[Precision psychiatry and neuroimaging: Towards improved treatment success in psychosis]. / Precisiepsychiatrie en neuro-imaging: op weg naar meer behandelsucces bij psychoses.

BACKGROUND: In the future, clinicians might use information about neurobiological processes, obtained through imaging techniques, to guide personalized prevention and intervention strategies for psychosis and related disorders. However, this requires more knowledge about these individuals’ brain function. AIM: To advance the current knowledge on neurobiological processes in patients with schizophrenia spectrum disorders (SSD) and individuals at increased risk of these disorders. METHOD: We conducted a systematic review to address dopaminergic alterations in individuals at increased risk of SSD. Additionally, we acquired PET and MRI scans in patients with SSD and controls to obtain information about neurotransmitters, such as dopamine. RESULTS: Striatal dopamine synthesis capacity was altered in individuals at increased risk of developing SSD compared to controls. In healthy volunteers, the concentration of neuromelanin, a breakdown product of dopamine, in the substantia nigra was negatively associated with striatal dopamine synthesis capacity. This was not the case for patients with SSD. CONCLUSION: We report differences in neurobiological processes and their interrelationships between patients with psychotic and related disorders and controls. This information may help predict psychosis susceptibility and treatment effectiveness in the future. Our findings can therefore contribute to the development of personalized treatments and better counselling of the patient.

Burden of mental health problems: quality of life and cost-of-illness in youth consulting Dutch walk-in youth health centres.

BACKGROUND: Little is known about the burden of (sub-threshold) mental health problems in youth. AIM: To examine the burden of mental health problems in terms of health-related quality of life (HRQoL) and cost-of-illness, for first visitors of the Dutch youth walk-in centres (@ease). METHOD: A bottom-up, prevalence-based burden of disease study from a societal perspective. HRQoL was assessed through the EuroQoL (EQ-5D-5L), and cost-of-illness via items about truancy and health care utilization. RESULTS: Participants (N = 80) showed a decreased HRQoL compared to the general population of Dutch youth. In the three months prior to their 1st attendance, participants skipped on average 4.11 days of school and had 1.03 health care visits, leading to total costs of €512.64 per person. Females had significantly higher health care costs and lower HRQoL. Health care use was lower in those not speaking the Dutch language. Living alone was a significant predictor of truancy (costs), and therefore total costs. CONCLUSIONS: Mental health problems in youth consulting @ease have a considerable impact on the individual's HRQoL, and an economic impact on society, yet almost 75% is not receiving care. A lack of interventions in this critical period in life may have major lifelong consequences.

Demographic, clinical, and service-use characteristics related to the clinician's recommendation to transition from child to adult mental health services.

PURPOSE: The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians' advice to continue treatment at AMHS. METHODS: Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians' transition recommendations. RESULTS: Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS. CONCLUSION: Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services.

[Monogenetic causes of psychiatric disorders: a review]. / Monogenetische oorzaken van psychiatrische aandoeningen: een overzicht.

BACKGROUND: Because of rapid developments in genetic technology, more underlying genetic causes of psychiatric disorders can be detected which may contribute to better monitoring and treatment of co-morbidities than previously. AIM: Review of monogenetic causes of psychiatric disorders. METHODE: Review of the literature. RESULTATS: Research in people with monogenetic disorders will generate new knowledge and insights on psychopathology and cognitive function in general and pave the way to new treatment targets. In this article we discuss four monogenetic disorders that are relevant for clinical psychiatry and (educational) psychology: fragile X syndrome, tuberous sclerosis, Rett Syndrome, and Huntington’s disease. CONCLUSION: Given the multisystem nature of these genetic disorders, a well-coordinated, multidisciplinary approach by specialized expert centers is highly recommended.

[A person comes to the psychiatrist: towards sex-gender sensitive mental health care]. / Komt een mens bij de psychiater; op weg naar sekse- en gendersensitieve ggz.

Background In psychiatric research there has been an increasing interest for sex- and genderspecific aspects in clinical presentation, outcome, and treatment of psychiatric disorders. Scientific studies on psychopathology pay more and more attention to the biological differences and differences in exposure to environmental risk factors between women and men. Aim To give a review on sex- and genderspecific aspects on psychiatric diagnostics and treatment. Method Review of most recent literature. Results The translation of this newly generated knowledge into clinical practice is still lagging behind. An important next step is to integrate this knowledge into clinical guidelines, and in teaching and training programs. Conclusion The development of sex-gender sensitive diagnostic instruments and outcome measures may contribute to personalized healthcare. These are essential steps on the way to sex-gender sensitive mental health care which will ultimately benefit the individual patient.

ENgage YOung people earlY (ENYOY): a mixed-method study design for a digital transdiagnostic clinical - and peer- moderated treatment platform for youth with beginning mental health complaints in the Netherlands.

BACKGROUND: The onset of mental disorders typically occurs between the ages of 12 and 25, and the burden of mental health problems is the most consequential for this group. Indicated prevention interventions to target individuals with subclinical symptoms to prevent the transition to clinical levels of disorders, even leading to suicide, have shown to be effective. However, the threshold to seek help appears to be high. Digital interventions could offer a solution, especially during the Covid-19 pandemic. This implementation study will investigate the digital indicated prevention intervention ENgage YOung people Early (ENYOY), the Dutch version of the original Moderated Online Social Therapy Platform (MOST+) from Australia. In addition, the relationship between stress biomarkers, symptoms and outcome measures of youth using the platform will be investigated in this study. METHODS: The MOST+ platform will be adapted, translated and developed for the situation in the Netherlands in collaboration with a Youth Panel. A prospective cohort of 125 young people (16-25 years) with beginning mental health complaints will be on the platform and followed for a year, of which 10 participants will have an additional smart watch and 10 participants will be asked to provide feedback about the platform. Data will be collected at baseline and after 3, 6 and 12 months. Outcome measures are Psychological Distress assessed with the Kessler Psychological Distress Scale (K10), Social and occupational functioning (measures by the SOFAS), positive mental health indicators measured by the Positive Health Instrument, stress biomarkers with a smart-watch, website journeys of visitors, and feedback of youth about the platform. It will be a mixed-method study design, containing qualitative and quantitative measures. DISCUSSION: This trial will specifically address young people with emerging mental health complaints, and offers a new approach for treatment in the Netherlands. Considering the waiting lists in (child and adolescent)-psychiatry and the increase in suicides among youth, early low-threshold and non-stigmatizing help to support young people with emerging psychiatric symptoms is of crucial importance. Moreover, this project aims to bridge the gap between child and adolescent and adult psychiatry. TRIAL REGISTRATION: Netherlands Trial Register ID NL8966 , retrospectively registered on the 19th of October 2020.

[Transitional psychiatry in Flanders: a proactive strategy]. / Transitiepsychiatrie in Vlaanderen; een proactieve strategie.

background Psychiatric disorders in adults often result from psychiatric problems during childhood and adolescence. aim In the light of prevention of psychiatric disorders in adults, we focus on adolescence. method Based on the working method of the transitional psychiatry unit, we describe the characteristics of the patient group and the necessities of adequate treatment and care for young people who are suffering from a stagnation in development due to psychiatric problems. results Family therapy, new authority/non-violent resistance and our own RAISING skills are tools for treating these young people. Here we focus on the adolescent's development. This early treatment prevents the development of irreversible symptoms and serious psychiatric illness during adulthood. conclusion Transitional psychiatry forms part of the answer in the search of pro-active medicine. Tijdschrift voor Psychiatrie 63(2021)2, 115-119.

[Psychosis and movement disorders in an adolescent with 22q11.2 deletion syndrome]. / Psychose en bewegingsstoornissen bij een adolescent met 22q11.2-deletiesyndroom.

The 22q11.2 deletion syndrome (22q11.2ds) is a genetic syndrome affecting multiple organ systems and is associated with increased risk of developing neuropsychiatric disorders. We describe a 15-year old female adolescent with 22q11.2ds, psychotic disorder, and catatonia. Individuals with 22q11.2ds are at increased risk of developing catatonia. Vulnerability for developing extrapyramidal symptoms and epileptic seizures may complicate pharmacological treatment for psychotic episodes. There may be a diagnostic delay of diagnosing Parkinson's disease in patients taking antipsychotics as parkinsonism may be viewed as a side effect. Health professionals working with people with 22q11.2ds should be aware of the increased prevalence of movement disorders and the threshold for referral to 22q11.2ds specialist services should be low.

Risk of non-affective psychotic disorder or bipolar disorder in autism spectrum disorder: a longitudinal register-based study in the Netherlands.

BACKGROUND: Individuals with autism spectrum disorder (ASD) appear to be at increased risk of non-affective psychotic disorder (NAPD) and bipolar disorder (BD). However, most previous studies examined the co-occurrence of ASD and NAPD or BD, ignoring possible diagnostic bias and selection bias. We used longitudinal data from Dutch psychiatric case registers to assess the risk of NAPD or BD among individuals with ASD, and compared the results to those obtained for the Dutch population in earlier studies. METHODS: Individuals with ASD (n = 17 234) were followed up between 16 and 35 years of age. Kaplan-Meier estimates were used to calculate the risk of NAPD or BD. We conducted separate analyses to reduce possible bias, including an analysis among individuals diagnosed with ASD before age 16 years (n = 8337). RESULTS: Of the individuals with ASD, 23.50% (95% confidence interval 21.87-25.22) were diagnosed with NAPD and 3.79% (3.06-4.69) with BD before age 35 years. The corresponding figures for the general population were 0.91% (0.63-1.28) and 0.13% (0.08-0.20). Risk estimates were substantially lower, but still higher than general population estimates, when we restricted our analyses to individuals diagnosed with ASD before age 16, with 1.87% (1.33-2.61) being diagnosed with NAPD and 0.57% (0.21-1.53) with BD before age 25 years. The corresponding figures for the general population were 0.63% (0.44-0.86) and 0.08% (0.05-0.12). CONCLUSIONS: Individuals with ASD are at increased risk of NAPD or BD. This is likely not the result of diagnostic or selection bias.

[Mental health care for people with borderline intellectual functioning or intellectual disabilities]. / Geestelijke gezondheidszorg voor mensen met zwakbegaafdheid of een verstandelijke beperking.

BACKGROUND: Despite the increasing attention for people with a (borderline) intellectual disability within the field of mental health care in The Netherlands and Flanders, access to mental health care for this vulnerable group is still limited.
AIM: To explore the access to mental health care in the Netherlands and Flanders for people with borderline intellectual functioning or an intellectual disability.
METHOD: A survey of scientific literature, recent reports and available practical knowledge about mental disorders in people with borderline intellectual functioning or an intellectual disability and their access to mental health care.
RESULTS: Insufficient knowledge about mental disorders in long term intellectual disability care and insufficient knowledge of, and experience with borderline intellectual functioning and intellectual disability among mental health care providers play a role in the limited access to good mental health care. More exchange of knowledge and sharing of experiences is necessary to ultimately properly address the needs of this group.
CONCLUSION: Structural collaboration between mental health care and care for people with an intellectual disability is needed.

[Transdiagnostic psychiatry: work in progress]. / Transdiagnostische psychiatrie: concept in ontwikkeling.

BACKGROUND: There is an increasing awareness that the current approach to clinical thought and work in psychiatry in relation to psychiatric diagnosis, treatment and research has its limitations. This necessitates a process to reform both the clinical practice and future scientific research. One way to reform this is the transdiagnostic approach. AIM: To clarify the psychological, biological and therapeutic aspects of a transdiagnostic approach in psychiatry. METHOD: An analysis of new approaches based on recent findings from the recent literature. RESULTS: Transdiagnostic psychiatry is a relatively new concept which is still under development. The examples extracted from the reviewed literature on developmental psychology, neurobiology and treatment demonstrate that this approach may lead to improvements in clinical care and generate new etiological insights. CONCLUSION: A transdiagnostic approach in psychiatry may lead to new insights that are relevant for clinical practice and future scientific research.

Cerebral dopamine deficiency, plasma monoamine alterations and neurocognitive deficits in adults with phenylketonuria.

BACKGROUND: Phenylketonuria (PKU), a genetic metabolic disorder that is characterized by the inability to convert phenylalanine to tyrosine, leads to severe intellectual disability and other cerebral complications if left untreated. Dietary treatment, initiated soon after birth, prevents most brain-related complications. A leading hypothesis postulates that a shortage of brain monoamines may be associated with neurocognitive deficits that are observable even in early-treated PKU. However, there is a paucity of evidence as yet for this hypothesis. METHODS: We therefore assessed in vivo striatal dopamine D2/3 receptor (D2/3R) availability and plasma monoamine metabolite levels together with measures of impulsivity and executive functioning in 18 adults with PKU and average intellect (31.2 ± 7.4 years, nine females), most of whom were early and continuously treated. Comparison data from 12 healthy controls that did not differ in gender and age were available. RESULTS: Mean D2/3R availability was significantly higher (13%; p = 0.032) in the PKU group (n = 15) than in the controls, which may reflect reduced synaptic brain dopamine levels in PKU. The PKU group had lower plasma levels of homovanillic acid (p < 0.001) and 3-methoxy-4-hydroxy-phenylglycol (p < 0.0001), the predominant metabolites of dopamine and norepinephrine, respectively. Self-reported impulsivity levels were significantly higher in the PKU group compared with healthy controls (p = 0.033). Within the PKU group, D2/3R availability showed a positive correlation with both impulsivity (r = 0.72, p = 0.003) and the error rate during a cognitive flexibility task (r = 0.59, p = 0.020). CONCLUSIONS: These findings provide further support for the hypothesis that executive functioning deficits in treated adult PKU may be associated with cerebral dopamine deficiency.

[Transitional psychiatry in the Netherlands: experiences and views of mental health professionals]. / Transitiepsychiatrie in Nederland: ervaringen en opvattingen van ggz-professionals.

BACKGROUND: Psychopathology manifests itself primarily in late adolescence and continues into adulthood. Continuity of care is essential during this phase of life. The current care service distinguishes between child/adolescent (CAMHS) and adult mental health services (AMHS). The separation of services can interfere with the continuity of care.
AIM: To map professionals' experiences of and views on the transition and associated problems that young people can experience as they are transferred from CAMHS to AMHS.
METHOD: We distributed an online questionnaire among professionals providing mental health care to young people (aged 15-25) with psychiatric problems.
RESULTS: The questionnaire was completed by 518 professionals. Decisions relating to transition were generally based on the professional's own deliberations. The preparation consisted mainly of discussing changes with the adolescent and his or her parents. The majority of transition-related problems were experienced in CAMHS, particularly with regard to collaboration with AMHS. Respondents were of the opinion that the developmental age ought to be the determining factor in the decision-making process with regard to transition and they considered it important that developmentally appropriate services should be available in order to bridge the gap.
CONCLUSION: Professionals in CAMHS and AMHS are encountering problems in preparing the transitional phase and in organising the required structural collaboration between the two separate services. The problems relate mainly to coordination, communication and rules and regulations. Professionals are keen to improve the situation and want to see greater flexibility. In their view, there should be a wider range of specialised facilities for young people, enabling them to benefit from transitional psychiatry.

Distinct white-matter aberrations in 22q11.2 deletion syndrome and patients at ultra-high risk for psychosis.

BACKGROUND: Patients with a deletion at chromosome 22q11.2 (22q11DS) have 30% lifetime risk of developing a psychosis. People fulfilling clinical criteria for ultra-high risk (UHR) for psychosis have 30% risk of developing a psychosis within 2 years. Both high-risk groups show white-matter (WM) abnormalities in microstructure and volume compared to healthy controls (HC), which have been related to psychotic symptoms. Comparisons of WM pathology between these two groups may specify WM markers related to genetic and clinical risk factors. METHOD: Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) were assessed using diffusion tensor magnetic resonance imaging (MRI), and WM volume with structural MRI, in 23 UHR patients, 21 22q11DS patients, and 33 HC. RESULTS: Compared to UHR patients 22q11DS patients had (1) lower AD and RD in corpus callosum (CC), cortical fasciculi, and anterior thalamic radiation (ATR), (2) higher FA in CC and ATR, and (3) lower occipital and superior temporal gyrus WM volume. Compared to HC, 22q11DS patients had (1) lower AD and RD throughout cortical fasciculi and (2) higher FA in ATR, CC and inferior fronto-occipital fasciculus. Compared to HC, UHR patients had (1) higher mean MD, RD, and AD in CC, ATR and cortical fasciculi, (2) no differences in FA. CONCLUSIONS: UHR and 22q11DS patients share a susceptibility for developing psychosis yet were characterized by distinct patterns of WM alterations relative to HC. While UHR patients were typified by signs suggestive of aberrant myelination, 22q11DS subjects showed signs suggestive of lower axonal integrity.

Pharmacological treatment of 22q11.2 deletion syndrome-related psychoses.

In their recent article in Pharmacopsychiatry Verhoeven and Egger report a case series of 28 patients and state that "treatment of psychotic symptoms in patients with 22q11.2 deletion syndrome (22q11.2DS) with quetiapine or clozapine in combination with valproic acid appears likely to be more effective than with other psychotropic compounds". In this letter, we discuss the limitations of their case series and the lack of evidence for such a sweeping conclusion. In lieu of strong evidence to the contrary, standard pharmacological treatments of psychotic illness in 22q11.2DS remains recommended, with attention to 22q11.2DS-related issues. The latter would include management strategies to help ameliorate the elevated risk of seizures (e. g. when using clozapine), and vigilance for Parkinson's disease or other potential movement disorders.

[Lithium therapy in patients with mild mental retardation]. / Lithium bij patiënten met een lichte verstandelijke beperking.

In the psychiatric treatment of patients with mild learning disabilities or borderline intellectual functioning, signs and symptoms of psychiatric disorders are sometimes misinterpreted as behaviour that reflects problems that are known to patients with mental retardation. We report on two case studies in which lithium therapy made a substantial contribution to (partial) recovery. One patient had bipolar disorder and the other had a major depressive disorder combined with suicidal behaviour. Each patient also had a mild learning disability or borderline intellectual functioning.

[Youth F-ACT: mapping the problems of a special population]. / Jeugd-F-ACT: problematiek van een bijzondere populatie in kaart gebracht.

BACKGROUND: Youth f-act teams have been set up for the purpose of providing the care needed by young people suspected of having complex psychiatric problems. AIM: To obtain insight into the problems of this population at the beginning and at the end of treatment provided by the youth f-act team in South Limburg. METHOD: We based our study on a cohort of 68 patients who met the criteria for f-act during the period from January 2013 up to and including October 2014. We evaluated the effect of f-act treatment of 41 patients who had completed their treatment during the above-mentioned period. We examined the records for patients' daily functioning and quality of life and we noted patient characteristics at beginning and end of treatment in order to collect more information about the problems of this population. RESULTS: Besides having psychiatric problems, our study population also appeared to have malfunctioned at several other areas. At the end of treatment patients' daily functioning was found to have improved, but there was little or no improvement in patients' quality of life. CONCLUSION: Treatment by the youth f-act team seems able to deal successfully with the problems of the young people under study. However, factors that influence patients' quality of life need to be studied more thoroughly so that in the future the quality of treatment will be of a higher standard.

[Auto-immune disorders as a possible cause of neuropsychiatric syndromes]. / Auto-immuunaandoeningen als mogelijke oorzaak van neuropsychiatrische syndromen.

BACKGROUND: Changes that occur in the behaviour of voltage-gated ion channels and ligand-gated receptor channels due to gene mutations or auto-immune attack are the cause of channelopathies in the central and peripheral nervous system. Although the relation between molecular channel defects and clinical symptoms has been explained in the case of many neuromuscular channelopathies, the pathophysiology of auto-immunity in neuropsychiatric syndromes is still unclear. AIM: To review recent findings regarding neuronal auto-immune reactions in severe neuropsychiatric syndromes. METHOD: Using PubMed, we consulted the literature published between 1990 and August 2014 relating to the occurrence of auto-immune antibodies in severe and persistent neuropsychiatric syndromes. RESULTS: Auto-antibodies have only limited access to the central nervous system, but if they do enter the system they can, in some cases, cause disease. We discuss recent findings regarding the occurrence of auto-antibodies against ligand-activated receptor channels and potassium channels in neuropsychiatric and neurological syndromes, including schizophrenia and limbic encephalitis. CONCLUSION: Although the occurrence of several auto-antibodies in schizophrenia has been confirmed, there is still no proof of a causal relationship in the syndrome. We still have no evidence of the prevalence of auto-immunity in neuropsychiatric syndromes. The discovery that an antibody against an ion channel is associated with some neuropsychiatric disorders may mean that in future it will be possible to treat patients by means of immunosuppression, which could lead to an improvement in a patient's cognitive abilities.

Psychopathology in adults with 22q11 deletion syndrome and moderate and severe intellectual disability.

BACKGROUND: 22q11 deletion syndrome (22q11DS) is associated with mild or borderline intellectual disability (ID). There are hardly any reports on subjects with 22q11DS with moderate or severe ID, and therefore its behavioural and psychiatric characteristics are unknown. METHOD: We describe behavioural and psychiatric characteristics of 33 adults with 22q11DS and a Full-Scale IQ (FSIQ) below 55. Participants were divided into two groups: one group having a FSIQ ≤ 55 caused by intellectual decline (n = 21) and one group with a FSIQ ≤ 55 who had always functioned at this level (n = 12). RESULTS: High scores on psychopathology sub-scales were found for both subgroups. 22q11DS patients with intellectual decline showed higher rates of co-morbid psychopathology, particularly psychosis. Furthermore, psychosis and intellectual decline were positive correlated. CONCLUSION: This is the first report addressing adult patients with 22q11DS and moderate to severe ID. Overall we found high levels of psychopathology with higher scores of psychopathology in the intellectual decline group. Life time psychosis seems to be related to deterioration.