[Relating the history of genetics to the field of psychiatric genetics: the discovery, reading and writing of DNA]. / De geschiedenis van de (psychiatrische) genetica: ontdekken, lezen en schrijven van DNA.

BACKGROUND: The importance of genetics in psychiatry has been a topic of ongoing debate. The futile search for candidate genes underlying psychiatric disorders in the decades before 2007 resulted in overall disappointment. Since then, however, researchers and clinicians have witnessed the discovery of a plethora of common and rare genetic variants associated with psychiatric disorders.
AIM: To relate the history of general genetics to the history of psychiatric genetics, underlining how.
METHOD: Literature research.
RESULTS: The anatomical and physiological phases of this history have shaped the field of psychiatric genetics. We describe pivotal discoveries that have facilitated the uncovering, reading and writing of DNA. We then discuss several milestone discoveries in the field of psychiatric genetics. We end with an outlook on where the field of psychiatric genetics may be heading in the decades to come, arguing that a ‘clinical phase’ of psychiatric genetics may be ahead of us.
CONCLUSION: The research with a focus on polygenic risk scores (PRS) could be translated into clinical practice in the coming years and we expect more attention to the question of how genetic variants cause psychiatric disorders. We look to future developments with some optimism.
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The genetic basis of major depression.

Major depressive disorder (MDD) is a common, debilitating, phenotypically heterogeneous disorder with heritability ranges from 30% to 50%. Compared to other psychiatric disorders, its high prevalence, moderate heritability, and strong polygenicity have posed major challenges for gene-mapping in MDD. Studies of common genetic variation in MDD, driven by large international collaborations such as the Psychiatric Genomics Consortium, have confirmed the highly polygenic nature of the disorder and implicated over 100 genetic risk loci to date. Rare copy number variants associated with MDD risk were also recently identified. The goal of this review is to present a broad picture of our current understanding of the epidemiology, genetic epidemiology, molecular genetics, and gene-environment interplay in MDD. Insights into the impact of genetic factors on the aetiology of this complex disorder hold great promise for improving clinical care.

Upscaling e-mental health in Europe: a six-country qualitative analysis and policy recommendations from the eMEN project.

E-mental health (eMH) encompasses the use of digital technologies to deliver, support, or enhance mental health services. Despite the growing evidence for the effectiveness of eMH interventions, the process of implementation of eMH solutions in healthcare remains slow throughout Europe. To address this issue, the e-Mental Health Innovation and Transnational Implementation Platform North-West Europe (eMEN) project was initiated to increase the dissemination and quality of eMH services in Europe. In this project, status analyses regarding eMH in the six participating countries (i.e., Belgium, France, Germany, Ireland, The Netherlands, and the UK) were conducted and eight recommendations for eMH were developed. Expert teams from the six participating countries conducted status analyses regarding the uptake of eMH based on a narrative literature review and stakeholder interviews. Based on these status analyses, the eMEN consortium developed eight policy recommendations to further support the implementation of eMH in Europe. The status analyses showed that the participating countries are in different stages of implementing eMH into mental healthcare. Some barriers to implementing eMH were common among countries (e.g., a limited legal and regulatory framework), while others were country-specific (e.g., fragmented, federal policies). The policy recommendations included fostering awareness, creating strong political commitment, and setting reliable standards related to ethics and data security. The eMEN project has provided the initial recommendations to guide political and regulatory processes regarding eMH. Further research is needed to establish well-tailored implementation strategies and to assess the generalizability of the recommendations beyond the countries involved in the eMEN project.

[The future of psychiatrists: subquota and quota-raising in Belgium]. / De toekomst van de psychiaters: over subquota en contingentering in België.

BACKGROUND: In Belgium, the number of medical students that can start a psychiatry residency is defined by a fixed number.
AIM: To present this calculation process.
METHOD: To reconstruct this process based on documents published by the planning committee, a federal committee comprised of a representation from different universities, several ministries, and Belgian communities.
RESULTS: With the help of an algorithm, the expected number of psychiatrists needed in the future is calculated by the planning committee and shared to be implemented by the communities.
CONCLUSION: The planning committee estimates the number of psychiatrists needed by an algorithm that uses both historical tendencies and more rapidly changing parameters. However, the incorporation of predicted epidemiological changes remains limited.

[Stratification: embracing the continuum]. / Stratificatie: het continuüm omarmen.

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[Education and training in psychiatry in 2019]. / Onderwijs en opleiding in de psychiatrie anno 2019.

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[Music therapy and depression]. / Muziektherapie bij depressie.

BACKGROUND: Music therapy is a predominantly non-verbal psychotherapy based on music improvisation, embedded in a therapeutic relationship. This is the reason why music therapy is also used to treat depression. AIM: To examine the efficacy of music therapy and to report on the results of recent research into the value of music therapy as a treatment for depression. METHOD: We reviewed the literature on recent research into music therapy and depression, reporting on the methods used and the results achieved, and we assessed the current position of music therapy for depression in the context of evidence-based scientific research. RESULTS: A wide variety of research methods was used to investigate the effects of using music therapy as a psychotherapy. Most studies focused usually on the added value that music therapy brings to the standard form of psychiatric treatment, when administered with or without psychopharmacological support. Music therapy produced particularly significant and favourable results when used to treat patients with depression. CONCLUSION: Current research into music therapy and depression points to a significant and persistent reduction in patients' symptoms and to improvements in their quality of life. However, further research is needed with regard to the best methods of illustrating the effects of music therapy.

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.

Assisted fertilization by subzonal insemination and intracytoplasmic sperm injection.

The results of 600 consecutive treatment cycles of subzonal insemination (SUZI) and intracytoplasmic sperm injection (ICSI) are described in couples with failed fertilization after standard IVF or insufficient spermatozoa in the ejaculate for IVF. More oocytes were damaged by ICSI (16.3%) than by SUZI (8.5%) and the normal fertilization rate was substantially higher after ICSI (49.1% v. 16.6%). Subsequent development of two-pronuclear oocytes in vitro was 80% after SUZI and 73.9% after ICSI. Significantly more triple embryo replacements were carried out after ICSI than after SUZI. Embryo transfers were possible in 421 of the 600 cycles. There were 63 pregnancies after ICSI (215 transfers) and 23 after SUZI (156 transfers); 10 additional pregnancies were achieved after 50 transfers of a mixture of SUZI and ICSI embryos. The results of fetal karyotypes and follow-up of the children do not indicate an increase in congenital malformations.

A hypogranular variant of acute promyelocytic leukaemia showing a heterogenic immunophenotype with CD34, CD2, HLA-DR positivity: a case report and review of the literature.

We report the case of a 46-year-old man who presented with the hypogranular variant of an acute promyelocytic leukaemia (APL). RT-PCR analysis for detection of the t(15;17) fusion transcript confirmed the cytological findings by demonstrating a bcr-3 type PML/RARalpha rearrangement. According to the WHO-classification, this leukaemia fulfilled the criteria for 'Acute promyelocytic leukaemia with t(15;17)(q22;q12)'(1). Immunophenotyping revealed a leukaemic population with an aberrant expression of markers. Besides the presence of the expected immunophenotypic markers in APL (CD45 with low density, CD13+, CD33+, CD15-, CD117+ and MPO+), the population showed a positivity for CD34, CD2 and HLA-DR for at least a part of the malignant promyelocytes. Since the expression of these three markers, all together, is rather unique, we reviewed the literature to prove the relationship of this specific immunophenotype with morphology, clinical and molecular findings.

Acute myeloid leukaemia of mixed megakaryocytic and erythroid origin: a case report and review of the literature.

We report the case of a 78-year-old man who presented with acute myeloid leukaemia showing subpopulations of cells expressing platelet-associated markers and the presence of a pan-myeloid component, besides glycophorin A-positive cells. Most of the immature cells had a proerythroblast-like morphology and we classified this case as an FAB-M6 variant, as suggested by Bain (1). According to the WHO classification, this leukaemia fulfilled the criteria of'AML with multilineage dysplasia' (2). Immunophenotyping characteristics showed two distinct aberrant subpopulations, a young pan-myeloid (CD45+ with low density, CD34+, CD117+, CD13+, CD33+, partial cytoplasmic myeloperoxidase (MPO)+) population with platelet-associated markers (CD41+, CD42+, CD61+) and a CD45+, CD117+, CD34- population with partial CD235a positivity indicative for erythroid maturation. This case belongs to the group of 'early' erythroblastic leukaemias where a subset of progenitor cells present with erythroid-megakaryocyte bipotentiality or are blocked at an early BFU-E (burst-forming unit erythrocyte)-like stage of erythroid differentiation (11, 12, 13).

Study of two markers of apoptosis and meiotic segregation in ejaculated sperm of chromosomal translocation carrier patients.

BACKGROUND: To try to explain the infertility of chromosomal translocation carrier patients, we compared the expression of two markers of apoptosis in the sperm of patients and of fertile donors, and we studied the meiotic segregation in the ejaculated sperm of these translocation carriers. METHODS: Twenty semen samples of translocation carriers, [reciprocal (n=14) and Robertsonian translocations (n=6)], were compared with the semen samples of donors (n=20). Different tests were applied: annexin V binding assay; terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL); and fluorescence in situ hybridization (FISH). RESULTS: The annexin V binding assay in sperm of patients with chromosomal translocation (n=17) showed a significantly increased proportion of sperm with externalized phosphatidylserine (PS) than in the control group (n=20, P

FISH analysis of chromosome X, Y and 18 abnormalities in testicular sperm from azoospermic patients.

BACKGROUND: Sperm extracted from testicular biopsies of azoospermic men can successfully be used for ICSI. The concern exists that testicular sperm from azoospermic men suffering from severe testicular failure may have a higher frequency of aneuploidy, which may lead to an increased risk for chromosomally abnormal offspring. METHODS: Testicular sperm from patients showing spermatogenic failure (n = 17) and from patients with normal spermatogenesis (n = 26) were analysed by fluorescence in-situ hybridization (FISH). Numerical chromosomal abnormalities for chromosomes X, Y and 18 were evaluated by FISH in a total of 1697 testicular sperm derived from 43 azoospermic patients. RESULTS: No difference was observed between the frequency of chromosomal abnormalities in testicular sperm from patients with normal spermatogenesis (5.6%) and from patients with spermatogenic failure (8.2%). However, the frequency of aneuploidy for chromosome 18 was higher in the group of azoospermic patients with spermatogenic failure than in the group with normal spermatogenesis (3.2 versus 1.3%). Within the obstructive group, sex chromosome aneuploidy (4.5%) occurred more frequently than chromosome 18 aneuploidy (1.3%; P < 0.001). Among testicular sperm derived from patients with spermatogenic failure, sex chromosomal aneuploidy (5.8%) was similar to that for chromosome 18 (3.2%). CONCLUSIONS: So far, no difference in the total frequency of chromosomal abnormalities has been observed between patients with normal spermatogenesis and patients with severe testicular failure. However, aneuploidy for chromosome 18 was higher in the group with spermatogenic failure.

First trimester chorionic villus sampling in twin gestations.

First-trimester prenatal diagnosis was offered to 104 twin pregnancies mainly for advanced maternal age and cytogenetic evaluation of a new fertilization technique. Chorionic villus sampling (CVS) was performed transcervically (35%), transabdominally (23%), or by combination of these two techniques (42%). Although no placental biopsy failures occurred, two errors in fetal sexing were recorded due to non-selective placental sampling. In these two cases, both fetuses were sampled transcervically. Cytogenetic results were available for all fetuses; six of them showed an abnormal direct chromosomal pattern, but long-term villi culture analysis or additional amniocentesis (n = 1) reduced the number to four. Early fetal loss (3.4%) and perinatal mortality (6.3%) after CVS were comparable with a control group of 101 consecutive twin pregnancies without prenatal diagnosis (respectively 6.9% and 5.3%). Perinatal loss in the CVS group was associated in 10 of 12 fetuses with preterm premature rupture of the membranes and consequent preterm delivery. Mean gestational age at delivery, mean birthweight and the frequency of preterm delivery, and low birthweight infants were nearly identical in both groups. This study shows that CVS in the first trimester of pregnancy is an accurate and fast approach for prenatal diagnosis in twin gestations with an acceptable risk of adverse pregnancy outcome. However, a transcervical approach for both fetuses is not recommended.

Clinical experience of sex determination by fluorescent in-situ hybridization for preimplantation genetic diagnosis.

In our centre we started using fluorescent in-situ hybridization (FISH) technique for sexing in couples with sex-linked diseases in May 1995. Probes specific for chromosomes X, Y and 18 were applied, allowing us to detect simultaneously both gender and ploidy status. The efficiency of the FISH procedure is 90.4% per biopsied blastomere or 95.2% per biopsied blastomere with a distinct nucleus visible at spreading. Up to December 1997, we treated 15 couples (20 treatment cycles) at risk for X-linked recessive disease and two couples with Yq deletion (two treatment cycles) with the aim of transferring only female embryos. In one cycle, no embryos suitable for biopsy were obtained and in five cycles no normal female embryos were available at diagnosis. In the remaining 16 cycles, transfer was possible and six pregnancies ensued: one miscarriage has occurred and six children have been born from the other five pregnancies. The implantation rate (fetal sacs) per transferred embryo was 20.8%. In 98 (61%) of the 161 diagnosed embryos, a diploid status was observed in one or in both biopsied blastomeres. In 10 out of the 161 (6.2%) embryos a heterogeneity among the two biopsied blastomeres was found: a diploid nucleus in one blastomere and a non-diploid pattern or binuclear status in the other. In the remaining 53 (32.9%) out of 161 diagnosed embryos, the biopsied blastomeres were abnormal. The embryos that were not transferred or frozen were further analysed. When two sex chromosomes and two autosomes were present in the biopsied blastomere, the sex determination of the biopsied blastomere was never in conflict with the sex determination in the rest of the embryo. Furthermore, if the biopsied cell was diagnosed as abnormal (triploid, aneuploid, chaotic) the embryo was indeed completely abnormal or at least mosaic. A FISH error could not be excluded in two embryos (1.2%); however, a wrong gender determination did not result from this.