Parental support and insecure attachment development: the cortisol stress response as a moderator.

The current study investigated whether variations at the level of the cortisol stress response moderate the association between parental support and attachment development. To test this hypothesis, we conducted a one-year longitudinal study with two waves in which 101 children (56% girls, Mage = 11.15, SDage = 0.70) participated. Attachment anxiety and avoidance were measured at baseline (Wave 1) and one year later (Wave 2). Parental support and children's cortisol stress response during the Trier Social Stress Test were measured at Wave 2. Children's cortisol stress response was found to moderate the association between parental support and relative change in anxious attachment. A strong cortisol stress response weakened the associated between parental support and relative change in anxious attachment. No moderation effects were found for relative change in avoidant attachment.

Delayed affective recovery to daily-life stressors signals a risk for depression.

OBJECTIVE: The aim of this study is to investigate the time to affective recovery from daily-life stressors between healthy controls (HC) and two groups with an increased risk for developing depression: individuals with subclinical symptoms of depression (SSD), and individuals remitted from a depressive episode with residual symptoms of depression (RRS). METHOD: The experience sampling method (ESM) was used to measure affective recovery to daily-life stressors. Affective recovery was defined as the moment that negative affect (NA) returned to baseline level following the first stressful event of the day. We assessed two different operationalizations of the baseline: NA at the moment before the stressful event (t-1), and mean-person NA. The effect of stress intensity, and cumulative stress were also assessed. RESULTS: Survival analyses showed significantly longer recovery times for the at risk groups in comparison to healthy individuals, albeit no significant difference was found between the two at risk groups (i.e. SSD and RRS). There was also an effect of cumulative stress, but not stress intensity on time to recovery in that cumulative stress resulted in significantly longer recovery times for all three groups. LIMITATIONS: The present study is limited by the ESM sampling design, assessments take place post-stress and therefore do not capture peak stress. Additionally, we are only able to assess patterns at the group level. Finally, there is a significant age difference between groups. CONCLUSION: Individuals at risk for depression display a delayed recovery to daily-life stressors when compared to healthy controls, which is not explained by differences in stress intensity or cumulative stress. Understanding what is driving this delay may help combat the development of depression.

Interplay of Val66Met and BDNF methylation: effect on reward learning and cognitive performance in major depression.

BACKGROUND: There is a growing interest in the role of brain-derived neurotrophic factor (BDNF) in major depressive disorder (MDD). BDNF potentially exhibits opposite effects in the pathways linked to anhedonia and reward learning on the one hand and cognitive performance, on the other hand. However, the epigenetic mechanisms behind this remain unknown. In the present study, we aimed to investigate the interplay of DNA methylation of different BDNF exons and the common Val66Met polymorphism on anhedonia, reward learning and cognitive performance in MDD. METHODS: We recruited 80 depressed patients and 58 age- and gender-matched healthy controls. Participants underwent clinical assessment including neuropsychological testing and a probabilistic reward task to assess reward learning. Val66Met polymorphism and DNA methylation of BDNF promoters I, IV and exon IX were assessed from whole blood derived DNA, using pyrosequencing. RESULTS: BDNF promoter I methylation was lower in MDD patients (p = 0.042) and was negatively associated with self-reported anhedonia. In depressed patients, both Val66Met polymorphism and DNA methylation of promoter I were significantly associated with reward bias (p < 0.050 and p = 0.040, respectively), without an interaction effect. On the other hand, methylation of exon IX had a negative impact on executive functioning (p = 0.002) and mediated the effect of Val66Met on this outcome in patients with MDD. CONCLUSIONS: Our results provide the first evidence of Val66Met susceptibility to differential epigenetic regulation of BDNF exons in reward learning and executive functioning in MDD, which needs to be further explored.

Simultaneous bilateral opening-wedge high tibial osteotomy with structural allograft impaction results in excellent early recovery and pain reduction similar unilateral osteotomy.

BACKGROUND: Patients suffering from bilateral combined medial osteoarthritis and varus alignment of the knee are eligible for bilateral high tibial osteotomy (HTO) in two-staged surgery. The impact of bilateral HTO surgery on rehabilitation and early outcomes have not yet been reported in the literature, even though these features are decisive in establishing whether a patient is preferably treated in one or two stages. METHODS: A total of 29 patients were followed after simultaneous bilateral HTO surgery. Numeric Rating Scale (NRS), Knee injury and Osteoarthritis Outcome Score - Physical Function Short Form (KOOS-PS) and Lysholm scores were recorded at 3, 6 and 12 months. Results were compared with outcomes of unilateral HTO surgery to asses the additional impact of simultaneous bilateral HTO surgery on the early rehabilitation and recovery of simultaneous bilateral HTO surgery. RESULTS: Three months after surgery, NRS pain scores decreased from 60.5 to 40.9 and subsequently to 30.4 and 24.3 after 6 and 12 months, respectively. KOOS-PS scores improved from 50.0 to 44.3 after 3 months, to 33.9 and 29.8 after 6 and 12 months, respectively. Lysholm scores did not improve after 3 months (45.2-44.2), but significantly improved after 6 and 12 months (66.1 and 75.7, respectively). Compared with unilateral HTO surgery, similar improvements were seen after 6 and 12 months. CONCLUSION: Simultaneous bilateral HTO surgery generates similar clinical outcomes compared with unilateral HTO surgery and moreover it does not excessively prolong time to achieve these outcomes. It is safe and presumably a more effective approach to treat patients suffering bilateral medial osteoarthritis and varus alignment of the knee compared with two-staged surgery.

The link between parental psychological control, depressive symptoms and epigenetic changes in the glucocorticoid receptor gene (NR3C1).

AIMS: This paper examines the relationship between parental Psychological Control (PC) and depressive symptoms in adolescents and assesses whether this relationship was mediated by DNA methylation, focusing on the glucocorticoid receptor gene (NR3C1), which plays a crucial role in HPA-axis functioning and is linked to environmental stress and depression. This is among the very few studies that looked at the relation between DNA methylation, environmental stress and depression in family trios. METHODS: The study cohort consisted of 250 families: father, mother and a biologically related adolescent (adolescents (48.9% boys), mean age: 15.14, SD= 1.9; mean age mothers: 45.83, SD= 4.2; mean age fathers: 47.77, SD= 4.7). Depressive symptoms and PC were measured in adolescents and in both parents. DNA methylation levels in NR3C1 were examined in all participants. RESULTS: Depressive symptoms in adolescents were predicted by PC of both mothers and fathers. Moreover, maternal depressive symptoms were associated with maternal PC, and fathers' depressive symptoms and PC. In fathers, only the level of their self-reported PC was associated with their depressive symptoms. There was no relation between adolescents' DNA methylation and depressive symptoms or the level of parental PC. Yet, there was a significant association between maternal depressive symptoms and maternal epigenetic patterns in NR3C1. CONCLUSIONS: These findings highlight the need for more research in order to better understand the biological and contextual mechanisms through which parenting and parental emotional well-being is related to the development of psychopathology.

Assessment of protein biomarkers for preoperative differential diagnosis between benign and malignant ovarian tumors.

OBJECTIVE: To estimate the diagnostic value of tumor and immune related proteins in the discrimination between benign and malignant adnexal masses, and between different subgroups of tumors. METHODS: In this exploratory diagnostic study, 254 patients with an adnexal mass scheduled for surgery were consecutively enrolled at the University Hospitals Leuven (128 benign, 42 borderline, 22 stage I, 55 stage II-IV, and 7 secondary metastatic tumors). The quantification of 33 serum proteins was done preoperatively, using multiplex high throughput immunoassays (Luminex) and electrochemiluminescence immuno-assay (ECLIA). We calculated univariable areas under the Receiver Operating Characteristic Curves (AUCs). To discriminate malignant from benign tumors, multivariable ridge logistic regression with backward elimination was performed, using bootstrapping to validate the resulting AUCs. RESULTS: CA125 had the highest univariable AUC to discriminate malignant from benign tumors (0.85, 95% confidence interval 0.79-0.89). Combining CA125 with CA72.4 and HE4 increased the AUC to 0.87. For benign vs borderline tumors, CA125 had the highest univariable AUC (0.74). For borderline vs stage I malignancy, no proteins were promising. For stage I vs II-IV malignancy, CA125, HE4, CA72.4, CA15.3 and LAP had univariable AUCs ≥0.80. CONCLUSIONS: The results confirm the dominant role of CA125 for identifying malignancy, and suggest that other markers (HE4, CA72.4, CA15.3 and LAP) may help to distinguish between stage I and stage II-IV malignancies. However, further research is needed, also to investigate the added value over clinical and ultrasound predictors of malignancy, focusing on the differentiation between subtypes of malignancy.

Parenting, Effortful Control, and Adolescents' Externalizing Problem Behavior: Moderation by Dopaminergic Genes.

Research shows that genetics and effortful control play an important role in the link between parenting and problem behavior. However, little is known about how these factors act simultaneously. This article used a moderated mediation model to examine whether effortful control mediated the link between parenting and externalizing problem behavior, and whether dopaminergic genes (i.e., polygenic index score including DAT1, DRD2, DRD4, COMT) moderated this link. Two three-wave studies were conducted on community samples (adolescents: Study 1: N = 457; Mage = 15.74; Study 2: N = 221; Mage = 12.84). There was no mediation by effortful control, but a moderation by dopaminergic reactivity was observed. Despite inconsistent evidence, this article indicates that the development of externalizing problem behavior is subject to genetic characteristics and parenting.

[Prenatal psychological stress and the development of affective disorders in children: literature review]. / Prenatale psychologische stress­factoren en de ontwikkeling van affectieve stoornissen bij het kind: literatuuroverzicht.

BACKGROUND: The prenatal period appears to be important not only for the development of somatic disorders, but also for the development of psychiatric disorders. Stress and the way people deal with this may play an important role.
AIM: To investigate to what extent prenatal maternal psychological stress is a risk factor for the development of affective disorders in the child. and to demonstrate the importance of systematic screening of the psychological well-being of pregnant mothers and mothers with a pregnancy wish.
METHOD: A systematic literature review via a search in PubMed and Web of Science for articles in English or Dutch.
RESULTS: Prenatal maternal anxiety, depression and subjectively experienced stress are important risk factors in the development of affective disorders in the child, influencing the development of both anxiety disorders and depression.
CONCLUSION: This literature research substantiates the fetal programming hypothesis in which prenatal maternal psychological stress (anxiety, depression and subjectively experienced stress) influences the development of affective disorders in the growing child.

Depressive symptoms in adolescence: The role of perceived parental support, psychological control, and proactive control in interaction with 5-HTTLPR.

BACKGROUND: Parenting dimensions are associated with depressive symptoms in adolescents. We investigated the role of perceived parenting dimensions and gene-environment interactions between these perceived parenting dimensions and five well-known variable number of tandem repeats (VNTRs): 5-HTTLPR, STin2, DAT1, DRD4, and MAO-A, in depressive symptoms. METHODS: From a non-clinical sample of 1111 Belgian adolescents (mean age: 13.79 years, SD=.94; 51% boys), 1103 adolescents consented for genetic research. Five VNTRs were analyzed using DNA from saliva samples. Perceived parenting dimensions (i.e., support, proactive control, psychological control, punishment, and harsh punishment) were examined using self-report scales completed by adolescents and their parents. Depressive symptoms were investigated using the CES-D self-report scale. Statistical analyses were performed in R using linear regression. RESULTS: Parental support, as perceived by the adolescent, was negatively associated with depressive symptoms (CES-D) and psychological control was positively associated with these symptoms. The only interaction effect withstanding correction for multiple testing was observed for 5-HTTLPR and the difference in proactive control as perceived by adolescents in comparison to parents. Short-allele carriers showed more depressive symptoms when there was a higher discrepancy in proactive control as perceived by adolescents versus parents. CONCLUSIONS: Our results suggest that perceived parenting dimensions are associated with depressive symptoms, as measured by the CES-D. We only found modest evidence for 5-HTTLPR as a moderator in the association between the difference in perception of proactive control (adolescents vs. parents) and depressive symptoms.

Inflammatory monocyte gene expression: trait or state marker in bipolar disorder?

BACKGROUND: This study aimed to examine whether inflammatory gene expression was a trait or a state marker in patients with bipolar disorder (BD). METHODS: 69 healthy controls (HC), 82 euthymic BD patients and 8 BD patients with a mood episode (7 depressed, 1 manic) were included from the MOODINFLAME study. Six of the eight patients who had a mood episode were also investigated when they were euthymic (6 of the 82 euthymic patients). Of these participants the expression of 35 inflammatory genes was determined in monocytes using quantitative-polymerase chain reaction, of which a total gene expression score was calculated as well as a gene expression score per sub-cluster. RESULTS: There were no significant differences in inflammatory monocyte gene expression between healthy controls and euthymic patients. Patients experiencing a mood episode, however, had a significantly higher total gene expression score (10.63 ± 2.58) compared to healthy controls (p = .004) and euthymic patients (p = .009), as well as when compared to their own scores when they were euthymic (p = .02). This applied in particular for the sub-cluster 1 gene expression score, but not for the sub-cluster 2 gene expression score. CONCLUSIONS: Our study indicates that in BD inflammatory monocyte, gene expression is especially elevated while in a mood episode compared to being euthymic.

DNA methylation in imprinted genes IGF2 and GNASXL is associated with prenatal maternal stress.

Epigenetic regulation of imprinted genes during embryonic development is influenced by the prenatal environment. Our aim was to examine the effect of maternal emotional stress and cortisol levels during pregnancy on methylation of imprinted genes, insulin-like growth factor 2 (IGF2) and guanine nucleotide-binding protein, alpha stimulating extra-large (GNASXL), using umbilical cord blood DNA. Maternal depressed mood (Edinburgh Depression Scale; EDS), pregnancy-related anxiety questionnaire (PRAQ) and cortisol day profiles were assessed throughout pregnancy. At birth, a cord blood sample (n = 80) was taken to study DNA methylation of IGF2 DMR0 (differentially methylated region), IGF2 anti-sense (IGF2AS) and GNASXL using Sequenom EpiTYPER. Linear mixed models were used to examine the relationship between DNA methylation and maternal stress, while correcting for confounders. We also studied the association of DNA methylation with the child ponderal index at birth. We found a cytosine-guanine dinucleotide (CpG)-specific association of PRAQ subscales with IGF2 DMR0 (CpG5, P < 0.0001) and GNASXL (CpG11, P = 0.0003), while IGF2AS was associated with maternal EDS scores (CpG33, P = 0.0003) and cortisol levels (CpG33, P = 0.0006; CpG37-38, P = 0.0005). However, there was no association of methylation with ponderal index at birth. In conclusion, maternal stress during pregnancy, as defined by cortisol measurements, EDS and PRAQ scores, is associated with DNA methylation of imprinted genes IGF2 and GNASXL. Our results provide further evidence that prenatal adversity can influence imprinted gene methylation, although future studies are needed to unravel the exact mechanisms.

[Mood disorders in the DSM-5]. / Stemmingsstoornissen in de DSM-5.

BACKGROUND: The DSM-5 was published in May, 2013. AIM: To discuss and comment on the important changes that appear in the sections of DSM-5 dealing with mood disorders. METHOD: The DSM-5 chapters on mood disorders are reviewed. RESULTS: Bipolar disorders and depressive disorders are now dealt with in separate categories. Some new diagnoses have been added to depressive disorders, namely 'disruptive mood dysregulation disorder', 'premenstrual dysphoric disorder' and 'persistent depressive disorder'. With regard to depression, some changes have been made in the specifiers, and new specifiers such as 'with anxious distress' have been added. There were only minor changes in the section on bipolar disorder; these stem from changes made in the section on depressive disorders. CONCLUSION: The alterations in the section on mood disorders are unlikely to lead to major changes in clinical practice. Psychiatrists are advised to be very wary about using the new DSM-5 terms 'disruptive mood dysregulation disorder' and 'premenstrual dysphoric disorder' as diagnoses for their patients.

Can anterior cruciate ligament reconstruction be performed routinely in day clinic?

Anterior cruciate ligament reconstruction is performed as an outpatient procedure in selected cases. Whether it can be safely performed on a routine basis in day clinic remains unclear. Our hypothesis was that routinely performing outpatient anterior cruciate ligament reconstruction would be equally safe as compared to inpatient procedures. A cohort of 355 patients who underwent outpatient primary reconstruction was analysed at an average follow-up of 3.8 years. Four patients (1.1%) could not be discharged or were readmitted within 24 hours. The 1-month readmission rate was 1.4%. The overall complication rate was 12.1% (43 cases) of which 4.2% (15 patients) occurred within the first 30 days. Performing anterior cruciate ligament reconstructions routinely in day clinic is associated with almost negligible readmission rates and has similar complication rates as for standard in-hospital anterior cruciate ligament reconstructions. Outpatient anterior cruciate ligament reconstructions can therefore be safely performed without specific preoperative patient selection protocols.

Self-critical perfectionism and its relationship to fatigue and pain in the daily flow of life in patients with chronic fatigue syndrome.

BACKGROUND: Research suggests that the personality factor of self-critical or maladaptive perfectionism may be implicated in chronic fatigue syndrome (CFS). However, it is not clear whether self-critical perfectionism (SCP) also predicts daily symptoms in CFS. Method In the present study we investigated whether SCP predicted fatigue and pain over a 14-day period in a sample of 90 CFS patients using a diary method approach. After completing the Depressive Experiences Questionnaire (DEQ) as a measure of SCP, patients were asked each day for 14 days to complete Visual Analogue Scales (VAS) of fatigue, pain and severity of depression. Data were analysed using multilevel analysis. RESULTS: The results from unconditional models revealed considerable fluctuations in fatigue over the 14 days, suggesting strong temporal variability in fatigue. By contrast, pain was relatively stable over time but showed significant inter-individual differences. Congruent with expectations, fixed-effect models showed that SCP was prospectively associated with higher daily fatigue and pain levels over the 14-day period, even after controlling for levels of depression. CONCLUSIONS: This is the first study to show that SCP predicts both fatigue and pain symptoms in CFS in the daily course of life. Hence, therapeutic interventions aimed at targeting SCP should be considered in the treatment of CFS patients with such features.

[Corticosteroid-induced paranoid psychosis: case report and review of the literature]. / Paranoïde psychose geïnduceerd door corticosteroïden: gevalsbeschrijving en literatuuroverzicht.

BACKGROUND: Our study focuses on a 30-year-old man who was hospitalised against his will because of his agitated psychotic state. His symptoms were indicative of a paranoid psychotic disorder resulting from the use of corticosteroids. We considered it important to report this case because corticosteroids have been widely prescribed since about 1950 to treat a broad spectrum of somatic illnesses and because there have been many reports of both mild and acute psychiatric side-effects. AIM: To obtain answers to the following questions: what is the incidence of steroid-induced psychotic symptoms? Do patients with a psychiatric history run a greater risk of developing a steroid-induced psychosis? What are the most important risk factors and how can we prevent the development of steroid-induced psychotic symptoms? METHOD: After discussing the case, we studied the literature systematically using Medline. RESULTS: Up till now, very little reliable evidence has been available relating to steroidinduced psychosis. Therefore there has been a lack of information about the incidence of psychotic symptoms caused by steroids, about the risks involved when the patient has a psychiatric history and about the preventive measures that can be taken. CONCLUSIONS: The most important risk factor seems to be the dose. Thus, if a patient requires treatment with steroid, it seems advisable to prescribe the lowest possible dose.

[Comorbid anxiety disorders and alcohol-related disorders in a population of bipolar I disorder: investigation in a Flemish population]. / Comorbide angststoornissen en stoornissen in alcoholgebruik bij bipolaire I-stoornis; onderzoek in een Vlaamse populatie.

BACKGROUND: Bipolar I disorder (bp i) is a very debilitating psychiatric disorder which is frequently associated with comorbid psychiatric and somatic disorders. Many studies in other countries show strongly elevated prevalences of anxiety disorders and alcohol-related disorders in the bp i population, but so far no data on this topic are available with regard to the Flemish population. AIM: To determine the prevalence of anxiety disorders and alcohol-related disorders in a Flemish population of bp i outpatients in remission and to find out whether comorbidity of these disorders is linked to the onset of the disorder at a younger age. METHOD: Sixty-nine bp i patients in remission were given structured interviews at home and the results were compared with the Belgian prevalence reported in the European Study of the Epidemiology of Mental Disorders (esemed) project. results Both the prevalence of the alcohol-related disorders (15 of 69 patients or 21.7%) and the prevalence of anxiety disorders (17 patients or 24.6%) were elevated compared to the general population (8.1 and 13.2% respectively). Among the anxiety disorders the prevalence was elevated for panic disorder, social phobia and post-traumatic stress disorder. No significant association was found between the comorbidity and the patient's age at the onset of the illness. CONCLUSION: The prevalence of anxiety disorders and alcohol-related disorders in an outpatient population of Flemish patients with bp i in remission is elevated.