Understanding deficient emotional self-regulation in adults with attention deficit hyperactivity disorder: a controlled study

While symptoms of deficient emotional self-regulation (DESR) such as low frustration tolerance, temper outbursts, emotional impulsivity, and mood lability are commonly associated with attention deficit hyperactivity disorder (ADHD), little is known about their nature. The main aim of this post hoc study was to examine the correlates of DESR in a large sample of adults with and without ADHD. Subjects were 206 adults with ADHD and 123 adults without ADHD from a family study of ADHD. Emotional impulsivity was operationalized using items from the Barkley Current Behavior Scale. Subjects were comprehensively assessed for psychiatric comorbidity using structured diagnostic interview methodology. We used the Quality of Life, Enjoyment, and Satisfaction Questionnaire-Short Form (QLES-Q-SF) and Social Adjustment Scale-Self-report (SAS-SR) to assess quality of life and psychosocial functioning. DESR was more common among ADHD compared with non-ADHD adults, and 55 % of adults with ADHD reported extreme DESR of greater severity than 95 % of control subjects. The association of ADHD and DESR was not entirely accounted for by either current or lifetime comorbid disorders. DESR was also associated with significant functional impairment as evaluated by the QLES-Q-SF and SAS-SR, and with reduced marital status, as well as higher risk for traffic accidents and arrests. DESR adversely impacts quality of life in adults with ADHD. More work is needed to further evaluate DESR in clinical and investigational studies of subjects with ADHD.     

Horizontally acquired DAP pathway as a unit of self-regulation

In this study, we report the acquisition of the diaminopimelic acid (DAP) pathway of lysine biosynthesis in choanoflagellate Monosiga brevicollis and investigate how this pathway is incorporated and regulated in the established metabolic network. Our data show that all major genes related to the DAP pathway in Monosiga were acquired from bacteria and algae. Although an endogenous lysC exists in Monosiga, the newly acquired lysC is fused to lysA and used specifically for lysine biosynthesis. In addition, these acquired genes encode two key rate-limiting enzymes, thus conferring Monosiga a self-regulated unit with ability to generate lysine. Our data suggest that a newly acquired metabolic capability can be added to the recipient organism without disturbing the previously established metabolic network. This finding also implies that the biochemical system of the recipient organism may determine the type and function of genes to be acquired.     

Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder

Schizophrenia, schizoaffective disorder, and bipolar disorder are common psychiatric disorders with high heritabilities and variable phenotypes. The Disrupted in Schizophrenia 1 (DISC1) gene, on chromosome 1q42, was originally discovered and linked to schizophrenia in a Scottish kindred carrying a balanced translocation that disrupts DISC1 and DISC2. More recently, DISC1 was linked to schizophrenia, broadly defined, in the general Finnish population, through the undertransmission to affected women of a common haplotype from the region of intron 1/exon 2. We present data from a case-control study of a North American white population, confirming the underrepresentation of a common haplotype of the intron 1/exon 2 region in individuals with schizoaffective disorder. Multiple haplotypes contained within four haplotype blocks extending between exon 1 and exon 9 are associated with schizophrenia, schizoaffective disorder, and bipolar disorder. We also find overrepresentation of the exon 9 missense allele Phe607 in schizoaffective disorder. These data support the idea that these apparently distinct disorders have at least a partially convergent etiology and that variation at the DISC1 locus predisposes individuals to a variety of psychiatric disorders.     

Genome scan meta-analysis of schizophrenia and bipolar disorder,part III: Bipolar disorder

Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for “very narrow” (i.e., BP-I and schizoaffective disorder–BP) and “narrow” (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A “broad” model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally significant P values were observed in adjacent bins on chromosomes 9p and 18p-q, across all three disease models on chromosomes 14q and 18p-q, and across two models on chromosome 8q. Relatively few BPD pedigrees have been studied under narrow disease models relative to the schizophrenia GSMA data set, which produced more significant results. There was no overlap of the highest-ranked regions for the two disorders. The present results for the very narrow model are promising but suggest that more and larger data sets are needed. Alternatively, linkage might be detected in certain populations or subsets of pedigrees. The narrow and broad data sets had considerable power, according to simulation studies, but did not produce more highly significant evidence for linkage. We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region.     

The relationship between membrane pathology and language disorder in schizophrenia

Receptive language disorder in schizophrenia has been hypothesized to involve a fundamental deficit in the temporal (time-based) dynamics of brain function that includes disruptions to patterns of activation and synchronization. In this paper, candidate mechanisms and pathways that could account for this basic deficit are discussed. Parallels are identified between the patterns of language dysfunction observed for schizophrenia and dyslexia, two separate clinical disorders that may share a common abnormality in cell membrane phospholipids. A heuristic is proposed which details a trajectory involving an interaction of brain fatty acids and second-messenger function that modulates synaptic efficacy, and, in turn, influences language processing in schizophrenia patients. It is additionally hypothesized that a primary deficit of functional excitation originating in the cerebellum, in combination with a compensatory decrease of functional inhibition in the prefrontal cortex, influences receptive language dysfunction in schizophrenia.     

Tourette's disorder and associated complex behaviors: a case report

A case of a man with Tourette's disorder associated with obsessive-compulsive disorder, multiple sexual paraphilias, and aggressive behavior is described. Treatment with haloperidol led to improvement in the characteristic tics of Tourette's disorder as well as to improvement in these three complex-associated behaviors. After haloperidol was discontinued, an exacerbation of tics and the associated behaviors occurred.     

Gastric intestinal metaplasia revisited: function and regulation of CDX2

Intestinal metaplasia of the stomach is a preneoplastic lesion that appears following Helicobacter pylori infection and confers increased risk for gastric cancer development. However, the molecular networks connecting infection to lesion formation and the cellular origin of this lesion remain largely unknown. A more comprehensive understanding of how intestinal metaplasia arises and is maintained will be a major breakthrough towards developing novel therapeutic interventions. Furthermore, after ascertaining the pivotal role of CDX2 in establishing and maintaining intestinal metaplasia, it becomes important to decipher the upstream molecular pathways leading to its ectopic expression. Here, we review the pathophysiology of intestinal metaplasia in the context of the molecular network involved in its establishment and maintenance, with emphasis on CDX2 function and regulation.     

The genetic variation of RELN expression in schizophrenia and bipolar disorder

Reelin plays an important role in the development and function of the brain and has been linked to different neuropsychiatric diseases. To further clarify the connection between reelin and psychiatric disorders, we studied the factors that influence the expression of reelin gene (RELN) and its different isoforms. We examined the total expression of RELN, allelic expression, and two alternative RELN isoforms in postmortem brain samples from patients with schizophrenia and bipolar disorder, as well as unaffected controls. We did not find a significant reduction in the total expression of RELN in schizophrenia or bipolar disorder. However, we did find a significant reduction of the proportion of the short RELN isoform, missing the C-terminal region in bipolar disorder, and imbalance in the allelic expression of RELN in schizophrenia. In addition, we tested the association between variation in RELN expression and rs7341475, an intronic SNP that was found to be associated with schizophrenia in women. We did not find an association between rs7341474 and the total expression of RELN either in women or in the entire sample. However, we observed a nominally significant effect of genotype-by-sex interaction on the variation in microexon skipping. Women with the risk genotype of rs7341475 (GG) had a higher proportion of microexon skipping, which is the isoform predominant in tissues outside the brain, while men had the opposite trend. Finally, we tested 83 SNPs in the gene region for association with expression variation of RELN, but none were significant. Our study further supports the connection between RELN dysfunction and psychiatric disorders, and provides a possible functional role for a schizophrenia associated SNP. Nevertheless, the positive associations observed in this study needs further replication as it may have implications for understanding the biological causes of schizophrenia and bipolar disorder.     

Culture and mental disorder: The case of bebainan in Bali

This is an investigation of bebainan, a disorder which Balinese believe to be caused by sorcery. Most attacks are brief, lasting % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaWaaSGaaeaaca% aIXaaabaGaaGinaaaaaaa!3778![{raise0.7exhbox{$1$} !mathord{left/ {vphantom {1 4}}right.kern-nulldelimiterspace}!lower0.7exhbox{$4$}}]–1 hour. The most common symptoms are sudden feelings of confusion, crying, screaming and shouting, followed by inability of the sufferer to control his or her actions. Most sufferers are aware of their behavior during an attack, and remember the occurrence afterwards.The investigator interviewed all the members (296 persons) in the compound of the descendants of the former royal family of Klungkung, among whom 27 people had suffered bebainan attacks. The victims, mostly females, offspring of endogamous marriges, experienced their first attack between the ages of 16 and 30. Analysis of the psychological and social pressures acting on these women suggests that bebainan attacks provide sufferers with an opportunity to release feelings of frustration and anger without risk of widespread disapprobation or stigmatization. However, bebainan is not instrumental in altering access to resources within the restricted environment of the royal compound, nor does it empower the victim within this environment in any but the most transitory ways. Bebainan cannot be regarded as a form of psychosis, even of the reactive or atypical type, it is neither an organic mental disorder, nor a form of neurosis. Instead bebainan can be considered a form of dissociation which is only understandable in the local context of Balinese culture.     

Wright-Fisher revisited: the case of fertility correlation

We study the non-genetic inheritance of fertility from parents to offspring. For this purpose, we propose an exchangeable extension of the Wright-Fisher model. This extension allows us to introduce non-genetic fertility correlation in the forward in time process and to study its effects on the genealogies of individuals (or genes) samples. Since it is independent of the gene considered, this effect is uniform on the genome, even in diploid populations. For values of fertility correlation observed in human populations, we show that coalescence times are strongly but inhomogenously reduced and that the shape of gene genealogies is markedly unbalanced. Despite the fact that our simulations concern stationary populations, the former non-genetic effect is very similar to what has been described for populations of variable size such as populations passing through demographic bottleneck. However, additional strong tree imbalance due to non-genetic causes is reported here for the first time.     

The Gomphidiaceae revisited: a worldwide perspective

Recent studies in the Gomphidiaceae have clearly delimited two genera, Gomphidius and Chroogomphus, both of which are mycorrhizal associates only with the Pinaceae. Ecological studies show Chroogomphus as a mycorrhizal associate of Pinus (Pinoideae), while Gomphidius is associated with the other three gymnosperm subfamilies Piceoideae, Lariceideae, and Abietoideae. The genus Brauniellula, which is based upon the secotioid habit and the presence of orthotropic, statismosporic basidia, falls within Chroogomphus in a clade with ballistosporic species. Brauniellula is, therefore, placed in synonymy with Chroogomphus. Molecular and morphological studies of new material from Nepal, Russia, Korea, and the United States have delimited two new species in each genus. The morphologically identical Chroogomphus rutilus clades are separate, one European and one North American. The relationship of the two genera in the Gomphidiaceae, with their mycorrhizal associates, is related to similar host relationships within other genera in the Suilloid Clade.     

The disposable soma theory revisited: Time as a resource in the theories of aging

All life processes are subject to time constraints. At the cellular level, damage repair and cell cycle arrest are interrelated, allowing sufficient time for repair prior to cell cycle progression. Organisms have evolved so that developmental timing is linked to environmental conditions, such as nutrient availability and predation. Recent results in mammals regarding species-specific differences in cell cycle arrest and DNA damage suggest that a stable cell cycle arrest is a feature of longer-lived species. The implication of these results is that longer-lived species delay cell cycle progression to a greater degree than shorter-lived species, allowing for higher fidelity repair. We suggest that the ability to devote longer periods of time to repair and maintenance is a key feature of longer-lived species, and that evolutionary pressure to complete repair and resume cell division is a determinant of species lifespan. Thus, time is a resource that must be managed by the organism to attempt to maximize the fidelity of repair while completing development and reproduction in the limited window of opportunity afforded by environmental pressures. This viewpoint on time as a resource has implications for theories regarding the aging process and the development of species lifespan.     

The possibility of evidence-based psychiatry: depression as a case

Considering psychiatry as a medical discipline, a diagnosis identifying a disorder should lead to an effective therapy. Such presumed causality is the basis of evidence-based psychiatry. We examined the strengths and weaknesses of research onto the causality of relationship between diagnosis and therapy of major depressive disorder and suggest what could be done to strengthen eventual claims on causality. Four obstacles for a rational evidence-based psychiatry were recognised. First, current classification systems are scientifically nonfalsifiable. Second, cerebral processes are-at least to some extent-nondeterministic, i.e. they are random, stochastic and/or chaotic. Third, the vague or lack of relationship between therapeutic regimens and suspected pathogenesis. Fourth, the inadequacy of tools to diagnose and delineate a functional disorder. We suggest a strategy to identify diagnostic prototypes that are characterised by a limited number of parameters (symptoms, markers and other characteristics). A prototypical diagnosis that may either support or reject particular elements of current diagnostic systems. Nevertheless, one faces the possibility that psychiatry will remain a relatively weak evidence-based medical discipline.