Intellectual disability and other neuropsychiatric outcomes in high-risk children of mothers with schizophrenia, bipolar disorder and unipolar major depression

BackgroundRecent evidence points to partially shared genetics of neuropsychiatric disorders.AimsWe examined risk of intellectual disability and other neuropsychiatric outcomes in 3174 children of mothers with schizophrenia, bipolar disorder or unipolar major depression compared with 3129 children of unaffected mothers.MethodWe used record linkage across Western Australian population-based registers. The contribution of obstetric factors to risk of intellectual disability was assessed.ResultsChildren were at significantly increased risk of intellectual disability with odds ratios (ORs) of 3.2 (95% CI 1.8–5.7), 3.1 (95% CI 1.9–4.9) and 2.9 (95% CI 1.8–4.7) in the maternal schizophrenia, bipolar disorder and unipolar depression groups respectively. Multivariate analysis suggests familial and obstetric factors may contribute independently to the risk. Although summated labour/delivery complications (OR = 1.4, 95% CI 1.0–2.0) just failed to reach significance, neonatal encephalopathy (OR = 7.7, 95% CI 3.0–20.2) and fetal distress (OR = 1.8, 95% CI 1.1–2.7) were independent significant predictors. Rates of rare syndromes in children of mothers with mental disorder were well above population rates. Risk of pervasive developmental disorders, including autism, was significantly elevated for children of mothers with bipolar disorder. Risk of epilepsy was doubled for children of mothers with unipolar depression.ConclusionsOur findings provide epidemiological support for clustering of neuropsychiatric disorders. Further larger epidemiological studies are warranted.

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COMT in major depression - UK candidate gene association study

European Psychiatry ◽

10.1016/s0924-9338(11)72518-4 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 813-813

Author(s):

A. Schosser ◽

M.Y. Ng ◽

A.W. Butler ◽

S. Cohen-Woods ◽

N. Craddock ◽

...

Keyword(s):

Bipolar Disorder ◽

Major Depression ◽

Unipolar Depression ◽

Candidate Gene Association ◽

Genetic Overlap ◽

Haplotypic Association ◽

Single Marker ◽

Icd 10 ◽

System 1 ◽

The Impact

Catechol-O-methyltransferase (COMT) has a central role in brain dopamine, noradrenalin and adrenalin signaling, and has been suggested to be involved in the pathogenesis and pharmacological treatment of affective disorders. The functional single nucleotide polymorphism (SNP) in exon 4 (Val158Met, rs4680) influences the COMT enzyme activity. The Val158Met polymorphism is a commonly studied variant in psychiatric genetics, and initial studies in schizophrenia and bipolar disorder presented evidence for association with the Met allele. In unipolar depression, while some of the investigations point at an association between the Met/Met genotype and others have found a link between the Val/Val genotype and depression, most of the studies cannot detect any difference in Val158Met allele frequency between depressed individuals and controls.In the present study, we further elucidated the impact of COMT polymorphisms including the Val158Met in MDD. We investigated 1,250 subjects with DSM-IV and/or ICD-10 diagnosis of major depression (MDD), and 1,589 control subjects from UK. A total of 24 SNPs spanning the COMT gene were successfully genotyped using the Illumina HumaHap610-Quad Beadchip (22 SNPs), SNPlex™ genotyping system (1 SNP), and Sequenom MassARRAY® iPLEX Gold (1 SNP). Statistical analyses were implemented using PASW Statistics18, FINETTI (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl), UNPHASED version 3.0.10 program and Haploview 4.0 program.Neither single-marker nor haplotypic association was found with the functional Val158Met polymorphism or with any of the other SNPs genotyped. Our findings do not provide evidence that COMT plays a role in MDD or that this gene explains part of the genetic overlap with bipolar disorder.

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Mentally Sick or Not—(Bio)Markers of Psychiatric Disorders Needed

Journal of Clinical Medicine ◽

10.3390/jcm9082375 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2375 ◽

Cited By ~ 4

Author(s):

Napoleon Waszkiewicz

Keyword(s):

Bipolar Disorder ◽

Major Depression ◽

Mental Disorders ◽

Psychiatric Disorders ◽

Developmental Disorders ◽

Mental Illnesses ◽

Major Depression Disorder ◽

Wide Group ◽

Substance Related Disorders ◽

Depression Disorder

Psychiatric disorders, also called mental illnesses or mental disorders, constitute a wide group of disorders including major depression disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ) and other psychoses, anxiety disorders (ANX), substance-related disorders (SRD), dementia, developmental disorders e [...]

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Psychiatric illness and regression in individuals with Phelan-McDermid syndrome

Journal of Neurodevelopmental Disorders ◽

10.1186/s11689-020-9309-6 ◽

2020 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Teresa M. Kohlenberg ◽

M. Pilar Trelles ◽

Brittany McLarney ◽

Catalina Betancur ◽

Audrey Thurm ◽

...

Keyword(s):

Bipolar Disorder ◽

Intellectual Disability ◽

Psychiatric Disorders ◽

Psychiatric Illness ◽

Psychiatric Symptoms ◽

Structured Interview ◽

Autism Spectrum ◽

Scaffolding Protein ◽

International Registry ◽

Increased Risk

Abstract Background Phelan-McDermid syndrome (PMS) is a genetic condition characterized by intellectual disability, speech and language deficits, hypotonia, autism spectrum disorder, and epilepsy. PMS is caused by 22q13.33 deletions or mutations affecting SHANK3, which codes for a critical scaffolding protein in excitatory synapses. SHANK3 variants are also known to be associated with an increased risk for regression, as well as for psychiatric disorders, including bipolar disorder and catatonia. This study aimed to further describe these phenomena in PMS and to explore any relationship between psychiatric illness and regression after early childhood. Methods Thirty-eight people with PMS were recruited to this study through the Phelan-McDermid Syndrome Foundation based on caregiver report of distinct development of psychiatric symptoms. Caregivers completed a clinician-administered semi-structured interview focused on eliciting psychiatric symptomatology. Data from the PMS International Registry were used to confirm genetic diagnoses of participants and to provide a larger sample for comparison. Results The mean age of the 38 participants was 24.7 years (range = 13 to 50; SD = 10.06). Females (31 of 38 cases; 82%) and sequence variants (15 of 38 cases; 39%) were over-represented in this sample, compared to base rates in the PMS International Registry. Onset of psychiatric symptoms occurred at a mean age of 15.4 years (range = 7 to 32), with presentations marked by prominent disturbances of mood. Enduring substantial loss of functional skills after onset of psychiatric changes was seen in 25 cases (66%). Symptomst indicative of catatonia occurred in 20 cases (53%). Triggers included infections, changes in hormonal status, and stressful life events. Conclusions This study confirms that individuals with PMS are at risk of developing severe neuropsychiatric illness in adolescence or early adulthood, including bipolar disorder, catatonia, and lasting regression of skills. These findings should increase the awareness of these phenotypes and lead to earlier diagnosis and the implementation of appropriate interventions. Our findings also highlight the importance of genetic testing in the work-up of individuals with intellectual disability and acute psychiatric illness or regression. Future research is needed to clarify the prevalence and nature of psychiatric disorders and regression among larger unbiased samples of individuals with PMS.

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Clinical status after two-weeks of antidepressant treatment: A prognostic factor in unipolar major depression?

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.1478 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S409-S409

Author(s):

I. Domínguez ◽

L. Nuño ◽

G. Oriolo ◽

R. Quintero ◽

V. Navarro ◽

...

Keyword(s):

Major Depression ◽

Pharmacological Treatment ◽

Depressive Episode ◽

Antidepressant Treatment ◽

Clinical Status ◽

Treatment Protocol ◽

Unipolar Depression ◽

Therapeutic Decisions ◽

Competing Interest ◽

Unipolar Major Depression

Although most unipolar depression clinical guidelines advise against evaluating the efficacy of antidepressant pharmacological treatment until it has been administered in therapeutic doses for a minimum of 4–6 weeks, there is an increasing tendency to make therapeutic decisions after only 2 weeks of treatment. We present a study which aim is to determine whether the clinical course, following 2 weeks of antidepressant treatment, allows therapeutic decisions to be made for patients affected by a moderate/severe depressive episode. The study has an 8-week, prospective, observational design in which all consecutive in- and outpatients with moderate/severe unipolar major depression aged over 17 years received antidepressant treatment based on a standardized treatment protocol. Clinical status was assessed at baseline and at 2-, 4-, and 8-weeks. The final sample consisted of a total of 114 subjects. In our sample, the rate of remitters versus non-remitters was similar between the 2-week improvers and the 2-week non-improvers. It should also be emphasized that it was not possible to explain, based on the epidemiological and clinical characteristics assessed, which 2-week non-improvers would tend towards remission and which would show a partial or full response. Based on these results, for patients affected by a moderate/severe unipolar depressive episode, it would not be appropriate to make new therapeutic decisions following 2 weeks of anti-depressive pharmacological treatment depending on whether the patient has shown clinical improvement or not.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Mental Health Service Use by Elderly Patients With Bipolar Disorder and Unipolar Major Depression

American Journal of Geriatric Psychiatry ◽

10.1097/00019442-200005000-00011 ◽

2000 ◽

Vol 8 (2) ◽

pp. 160-166 ◽

Cited By ~ 54

Author(s):

Stephen J. Bartels ◽

Brent Forester ◽

Keith M. Miles ◽

Tracey Joyce

Keyword(s):

Mental Health ◽

Bipolar Disorder ◽

Mental Health Service ◽

Major Depression ◽

Health Service ◽

Elderly Patients ◽

Service Use ◽

Mental Health Service Use ◽

Health Service Use ◽

Unipolar Major Depression

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Artistic creativity and risk for schizophrenia, bipolar disorder and unipolar depression: a Swedish population-based case–control study and sib-pair analysis

The British Journal of Psychiatry ◽

10.1192/bjp.2018.23 ◽

2018 ◽

Vol 212 (6) ◽

pp. 370-376 ◽

Cited By ~ 15

Author(s):

J. H. MacCabe ◽

A. Sariaslan ◽

C. Almqvist ◽

P. Lichtenstein ◽

H. Larsson ◽

...

Keyword(s):

Bipolar Disorder ◽

Mental Disorder ◽

Odds Ratio ◽

Case Control Study ◽

Tertiary Education ◽

Unipolar Depression ◽

Population Based ◽

Case Control ◽

Increased Risk ◽

Control Study

BackgroundMany studies have addressed the question of whether mental disorder is associated with creativity, but high-quality epidemiological evidence has been lacking.AimsTo test for an association between studying a creative subject at high school or university and later mental disorder.MethodIn a case–control study using linked population-based registries in Sweden (N = 4 454 763), we tested for associations between tertiary education in an artistic field and hospital admission with schizophrenia (N = 20 333), bipolar disorder (N = 28 293) or unipolar depression (N = 148 365).ResultsCompared with the general population, individuals with an artistic education had increased odds of developing schizophrenia (odds ratio = 1.90, 95% CI = [1.69; 2.12]) bipolar disorder (odds ratio = 1.62 [1.50; 1.75]) and unipolar depression (odds ratio = 1.39 [1.34; 1.44]. The results remained after adjustment for IQ and other potential confounders.ConclusionsStudents of artistic subjects at university are at increased risk of developing schizophrenia, bipolar disorder and unipolar depression in adulthood.Declaration of interestNone.

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Genomic analyses in a large clinical cohort reveal high prevalence of MECP2 variants associated with neuropsychiatric phenotypes in adulthood

10.1101/2021.05.31.21257498 ◽

2021 ◽

Author(s):

Claudia Gonzaga-Jauregui ◽

Alina Kurolap ◽

Lauren Walsh ◽

Jeffrey Staples ◽

Cristopher Van Hout ◽

...

Keyword(s):

Major Depression ◽

Rett Syndrome ◽

Clinical Care ◽

Clinical Information ◽

Neuropsychiatric Disorders ◽

Mecp2 Gene ◽

Sequencing Data ◽

Clinical Cohort ◽

Pathogenic Variants ◽

Increased Risk

Abstract Purpose: To evaluate the phenotypes of individuals with pathogenic and likely pathogenic variants in the MECP2 gene. Methods: We surveyed exome sequencing data from a large clinical care cohort for deleterious variation in the MECP2 gene. We reviewed de-identified clinical information for these individuals to interrogate for neurodevelopmental and neuropsychiatric phenotypes. Results: We identified pathogenic and likely pathogenic variants in MECP2 in individuals with typical and atypical Rett syndrome, and neuropsychiatric phenotypes, and estimate a prevalence of MECP2-associated disorders of 1 in 2,645 individuals. We observed a 7.45x increased relative risk of neuropsychiatric phenotypes, especially major depression, in adult individuals with deleterious variants in MECP2 without a diagnosis of Rett syndrome. Male individuals with missense pathogenic variants in MECP2 appear to have more severe neuropsychiatric phenotypes. Conclusions: We identified and report individuals with heterozygous pathogenic variants in MECP2 and their phenotypes in a large clinical cohort. The observed prevalence of MECP2-associated disorders in our cohort is higher than estimated in the literature. Individuals with pathogenic variants in MECP2 can survive into adulthood but are at increased risk of developing neuropsychiatric disorders, mainly major depression. Pathogenic variation in MECP2 is a likely important contributor to neuropsychiatric disorders in the general population.

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Are psychiatric disorders risk factors for COVID-19 susceptibility and severity? a two-sample, bidirectional, univariable and multivariable Mendelian Randomization study

10.1101/2020.11.29.20240481 ◽

2020 ◽

Author(s):

Jurjen J. Luykx ◽

Bochao D. Lin

Keyword(s):

Bipolar Disorder ◽

Psychiatric Disorders ◽

Observational Studies ◽

Mendelian Randomization ◽

Neuropsychiatric Disorders ◽

Sensitivity Analyses ◽

Effect Estimate ◽

Genome Wide Association Studies ◽

Genetic Liability ◽

Increased Risk

AbstractImportanceObservational studies have suggested bidirectional associations between psychiatric disorders and COVID-19 phenotypes, but results of such studies are inconsistent. Mendelian Randomization (MR) may overcome limitations of observational studies, e.g. unmeasured confounding and uncertainties about cause and effect.ObjectiveTo elucidate associations between neuropsychiatric disorders and COVID-19 susceptibility and severity.MethodIn November, 2020, we applied a two-sample, bidirectional, univariable and multivariable MR design to genetic data from genome-wide association studies (GWASs) of neuropsychiatric disorders and COVID-19 phenotypes (released on 20 Oct. 2020). Our study population consisted of almost 2 million participants with either a (neuro)psychiatric disorder or data on COVID-19 status. Outcomes and exposures were anxiety, anxiety-and-stress related disorders, major depressive disorder, schizophrenia, bipolar disorder, schizophrenia-bipolar disorder combined (BIP-SCZ), and Alzheimer’s dementia on the one hand; and self-reported, confirmed, hospitalized, and very severe COVID-19 on the other.ResultsIn single-variable MR analysis the most significant and only Bonferroni-corrected significant result was found for BIP-SCZ (a combined anxiety of bipolar disorder and schizophrenia as cases vs. controls): the effect estimate was consistent with increased risk of COVID-19 (OR = 1.17, 95% CI, 1.06-1.28; p = 0.0012). Nominally significant univariable results were in line with slightly elevated risks of COVID-19 for genetic liabilities to bipolar disorder and schizophrenia. No COVID-19 phenotype consistently increased risk of (neuro)psychiatric disorders. In multivariable MR, bipolar disorder was the only phenotype showing a Bonferroni-corrected significant effect on a COVID-19 phenotype, namely severe COVID-19 (OR = 1.293; 95% CI, 1.095-1.527; p = 0.003). All sensitivity analyses confirmed the results.ConclusionsGenetic liability to bipolar disorder slightly increases COVID-19 susceptibility and severity. The contribution of bipolar disorder to these COVID-19 phenotypes was smaller than the odds ratios estimated by observational studies. Strength of association and direction of effect for genetic liability to schizophrenia were similar, albeit less significant. We found no consistent evidence of reverse effects, i.e. of genetic liability to COVID-19 on psychiatric disorders.

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