[Neurological soft signs in schizophrenia: correlations with age, sex, educational status and psychopathology].

Though the pathobiology of schizophrenia can be examined in multiple levels, the organic notion of brain disease suggests that neurological features will be present. One straightforward, inexpensive method of investigating brain dysfunction in schizophrenia is thought the bedside assessment of neurological abnormalities with a standard neurological examination. Neurological abnormalities are traditionally classified as "hard signs" (impairments in basic motor, sensory, and reflex behaviors, which do not appear to be affected in schizophrenia) and "soft signs", which refer to more complex phenomena such as abnormalities in motor control, integrative sensory function, sensorimotor integration, and cerebral laterality. Additionally, neurological soft signs (NSS) are minor motor and sensory abnormalities that are considered to be normal in the course of early development but abnormal when elicited in later life or persist beyond childhood. Soft signs also, have no definitive localizing significance but are indicative of subtle brain dysfunction. Most authors believe that they are a reflection not only of deficient integration between the sensory and motor systems, but also of dysfunctional neuronal circuits linking subcortical brain structures such as the basal ganglia, the brain stem, and the limbic system. Throughout the last four decades, studies have consistently shown that NSS are more frequently present in patients with schizophrenia than in normal subjects and non-psychotic psychiatric patients. However, the functional relevance of NSS remains unclear and their specificity has often been challenged, even though there is indication for a relative specificity with regard to diagnosis, or symptomatology. Many studies have considered soft signs as categorical variables thus hampering the evaluation of fluctuation with symptomatology and/or treatment, whereas other studies included insufficient number of assessed signs, or lacked a comprehensive assessment of extrapyramidal symptomatology. Factors such as sex, age or family history of schizophrenia, are said to influence the performance of neurological examination, whereas relative few studies have provided longitudinal follow-up data on neurological soft signs in a sufficient number of patients, in order to address a possible deterioration of neurological functions. Finally, one additional difficulty when analyzing the NSS literature lies in the diversity of symptoms that are evaluated in the studies and/or non-standardized procedures or scoring. We will review some basic issues concerning recurrent difficulties in the measurement and definition of soft signs, as well as controversies on the significance of these signs with respect to clinical subtyping of schizophrenia, and social and demographic variables.

Status epilepticus in a patient treated with olanzapine and mirtazapine.

OBJECTIVE: Few cases of seizures associated with olanzapine therapy and even fewer with mirtazapine have been published, most of them in patients with confounding risk factors. Our objective was to report a case of Status epilepticus in a patient receiving olanzapine and mirtazapine, with no previous history of seizure and no confirmed underlying cause for seizure. CASE SUMMARY: A 48-year-old white, psychotic woman developed generalized tonic-clonic seizures that progressed to Status epilepticus during hospitalization. 4 days before the incident, mirtazapine (30 mg) was added to the treatment, while 2 days before the incident, the treatment switched from quetiapine to olanzapine, and mirtazapine was increased to 60 mg. No other toxic, metabolic, electrolyte or anatomic abnormality was identified. After discontinuation of olanzapine, the patient remained seizure-free. CONCLUSION: To our knowledge, this is the second reported case of Status epilepticus that has been associated with the use of olanzapine, while only one report of seizures, but none of Status epilepticus connected to mirtazapine is found in the literature. Although olanzapine has infrequently been associated with epileptogenic risk, it should be used cautiously especially when concomitant medication or other predisposing factors exist.

[Renal failure: Biological and Psychosocial consequences].

One of the most challenging patient groups that the psychiatrist of consultation-liaison psychiatry is called to work with, are the patients with Renal Failure, since this disease is related to complicated and multidimensional physical and psychosocial problems. In this review, a holistic approach is attempted, considering the biological, psychological and psychosocial factors related to the disease and to specific therapeutical programs as well. The interaction of these factors and their impact not only on the course of the disease, but also on the quality of life are discussed. Finally, a brief report on psychosocial and pharmaceutical interventions indicated for this group of patients is made, especially concerning the psychological and psychosocial consequences of renal failure.

Functional outcome in bipolar disorder: the role of clinical and cognitive factors.

INTRODUCTION: Few studies have examined the clinical, neuropsychological and pharmacological factors involved in the functional outcome of bipolar disorder despite the gap between clinical and functional recovery. METHODS: A sample of 77 euthymic bipolar patients were included in the study. Using an a priori definition of low versus good functional outcome, based on the psychosocial items of the Global Assessment of Functioning (GAF, DSM-IV), and taking also into account their occupational adaptation, the patients were divided into two groups: good or low occupational functioning. Patients with high (n = 46) and low (n = 31) functioning were compared on several clinical, neuropsychological and pharmacological variables and the two patient groups were contrasted with healthy controls (n = 35) on cognitive performance. RESULTS: High- and low-functioning groups did not differ with respect to clinical variables. However, bipolar patients in general showed poorer cognitive performance than healthy controls. This was most evident in low-functioning patients and in particular on verbal memory and executive function measures. CONCLUSIONS: Low-functioning patients were cognitively more impaired than highly functioning patients on verbal recall and executive functions. The variable that best predicted psychosocial functioning in bipolar patients was verbal memory.

Is it possible to predict the long-term response to venlafaxine with the use of biological markers and psychophysiological methods?

INTRODUCTION: The present study investigated whether it is possible to predict the medium term response to venlafaxine using biological markers and psychophysiological methods. MATERIAL: Fourteen (14) patients aged 21-60 years suffering from Major Depression according to DSM-IV were included in the study. METHODS: The SCAN v 2.0 and the IPDE were used to assist clinical diagnosis. Patients were investigated with electrooculogram (EOG), Pattern-Reversal Visual Evoked Potentials (PR-VEPs), Dexamethasone Suppression Test (DST), D-fenfluramine Challenge Test, and brain Single Photon Emission Tomography (SPECT). Venlafaxine 150-225 mg per os daily was administered. The follow-up period was 2 years. STATISTICAL ANALYSIS: Chi-square test and ANOVA were used for the analysis of data. RESULTS: There was a lower left globus pallidus regional cerebral blood flow in patients with better response. On the contrary, chronic patients were closer to normality. DISCUSSION: The results of the current study provide preliminary evidence concerning our ability to predict response to venlafaxine and to understand its way of action.

Beneficial effect of long-acting injectable risperidone on the neurocognitive deficit of a schizophrenic patient: A case report.

We report the case of a 37-year-old female patient suffering from schizophrenia, disorganized type. Adherence to treatment was always a major problem. During the last 2 years the patient was disorganized and was refusing treatment. Since the patient was already receiving a very high (double) dose per os, it was decided to administer two 50 ml ampoules of long-acting, injectable risperidone plus 5 mg of haloperidol per os daily. After 80 days of treatment, all positive, negative and even neurocognitive symptoms improved markedly. Extrapyramidal side effects did not appear at any stage of treatment. The most impressive neurocognitive improvement concerned the clock drawing test, which was in parallel with her improvement in both the positive and negative symptoms of the PANSS.

Treatment guidelines for bipolar disorder: a critical review.

INTRODUCTION: The development of treatment guidelines emerged as an important element so as to standardize treatment and to provide clinicians with algorithms, which would be able to carry research findings to the everyday clinical practice. MATERIAL AND METHOD: The MEDLINE was searched with the combination of each one of the key words 'mania', 'manic', 'bipolar', 'manic-depression', 'manic-depressive' with 'treatment guidelines'. RESULTS: The search was updated until March 1st, 2004 and returned 224 articles. Twenty-seven papers concerning the publication of treatment algorithms were traced. DISCUSSION: Despite supposedly being evidence-based, guidelines for the treatment of bipolar disorder vary significantly across committees or working groups. Overall, however, at the first stage of the mania/hypomania algorithm, monotherapy with lithium, divalproex sodium or olanzapine is generally recommended. At latter stages combination therapy is strongly recommended. It is clearly stated that in bipolar depression antidepressants should be used only in combination with antimanic agents in order to avoid switching of phases. During the maintenance phase all patients should receive antimanic agents, while some may need the addition of antidepressants. The most recent guidelines emphasize the use of atypical antipsychotics for mania and lamotrigine for depression. The main problem with guidelines is that they are rapidly outdated and that the evidence base relies mainly on registration monotherapy trials that hardly reflect treatment in routine clinical conditions. CONCLUSION: Treatment guidelines may be useful to avoid non-evidence-based treatment decisions, but they are quickly out-of-date and may not fully apply to the clinical setting. The more recent guidelines point the value of atypical antipsychotics, lithium, and valproate in the treatment of mania; the role of lithium, lamotrigine, and olanzapine as options for maintenance therapy; and the scarcity of options for the treatment of bipolar depression. Psychoeducation is also supported by most guidelines as an adjunctive treatment.

Relationship among Dexamethasone Suppression Test, personality disorders and stressful life events in clinical subtypes of major depression: An exploratory study.

: BACKGROUND: The present study aimed to investigate the relationship between dexamethasone suppression test, personality disorder, stressful life events and depression. MATERIAL: Fifty patients (15 males and 35 females) aged 41.0 +/- 11.4 years, suffering from Major Depression according to DSM-IV criteria entered the study. METHOD: Diagnosis was obtained with the aid of the SCAN v 2.0 and the IPDE. Psychometric assessment included the HDRS, HAS, the Newcastle Scale (version 1965 and 1971), the Diagnostic Melancholia Scale, the Personality Deviance Scale and the GAF scale. The 1 mg DST was used. STATISTICAL ANALYSIS: Included MANOVA, ANOVA with LSD post hoc test and chi-square test. RESULTS: Sixteen (32%) patients were non-suppressors. Eight patients without Personality Disorder (PD) (23.5%), and 5 of those with PD of cluster B (50%) were non-suppressors. Atypical patients were the subtype with the highest rate of non-suppression (42.85%). No difference between suppressors and non-suppressors was detected in any of the scales. DISCUSSION: The results of the current study suggest that pathological DST is not a core feature of major depression. They also suggest that there are more than one subtypes of depression, concerning the response to stress. It seems that the majority of depressed patients (50%) does not experience high levels of stress either in terms of self reported experience or neuroendocrine function. The rest of patients however, either experience high levels of stress, or manifest its somatic analogue (DST non-suppression) or have a very low threshold of stress tolerance, which makes them to behave in a hostile way.

Remission rates with venlafaxine extended release in Greek outpatients with generalized anxiety disorder. A double-blind, randomized, placebo controlled study.

The primary endpoints in this study were the remission rates [final Hamilton Rating Scale for Anxiety (HAM-A) total score < or =7] and reduction from baseline in the HAM-A total score in patients with generalized anxiety disorder (GAD) and no associated depression. Patients with GAD (DSM-IV and HAM-A total score >18) were randomly assigned to treatment with venlafaxine XR or placebo for 8 weeks. A 1-week placebo run-in period preceded the double-blind phase. Patients with a >20% drop in their total HAM-A score during the run-in period, were excluded from the double-blind phase. All patients started therapy with 75 mg/day venlafaxine XR or matched placebo. Patients with less than 30% decrease in their HAM-A total score at the end of the second week, doubled their dose. Patients on the 150 mg/day dose underwent a 1-week taper period. Of the 24 patients in the venlafaxine XR group, 62.5% achieved remission versus 9.1% in the placebo group (P=0.0006). The mean decrease from baseline in HAM-A total score was 19.2 points for the venlafaxine XR group and 10.8 points for the placebo group (P<0.001). Eleven placebo-treated patients and seven venlafaxine XR treated patients doubled their dose at the end of the second week of double-blind treatment. No patient interrupted therapy because of side-effects. No changes in systolic or diastolic blood pressure were observed. Venlafaxine XR 75-150 mg/day was well tolerated. The remission rates achieved with venlafaxine 75-150 mg/day in non-depressed GAD patients were high with good tolerability.

The relationship between job stress, burnout and clinical depression.

The definition and phenomenological features of 'burnout' and its eventual relationship with depression and other clinical conditions are reviewed. Work is an indispensable way to make a decent and meaningful way of living, but can also be a source of stress for a variety of reasons. Feelings of inadequate control over one's work, frustrated hopes and expectations and the feeling of losing of life's meaning, seem to be independent causes of burnout, a term that describes a condition of professional exhaustion. It is not synonymous with 'job stress', 'fatigue', 'alienation' or 'depression'. Burnout is more common than generally believed and may affect every aspect of the individual's functioning, have a deleterious effect on interpersonal and family relationships and lead to a negative attitude towards life in general. Empirical research suggests that burnout and depression are separate entities, although they may share several 'qualitative' characteristics, especially in the more severe forms of burnout, and in vulnerable individuals, low levels of satisfaction derived from their everyday work. These final issues need further clarification and should be the focus of future clinical research.

Reliability, validity and psychometric properties of the Greek translation of the Major Depression Inventory.

BACKGROUND: The Major Depression Inventory (MDI) is a brief self-rating scale for the assessment of depression. It is reported to be valid because it is based on the universe of symptoms of DSM-IV and ICD-10 depression. The aim of the current preliminary study was to assess the reliability, validity and psychometric properties of the Greek translation of the MDI. METHODS: 30 depressed patients of mean age 23.41 (+/- 5.77) years, and 68 controls patients of mean age 25.08 (+/- 11.42) years, entered the study. In 18 of them, the instrument was re-applied 1-2 days later and the Translation and Back Translation made. Clinical diagnosis was reached with the use of the SCAN v.2.0 and the International Personality Disorders Examination (IPDE). The Center for Epidemiological Studies-Depression (CES-D) and the Zung Depression Rating Scale (ZDRS) were applied for cross-validation purposes. Statistical analysis included ANOVA, the Spearman Product Moment Correlation Coefficient, Principal Components Analysis and the calculation of Cronbach's alpha. RESULTS: Sensitivity and specificity were 0.86 and 0.94, respectively, at 26/27. Cronbach's alpha for the total scale was equal to 0.89. The Spearman's rho between MDI and CES-D was 0.86 and between MDI and ZDRS was 0.76. The factor analysis revealed two factors but the first accounted for 54% of variance while the second only for 9%. The test-retest reliability was excellent (Spearman's rho between 0.53 and 0.96 for individual items and 0.89 for total score). CONCLUSION: The current study provided preliminary evidence concerning the reliability and validity of the Greek translation of the MDI. Its properties are similar to those reported in the international literature, but further research is necessary.

Reliability and cultural applicability of the Greek version of the International Personality Disorders Examination.

BACKGROUND: The International Personality Disorders Examination (IPDE) constitutes the proposal of the WHO for the reliable diagnosis of personality disorders (PD). The IPDE assesses pathological personality and is compatible both with DSM-IV and ICD-10 diagnosis. However it is important to test the reliability and cultural applicability of different IPDE translations. METHODS: Thirty-one patients (12 male and 19 female) aged 35.25 +/- 11.08 years, took part in the study. Three examiners applied the interview (23 interviews of two and 8 interviews of 3 examiners, that is 47 pairs of interviews and 70 single interviews). The phi coefficient was used to test categorical diagnosis agreement and the Pearson Product Moment correlation coefficient to test agreement concerning the number of criteria met. RESULTS: Translation and back-translation did not reveal specific problems. Results suggested that reliability of the Greek translation is good. However, socio-cultural factors (family coherence, work environment etc) could affect the application of some of the IPDE items in Greece. The diagnosis of any PD was highly reliable with phi >0.92. However, diagnosis of non-specific PD was not reliable at all (phi close to 0) suggesting that this is a true residual category. Diagnosis of specific PDs were highly reliable with the exception of schizoid PD. Diagnosis of antisocial and Borderline PDs were perfectly reliable with phi equal to 1.00. CONCLUSIONS: The Greek translation of the IPDE is a reliable instrument for the assessment of personality disorder but cultural variation may limit its applicability in international comparisons.

Morning and evening plasma melatonin and dexamethasone suppression test in patients with nonseasonal major depressive disorder from northern Greece (latitude 40-41.5 degrees ).

INTRODUCTION: The present study aimed to search for correlations between melatonin (MT) levels and the dexamethasone suppression test (DST) and clinical variables. METHODS: Fifty depressed patients aged 21-60 years took part in the study. The Schedules for Clinical Assessment in Neuropsychiatry, version 2.0, and the International Personality Disorders Examination were used for diagnosis. Psychometric assessment included the Hamilton Depression Rating Scale, the Hamilton Anxiety Scale, the General Assessment of Funtioning Scale, the Newcastle scales and the Diagnostic Melancholia Scale. The DST and 9.00 and 23.00 h MT values were assessed. Statistical analysis included Student's t test, Pearson product moment correlation coefficient and forward stepwise multiple linear regression analysis. RESULTS: Melancholic patients had lower 23.00 h MT values in comparison to the rest of the patients and the atypical and 'undifferentiated' patients. CONCLUSION: The current study shows that low MT values were closely related to melancholic depression. Distinct quality of mood, psychomotor agitation or retardation and anorexia or weight loss seemed to be responsible for this relationship.

Reliability, validity and psychometric properties of the Greek translation of the Center for Epidemiological Studies-Depression (CES-D) Scale.

INTRODUCTION: The aim of the current study was to assess the reliability, validity and psychometric properties of the Greek translation of the Center for Epidemiological Studies- Depression Scale (CES-D). METHODS: 40 depressed patients 29.65 +/- 9.38 years old, and 120 normal controls 27.23 +/- 10.62 years old entered the study. In 20 of them (12 patients and 8 controls) the instrument was re-applied 1-2 days later. Translation and Back Translation was made. Clinical Diagnosis was reached by consensus of two examiners with the use of the SCAN v.2.0 and the IPDE. Statistical Analysis included ANOVA, the Pearson Product Moment Correlation Coefficient, Principal Components Analysis and Discriminant Function Analysis and the calculation of Cronbach's alpha (alpha) RESULTS: Both Sensitivity and specificity exceed 90.00 at 23/24, Chronbach's alpha for the total scale was equal to 0.95. Factor analysis revealed three factors (positive affect, irritability and interpersonal relationships, depressed affect and somatic complains). The test-retest reliability was satisfactory (Pearson's R between 0.45 and 0.95 for individual items and 0.71 for total score). CONCLUSION: The Greek translation of the CES-D scale is both reliable and valid and is suitable for clinical and research use with satisfactory properties. Its properties are similar to those reported in the international literature. However one should always have in mind the limitations inherent in the use of self-report scales.