Defining a developmental subtype of bipolar disorder in a sample of nonreferred adults by age at onset

Objective To test the hypothesis that the age at onset of bipolar disorder would identify a developmental subtype of bipolar disorder in adults characterized by increased levels of irritability, chronic course, rapid cycling, and comorbidity with attention deficit hyperactivity disorder. Methods Forty-four adult subjects diagnosed with bipolar disorder were selected from large family studies of youth with and without attention deficit hyperactivity disorder. These subjects were stratified by the age at onset in childhood (younger than 13 years; n = 8, 18%), adolescence (13–18 years; n = 12, 27%, or adulthood (older than 19 years; n = 24, 55%). All subjects were administered structure diagnostic interviews and a brief cognitive battery. Results In contrast with adult-onset bipolar disorder, child-onset bipolar disorder was associated with a longer duration of illness, more irritability than euphoria, a mixed presentation, a more chronic or rapid-cycling course, and increased comorbidity with childhood disruptive behavior disorders and anxiety disorders. Conclusion Stratification by age at onset of bipolar disorder identified subgroups of adult subjects with differing clinical correlates. This pattern of correlates is consistent with findings documented in children with pediatric bipolar disorder and supports the hypothesis that child-onset bipolar disorder may represent a developmental subtype of the disorder.

Association of NOS1AP variants and depression phenotypes in schizophrenia

Background The nitric oxide synthase 1 adaptor protein gene (NOS1AP) has previously been recognised as a schizophrenia susceptibility gene due to its role in glutamate neurotransmission. The gene is believed to inhibit nitric oxide (NO) production activated by the N-methyl-d-aspartate (NMDA) receptor and reduced NO levels have been observed in schizophrenia patients. However, association studies investigating NOS1AP and schizophrenia have produced inconsistent results, most likely because schizophrenia is a clinically heterogeneous disorder. This study aims to investigate the association between NOS1AP variants and defined depression phenotypes of schizophrenia. Methods Nine NOS1AP SNPs, rs1415259, rs1415263, rs1858232, rs386231, rs4531275, rs4656355, rs4657178, rs6683968 and rs6704393 were genotyped in 235 schizophrenia subjects screened for various phenotypes of depression. Result One NOS1AP SNP (rs1858232) was associated with the broad diagnosis of schizophrenia and eight SNPs were associated with depression related phenotypes within schizophrenia. The rs1415259 SNP showed strong association with sleep dysregulation phenotypes of depression. Conclusion Results suggest that NOS1AP variants are associated with various forms of depression in schizophrenia and are more prevalent in males. Limitation Schizophrenia is a clinically heterogeneous disease that can vary greatly between different ethnic and geographic populations so our observations should be viewed with caution until they are independently replicated, particularly in larger patient cohorts.

Dysbindin (DTNBP1) variants are associated with hallucinations in schizophrenia

BACKGROUND: Dystrobrevin binding protein 1 (DTNBP1) is a schizophrenia susceptibility gene involved with neurotransmission regulation (especially dopamine and glutamate) and neurodevelopment. The gene is known to be associated with cognitive deficit phenotypes within schizophrenia. In our previous studies, DTNBP1 was found associated not only with schizophrenia but with other psychiatric disorders including psychotic depression, post-traumatic stress disorder, nicotine dependence and opiate dependence. These findings suggest that DNTBP1 may be involved in pathways that lead to multiple psychiatric phenotypes. In this study, we explored the association between DTNBP1 SNPs (single nucleotide polymorphisms) and multiple psychiatric phenotypes included in the Diagnostic Interview of Psychosis (DIP). METHODS: Five DTNBP1 SNPs, rs17470454, rs1997679, rs4236167, rs9370822 and rs9370823, were genotyped in 235 schizophrenia subjects screened for various phenotypes in the domains of depression, mania, hallucinations, delusions, subjective thought disorder, behaviour and affect, and speech disorder. SNP-phenotype association was determined with ANOVA under general, dominant/recessive and over-dominance models. RESULTS: Post hoc tests determined that SNP rs1997679 was associated with visual hallucination; SNP rs4236167 was associated with general auditory hallucination as well as specific features including non-verbal, abusive and third-person form auditory hallucinations; and SNP rs9370822 was associated with visual and olfactory hallucinations. SNPs that survived correction for multiple testing were rs4236167 for third-person and abusive form auditory hallucinations; and rs9370822 for olfactory hallucinations. CONCLUSION: These data suggest that DTNBP1 is likely to play a role in development of auditory related, visual and olfactory hallucinations which is consistent with evidence of DTNBP1 activity in the auditory processing regions, in visual processing and in the regulation of glutamate and dopamine activity

A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers

Multiphenotype genome-wide association studies (GWAS) may reveal pleiotropic genes, which would remain undetected using single phenotype analyses. Analysis of large pedigrees offers the added advantage of more accurately assessing trait heritability, which can help prioritise genetically influenced phenotypes for GWAS analysis. In this study we performed a principal component analysis (PCA), heritability (h2) estimation and pedigree-based GWAS of 37 cardiovascular disease -related phenotypes in 330 related individuals forming a large pedigree from the Norfolk Island genetic isolate. PCA revealed 13 components explaining >75% of the total variance. Nine components yielded statistically significant h2 values ranging from 0.22 to 0.54 (P<0.05). The most heritable component was loaded with 7 phenotypic measures reflecting metabolic and renal dysfunction. A GWAS of this composite phenotype revealed statistically significant associations for 3 adjacent SNPs on chromosome 1p22.2 (P<1x10-8). These SNPs form a 42kb haplotype block and explain 11% of the genetic variance for this renal function phenotype. Replication analysis of the tagging SNP (rs1396315) in an independent US cohort supports the association (P = 0.000011). Blood transcript analysis showed 35 genes were associated with rs1396315 (P<0.05). Gene set enrichment analysis of these genes revealed the most enriched pathway was purine metabolism (P = 0.0015). Overall, our findings provide convincing evidence for a major pleiotropic effect locus on chromosome 1p22.2 influencing risk of renal dysfunction via purine metabolism pathways in the Norfolk Island population. Further studies are now warranted to interrogate the functional relevance of this locus in terms of renal pathology and cardiovascular disease risk.

Vineland Adaptive Behavior Scales - II profile of young children with Autism Spectrum Disorder

Adaptive behaviour is a crucial area of assessment for individuals with Autism Spectrum Disorder (ASD). This study examined the adaptive behaviour profile of 77 young children with ASD using the Vineland-II, and analysed factors associated with adaptive functioning. Consistent with previous research with the original Vineland a distinct autism profile of Vineland-II age equivalent scores, but not standard scores, was found. Highest scores were in motor skills and lowest scores were in socialisation. The addition of the Autism Diagnostic Observation Schedule (ADOS) calibrated severity score did not contribute significant variance to Vineland-II scores beyond that accounted for by age and nonverbal ability. Limitations, future directions, and implications are discussed.

Post-school needs of young people with high-functioning Autism Spectrum Disorder

This study describes the post-school circumstances and service needs of older teenagers and adults with high-functioning Autism Spectrum Disorder, living in Queensland, Australia. The respondents were 95 parents. Results indicated that the majority of the young people lived in the family home and were unemployed. Of those who worked, 56% had unskilled jobs. They were estimated to spend a significant proportion of their time engaged in solitary, technology-based activities, and comparatively little time in employment or socialising. Parents rated employment support as the greatest service priority for their sons and daughters, followed by specialised support to assist with completing post-school education and training, assistance to support the transition from high school to adulthood, and social skills training.

Genome-wide association study of major depressive disorder: New results, meta-analysis, and lessons learned

Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were: (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10), and; (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.

The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data

The relationship between major depressive disorder (MDD) and bipolar disorder (BD) remains controversial. Previous research has reported differences and similarities in risk factors for MDD and BD, such as predisposing personality traits. For example, high neuroticism is related to both disorders, whereas openness to experience is specific for BD. This study examined the genetic association between personality and MDD and BD by applying polygenic scores for neuroticism, extraversion, openness to experience, agreeableness and conscientiousness to both disorders. Polygenic scores reflect the weighted sum of multiple single-nucleotide polymorphism alleles associated with the trait for an individual and were based on a meta-analysis of genome-wide association studies for personality traits including 13,835 subjects. Polygenic scores were tested for MDD in the combined Genetic Association Information Network (GAIN-MDD) and MDD2000+ samples (N=8921) and for BD in the combined Systematic Treatment Enhancement Program for Bipolar Disorder and Wellcome Trust Case-Control Consortium samples (N=6329) using logistic regression analyses. At the phenotypic level, personality dimensions were associated with MDD and BD. Polygenic neuroticism scores were significantly positively associated with MDD, whereas polygenic extraversion scores were significantly positively associated with BD. The explained variance of MDD and BD, approximately 0.1%, was highly comparable to the variance explained by the polygenic personality scores in the corresponding personality traits themselves (between 0.1 and 0.4%). This indicates that the proportions of variance explained in mood disorders are at the upper limit of what could have been expected. This study suggests shared genetic risk factors for neuroticism and MDD on the one hand and for extraversion and BD on the other.

Migraine symptomatology and major depressive disorder

INTRODUCTION AND OBJECTIVE Migraine and major depressive disorder (MDD) frequently co-occur, but it is unclear whether depression is associated with a specific subtype of migraine. The objective of this study was to investigate whether migraine is qualitatively different in MDD patients (N = 1816) and non-depressed controls (N = 3428). METHODS Migraine symptom data were analyzed using multi-group Latent Class Analysis, and a qualitative comparison was made between the symptom profiles of MDD patients and controls, while allowing for differences in migraine prevalence and severity between groups. RESULTS In both groups, three migrainous headache classes were identified, which differed primarily in terms of severity. Both mild and severe migrainous headaches were two to three times more prevalent in MDD patients. Migraine symptom profiles showed only minor qualitative differences in the MDD and non-MDD groups: in the severe migrainous headache class, significant differences were observed only in the prevalence of aggravation by physical activity (83% and 91% for the non-MDD and MDD groups, respectively) and aura (42% vs. 53%, respectively). CONCLUSION The similar overall symptom profiles observed in the MDD and non-MDD subjects suggest that a similar disease process may underlie migraine in both groups.

Natural disasters have unexpected impacts on mental health

Radical circumstances (bushfires and natural disasters) flush out the mental illness in society. Whenever there’s a disaster, there’s a rush on hospital admissions for psychiatric problems. But on the whole, the illness is already there. Emergencies naturally make fodder for delusions and the emergency efforts, for mania. Obviously, there are direct mental health consequences – a small rise in post-traumatic stress disorder inevitably follows disaster. This correlates with the severity of the consequences of the disaster (loss of family, friends, animals and property). And there’s usually a big rethink, with about a third of those affected leaving the area permanently. But, for the most part, this isn’t driven by mental health issues, it results from the very real fears about whether living in a fire (or other disaster) zone is worth it.

The architecture of the psychiatric milieu

The last time a peer-reviewed volume on the future of mental health facilities was produced was in 1959, following a symposium organised by the American Psychological Association. The consensus was easy enough to follow and still resonates today: the best spaces to treat psychiatric illness will be in smaller, less restrictive units that offer more privacy and allow greater personalisation of space – possibly a converted hotel (Goshen, 1959). In some way, all those ideals have come to pass. An ideal typology was never established, but even so, units have shrunk from thousands of beds to units that typically house no more than 50 patients. Patients are generally more independent and are free to wander (within a unit) as they please. But the trend toward smaller and freer is reversing. This change is not driven by a desire to find the ideal building nor better models of care, but by growing concerns about budgets, self-harm and psychiatric violence. This issue of the Facilities comes at a time when the healthcare design is increasingly dominated by codes, statutes and guidelines. But the articles herein are a call to stop and think. We are not at the point where guidelines can be helpful, because they do not embody any depth of knowledge nor wisdom. These articles are intended to inject some new research on psychiatric/environmental interactions and also to remind planners and managers that guidelines might not tackle a core misunderstanding: fear-management about patient safety and the safety of society is not the purpose of the psychiatric facility. It is purpose is to create spaces that are suitable for improving the well-being of the mentally ill.

Psychiatric design : Using a salutogenic model for the development and management of mental health facilities

The prevailing model of psychiatric facility design does not fulfil its potential in supporting the healing process. A salutogenic approach can improve coherence and foster meaning, will actually improve mental health outcomes, not only manage patient behaviour.

Comments on: "The role of the social environment in psychiatric research: Outstanding challenges and future directions by Dana March, James Kirkbride, Wim Veling"

On 17 March 2009, we hosted a live discussion of fresh new ideas in the epidemiology of schizophrenia. Discussion leaders Dana March of Columbia University, James Kirkbride of the University of Cambridge, and Wim Veling of Parnassia Psychiatric Institute delivered a wide-ranging discussion of social factors such as migration, ethnicity, and urbanicity, but also asked how this research could benefit from genetic insights. Finally, they discussed possible biological mechanisms that might transduce social factors into psychosis

A systematic review of instruments for assessment of capacity in activities of daily living in children with developmental co-ordination disorder

Children with developmental co-ordination disorder (DCD) face evident motor difficulties in activities of daily living (ADL). Assessment of their capacity in ADL is essential for diagnosis and intervention, in order to limit the daily consequences of the disorder. The aim of this study is to systematically review potential instruments for standardized and objective assessment of children's capacity in ADL, suited for children with DCD. As a first step, databases of MEDLINE, EMBASE, CINAHL and PsycINFO were searched to identify studies that described instruments with potential for assessment of capacity in ADL. Second, instruments were included for review when two independent reviewers agreed that the instruments: (1) are standardized and objective; (2) assess at activity level and comprise items that reflect ADL, and; (3) are applicable to school-aged children that can move independently. Out of 1507 publications, 66 publications were selected, describing 39 instruments. Seven of these instruments were found to fulfil the criteria and were included for review: the Bruininks-Oseretsky Test of Motor Performance-2 (BOT2); the Do-Eat (Do-Eat); the Movement Assessment Battery for Children-2 (MABC2); the school-Assessment of Motor and Process Skills (schoolAMPS); the Tuffts Assessment of Motor Performance (TAMP); the Test of Gross Motor Development (TGMD); and the Functional Independence Measure for Children (WeeFIM). As a third step, for the included instruments, suitability for children with DCD was discussed based on the ADL comprised, ecological validity and other psychometric properties. We concluded that current instruments do not provide comprehensive and ecologically valid assessment of capacity in ADL as required for children with DCD.