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.

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.

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.

[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.

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.

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.

[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.

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.

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.

[Psychiatric disorders in velo-cardio-facial syndrome]. / Psychiatrische problemen bij het velocardiofaciaal syndroom.

Velo-cardio-facial syndrome (vcfs) is a congenital disorder with a markedly variable clinical expression. The majority of those affected have cognitive-behavioural symptoms and psychiatric problems. Most of the somatic characteristics can be treated effectively. The quality of life of patients with vcfs is therefore determined largely by cognitive and behavioural symptoms, including the increased risk of psychiatric disorders. On the basis of a case-study featuring a 41-year-old vcfs patient and by reviewing the literature we describe the psychiatric disorders that can occur in conjunction with this syndrome.

[Personality traits of patients who have recovered completely from depression]. / Persoonlijkheidskenmerken bij patiënten die volledig hersteld zijn van een depressieve stoornis.

BACKGROUND: The psychobiological model of personality developed by Cloninger includes four dimensions of temperament and three dimensions of character. Studies have indicated that the personality dimensions of patients with depression differ from those of control subjects without depression. AIM: To assess whether the personality traits of persons who have experienced one or more depressive episodes in the past and have made full recovery differ from the personality traits of persons who have never suffered from depression. METHOD: The personality dimensions for 40 persons in remission but with a previous history of depression and for 49 healthy controls were determined by means of a Dutch version of the Temperament and Character Inventory (tci) questionnaire. results Compared to the control subjects, patients in remission showed a significant increase on the temperament scale Harm Avoidance and a statistically significant decrease on the character scale Self-Directedness. The increase also applied to all subscales of Harm Avoidance and the decrease applied to four of the five subscales of Self-Directedness. CONCLUSION: Compared to healthy control subjects, patients in remission showed a distinctly different personality profile. None of these differences can therefore be regarded merely as a transient phenomenon during a depressive episode ('state effect'). However, it cannot be concluded from the current study whether the altered personality profile is a consequence of having had a depression or whether it is a 'scarring effect' of a pre-existing vulnerability factor.

[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.

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.

Chromosome 10q harbors a susceptibility locus for bipolar disorder in Ashkenazi Jewish families.

We report the results of a 10 cM density genome-wide scan and further fine mapping of three chromosomal candidate regions in 10 Belgian multigenerational families with bipolar (BP) disorder. This two-stage approach revealed significant evidence for linkage on chromosome 10q21.3-10q22.3, showing a maximum multipoint parametric heterogeneity logarithm of odds (HLOD) score of 3.28 and a nonparametric linkage (NPL) score of 4.00. Most of the chromosome 10q evidence was derived from a single, large Ashkenazi Jewish pedigree. Haplotype analysis in this pedigree shows that the patients share a 14-marker haplotype, defining a chromosomal candidate region of 19.2 cM. This region was reported previously as a candidate region for BP disorder in several independent linkage analysis studies and in one large meta-analysis. It was also implicated in a linkage study on schizophrenia (SZ) in Ashkenazi Jewish families. Additionally, we found suggestive evidence for linkage on chromosome 19q13.2-13.4 (HLOD 2.01, NPL 1.09) and chromosome 7q21-q22 (HLOD 1.45, NPL 2.28). Together, these observations suggest that a gene located on chromosome 10q21.3-10q22.3 is underlying the susceptibility both for SZ and for BP disorder in at least the Ashkenazi Jewish population.

Meta-analyses of genetic studies on major depressive disorder.

The genetic basis of major depressive disorder (MDD) has been investigated extensively, but the identification of MDD genes has been hampered by conflicting results from underpowered studies. We review all MDD case-control genetic association studies published before June 2007 and perform meta-analyses for polymorphisms that had been investigated in at least three studies. The study selection and data extraction were performed in duplicate by two independent investigators. The 183 papers that met our criteria studied 393 polymorphisms in 102 genes. Twenty-two polymorphisms (6%) were investigated in at least three studies. Seven polymorphisms had been evaluated in previous meta-analyses, 5 of these had new data available. Hence, we performed meta-analyses for 20 polymorphisms in 18 genes. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistically significant associations were found for the APOE varepsilon2 (OR, 0.51), GNB3 825T (OR, 1.38), MTHFR 677T (OR, 1.20), SLC6A4 44 bp Ins/Del S (OR, 1.11) alleles and the SLC6A3 40 bpVNTR 9/10 genotype (OR, 2.06). To date, there is statistically significant evidence for six MDD susceptibility genes (APOE, DRD4, GNB3, MTHFR, SLC6A3 and SLC6A4).

[Stress and depression: clinical, neurobiological and genetical perspectives]. / Stress en depressie: klinisch, neurobiologisch en genetisch perspectief.

Major depressive disorder (mdd) can be elicited by various kinds of stress, such as negative life events, chronic stress and experiences of abuse early in life. These stressors interact with personality traits and with a genetic predisposition to depression, thereby bringing about mdd. Therefore, the neurobiology of depression cannot be separated from the neurobiology of stress system. A substantial number of publications have in fact demonstrated that mdd patients show abnormalities of the hypothalamic-pituitary-adrenal (hpa) axis, which is a key element of the stress response. Such disturbances are exacerbated by chronic stress, early experiences of abuse and even prenatal exposure to stress. On the other hand, genetic variations can play a role in the hpa axis dysfunction and in vulnerability to depression. Evidence is emerging that certain genes are directly involved in the functioning of the hpa axis. Other genetic factors, not directly related to the hpa axis, are probably relevant as well, the best known example being the serotonin transporter gene.

[Emergency psychiatry in Belgium; a challenge for the mental health services]. / Urgentiepsychiatrie in België; een uitdaging voor de geestelijke gezondheidszorg.

In Belgium emergency psychiatry is a discipline that has developed only recently, following two federal pilot projects, one in 1993 and one in 2002. At present there are 10 subsidised psychiatric emergency rooms (pers) in Belgium, serving about 13,000 patients annually. Many of those seeking help are 'revolving-door' patients, but the pers also serve patients who have had no prior contact with the mental health care service. The disorders that are encountered most often have to do with substance abuse (about 30%) and mood disorders (17%). More than 4 in 10 patients were admitted to a psychiatric clinic after being referred to a per. Research suggests that the link to continuous care may reduce the 'revolving-door' phenomenon.