Chronic Psychophysiological Insomnia: Hyperarousal and/or Inhibition Deficits? An ERPs Investigation

STUDY OBJECTIVES: Chronic primary insomnia has been hypothesized to result from conditioned arousal or the inability to initiate normal sleep processes. The event-related potentials (ERPs) N1, P2, and N350 are useful indexes of arousal. The objective is to compare these ERPs in primary chronic psychophysiological insomniacs (INS) and good sleepers (GS) during multiple recordings. PARTICIPANTS: Participants were 15 INS (mean age = 46 years, SD = 7.5) and 16 GS (mean age = 37 years, SD = 10.1). METHODS AND PROCEDURE: Following a multistep clinical evaluation, INS and GS participants underwent 4 consecutive nights of PSG recordings (N1 to N4). ERPs were recorded on the 3rd and 4th nights in the sleep laboratory (N3 and N4). ERPs recordings were made during wake on both nights (in the evening and upon awakening), with the addition of sleep-onset recordings on N4. Auditory stimuli consisted of "standard" and "deviant" tones. STATISTICAL ANALYSIS: Repeated measures ANOVAs were computed for each ERP for each recording for each type of stimulus. RESULTS: The amplitude of P2 and N350 was greater for the deviant than for the standard stimulus in both groups. The amplitude of N1 was larger in INS than GS in the morning and the evening. While the amplitude of N350 was larger in GS than in INS at sleep onset, the amplitude of P2 was greater in INS than in GS at that time. CONCLUSION: Signs of greater cortical arousal in psychophysiological insomnia individuals are observed, especially upon awakening in the morning. However, at sleep onset, difficulties from disengaging from wake processes and some inability at initiating normal sleep processes appear also present in individuals with insomnia compared to good sleepers.     

Laboratory diagnosis of influenza--virology or serology?

Although classical influenza is a clinically typical illness ("unchanging disease due to a changing agent"), laboratory investigations are essential at the beginning of each influenza epidemic. They should confirm suspected influenza cases and exclude "flu-like illnesses" which may be caused by numerous other viral and bacterial agents. Different virological as well as serological methods are available. For early diagnosis of acute influenza virus infections, virus detection using rapid procedures for virus isolation or antigen staining and molecular biological techniques have been developed. The determination of specific antibodies (IgG, IgM) has traditionally been widely used diagnostically. Conventional serological diagnosis is possible by means of the complement fixation and hemagglutination inhibition tests and allows the detection of type- and subtype-specific antibodies, respectively. As part of an automated serology, immunofluorescence test and enzyme-linked immunosorbent assay are the mostly widely available methods. In comparison, virus detection is clearly superior to antibody determination for diagnosis of influenza virus infections. However, antibody testing may be useful as a complementary tool to confirm the diagnosis retrospectively.     

Daytime Functioning in Primary Insomnia: Does Attentional Focus Contribute to Real or Perceived Impairment?

A study was conducted to test the proposal that self-focused attention or monitoring exacerbates the perception of poor daytime functioning in the absence of objective deficits among individuals with insomnia. Fifty-one participants meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for primary insomnia were randomly assigned to a self-focus group (viewing themselves on a TV monitor), a monitoring group (instructed to focus on their thoughts, body sensations, mood, and performance), or a no instruction group while completing a battery of neuropsychological tests. The results indicated that all participants performed within published normative ranges on all tests. The groups did not differ on their objective test performance, but the self-focus group perceived their performance on the tests as significantly worse than the no instruction group. These findings suggest that self-focused attention may contribute to perceived impairment in daytime functioning in primary insomnia.     

Molecular diagnosis in LGMD2A: Mutation analysis or protein testing?

Limb girdle muscular dystrophy (LGMD) type 2A (LGMD2A) is caused by mutations in the CAPN3 gene encoding for calpain-3, a muscle specific protease. While a large number of CAPN3 gene mutations have already been described in calpainopathy patients, the diagnosis has recently shifted from molecular genetics towards biochemical assay of defective protein. However, an estimate of sensitivity and specificity of protein analysis remains to be established. Thus, we first correlated protein and molecular data in our large LGMD2A patient population. By a preliminary immunoblot screening for calpain-3 protein of 548 unclassified patients with various phenotypes (LGMD, myopathy, or elevated levels of serum creatine kinase [hyperCKemia]), we selected 208 cases for CAPN3 gene mutation analysis: 69 had protein deficiency and 139 had normal expression. Mutation search was conducted using SSCP, denaturing high performance liquid chromatography (DHPLC), amplification refractory mutation system (ARMS-PCR), and direct sequencing methods. We identified 58 LGMD2A mutant patients: 46 (80%) had a variable degree of protein deficiency and 12 (20%) had normal amount of calpain-3. We calculated that the probability of having LGMD2A is very high (84%) when patients show a complete calpain-3 deficiency and progressively decreases with the amount of protein; this new data offers an important tool for genetic counseling when only protein data are available. A total of 37 different CAPN3 gene mutations were detected, 10 of which are novel. In our population, 87% of mutant alleles were concentrated in seven exons (exons 1, 4, 5, 8, 10, 11, and 21) and 61% correspond to only eight mutations, indicating the regions where future molecular analysis could be restricted. This study reports the largest collection of LGMD2A patients so far in which both protein and gene mutations were obtained to draw genotype-protein-phenotype correlations and provide insights into a critical protein domain.     

ART in recurrent miscarriage: preimplantation genetic diagnosis/screening or surrogacy?

Recently, assisted reproductive techniques have been used to prevent further miscarriages in women with recurrent miscarriage. One approach uses either screening or diagnosis of embryonic chromosomes prior to embryo replacement [preimplantation genetic screening (PGS)/preimplantation genetic diagnosis (PGD)]. The second approach involves surrogacy. However, PGS/PGD assumes that the embryo is chromosomally abnormal, and that the mother should receive a chromosomally normal embryo. Surrogacy assumes that the embryo is normal and that the maternal environment needs to be substituted. This article examines the place of both techniques in different types of recurrent miscarriage, and tries to give guidelines as to which technique is preferable depending on the likelihood of an embryonic chromosome aberration. In repeated fetal aneuploidy or in the older patient, PGS or PGD are preferable. However, with high numbers of miscarriages, or in autoimmune pregnancy loss, surrogacy is preferable. In the light of recent work, it is uncertain which treatment mode is indicated in balanced parental chromosome aberrations. In conclusion, both techniques have a place, but probably only in those patients with a poor prognosis in whom assisted reproductive techniques will be shown to improve the subsequent live birth rate above the spontaneous rate.     

Primary immunodeficiency or not? Making the correct diagnosis

Making a correct diagnosis of a primary immunodeficiency disease is crucial for the selection of proper therapy. Although many cases go undiagnosed, there are also many instances of incorrect diagnosis that result in years of inappropriate treatment and failure to implement beneficial treatment. This article summarizes 2 actual cases in which incorrect diagnoses led to recommendations of unwarranted high-risk or costly treatments. Had the physicians chosen tests of immune function rather than relying on immunoglobulin levels or cell counts, they would have arrived at the true diagnoses.     

Sinonasal tubulopapillary low-grade adenocarcinoma: a specific diagnosis or just another seromucous adenocarcinoma?

Histopathologically, sinonasal adenocarcinomas fall into four categories: the intestinal type, the conventional salivary gland type (eg, adenoid cystic carcinoma, acinic cell carcinoma), the seromucous type, and the low-grade not otherwise specified type. Recently, a new type of sinonasal adenocarcinoma has been described, called tubulopapillary low-grade adenocarcinoma. In this commentary, the histologic features of this type of tumor are compared with those of the other types of sinonasal adenocarcinoma. The clinicopathologic characteristics and probable origin of this type of adenocarcinoma are also discussed.     

Hypoplastic myelodysplastic syndrome-a clinical,morphologic, or genetic diagnosis?

We report a middle-aged female with an 11-year history of nonprogressive pancytopenia and severely hypoplastic marrow with minimal morphologic dysplasia. A diagnosis of hypoplastic myelodysplastic syndrome (MDS) was made because of the finding of a persistent clonal abnormality, del(13)(q12q14), and the subsequent demonstration of a single Auer rod-containing blast in the peripheral blood smear. The case illustrates the problems in the differentiation between aplastic anemia and hypoplastic MDS.     

Is pain a somatic symptom?

The grouping of symptoms into "somatic" or "physical" on the one hand and "mental", "somatoform", or "psychological" on the other are vestiges of an era in medicine when it seemed useful to divide all the phenomena of disease into two groups - one related to the soma and other to the psyche. Today, this division is becoming obsolete and is harmful. Obsolete, because we are discovering changes in the tissues or in biochemical and immunological functions of the body in people with mental disorders, and because psychological complaints are frequent in all physical illnesses. Harmful, because the labels "psychological", "psychogenic", or "somatoform" are so loaded with connotations of being simulations or complaints about nothing that patients are unlikely to recive the help they need.     

Whatever happened to symptom substitution?

Symptom substitution is a theoretical consequence of the psychodynamic model of psychopathology and symptom formation that contrasts markedly with behavioral models. Symptom substitution was a major scientific and clinical question about a half century ago that was abandoned rather than answered partly because it did not seem to occur and partly because perceived methodological problems impeded empirical research. The contemporary relevance of symptom substitution is that the psychodynamic model of psychopathology and symptom formation from which the prediction of symptom substitution stems continues to be widely taught and to broadly inform clinical practice. This article revisits the psychodynamic model of symptom formation and substitution, restates perceived methodological limitations to its empirical study, demonstrates that symptom substitution is an empirically testable prediction, reviews the relevant empirical literature, and discusses implications for the science and practice of clinical psychology including a proposed research design for certifying bona fide psychoanalytic symptoms.     

Mood and anxiety symptom questionnaire anxiety items in an adult british clinical sample: One scale or two?

In seeking to establish British clinical normative data for the two anxiety scales (anxious symptoms and anxious arousal) of the Mood and Anxiety Symptom Questionnaire (MASQ), the responses of 237 British National Health Service outpatients were examined. Factor analyses (exploratory and confirmatory) failed to confirm the expected structure. Data were presented and discussed, considering the 28 anxiety item pool in terms of being either two highly correlated scales of somatic anxiety versus psychological anxiety, or as a single general anxiety scale. As neither of these outcomes accorded with the test constructors' assumptions, it was concluded that the MASQ is not a suitable measure for assessing the tripartite model of adverse mood states in British clinical samples. Copyright © 2010 John Wiley & Sons, Ltd. Key Practitioner Message: ? Exploratory and confirmatory factor analyses failed to confirm the a priori MASQ anxiety items' structure. ? Alternative explanations were of either a) two highly correlated scales of somatic anxiety and psychological anxiety or b) a single general anxiety scale.