Bipolar disorder: Kinesin-12 to the rescue

Comment on: Florian S, et al. Cell Cycle 2011; 10:3533–44     

Molecular genetics of attention-deficit hyperactivity disorder (ADHD): an update

Attention-deficit hyperactivity disorder (ADHD) is a heritable and behavioral condition of childhood, affecting 5-10% of school-age children worldwide. Affected patients exhibit various behavioral problems such as carelessness, restlessness, disobedience and failure to stay quiet in class. The etiology of ADHD is not known. However, family, twin and adoption studies have provided strong evidence for a genetic etiology of the disorder. A genome-wide scan has identified six chromosomal loci with LOD scores suggestive of linkage. Animal studies suggest the involvement of the brain dopamine pathway and its alteration in ADHD but there is no direct evidence to support this hypothesis. In addition, there are at least 20 candidate genes of small effect that have been studied but none of them appear to be the major gene causing ADHD. Medical intervention along with psychosocial therapy proved to be beneficial for controlling ADHD, although some undesirable side effects have been encountered during medical treatment. In the future, identification of environmental factors, study of additive gene effects and the interaction of genes and environmental factors may provide better insight into the pathophysiology of ADHD. This may lead to an effective new treatment strategy.     

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.     

Monoamines in autism: an update of neurochemical research on a pervasive developmental disorder

Recent neurochemical studies of norepinephrine (NE), dopamine (DA), and serotonin (5HT) in autism are reviewed. Most studies of the catecholamines, their metabolites, and associated enzymes have not found differences between autistic and normal subjects. However, a robust increase in platelet 5HT has been well replicated and characterized. Studies on the possible causes of the increased platelet 5HT in autism suggest that an alteration in platelet physiology is the cause of the increase. Future directions for research on the platelet are discussed as are other potentially fruitful methods for examining monoamine functioning in autism.     

Ivermectin: an update

Ivermecan was introduced as an antiparasitic agent in 1981. It is now registered for animal-health use in 35 countries and is being evaluated for possible use in man. This review summarises its antiparasitic efficacy and apparent mode of action. Additional information is given in previous review articles.     

Yersinia: an update

The 8th International Symposium on Yersinia was held in Turku, Finland, 4–8 September 2002.     

Clonorchiasis: an update

Clonorchis sinensis, the Chinese or oriental liver fluke, is an important human parasite and is widely distributed in southern Korea, China (including Taiwan), Japan, northern Vietnam and the far eastern part of Russia. Clonorchiasis occurs in all parts of the world where there are Asian immigrants from endemic areas. The human and animal reservoir hosts (dogs, pigs, cats and rats) acquire the infection from the ingestion of raw fish containing infectious metacercariae. The first intermediate snail hosts are mainly species of Parafossarulus and Bithynia. Numerous species of freshwater fish serve as the second intermediate hosts of C. sinensis. Extensive studies of clonorchiasis during several decades in Japan, Korea, China and other countries have shown much progress in proving its morphological features including ultrastructure, biology, pathogenesis, epidemiology, clinical manifestations and chemotherapy. The present review deals with mainly current results obtained on the epidemiological, pathological and clinical aspects, as well as control measures in endemic areas. As for the complications of clonorchiasis, formation of calculi in the intrahepatic biliary passages is one of the most characteristic pathological features. It is sometimes accompanied by suppurative cholangitis, cholecystitis, cholangiohepatitis and ultimately can cause cholangiocarcinoma. Experimental results on the relationship to the occurrence of cholangiocarcinoma are presented. Clinical diagnosis by radiological findings including cholangiography, sonography and computerized tomography as well as magnetic resonance imaging for biliary or pancreatic ducts are outlined. Current studies on immunology and molecular biology of C. sinensis were introduced. Praziquantel is the drug of choice for clonorchiasis. The most effective regimen is 25 mg kg(-1) three times daily (total dose, 75 mg kg(-1)) administered orally at 5- to 6-h intervals over a single day. Prevention and control measures are also discussed.     

Bipolar disorder risk alleles in adult ADHD patients

Attention-deficit/hyperactivity disorder (ADHD) has an estimated prevalence of 3-5% in adults. Genome-wide association (GWA) studies have not been performed in adults with ADHD and studies in children have so far been inconclusive, possibly because of the small sample sizes. Larger GWA studies have been performed on bipolar disorder (BD) and BD symptoms, and several potential risk genes have been reported. ADHD and BD share many clinical features and comorbidity between these two disorders is common. We therefore wanted to examine whether the reported BD genetic variants in CACNA1C, ANK3, MYO5B, TSPAN8 and ZNF804A loci are associated with ADHD or with scores on the Mood Disorder Questionnaire (MDQ), a commonly used screening instrument for bipolar spectrum disorders. We studied 561 adult Norwegian ADHD patients and 711 controls from the general population. No significant associations or trends were found between any of the single nucleotide polymorphisms (SNPs) studied and ADHD [odds ratios (ORs) ≤ 1.05]. However, a weak association was found between rs1344706 in ZNF804A (OR = 1.25; P = 0.05) and MDQ. In conclusion, it seems unlikely that these six SNPs with strong evidence of association in BD GWA studies are shared risk variants between ADHD and BD.     

Photodynamic therapy: an update

Photodynamic therapy (PDT) is a promising local treatment modality based on the selective accumulation of a photosensitizer in malignant tissues and the subsequent irradiation with laser light. Photodynamic therapy of malignant tumors includes biological, photochemical and photophysical processes. These processes involve: (a) absorption of photosensitizing agent; (b) selective retention of the photosensitizer in tumors and (c) irradiation of sensitized tumor by laser radiation. This report provides a review of photosensitizers, photochemistry, subcellular targets, side effects and laser involved in photodynamic therapy. In addition, gradual increase in knowledge related to in vitro and in vivo mechanisms of action of PDT, as well as some clinical applications of photodynamic therapy are presented.     

Deficit schizophrenia: an update

The criteria for deficit schizophrenia were designed to define a group of patients with enduring, primary (or idiopathic) negative symptoms. In 2001, a review of the literature suggested that deficit schizophrenia constitutes a disease separate from nondeficit forms of schizophrenia. Here we provide a review of new studies, not included in that paper, in which patients with deficit schizophrenia and those with nondeficit schizophrenia were compared on dimensions typically used to distinguish diseases: signs and symptoms, course of illness, pathophysiological correlates, risk and etiological factors, and treatment response. Replicated findings and new evidence of double dissociation supporting the separate disease hypothesis are highlighted. Weaknesses in research and treatment options for these patients are also emphasized.     

Senile osteoporosis: an update

Knowledge of the mechanisms underlying the development of osteoporosis in the elderly has advanced greatly in the past few years. After an initial sudden loss of bone mineral mass in the peri-menopausal period there follows a more progressive and gradual loss that has also been seen in men. This initial drop in bone mass is due to a significant increase in bone resorption. There is also a significant reduction in bone formation with age that is mainly due to osteoblastogenesis in the bone marrow passing to a second plane, transferring its main role to adipogenesis. In this article, the latest evidence on the pathophysiology of senile osteoporosis is reviewed, highlighting the mechanisms of action of available treatments. Potential future treatments are also considered, which include new therapeutic approaches based on the pathophysiology of osteoporosis in the elderly, mainly on the potential reversibility of the adipogenesis.     

Secondary psychoses: an update

Psychotic disorders due to a known medical illness or substance use are collectively termed secondary psychoses. In this paper, we first review the historic evolution of the concept of secondary versus primary psychosis and how this distinction supplanted the earlier misleading classification of psychoses into organic and functional. We then outline the clinical features and approach to the diagnosis of secondary psychotic disorders. Features such as atypical presentation, temporal relation to detectable medical cause, evidence of direct physiological causal relationship to the etiological agent, and the absence of evidence of a primary psychotic illness that may better explain the presentation suggest consideration of a secondary psychosis. Finally, we discuss how careful studies of secondary psychotic disorders can help elucidate the pathophysiology of primary, or idiopathic, psychotic disorders such as schizophrenia. We illustrate this issue through a discussion of three secondary psychotic disorders — psychoses associated with temporal lobe epilepsy, velocardiofacial syndrome, and N‐methyl D‐aspartate (NMDA) receptor encephalitis — that can, respectively, provide neuroanatomical, genetic, and neurochemical models of schizophrenia pathogenesis.