Enrichment of rare copy number variation in children with developmental language disorder.

Developmental language disorder (DLD) is a common neurodevelopmental disorder with largely unknown etiology. Rare copy number variants (CNVs) have been implicated in the genetic architecture of other neurodevelopmental disorders (NDDs), which have led to clinical genetic testing recommendations for these disorders; however, the evidence is still lacking for DLD. We analyzed rare and de novo CNVs in 58 probands with severe DLD, their 159 family members and 76 Swedish typically developing children using high-resolution microarray. DLD probands had larger rare CNVs as measured by total length (P = .05), and average length (P = .04). In addition, the rate of rare CNVs overlapping coding genes was increased (P = .03 and P = .01) and in average more genes were affected (P = .006 and P = .03) in the probands and their siblings, respectively. De novo CNVs were found in 4.8% DLD probands (2/42) and 2.4% (1/42) siblings. Clinically significant CNVs or chromosomal anomalies were found in 6.9% (4/58) of the probands of which 2 carried 16p11.2 deletions. We provide further evidence that rare CNVs contribute to the etiology of DLD in loci that overlap with other NDDs. Based on our results and earlier literature, families with DLD should be offered molecular genetic testing as a routine in their clinical follow-up.

An open-label, multicenter observational study for patients with Alzheimer's disease treated with memantine in the clinical practice.

BACKGROUND/AIMS: In this post-marketing observational study, the safety and effectiveness of memantine were evaluated in patients with Alzheimer's disease (AD). METHODS: In a 6-month, observational, open-label study at 202 specialist sites in Greece, the effectiveness of memantine was evaluated using the Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale at baseline, and after 3 and 6 months. Discontinuation rates and adverse drug reactions (ADRs) were also recorded to evaluate the safety profile of memantine. RESULTS: 2,570 patients participated in the study. Three and 6 months after baseline, MMSE and IADL scores were significantly improved compared to baseline. At the end of the study, 67% of the patients had improved their MMSE score; 7.1% of the patients reported ≥1 ADRs, and treatment was discontinued due to ADR in 0.7%. CONCLUSION: Memantine was well tolerated and had a positive effect on the patient's cognitive and functional ability in real-life clinical practice, in agreement with randomized, controlled trials.

Memantine in everyday clinical practice: a comparison of studies in Germany and Greece.

BACKGROUND/AIMS: Results from German and Greek non-interventional studies were compared to investigate possible differences concerning efficacy, tolerability and compliance between both countries. METHODS: In two open-label, multicentre, non-interventional studies, 4,305 patients with mild to severe Alzheimer's disease (AD) were treated with daily doses of 20 mg memantine for 6 months. Efficacy was assessed using the Mini-Mental State Examination (MMSE) and instrumental activities of daily living (IADL) scales. Safety and tolerability were recorded. RESULTS: After 6 months, the patients showed an improvement of their cognitive performance by 2 MMSE points compared to baseline (p < 0.001). MMSE values were improved in 67.4% of the patients, while 15.1% remained stable, and MMSE deteriorated in 17.5% only. The ability to perform IADL increased, as is indicated by lower values (baseline: 70.5; after 6 months: 66.6 points). Improvement of cognition and IADL was nearly identical in both countries. Treatment discontinuation was significantly more frequent in the Greek population, mainly due to non-adherence (9.4% of the safety population). 345 adverse events were recorded in 245 patients (6.3%), and they were significantly associated with country and age. CONCLUSION: The results correspond to those of clinical trials and support the efficacy and good tolerability of memantine in a realistic setting. Differences between the countries were observed regarding the baseline characteristics of patients (more female, older and more severe patients in Germany as well as less pretreatment with cholinesterase inhibitors) and regarding premature discontinuation and reported adverse drug reactions, which were both higher in Greece.

[Depression in schizophrenia: diagnosis, epidemiology, predisposing factors].

The observation and debates concerning the coexistence of depression and schizophrenia date back to Kraepelin and Bleuler. Both recognized that among the basic symptoms of 'dementia praecox' and "schizophrenia", are the flattening of affect and the depressed affect and both included in their clinical descriptions of schizophrenia the depressive symptoms. During the recent years this observation has been made official, with the inclusion of diagnoses like schizoaffective psychosis as well as the post psychotic or post schizophrenic depression in the international disease categorization systems DSM and ICD. Several theories have been proposed to explain the relation of depression and schizophrenia, especially when there both appear simultaneously in the same patient. Depression can be present during the prepsychotic prodromal phase, during the acute phase or after the remission of the psychotic features. In addition depressive symptoms could be part of the clinical picture of chronic stabilized patients. Depression in schizophrenia is defined in different ways, i.e. through the criteria of DSM and ICD, through the relevant items of psychopathological scales or through the total rating of depression scales if the score exceeds a certain cut-off. Since the existing depression scales have been created to evaluate depressed patients and therefore there were questions of validity of their use in schizophrenic patients, recently it has been proposed a special scale to evaluate depression specifically in schizophrenic patients (Calgary Depression Scale for Schizophrenia). This scale has been standardized in a Greek sample. In general, according to the existing studies 7-70% of all schizophrenic patients suffer from some form of clinically relevant depression and the median frequency from all the available studies is 25%. The frequency of depression in new schizophrenic patients is 21-24% during the acute phase and it seems that this frequency progressively decreases with the time and stabilizes around 8% in remitted patients. These frequencies may vary upwards depending on the definition of depression. One in four schizophrenic patients with depression presents with suicide ideation and therefore requires appropriate identification and management. As far as predisposing factors for the appearance of depression concerns, the existing data are inadequate and contradictory to extract safe conclusions and therefore further research is in line.

[Depression in schizophrenia: Relationship with other symptoms, differential diagnosis, prognosis,treatment].

The relationship between depressive symptoms and other symptom categories in schizophrenia have been studied by many authors. According to the existing studies depression in schizophrenic patients is related to the presense of positive symptoms, especifically delusions and hallucinations.As far as negative symptoms concerns it seems that there coexist with the depressive symptoms in any phase of the disease at least in a subgroup of schizophrenic patients. In addition, according to the pyramidal model of Kay, when positive and depressive symptoms coexist, they create theclinical picture of the paranoid subtype of schizophrenia. The same holds for the combination of negative and depressive symptoms, which most frequently describe the residual subtype of the disease. Extrapyramidal symptoms are side effects of antipsychotic drugs (especially the classicalones). According to the existing literature it seems that antipyramidal side effects appear more often in schizophrenic patients with depressive symptoms. The differential diagnosis of depressive symptoms in schizophrenic patients should start with the evaluation of possible presence of organiccauses like somatic disease, medication induced extrapyramidal symptoms, substance abuse. Yet, symptoms of depression need to be differentiated from the negative symptoms of schizophrenia. Psychiatric syndromes like schizoaffective disorder, bipolar disorder and depression with psychotic features need to be also considered. In this case is very important to identify accurately the duration of depressive symptoms as well as the succession of appearance of the depressive vs. psychotic symptoms. Depressive symptoms appear to be bad prognostic sign for the long-term outcome of schizophrenia, because of the increased risk for suicide but also because of the worsening of the quality of life and the general wellbeing of the schizophrenic patient. Depressive symptoms during the acute phase of the disease usually respond to antipsychotic therapy, but in some cases the treating physician may consider the use of atypical antipsychotics. In the case of post psychotic depression the concurrent administration of antidepressants is indicated.

Escitalopram in clinical practice in Greece: treatment response and tolerability in depressed patients.

OBJECTIVE: To evaluate the effectiveness and tolerability of escitalopram (10-20 mg/day) in adult outpatients suffering from major depressive disorder in naturalistic settings. METHODS: An open-label, 3-month, surveillance study was conducted in 434 investigative sites in Greece enrolling 5175 patients. Clinical Global Impression-Severity (CGI-S) scale and patient-rated Sheehan Disability Scale (SDS) were used as efficacy measurements and treatment discontinuation rates due to adverse events was used to assess tolerability. RESULTS: Clinically significant improvement in CGI-S scores was recorded after 3 months. At baseline, patients reported marked or extreme disability for work (38%), social life (41%) and family life (37%), whereas after 3 months of treatment, 80.6%, 79.5% and 83.5% of patients indicated either no or mild disability, respectively. Escitalopram had good tolerability, demonstrated by a very low rate of discontinuations due to adverse events. CONCLUSION: In this large naturalistic study, escitalopram was well tolerated and improved both depressive symptoms and function.

Impaired P600 in neuroleptic naive patients with first-episode schizophrenia.

Deficits of working memory (WM) are recognized as an important pathological feature in schizophrenia. Since the P600 component of event related potentials has been hypothesized that represents aspects of second-pass parsing processes of information processing, and is related to WM, the present study focuses on P600 elicited during a WM test in drug-naive first-episode schizophrenics (FES) compared to healthy controls. We examined 16 drug-naive first-episode schizophrenic patients and 23 healthy controls matched for age and sex. Compared with controls schizophrenic patients showed reduced P600 amplitude on left temporoparietal region and increased P600 amplitude on left occipital region. With regard to the latency, the patients exhibited significantly prolongation on right temporoparietal region. The obtained pattern of differences classified correctly 89.20% of patients. Memory performance of patients was also significantly impaired relative to controls. Our results suggest that second-pass parsing process of information processing, as indexed by P600, elicited during a WM test, is impaired in FES. Moreover, these findings lend support to the view that the auditory WM in schizophrenia involves or affects a circuitry including temporoparietal and occipital brain areas.

Comparison of four scales measuring depression in schizophrenic inpatients.

Several scales have been used to diagnose and evaluate depression in schizophrenia. However, the association between different depression scales and between depression scales and negative symptoms has not been studied adequately. Sixty-four consecutively admitted schizophrenic patients to Eginition Hospital, Department of Psychiatry, Athens, were assessed on the following scales: the Calgary Depression Scale for Schizophrenia (CDSS), the Hamilton Depression Rating Scale (HDRS), the Expanded Brief Psychiatric Rating Scale-Depression subscale (EBPRS-D), the Positive and Negative Syndrome Scale-Depression subscale (PANSS-D) and the Negative Symptoms subscale (PANSS-N). The depression scales were found to be highly intercorrelated with the exception of the comparison between the EBPRS-D and the PANSS-D. Out of the four depression scales studied, only CDSS and EBPRS-D can discriminate between depression and a PANSS-Negative Symptoms subscale score or negative item scores.

The Greek version of the calgary depression scale for schizophrenia.

The aim of this study was to evaluate the reliability and validity, as well as the specificity, of the Greek version of the Calgary Depression Scale for Schizophrenia (CDSS). Schizophrenic inpatients consecutively admitted at the Eginition Hospital, University of Athens, were included in the study. Patients were assessed on admission using the CDSS, the Hamilton Depression Rating Scale (HDRS), the Positive and Negative Syndrome Scale (PANSS), the Rating Scale for Extrapyramidal Side Effects (RSESE), the Rating Scale for Drug-Induced Akathisia (RSDIA) and the Abnormal Involuntary Movement Scale (AIMS). The CDSS was found to have a high inter-rater reliability, as well as test-retest reliability or split-half reliability. The internal consistency of the CDSS was good (a=0.87). There were positive correlations between the CDSS and the HDRS, or the depression cluster of the PANSS. The mean score on the CDSS showed no significant correlations with that of the PANSS negative subscale (r=0.123); a negative but not significant correlation with that of the PANSS positive subscale (r=-0.036); a weak correlation with that of the PANSS general psychopathology subscale (r=0.218); and no significant correlations with that of the RSESE (r=0.197), the RSDIA (r=0.160) or the AIMS (r=0.031). Our results give further support to the reliability, the validity, and the specificity of the CDSS.

Nutritive value of dried citrus pulp and its effect on milk yield and milk composition of lactating ewes.

In a digestibility experiment, six adult wethers of the Karagouniko breed were used to determine the nutritive value of dried citrus pulp. The rations consisted of 800 g of hay and 75, 150, 225, 300, 375, and 450 g of citrus pulp. The apparent digestibilities of the DM, OM, CP, ether extract, crude fiber, and N-free extract for dried citrus pulp were 78.6, 87.2, 52.7, 82.0, 93.2, and 83.1%, respectively. Energy content was estimated to be 1.66 Mcal of NE(L)/kg of DM. In a second experiment, 26 lactating ewes of the Karagouniko breed were used to study the nutrient utilization of dried citrus pulp for milk yield when citrus pulp was used as a replacement for cereal grains. The ewes were divided into two groups immediately postweaning and fed daily 700 g of alfalfa hay, 300 g of wheat straw, and 580 or 550 g of concentrates with or without 30% citrus pulp, respectively. The inclusion of citrus pulp in rations for ewes had no significant effect on milk yield and composition but decreased the C4 to C10 fatty acids. Citrus pulp is a valuable, high energy by-product that can partly replace cereal grains in sheep rations without adverse effect on milk yield or composition.