Residual cognitive and psychosocial functional impairment in outpatients in Greece who responded to conventional antidepressant monotherapy treatments for major depressive disorder (MDD).

BACKGROUND: Patients with MDD may experience diverse residual symptoms after clinical response to antidepressant treatment. Among these symptoms, cognitive problems in executive functioning are prominent and make functional recovery largely an unmet need for MDD patients. In this study we assessed cognitive symptoms and functional impairment in patients with MDD responding to antidepressant treatment. METHODS: This was a national, multi-site, non-interventional, cross-sectional study of depressive symptomatology, cognitive performance and psychosocial functioning in Greek outpatients with MDD who had clinically responded to antidepressant treatment. Both clinician- and patient- rated measures were employed. Symptom remission was assessed with the Montgomery Asberg Depression Rating Scale (MADRS) total score (≤12) and functional recovery was assessed with the Sheehan Disability Scale (SDS) score (<6). RESULTS: 335 MDD patients participated in the study. After antidepressant monotherapy approximately 60 % of responders and 40 % of remitted patients did not meet the functional recovery criterion. More than 60 % of responders had concentration difficulties as assessed by MADRS item. Patient reported cognitive symptoms were statistically significantly associated with functionality (ß coefficient = 0.126, p-value = 0.027). LIMITATIONS: Non-interventional study design and lack of a control group or active comparator/reference. CONCLUSIONS: This study highlights the persistence of decreased cognitive performance, particularly in executive functioning in patients with MDD who have shown response and/or remission to antidepressant treatment. This appears to contribute to psychosocial functional impairment. Patient-reported cognitive and psychosocial functioning impairment should be included in routine clinical monitoring of outcomes in MDD treatments.

Clinical pharmacogenomics in action: design, assessment and implementation of a novel pharmacogenetic panel supporting drug selection for diseases of the central nervous system (CNS).

BACKGROUND: Pharmacogenomics describes the link between gene variations (polymorphisms) and drug responses. In view of the implementation of precision medicine in personalized healthcare, pharmacogenetic tests have recently been introduced in the clinical practice. However, the translational aspects of such tests have been limited due to the lack of robust population-based evidence. MATERIALS: In this paper we present a novel pharmacogenetic panel (iDNA Genomics-PGx-CNS or PGx-CNS), consisting of 24 single nucleotide polymorphisms (SNPs) on 13 genes involved in the signaling or/and the metabolism of 28 approved drugs currently administered to treat diseases of the Central Nervous System (CNS). We have tested the PGx-CNS panel on 501 patient-derived DNA samples from a southeastern European population and applied biostatistical analyses on the pharmacogenetic associations involving drug selection, dosing and the risk of adverse drug events (ADEs). RESULTS: Results reveal the occurrences of each SNP in the sample and a strong correlation with the European population. Nonlinear principal component analysis strongly indicates co-occurrences of certain variants. The metabolization efficiency (poor, intermediate, extensive, ultra-rapid) and the frequency of clinical useful pharmacogenetic, associations in the population (drug relevance), are also described, along with four exemplar clinical cases illustrating the strong potential of the PGx-CNS panel, as a companion diagnostic assay. It is noted that pharmacogenetic associations involving copy number variations (CNVs) or the HLA gene were not included in this analysis. CONCLUSIONS: Overall, results illustrate that the PGx-CNS panel is a valuable tool supporting therapeutic medical decisions, urging its broad clinical implementation.

Theory of Mind as a potential trait marker of schizophrenia: a family study.

INTRODUCTION: Although there is some evidence that Theory of Mind (ToM) deficits may be trait markers of schizophrenia it is not clear yet if ToM deficits are primary deficits, that is, to be independent of deficits in general intellectual abilities and executive function. The aim was to examine if ToM deficits may be trait markers of the illness and the effect of cognitive inhibition, general intellectual abilities and depression on ToM abilities of patients with schizophrenia and their unaffected parents. METHODS: We assessed ToM abilities (first-order and second-order ToM stories, The Revised Eyes Test), cognitive inhibition (Stroop Task), general intellectual ability (Standard Progressive Matrices Test Plus) in patients with schizophrenia (N=21) and their unaffected fathers (N=21) and mothers (N=21) in comparison with healthy control families (healthy control males, N=21, healthy control fathers, N=21, healthy control mothers, N=21) RESULTS: Patients showed deficits in first-order ToM tasks but some of these deficits were mediated by general intellectual abilities. Impairments in cognitive inhibition mediated only patients' performance in The Revised Eyes Test. Patients showed deficits in second-order ToM stories independently of deficits in general intellectual abilities and cognitive inhibition. Unaffected parents did not show deficits in first-order ToM tasks, whereas they showed deficits in second-order ToM stories. However, the deficits that unaffected parents showed in second-order ToM stories were mediated by their deficits in general intellectual abilities, and there was an effect of remitted depression on the unaffected mothers' performance. CONCLUSIONS: The results suggest that intact neurocognitive and general intellectual abilities are necessary in order patients and their unaffected parents to pass successfully ToM tasks. Patients and their unaffected parents show ToM deficits but these deficits are not similar. Patients show ToM deficits but these deficits seem to be a component of the pathophysiology of the illness (e.g., deficits in executive function, general intellectual abilities).

PTEN expression in non small cell lung carcinoma based on digitized image analysis.

PURPOSE: HER2 depended signalling pathway is dereg-ulated in a subset of non small cell lung carcinoma (NSCLC). The tumor suppressor gene PTEN (10q21) regulates the HER2/PI3K/Akt signalling pathway. Our aim was to evaluate PTEN protein expression in NSCLC based on a quantitative analysis method correlating also the results with clinicopathological parameters. METHODS: Protein expression was determined by immunohistochemistry (IHC) in 61 paraffin-embedded cases of patients with NSCLC. Digital image analysis (staining intensity levels) was performed in the corresponding immunostained slides. RESULTS: Loss of PTEN expression was observed in 24 (39.34%) cases, low expression in 29 (47.54%) and overexpression in 8 (13.12%) cases. Multivariate analysis determined that PTEN overexpression was associated with lower risk to develop metastases (p=0.05). CONCLUSION: PTEN deregulation is a relatively frequent genetic event in NSCLC, associated with progressive metastatic process in those patients. Because of binding to the ErbB2 receptor, trastuzumab stabilizes and activates PTEN gene, and loss of its expression negatively affects the response rates in such patients.