An MR spectroscopy study of temporal areas excluding primary auditory cortex and frontal regions in subjective bilateral and unilateral tinnitus.

Previous studies indicate changes in neurotransmission along the auditory pathway in subjective tinnitus. Most authors, however, investigated brain regions including the primary auditory cortex, whose physiology can be affected by concurrent hearing deficits. In the present MR spectroscopy study we assumed increased levels of glutamate and glutamine (Glx), and other Central Nervous System metabolites in the temporal lobe outside the primary auditory cortex, in a region involved in conscious auditory perception and memory. We studied 52 participants with unilateral (n = 24) and bilateral (n = 28) tinnitus, and a control group without tinnitus (n = 25), all with no severe hearing losses and a similar hearing profile. None of the metabolite levels in the temporal regions of interest were found related to tinnitus status or laterality. Unexpectedly, we found a tendency of increased concentration of Glx in the control left medial frontal region in bilateral vs unilateral tinnitus. Slightly elevated depressive and anxiety symptoms were also shown in participants with tinnitus, as compared to healthy individuals, with the bilateral tinnitus group marginally more affected. We discuss no apparent effect in the temporal lobes, as well as the role of frontal brain areas, with respect to hearing loss, attention and psychological well-being in chronic tinnitus. We furthermore elaborate on the design-related and technical obstacles of MR spectroscopy.

False Belief Understanding in Deaf Children With Cochlear Implants.

Theory of mind (ToM) is crucial for social interactions. Previous research has indicated that deaf and hard-of-hearing children born into hearing families (DoH) are at risk of delayed ToM development. However, it is unclear whether this is the case for DoH children who receive cochlear implants (CIs) before and around the second year of life. The present study aimed to investigate false belief understanding (FBU) in DoH children with CIs. The relationships between false belief task (FBT) performance, sentence comprehension, age at implantation, duration of CI use, and Speech Recognition Threshold were explored. A total of 94 children with typical levels of hearing (TH) and 45 DoH children (age range: 3-8), who received their first CI between 6 and 27 months of age, were tested on the FBT and a sentence comprehension test. Results showed that 4- and 5-year-old children with CIs performed significantly worse than their peers with TH on the FBT; 6- to 8-year-old children with CIs performed similarly to age-matched children with TH. Age at implantation and duration of CI use were correlated with sentence comprehension but not with the FBT. The results indicated that FBU was delayed until the age of 6 years in most of children with CIs.

Cost-Utility Analysis of Bilateral Cochlear Implantation in Adults With Severe to Profound Sensorineural Hearing Loss in Poland.

OBJECTIVE: The aim of the study was to develop a Markov model and apply it for the evaluation of three different treatment scenarios for adult patients with severe to profound bilateral sensorineural hearing loss. STUDY DESIGN: Prospective Observational Study. SETTINGS: Hospital. PATIENTS: A clinical group of 22 adult patients (59.1% men, 40.9% women) aged from 59.13 ±â€Š8.9 years were included in the study. The study comprised two arms: patients in group 1 received the second cochlear implant one to three months after the first implant; while patients in group 2 got the second cochlear implant approximately one year after the first implant. MAIN OUTCOME MEASURES: All participants were first asked to complete an AQoL-8D questionnaire. For the cost-effectiveness analyses, a Markov model analyzed as microsimulation was developed to compare the different treatment options. RESULTS: The analyses show that bilateral cochlear implantation strategies are cost-effective compared to the 'no treatment' alternative when having a 10-year model time horizon. When all three model scenarios are compared, the bilateral simultaneous cochlear implantation strategy (Scenario 3) compared to the 'no treatment' option is even more cost-effective than the Scenarios 1 and 2, compared with the 'no treatment' alternative. CONCLUSIONS: The model results summarize that bilateral (sequential and simultaneous) cochlear implantation that are represented in the model scenarios, are cost-effective strategies for Polish adult patients with bilateral severe to profound sensorineural hearing loss.

The relationship between alpha burst activity and the default mode network.

Alpha rhythm, described by Hans Berger, is mainly recorded from the occipital cortex (OCC) of relaxed subjects with their eyes closed.Early studies indicated the thalamo­cortical circuit as the origin of alpha rhythm. Recent works suggest an additional relationship between alpha rhythm and the Default Mode Network (DMN). We simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) signals in 36 young males asked to alternately close and open their eyes in 30­s blocks. Using an EEG source channel montage (the recorded signal was interpolated to designated source positions corresponding to certain brain regions) we found an alpha rhythm sub­activity composed of its intrinsic events, called alpha bursting segments (ABS). More ABS were observed on source channels related to the DMN than those located over the OCC. Similarly, both the beamformer source analysis and fMRI indicated that the specific ABS activity detected on the posterior cingulate cortex/precuneus (PCC) source channel was less related to the OCC than to the DMN source channels. The fMRI analysis performed using the PCC­ABS as a general linear model regressor indicated an increased blood oxygenation level­dependent signal change in DMN nodes - precuneus and prefrontal cortex. These results confirm the OCC source of alpha activity a nd additional specific sources of ABS in the DMN.

The importance of TCF4 gene in the etiology of recurrent depressive disorders.

BACKGROUND: A recurrent depressive disorder is one of the most commonly diagnosed disease entities among psychiatric disorders. The prevalence and morbidity of depression are constantly increasing. Numerous studies have demonstrated the role of genetic factors in the etiology of depressive disorders. Many studies are being conducted to identify genes that predispose to depression. The purpose of this study was to investigate the role of TCF4 gene in the etiology of recurrent depressive disorders and, in particular, to assess expression of the TCF4 gene at the mRNA and protein level in patients with recurrent depressive disorders versus healthy individuals. MATERIAL AND METHODS: The examined population consisted of 170 individuals suffering from depression and 90 healthy individuals. The expressions of the TCF4 gene at the mRNA and protein level were assessed. RESULTS: Decreased TCF4 expression at the mRNA and protein level was found in patients with depressive disorder versus healthy individuals. Expression of the studied gene was not affected by the patients' sex and age. The statistical analysis also showed no correlation between the expression of TCF4 at the mRNA and protein level and the number of episodes or the severity of symptoms. Among the clinical manifestations of depression, only the duration of the illness correlated with the expression of TCF4 at the mRNA level. CONCLUSIONS: Expression of TCF4 at the mRNA and protein level may be significant in the pathomechanism of recurrent depressive disorder and it is not dependent on sex and age.

The anti-inflammatory mechanism of antidepressants - SSRIs, SNRIs.

The cytokine theory of depression no longer brings about any doubts. Experiments and research studies conducted in the last ten years have confirmed that both physical and psychological (emotional) stress increases the likelihood of occurrence of mental disorders (including depressive disorders) owing to the action of a series of hormonal and biochemical mechanisms. Selective serotonin reuptake inhibitors (SSRI) as well as serotonin and norepinephrine reuptake inhibitors (SNRIs) are some of the most commonly applied drugs in the world during pharmacotherapy of recurrent depressive disorder. The underestimated anti-inflammatory and anti-oxidative effect may be one of the potential mechanisms of action of the preparations mentioned above. The detailed specificity of action of this mechanism still remains unknown. The aim of our work will be to perform a review of contemporary literature in order to present the latest scientific reports regarding the anti-inflammatory effects of SSRIs and SNRIs. The mechanism of anti-inflammatory action may serve as a possible explanation for the efficacy of antidepressants from the groups of SSRIs and SNRIs.

Tonotopic organisation of the auditory cortex in sloping sensorineural hearing loss.

Although the tonotopic organisation of the human primary auditory cortex (PAC) has already been studied, the question how its responses are affected in sensorineural hearing loss remains open. Twenty six patients (aged 38.1 ± 9.1 years; 12 men) with symmetrical sloping sensorineural hearing loss (SNHL) and 32 age- and gender-matched controls (NH) participated in an fMRI study using a sparse protocol. The stimuli were binaural 8s complex tones with central frequencies of 400 HzCF, 800 HzCF, 1600 HzCF, 3200 HzCF, or 6400 HzCF, presented at 80 dB(C). In NH responses to all frequency ranges were found in bilateral auditory cortices. The outcomes of a winnermap approach, showing a relative arrangement of active frequency-specific areas, was in line with the existing literature and revealed a V-shape high-frequency gradient surrounding areas that responded to low frequencies in the auditory cortex. In SNHL frequency-specific auditory cortex responses were observed only for sounds from 400 HzCF to 1600 HzCF, due to the severe or profound hearing loss in higher frequency ranges. Using a stringent statistical threshold (p < 0.05; FWE) significant differences between NH and SNHL were only revealed for mid and high-frequency sounds. At a more lenient statistical threshold (p < 0.001, FDRc), however, the size of activation induced by 400 HzCF in PAC was found statistically larger in patients with a prelingual, as compared to a postlingual onset of hearing loss. In addition, this low-frequency range was more extensively represented in the auditory cortex when outcomes obtained in all patients were contrasted with those revealed in normal hearing individuals (although statistically significant only for the secondary auditory cortex). The outcomes of the study suggest preserved patterns of large-scale tonotopic organisation in SNHL which can be further refined following auditory experience, especially when the hearing loss occurs prelingually. SNHL can induce both enlargement and reduction of the extent of responses in the topically organized auditory cortex.

Human neuropsin gene in depression.

BACKGROUND: Neuropsin (NP, kallikrein 8, KLK8) - a kallikrein gene-related (KLK) endoprotease - plays a key role in neuroplasticity processes, since intracellular signal cascades and regulation of gene expression are engaged in long-term synaptic plasticity. The main aim of this paper is to compare expression of the human neuropsin gene on the mRNA level in a group of patients diagnosed with depression and in a group of healthy subjects who have never been treated psychiatrically. SUBJECTS AND METHODS: 291 people, aged 18-67, were qualified to participate in the experiment: major recurrent depression group (MRD) and the control group (CG). Designations were carried out for the human NP gene (hNP). RESULTS: For hNP gene expression at the mRNA level was higher in patients with depression than in the CG (p<0.005). A Spearman's rank correlation analysis did not reveal any statistically significant relationship between the intensity of the disease measured using the HDRS scale and expression on the mRNA level for the hNP gene. Expression for the hNP gene in the entire group analysed increased with age of the examined individuals (p<0.005). CONCLUSION: Expression of the hNP gene on the mRNA level, evaluated based on peripheral blood, is significantly higher in the patients with MRD than in the healthy subjects.

The significance of microRNAs in the course of rDD.

BACKGROUND: In recent years, special attention in genetic studies dedicated to the development of various diseases, including mental disorders, has been paid to micro ribonucleic acids (miRNA, microRNA). As an object of our analysis we have selected the miRNAs which - due to the profile of their activity - may be significant in the aetiology and course of recurrent depressive disorders, i.e. miRNA-370, miRNA-411, miRNA-433, miRNA-487b and miRNA-539. METHODS: The examined population included 138 patients suffering from depression and 95 individuals from the control group (CG). The subjects suffering from depression were divided into two sub-groups: ED-I group (46 patients), rDD group (92 patients). RESULTS: No significant statistical differences were observed between the ED-I and rDD group for all the variables included in the analysis. No significant interrelation was noticed between the number of depression episodes, the severity of depressive disorders and the expression of miRNA selected. Results of the analysis indicate statistically significant differences between the control subjects and the patients with symptoms of depression in terms of all the variables analysed. CONCLUSIONS: 1. There is no significant difference in miRNAs expression between patients with recurrent depressive disorders and those in the first episode of depression. 2. The differences in terms of expression of the analysed variables between the subjects with symptoms of depression and healthy individuals were confirmed.

[Results of the Trail Making Test among patients suffering from depressive disorders and organic depressive disorders]. / Wykonanie Testu Laczenia Punktów przez osoby z depresja i organicznymi zaburzeniami depresyjnymi.

AIM: Coexistence of depression and dementia for many years has been widely studied for many years. According to the authors for clinical practice, both psychiatric and psychological, it is also important to effectively differentiate between these disease entities. The aim of this study is to compare the implementation of the Trail Making Test (TMT) in patients diagnosed with depressive disorders and those with organic depressive disorders. METHODS: A sample of 150 persons aged 18-68 years participated in the study. Patients who took part in the investigation were divided into three groups: depressive disorders (DD, n=50), organic depressive disorders (ODD, n=50) and healthy controls (C, n=50). Cognitive functions were evaluated by the Trail Making Test. RESULTS: Relevant statistical differences among examined group were observed: in TMT part A: DD/ODD: p=0.006; DD/C: p<0.001; TMT part B: DD/ODD: p<0.001; DD/C: p<0.001. In both cases, patients with ZD group scored higher than patients from the OZD group, but lower than those in the control group. CONCLUSIONS: 1. Patients with organic depressive disorders achieved significantly lower results than patients with depressive disorders in TMT. 2. Subjects with depressive disorder compared to the healthy control group achieved significantly lower scores in TMT. 3. The authors determined the TMT performance indicators differentiating between groups: TMT part A: C=20-40 sec., DD>40 sec. - 90 sec.; ODD>90 sec.; TMT part B: C<60 sec.; DD>60 sec. - 180 sec.; ODD>180 sec.

Interaction between poor glycemic control and 9p21 locus on risk of coronary artery disease in type 2 diabetes.

CONTEXT: A common allele on chromosome 9p21 has been repeatedly associated with increased risk of coronary artery disease (CAD) in the general population. However, the magnitude of this effect in the population with diabetes has not been well characterized. OBJECTIVE: To examine the association of the 9p21 variant with CAD in individuals with type 2 diabetes and evaluate its interaction with poor glycemic control. DESIGN, SETTING, AND PARTICIPANTS: (1) Case-control study of 734 type 2 diabetes patients (322 with angiographically diagnosed CAD and 412 with no evidence of CAD) who were recruited between 2001 and 2006 at the Joslin Clinic, Beth Israel Deaconess Medical Center; and (2) independent cohort study of 475 type 2 diabetes patients from the Joslin Clinic whose survival status was monitored from their recruitment between 1993 and 1996 until December 31, 2004. Participants for both studies were genotyped for a representative single-nucleotide polymorphism at 9p21 (rs2383206) and characterized for their long-term glycemic control by averaging multiple hemoglobin A(1c) (HbA(1c)) measurements taken in the years before study entry. MAIN OUTCOME MEASURES: For the case-control study, association between single-nucleotide polymorphism rs2383206 and CAD defined as angiographically documented stenosis greater than 50% in a major coronary artery or a main branch thereof was assessed and for the cohort study, cumulative 10-year mortality was documented. RESULTS: Individuals who were homozygous for the risk allele were significantly more frequent among case than control participants (42.3% vs 28.9P = .0002). This association was unaffected by adjustment for cardiovascular risk factors, but the effect of the risk genotype was significantly magnified (adjusted P for interaction = .048) in the presence of poor glycemic control (worst tertile of the distribution of HbA(1c) at examination). Relative to the CAD risk for patients with neither a 9p21 risk allele nor poor glycemic control, the CAD odds for participants having 2 risk alleles but not poor glycemic control were increased 2-fold (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.17-3.41), whereas the odds for study participants with the same genotype and with poor glycemic control were increased 4-fold (OR, 4.27; 95% CI, 2.26-8.01). The interaction was stronger (adjusted P = .005) when a measure of long-term glycemic control (7-year average rather than most recent HbA(1c)) was used with ORs of 7.83 (95% CI, 3.49-17.6) for participants having 2 risk alleles and a history of poor glycemia and 1.54 (95% CI, 0.72-3.30) for participants with the same genotype but without this exposure. A similar interaction between 9p21 variant and poor glycemic control was observed with respect to cumulative 10-year mortality in the cohort study (43.6% in patients with 2 risk alleles and poor glycemic control, 23.1% in individuals with only the 2 risk alleles, 30.0% in individuals with only poor glycemic control, and 31.6% in individuals with neither factor, P for interaction, = .036). CONCLUSION: In this study population, the CAD risk associated with the 9p21 variant was increased in the presence of poor glycemic control in type 2 diabetes.

Constitutive activation of met kinase in non-small-cell lung carcinomas correlates with anchorage-independent cell survival.

Lung cancer is currently the most frequent cause of cancer death in North America. Hepatocyte growth factor (HGF) and its receptor Met are frequently over-expressed in non-small-cell lung carcinomas (NSCLC), but their potential role in tumor progression is not clearly known. To assess the role of HGF/Met signaling in lung carcinomas, we have examined the expression, activation status, and function of Met in NSCLC cell lines (n = 7), established from primary tumors or pleural fluids of cancer patients. We observed Met expression in three NSCLC cell lines, two of which exhibited constitutive tyrosine-phosphorylation of Met, and Met kinase activity. In addition, the observed constitutive activation of Met was sustained under anchorage-independent conditions, and correlated with phosphatidyl inositol 3-kinase-dependent cell survival. Immunoreactive HGF-like protein was secreted by two Met-positive and two Met-negative NSCLC cell lines. However HGF activity, as determined by the ability to induce cell scattering and tyrosine-phosphorylation of Met in reporter cell lines, was detected in conditioned medium from only one Met-negative NSCLC cell line: none of the conditioned media from Met-expressing NSCLC cell lines showed detectable HGF activity. Thus, constitutive activation of Met in NSCLC cell lines may occur at least in part through intracrine, or HGF-independent mechanisms. Interestingly, additional paracrine stimulation with exogenous recombinant HGF was required for DNA synthesis and correlated with increased activation of ERK1/2 in all Met-positive NSCLC cell lines, regardless of the basal activation status of Met. These findings indicate that a medium level of constitutive activation of Met occurs in some NSCLC cell lines, and correlates with survival of detached carcinoma cells; whereas additional paracrine stimulation by recombinant HGF is required for DNA synthesis. Thus constitutive and paracrine activation of Met may provide complementary signals that promote survival and proliferation, respectively, during tumor progression of NSCLC.