'I am proud of how I handled it'. Exploring the impact of the COVID-19 pandemic and related restrictions on well-being of adults with severe mental illness using qualitative methods.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic and related restrictions globally impacted mental health, particularly for those with pre-existing severe mental illness (SMI). This qualitative study examined how adults with SMI perceived the effects of the COVID-19 pandemic and related restrictions in the Netherlands, focusing on their personal recovery, well-being and daily life, including an exploration of factors influencing these effects. METHODS: Semi-structured interviews were conducted, audio-recorded and transcribed verbatim. Reflexive thematic analysis was applied. Purposive sampling was used to ensure diversity of individuals with SMI (i.e., age, gender, diagnosis, cultural background and mental healthcare institution). RESULTS: Twenty participants (median age: 45 years [SD: 12, 8]; 11 females) were interviewed between May and July 2023. Findings revealed a wide range of experiences: while some individuals reported a negative impact on their existing psychiatric symptoms, others described adaptability, resilience and even positive effects of COVID-19 restrictions on their mental health and well-being. Factors influencing the heterogeneic perceptions of the COVID-19 pandemic and related restrictions include the availability of trusted social relationships and enduring interactions with health professionals. CONCLUSION: Personalised support, both socially and professionally, is crucial for addressing fears, building resilience, reducing isolation and encouraging positive coping strategies for individuals with SMI during external crises. In this project, a participatory research approach that integrated the lived experience perspective helped uncover the unique perceptions of people with SMI with regard to the pandemic and related restrictions. PATIENT OR PUBLIC CONTRIBUTION: The study used a participatory action research approach, with experts-by-experience involved in every stage of the project as part of the research team. This included engagement with the funding application process, recruitment strategies for interviews, developing the interview guide, piloting the interview, interpreting findings, and knowledge dissemination activities.

[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.

[Genetic risk of mental illness: what do we know and how do we communicate this?] / Genetisch risico van psychiatrische ziekten: wat weten we en hoe communiceren we dat?

BACKGROUND: Insights from psychiatric genetics research and large international psychiatric genetics consortia are promising but still remain outside the realm of clinical practice.
AIM: To provide an overview of developments in the field of psychiatric genetics; and to offer guidance for health professionals how to assess and manage clinical implications of these developments.
METHOD: In this review, we address: recent developments in psychiatric genetics, with a focus on polygenic risk scores (PRS); ethical dilemmas associated with clinical application of PRS; and basic principles of genetic counseling for psychiatric disorders.
RESULTS: PRS are not yet ready for implementation in clinical practice because of limited predictive value and poor generalizability. In addition, it is still unclear how genetic risk and PRS can be communicated clearly to patients and families.
CONCLUSION: Advances in psychiatric genetics and increased availability of genetic risk scores may lead to questions from patients and families coping with psychiatric illness. These questions may be best addressed using psychiatric genetic counseling techniques. We recommend that psychiatrists have some basic knowledge of psychiatric genetics and know how to refer their patients to a clinical geneticist. Implementing a psychiatric genetics theme in training and education may be helpful.
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[Guidelines on genetic testing in psychiatry: an overview]. / Leidraad genetisch testen in de psychiatrie.

BACKGROUND: In recent years, technological advances have led to the identification of numerous genetic variations that are associated with psychiatric symptoms. Establishing a genetic cause may provide patients and family members with an explanation for the problems and in specific cases allows targeted treatment of psychiatric and somatic (co)morbidity. At present, patients with psychiatric disorders are rarely referred for genetic testing. AIM: To provide an overview of literature and (inter)national guidelines in the field of genetic testing for patients with psychiatric disorder, and to present guidance on indications for genetic testing in clinical practice. METHOD: A systematic search was conducted in PubMed and Embase focusing on articles with recommendations on genetic testing in psychiatric disorders. In addition, national and international guidelines on genetic testing in psychiatry were studied. The main findings were summarized in an infographic. RESULTS: Based on the current literature and (inter)national guidelines, patients with (comorbid) intellectual disability should always be referred to a clinical geneticist. Psychiatrists should consider genetic testing in patients with other psychiatric disorders if there are ‘red flags’ such as a positive family history, congenital abnormalities, developmental delay, dysmorphic features, movement disorders or cognitive decline. Psychiatrists may request genetic testing themselves or refer patients to clinical geneticists. CONCLUSION: Psychiatric disorders may be underpinned by a genetic anomaly, particularly in patients presenting with psychiatric as well as somatic symptomatology. Psychiatrists should recognize symptoms and warning signs indicative of an underlying genetic abnormality, and know when to refer their patients for genetic testing.

[From genetic findings to clinical practice in psychiatry: how genetics may enable Precision Psychiatry]. / Van genetische bevindingen naar de klinische praktijk van de psychiater: hoe genetica precisiepsychiatrie mogelijk kan maken.

BACKGROUND: Most psychiatric disorders are characterized by a complex genetic background where many common variants are involved. Nowadays, we are able to 'read' these variants, test for their association with phenotypes in genome-wide association studies (GWAS), and perform further downstream analyses. However, the impact of such findings on clinical psychiatry has remained largely unclear.
AIM: To provide new insight into the degree of genetic overlap between psychiatric disorders and neurological disorders. And to investigate how genetic findings may impact clinical practice in psychiatry.
METHOD: Bioinformatics and statistical methods were applied to perform analyses in large genetic datasets. In particular, we focused on: pathway analyses in schizophrenia; a multivariate GWAS of stress and trauma phenotypes; and genetic overlap analyses between amyotrophic lateral sclerosis (ALS) and schizophrenia. Finally, we assessed for which psychiatric disorders genetic findings are most likely to impact clinical practice in the near future.
RESULTS: First, we found enrichment of common genetic variants associated with schizophrenia in synaptic signalling pathways relating to dopaminergic, acetylcholinergic and glutamatergic neurons. Second, we found that ALS and schizophrenia partly share common genetic risk. And third, we outline the clinical relevance of genetic cross-disorder studies in psychiatry, and posit that these studies have meaning for diagnostics, prognostics and treatment prediction in psychiatry.
CONCLUSION: The summarized and previous genetic studies into psychiatric disorders will hopefully soon enable precision psychiatry, as genetics is a powerful tool to elucidate individualized risk profiles of patients and their responses to psychotropic medication. Genetic counselling allows clinicians to carefully balance the wide range of considerations in those patients and relatives with questions related to genetic underpinnings of disease and treatment response.

[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.

Beloop van covid-19-infecties en impact op mentale gezondheid; opzet van een landelijk casusregister.

Course of covid-19 infections and impact on mental health; setting up a national case register.

[Practical guidelines for prescribing psychotropic medication to people with intellectual disability]. / Voorschrijven van psychofarmaca bij mensen met een verstandelijke beperking: handvatten voor de praktijk.

BACKGROUND: In people with intellectual disability (id) prescription of psychotropic drugs is often chronic and outside licensed indications.
AIM: To provide practical strategies for prescribing psychotropic drugs in people with id.
METHOD: We reviewed the literature and existing guidelines to summarize recommendations for prescribing psychotropic drugs in people with id.
RESULTS: The Diagnostic Manual - Intellectual Disability is a useful tool to facilitate diagnosis of mental disorders in people with id. Challenging behaviour in the absence of a psychiatric disorder is not a licensed indication for prescribing psychotropic drugs. Because of increased vulnerability for side effects in people with id, it is crucial to carry out a risk-benefit analysis before prescribing psychotropic drugs. In line with existing guidelines, we recommend monitoring of treatment and adverse effects with standardized scales adapted for id.
CONCLUSION: A careful decision-making process regarding initiation and continuation is essential to prevent insufficient as well as excessive pharmacotherapy in people with id.

White-matter relaxation time and myelin water fraction differences in young adults with autism.

BACKGROUND: Increasing evidence suggests that autism is associated with abnormal white-matter (WM) anatomy and impaired brain 'connectivity'. While myelin plays a critical role in synchronized brain communication, its aetiological role in autistic symptoms has only been indirectly addressed by WM volumetric, relaxometry and diffusion tensor imaging studies. A potentially more specific measure of myelin content, termed myelin water fraction (MWF), could provide improved sensitivity to myelin alteration in autism. METHOD: We performed a cross-sectional imaging study that compared 14 individuals with autism and 14 age- and IQ-matched controls. T 1 relaxation times (T 1), T 2 relaxation times (T 2) and MWF values were compared between autistic subjects, diagnosed using the Autism Diagnostic Interview - Revised (ADI-R), with current symptoms assessed using the Autism Diagnostic Observation Schedule (ADOS) and typical healthy controls. Correlations between T 1, T 2 and MWF values with clinical measures [ADI-R, ADOS, and the Autism Quotient (AQ)] were also assessed. RESULTS: Individuals with autism showed widespread WM T 1 and MWF differences compared to typical controls. Within autistic individuals, worse current social interaction skill as measured by the ADOS was related to reduced MWF although not T 1. No significant differences or correlations with symptoms were observed with respect to T 2. CONCLUSIONS: Autistic individuals have significantly lower global MWF and higher T 1, suggesting widespread alteration in tissue microstructure and biochemistry. Areas of difference, including thalamic projections, cerebellum and cingulum, have previously been implicated in the disorder; however, this is the first study to specifically indicate myelin alteration in these regions.

[DSM-5: neurodevelopmental disorders]. / Het hoofdstuk 'neurodevelopmental disorders' in de DSM-5.

BACKGROUND: The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) was published in May, 2013. AIM: To review the changes in the diagnostic criteria for autism spectrum disorder (ASD) and ADHD in DSM-5, compared to DSM-IV. METHOD: The diagnostic criteria for ASD and ADHD in DSM-IV and DSM-5 are compared. The new diagnostic criteria are summarised and relevant literature is discussed. RESULTS: The new category ASD includes the majority of the pervasive developmental disorders; however, in DSM-5, patients without stereotypical patterns of behaviour or interests will, from now on, be classified as having Social Communication Disorder. The threshold for meeting the diagnostic criteria for adhd has been lowered slightly. However, this is supported by clinical and epidemiological data and is unlikely to result in over-diagnosis. CONCLUSION: Research into subtypes of asd may stagnate as a result of the changes introduced in DSM-5. For clinicians, the diagnostic criteria for ASD and ADHD may be more clear-cut and possibly more user-friendly than the diagnostic criteria for these disorders as given in dsm-iv.

Polygenic risk scores for genetic counseling in psychiatry: Lessons learned from other fields of medicine.

Polygenic risk scores (PRS) may aid in the identification of individuals at-risk for psychiatric disorders, treatment optimization, and increase in prognostic accuracy. PRS may also add significant value to genetic counseling. Thus far, integration of PRSs in genetic counseling sessions remains problematic because of uncertainties in risk prediction and other concerns. Here, we review the current utility of PRSs in the context of clinical psychiatry. By comprehensively appraising the literature in other fields of medicine including breast cancer, Alzheimer's Disease, and cardiovascular disease, we outline several lessons learned that could be applied to future studies and may thus benefit the incorporation of PRS in psychiatric genetic counseling. These include integrating PRS with environmental factors (e.g. lifestyle), setting up large-scale studies, and applying reproducible methods allowing for cross-validation between cohorts. We conclude that psychiatry may benefit from experiences in these fields. PRS may in future have a role in genetic counseling in clinical psychiatric practice, by advancing prevention strategies and treatment decision-making, thus promoting quality of life for (potentially) affected individuals.

Methylphenidate for attention-deficit/hyperactivity disorder in patients with Smith-Magenis syndrome: protocol for a series of N-of-1 trials.

BACKGROUND: Smith-Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder characterized by intellectual disability and severe behavioural and sleep disturbances. Often, patients with SMS are diagnosed with attention-deficit/hyperactivity disorder (ADHD). However, the effectiveness of methylphenidate (MPH), the first-line pharmacological treatment for ADHD, in patients with SMS is unclear. Our objective is to examine the effectiveness of MPH for ADHD symptoms in individuals with SMS, proposing an alternative trial design as traditional randomized controlled trials are complex in these rare and heterogeneous patient populations. METHODS AND ANALYSIS: We will initiate an N-of-1 series of double-blind randomized and placebo-controlled multiple crossover trials in six patients aged ≥ 6 years with a genetically confirmed SMS diagnosis and a multidisciplinary established ADHD diagnosis, according to a power analysis based on a summary measures analysis of the treatment effect. Each N-of-1 trial consists of a baseline period, dose titration phase, three cycles each including randomized intervention, placebo and washout periods, and follow-up. The intervention includes twice daily MPH (doses based on age and body weight). The primary outcome measure will be the subscale hyperactivity/inattention of the Strengths and Difficulties Questionnaire (SDQ), rated daily. Secondary outcome measures are the shortened version of the Emotion Dysregulation Inventory (EDI) reactivity index, Goal Attainment Scaling (GAS), and the personal questionnaire (PQ). Statistical analysis will include a mixed model analysis. All subjects will receive an assessment of their individual treatment effect and data will be aggregated to investigate the effectiveness of MPH for ADHD in SMS at a population level. CONCLUSIONS: This study will provide information on the effectiveness of MPH for ADHD in SMS, incorporating personalized outcome measures. This protocol presents the first properly powered N-of-1 study in a rare genetic neurodevelopmental disorder, providing a much-needed bridge between science and practice to optimize evidence-based and personalized care. TRIAL REGISTRATION: This study is registered in the Netherlands Trial Register (NTR9125).

Efficacy and tolerability of riluzole in psychiatric disorders: A systematic review and preliminary meta-analysis.

There is a pressing need for better pharmacological treatment strategies for psychiatric disorders as current treatment often results in partial symptom remission and unwanted side effects. A point of entry may be the glutamatergic system since glutamatergic dysregulation contributes to multiple psychiatric disorders. We evaluated the evidence from randomized controlled trials (RCTs) regarding the use of the glutamatergic drug riluzole in mental illnesses; and conducted preliminary meta-analyses of its effectiveness in treating obsessive-compulsive disorder (OCD) and depression. A systematic search was performed using PubMed (Medline), Embase, Cochrane Database of Systematic Reviews and PsycINFO. Meta-analyses were performed using Comprehensive Meta-Analysis software. Twenty-three RCTs were included for qualitative analysis and showed positive effects of adjunctive/monotherapy riluzole in patients with OCD, depression, autism, substance abuse and schizophrenia. Seven studies were also used for quantitative analysis, which revealed positive but non-significant effects on OCD and depression. Riluzole was generally well tolerated with few serious adverse events. The studies included in this systematic review were highly heterogeneous and the number of studies was limited per diagnostic condition. Moreover, few studies have examined riluzole as a single treatment. We suggest carrying out further work to provide definitive evidence for the benefit of riluzole in psychiatric illness.

Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder.

Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the 'responsivity' of the E-I system to pharmacologic challenge; or whether E-I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder. Therefore, we used magnetic resonance spectroscopy ([1H]MRS) to measure prefrontal E-I flux in response to the glutamate and GABA acting drug riluzole in adult men with and without ASD. We compared the change in prefrontal 'Inhibitory Index'-the GABA fraction within the pool of glutamate plus GABA metabolites-post riluzole challenge; and the impact of riluzole on differences in resting-state functional connectivity. Despite no baseline differences in E-I balance, there was a significant group difference in response to pharmacologic challenge. Riluzole increased the prefrontal cortex inhibitory index in ASD but decreased it in controls. There was also a significant group difference in prefrontal functional connectivity at baseline, which was abolished by riluzole within the ASD group. Our results also show, for we believe the first time in ASD, that E-I flux can be 'shifted' with a pharmacologic challenge, but that responsivity is significantly different from controls. Further, our initial evidence suggests that abnormalities in functional connectivity can be 'normalised' by targeting E-I, even in adults.