL expression was significantly decreased in women with clinically diagnosed depression (44%, p < 0.05) and in those with high depression scores (31% and 21%, respectively).
This study provides the first evidence that maternal prenatal depression is associated with changes in the placental expression of PEG3, co-incident with decreased expression of hPL. This aberrant placental gene expression could provide a possible mechanistic explanation for the co-occurrence of maternal depression, fetal growth restriction, impaired maternal behaviour and poorer offspring outcomes.
Many paleoclimate and landscape change studies in the American Midwest have focused on the Late Glacial and early Holocene time periods (~ 16–11 ka), but little work has addressed landscape change in this area between the Last Glacial Maximum and the Late Glacial (~ 22–16 ka). Sediment cores were collected from 29 new lake and bog sites in Ohio and Indiana to address this gap. The basal radiocarbon dates from these cores show that initial ice retreat from the maximal last-glacial ice extent occurred by 22 ka, and numerous sites that are ~ 100 km inside this limit were exposed by 18.9 ka. Post-glacial environmental changes were identified as stratigraphic or biologic changes in select cores. The strongest signal occurs between 18.5 and 14.6 ka. These Midwestern events correspond with evidence to the northeast, suggesting that initial deglaciation of the ice sheet, and ensuing environmental changes, were episodic and rapid. Significantly, these changes predate the onset of the Bølling postglacial warming (14.8 ka) as recorded by the Greenland ice cores. Thus, deglaciation and landscape change around the southern margins of the Laurentide Ice Sheet happened ~ 7 ka before postglacial changes were felt in central Greenland.
We have analyzed the distributions of CO and temperature in a large suite of simulated
molecular clouds, in order to help us understand how to interpret CO line emission from
real molecular clouds. We find that most of the CO is located at densities over
103cm-3 where the temperature is roughly 10–20 K independently of
the mean density, metallicity and UV field strength. Although, most of the volume is in
warmer and thinner regions where CO abundance is small. On that account, CO observations
alone give a misleading view of the physical conditions in the clouds.
We study the relationship between the H2 and CO abundances in simulated molecular clouds using a fully dynamical model of magnetized turbulence coupled to a detailed chemical network. We find that the CO-to-H2 conversion factor for a given molecular cloud, the so-called X-factor, is determined primarily by the mean extinction of the cloud, rather than by its metallicity. Our results explain the discrepancy observed in low metallicity systems between cloud masses derived from CO observations and other techniques such as infrared emission, and predict that CO-bright clouds in low metallicity systems should be systematically larger and/or denser than Milky Way clouds.
We report results from numerical simulations of star formation in the early universe that focus on the role of subsonic turbulence, and investigate whether it can induce fragmentation of the gas. We find that dense primordial gas is highly susceptible to fragmentation, even for rms turbulent velocity dispersions as low as 20% of the initial sound speed. The resulting fragments cover over two orders of magnitude in mass, ranging from ~0.1 M⊙ to ~40 M⊙. However, our results suggest that the details of the fragmentation depend on the local properties of the turbulent velocity field and hence we expect considerable variations in the resulting stellar mass spectrum in different halos.
The first stars were key drivers of early cosmic evolution. We review the main physical elements of the current consensus view, positing that the first stars were predominantly very massive. We continue with a discussion of important open questions that confront the standard model. Among them are uncertainties in the atomic and molecular physics of the hydrogen and helium gas, the multiplicity of stars that form in minihalos, and the possible existence of two separate modes of metal-free star formation.
The formation of the first galaxies at redshifts z ~ 10−15 signaled the transition from the simple initial state of the universe to one of ever increasing complexity. We here review recent progress in understanding their assembly process with numerical simulations, starting with cosmological initial conditions and modelling the detailed physics of star formation. In this context we emphasize the importance and influence of selecting appropriate initial conditions for the star formation process. We revisit the notion of a critical metallicity resulting in the transition from primordial to present-day initial mass functions and highlight its dependence on additional cooling mechanisms and the exact initial conditions. We also review recent work on the ability of dust cooling to provide the transition to present-day low-mass star formation. In particular, we highlight the extreme conditions under which this transition mechanism occurs, with violent fragmentation in dense gas resulting in tightly packed clusters.
Pneumoparotitis is a rare cause of parotid enlargement. It is due to a reflux of air through Stensen's duct into the acini of the parotid gland with subsequent dilatation. We report a case which followed a long history of autoinflation of the middle ears by the Valsalva manoeuvre. The plain radiographic, sialographic and ultrasound findings are presented.
Upon heating Ba2+, Sr2+ and Cd2+-exchanged zeolite RHO, abrupt changes have been observed in the cubic unit cell parameters [1–3]. Calculations of the powder x-ray diffraction patterns indicate these changes result from relocation of the extra-framework cations. For Ba2+ and Sr2+-exchanged RHO, a shift from the single 8-ring (S8R) to the double 8-ring (D8R)-site is accompanied by contraction of the unit cell. However, for the Cd2+-exchanged material relocation from the S8R to the single 6-ring (S6R)-site coincides with cell expansion. Further, with relocation of Cd2+ the low temperature acentric (A) form is transformed to a centric (C) structure above 300°C. The shift of Cd2+ ion occurs over a distance of 5.7Å, the largest observed in a zeolite.
Urinary output of homovanillic acid and 4-hydroxy-3-methoxymandelic acid was decreased both in patients with panic attacks and in normal controls during lactate infusion, whereas that of tribulin (an endogenous monoamine oxidase inhibitor and benzodiazepine receptor binding inhibitor) was increased. There was no change in urinary excretion of any of these compounds during saline infusion. These findings provide further evidence of a link between tribulin output and stress and anxiety in man and point to its possible in vivo action as a monoamine oxidase inhibitor.