Psychiatric features of individuals with problematic internet use

BACKGROUND: Problematic internet use has been described in the psychological literature as 'internet addiction' and 'pathological internet use'. However, there are no studies using face-to-face standardized psychiatric evaluations to identify behavioral characteristics, psychiatric comorbidity or family psychiatric history of individuals with this behavior. METHODS: Twenty individuals with problematic internet use were evaluated. Problematic internet use was defined as (1) uncontrollable, (2) markedly distressing, time-consuming or resulting in social, occupational or financial difficulties and (3) not solely present during hypomanic or manic symptoms. Evaluations included a semistructured interview about subjects' internet use, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV (SCID-IV), family psychiatric history and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) modified for internet use. RESULTS: All (100%) subjects' problematic internet use met DSM-IV criteria for an impulse control disorder (ICD) not otherwise specified (NOS). All 20 subjects had at least one lifetime DSM-IV Axis I diagnosis in addition to their problematic internet use (mean+/-SD=5.1+/-3.5 diagnoses); 14 (70.0%) had a lifetime diagnosis of bipolar disorder (with 12 having bipolar I disorder). LIMITATIONS: Methodological limitations of this study included its small sample size, evaluation of psychiatric diagnoses by unblinded investigators, and lack of a control group. CONCLUSIONS: Problematic internet use may be associated with subjective distress, functional impairment and Axis I psychiatric disorders.     

Familiality of temperament in bipolar disorder: support for a genetic spectrum

BACKGROUND: The array of different diagnoses and clinical presentations seen in the family members of bipolar probands suggests a quantitative or spectrum phenotype. Consistent with this idea, it has been proposed that an underlying quantitative variation in temperament may be the primary phenotype that is genetically transmitted and that it in turn predisposes to bipolar disorder (BP). Choosing the appropriate phenotypic model for BP is crucial for success in genetic mapping studies. To test this theory, various measures of temperament were examined in the family members of bipolar probands. We predicted that a gradient of scores would be observed from those with BP to those with major depression to unaffected relatives to controls. METHODS: Members of 85 bipolar families and 63 control subjects were administered clinical interviews for diagnosis (SCID) and two temperament assessments, the TEMPS-A and TCI-125. Subjects with BP, major depressive disorder, unaffected relatives, and controls were compared on each temperament scale and on eight factors extracted from a joint factor analysis of the TEMPS-A and TCI-125. RESULTS: The four groups were found to be significantly different and with the expected order of average group scores for four of the TEMPS-A scales, three of the TCI-125 scales, and one of the extracted factors. On the fifth TEMPS-A scale, hyperthymic, controls scored higher than the other three subject groups contrary to expectations. Significant differences were seen between unaffected relatives and controls on the hyperthymic scale and on the first extracted factor, anxious/reactive. LIMITATIONS: Controls were mainly recruited through advertisements, which may have introduced an ascertainment bias. It is also possible that mood state at the time of completing the questionnaire influenced subject's rating of their temperament. Additionally, bipolar I and bipolar II subjects were placed in the same group even though they had some differing clinical features. CONCLUSIONS: Our data support the theory that some dimensions of temperament are transmitted in families as quantitative traits that are part of a broader bipolar spectrum. In particular, the hyperthymic scale of the TEMPS-A and the anxious/reactive extracted factor distinguished unaffected relatives from controls. The hyperthymic scale yielded results opposite to expectation with controls higher than any family group. This may be an artifact of the self-rated form of the questionnaire, a consequence of our grouping bipolar I and II subjects together, or the result of a "protective" factor and bears further study. Nevertheless, both of these scales may be useful quantitative traits for genetic mapping studies.     

The expanding phenotype of laminin alpha2 chain (merosin) abnormalities: case series and review

Initial reports of patients with laminin alpha2 chain (merosin) deficiency had a relatively homogeneous phenotype, with classical congenital muscular dystrophy (CMD) characterised by severe muscle weakness, inability to achieve independent ambulation, markedly raised creatine kinase, and characteristic white matter hypodensity on cerebral magnetic resonance imaging. We report a series of five patients with laminin alpha2 deficiency, only one of whom has this severe classical CMD phenotype, and review published reports to characterise the expanded phenotype of laminin alpha2 deficiency, as illustrated by this case series. While classical congenital muscular dystrophy with white matter abnormality is the commonest phenotype associated with laminin alpha2 deficiency, 12% of reported cases have later onset, slowly progressive weakness more accurately designated limb-girdle muscular dystrophy. In addition, the following clinical features are reported with increased frequency: mental retardation (~6%), seizures (~8%), subclinical cardiac involvement (3-35%), and neuronal migration defects (4%). At least 25% of patients achieve independent ambulation. Notably, three patients with laminin alpha2 deficiency were asymptomatic, 10 patients had normal MRI (four with LAMA2 mutations reported), and between 10-20% of cases had maximum recorded creatine kinase of less than 1000 U/l. LAMA2 mutations have been identified in 25% of cases. Sixty eight percent of these have the classical congenital muscular dystrophy, but this figure is likely to be affected by ascertainment bias. We conclude that all dystrophic muscle biopsies, regardless of clinical phenotype, should be studied with antibodies to laminin alpha2. In addition, the use of multiple antibodies to different regions of laminin alpha2 may increase the diagnostic yield and provide some correlation with severity of clinical phenotype.     

Characterization of fragmented heavy-ion beams using a three-stage telescope detector: detector configuration and instrumentation

Accelerated heavy-ion beams used in biological and medical research are often utilized in conjunction with absorbers which lead to the fragmentation of the beam. The BERKLET, initially a two-stage solid-state telescope detector, was designed to make rapid, on-line energy and linear energy transfer (LET) measurements of individual particles in a heavy-ion beam, thus allowing characterization of fragmented beams. From data collected with the BERKLET, one is able to determine a number of important parameters. These include: residual energy and LET histograms for the full beam and for the individual Z components, relative number of particles with a given Z, and dose and track average LET's for the full beam and for the individual Z's. Improvements to the BERKLET design and changes in data analysis are discussed and contrasted with the results of an earlier BERKLET configuration. The most notable improvements are the addition of a thin scintillation detector for improved LET measurement, a tenfold improvement in the dynamic range of the event discriminator, reported here as 1:2000, and dual high-and low-gain amplification of the LET signals, permitting the identification of particles with Z's ranging from 12 down to 1.     

Neocortical morphometry and cholinergic neurochemistry in Pick''s disease.

With a computerized image-analysis apparatus for neocortical morphometry and chemical methods for evaluation of the cholinergic system, five brain specimens of Pick's disease (PD) were studied and the results compared to those from specimens of age-matched normal subjects and Alzheimer's disease (AD). The PD specimens showed major reductions in brain weight, frontal and temporal cortical thickness, and large neuron populations, compared with controls. Lesser reductions were seen in small neurons and thickness of the inferior parietal cortex. The authors found no relationship between age of onset or disease duration and either the degree of cortical thinning or neuron loss or the number of Pick bodies in the neocortex and hippocampus. PD specimens were more atrophic than AD brains, having lower brain weights and more fronto-temporal thinning. Large neurons were comparably reduced in the two conditions in the frontal and temporal lobes, but small neuron losses were greater in the PD midfrontal area. Only the AD cases showed loss of large neurons in the inferior parietal region. Levels of choline acetyltransferase were normal in PD and reduced in AD, whereas muscarinic receptor binding was decreased in both.     

Specific characterization of isoelectrofocused immunoglobulins in polyacrylamide gel by reaction with 125 I-labeled protein antigens or antibodies

A method is described for the visualization and characterization of isoelectrofocused antibodies, immunoglobulins in general, and many other proteins in thin plates of polyacrylamide gel. The novel aspect of the method is that the protein bands after electrofocusing are immobilized in the gel by treatment with glutaraldehyde after soaking with 18 % sodium sulfate solution. Such treatment is shown not to affect the binding activity of antibodies. Antibody bands are located by treatment of the plates with ¹²⁵I-labeled specific antigen. Other proteins can be located by ¹²⁵I-labeled specific antibody. The bands thus located are visualized by radioautography. The immobilization of the focused proteins allows the excess radiolabeled reagent macromolecules to be washed out of the plates without disrupting the focused pattern. Under the conditions described, background radioactivity and nonspecific pickup by other serum proteins in the plates are negligible. Examples of the use of the method are given for anti-4-azonaphthalene-1-sulfonate and anti-4-hydroxy-5-iodo-3-nitro-phenacetyl antibodies, using the ¹²⁵I-labeled hapten-specific antigens, and for a mouse IgG myeloma protein, MOPC 195, using ¹²⁵I-labeled goat anti-mouse IgG antibody. Extension of the method would allow differences between proteins to be characterized by appropriate ¹²⁵I-labeled antibodies. Thus immunoglobulins could be characterized by ¹²⁵I-labeled antibodies specific for immunoglobulin markers (e.g. Ig class, L chain type, etc.). The advantages of this method over other methods include the ease and generality of using radioiodine labeled macromolecules – especially antibodies – as compared to the restriction imposed by other methods which require small labeled ligands. The method can be extended to the use of fluorescent-labeled proteins and radiolabeled polysaccharide antigens as locators.     

Risk factors for wheezing in a subtropical environment: role of respiratory viruses and allergen sensitization

BACKGROUND: Risk factors for acute wheezing among children in subtropical areas are largely unknown. OBJECTIVE: To investigate the role of viral infections, allergen sensitization, and exposure to indoor allergens as risk factors for acute wheezing in children 0 to 12 years old. METHODS: One hundred thirty-two children 0 to 12 years of age who sought emergency department care for wheezing and 65 children with no history of wheezing were enrolled in this case-control study. Detection of respiratory syncytial virus antigen, rhinovirus and coronavirus RNA, adenovirus, influenza, and parainfluenza antigens was performed in nasal washes. Total IgE and specific IgE to mites, cockroach, cat, and dog were measured with the CAP system. Major allergens from mites, cockroach, cat, and dog were quantified in dust samples by ELISA. Univariate and multivariate analyses were performed by logistic regression. RESULTS: In children under 2 years of age, infection with respiratory viruses and family history of allergy were independently associated with wheezing (odds ratio, 15.5 and 4.2; P = .0001 and P = .008, respectively). Among children 2 to 12 years old, sensitization to inhalant allergens was the major risk factor for wheezing (odds ratio, 2.7; P = .03). High-level allergen exposure, exposure to tobacco smoke, and lack of breast-feeding showed no association with wheezing. CONCLUSIONS: Some risk factors for wheezing previously identified in temperate climates were present in a subtropical area, including respiratory syncytial virus infection in infants and allergy in children older than 2 years. Rhinovirus was not associated with wheezing and did not appear to be a trigger for asthma exacerbations.     

The use of multistate life-table models for improving population health

We demonstrate how incidence, prevalence, remission, mortality(IPRM) models may be constructed on population life-tables,how the incidence of a condition may be calculated, and howthe consequences of demographic changes and public health interventionsmay be predicted. We illustrate the methodology by applyingit to the epidemiology of diabetes, physical inactivity andobesity in New Zealand.     

Information processing in long delay memory-guided saccades: further insights from TMS

The performance of memory-guided saccades with two different delays (3 s and 30 s of memorisation) was studied in eight subjects. Single pulse transcranial magnetic stimulation (TMS) was applied simultaneously over the left and right dorsolateral prefrontal cortex (DLPFC) 1 s after target presentation. In both delays, stimulation significantly increased the percentage of error in amplitude of memory-guided saccades. Furthermore, the interfering effect of TMS was significantly higher in the short delay compared to that of the long delay paradigm. The results are discussed in the context of a mixed model of spatial working memory control including two components: First, serial information processing with a predominant role of the DLPFC during the early period of memorisation and, second, parallel information processing, which is independent from the DLPFC, operating during longer delays.     

Long-chain acyl-CoA esters and phosphatidylinositol phosphates modulate ATP inhibition of Katp channels by the same mechanism

Phosphatidylinositol phosphates (PIPs, e.g. PIP₂) and long-chain acyl-CoA esters (e.g. oleoyl-CoA) are potent activators of K _atp channels that are thought to link K _atp channel activity to the cellular metabolism of PIPs and fatty acids. Here we show that the two types of lipid act by the same mechanism: oleoyl-CoA potently reduced the ATP sensitivity of cardiac (Kir6.2/SUR2A) and pancreatic (Kir6.2/SUR1) K _atp channels in a way very similar to PIP₂. Mutations (R54Q, R176A) in the C- and N-terminus of Kir6.2 that greatly reduced the PIP₂ modulation of ATP sensitivity likewise reduced the modulation by oleoyl-CoA, indicating that the two lipids interact with the same site. Polyvalent cations reduced the effect of oleoyl-CoA and PIP₂ on the ATP sensitivity with similar potency suggesting that electrostatic interactions are of similar importance. However, experiments with differently charged inhibitory adenosine phosphates (ATP^4-, ADP^3- and 2'(3')- O -(2,4,6-trinitrophenyl)adenosine 5'-monophosphate (TNP-AMP^2-)) and diadenosine tetraphosphate (Ap₄A^5-) ruled out a mechanism where oleoyl-CoA or PIP₂ attenuate ATP inhibition by reducing ATP binding through electrostatic repulsion. Surprisingly, CoA (the head group of oleoyl-CoA) did not activate but inhibited K _atp channels (IC₅₀= 265 ± 33 μM). We provide evidence that CoA and diadenosine polyphosphates (e.g. Ap₄A) are ligands of the inhibitory ATP-binding site on Kir6.2.