Influence of birth cohort on age of onset cluster analysis in bipolar I disorder.

PURPOSE: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. METHODS: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. RESULTS: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. CONCLUSION: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.

[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.

Depression in diabetes mellitus: a comprehensive review.

Although the prevalence of a mental disorder, in general, in patients with diabetes mellitus is regarded to be comparable to the general population, an increased prevalence of depressive disorders, often comorbid with anxiety, has been reported in patients with diabetes mellitus. The co-occurrence of depression in diabetes is attributed to a variety of factors, including the psychological and psychosocial impact of the disease, a potential common genetic susceptibility and common pathophysiological abnormalities involving neuroimmunological and neuroendocrinical pathways, as well as microvascular brain lesions due to diabetes mellitus. However, issues concerning pathogenesis and causality of this high co-occurrence are not fully determined yet. Still, the presence of depression in patients with diabetes mellitus is of vast importance, as it is usually associated with poor disease control, adverse health outcomes and quality of life impairment. This article aims to provide a comprehensive review of epidemiological findings, clinical considerations and management strategies concerning depression in patients with diabetes mellitus.

[Development of the Risk Assessment Suicidality Scale (RASS): a population-based study].

Suicide and suicide attempts are significant and costly public health problems. In order to prevent suicidal and other self-injurious behavior, research on the multiple factors involved in these behaviors with comprehensive and user-friendly instruments is necessary. The aim of the current study was to construct a self-report instrument with emphasis on the items which describe suicide-related behavior itself rather than strongly related clinical features on the basis of a general population study. Twelve items comprising a new scale were applied to 734 subjects from the general population (40.6% males and 59.4% females) aged 40.8 +/- 11.5, along with the STAI and the CES-D. The scoring method was developed on the basis of frequency table of responses to the individual scale items. The factor analysis returned 3 factors explaining 59.19% of total variance (Intention, Life, and History). The Cronbach's alpha was 0.85 for the Intention, 0.69 for the Life and 0.52 for the History subscale. The RASS is a reliable and valid instrument which might prove valuable in the assessment of suicidal risk in the general population as well as in mental patients.

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.

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.

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.

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.

Difference in symptom profile between generalized anxiety disorder and anxiety secondary to hyperthyroidism.

OBJECTIVE: The differential diagnosis between subclinical hyperthyroidism and Generalized Anxiety Disorder (GAD) is often a difficult problem to solve without laboratory examination. The aim of this pilot study was to assess whether there are differences in the symptom profile between these two disorders. METHODS: Fifty patients took part in the study: Twenty-five were hyperthyroid patients, and twenty-five were GAD patients. The diagnosis was based on the TSH values and the DSM-IV criteria, respectively. The Hamilton Anxiety Scale (HAS) and the list of fifty-one symptoms produced by the detailed expansion of HAS items were used to quantify the anxiety symptomatology. The differences in the frequencies between the two diagnostic groups were calculated at each categorical response for every item of both scales. Forward Stepwise Discriminant Function Analysis was performed twice using HAS items and the fifty-one-list items. RESULTS: The symptoms of anxiety in subclinical hyperthyroidism were not identical to those of GAD. Four Hyperthyroid/Anxiety Indices (HAI I-IV) were developed. These indices reach optimum classification of patients (3 of them reach 100% sensitivity and specificity). CONCLUSION: The results of the current study suggest that it is possible to differentiate between GAD and subclinical cases of hyperthyroidism by the careful study of clinical symptomatology. This may be of particular help in isolated areas without laboratory support, but replication of the indices in other samples is indicated.

Do depressive patients with family history of dementia constitute a separate group? A case report study.

INTRODUCTION: Recently it has been suggested that patients with both depression and a family history of dementia are seven times as likely to develop Alzheimer's disease as are controls. METHOD: Fifty patients aged 21 - 60 years suffering from DSM-IV Major Depression entered the study; three of them (6%) had a positive family history of dementia. Diagnosis was by SCAN v 2.0. The family history method was used to record family history. All depressed patients were investigated with the Dexamethasone Suppression Test (DST), brain SPECT, electro-oculogram (EOG), flash-electroretinogram (f-ERG) and Pattern-Reversal Visual Evoked Potentials (PR-VEPs). Student's t-test was used to analyse the results. All patients with positive family history had atypical features. RESULTS: Two of them suffered from borderline personality disorder, in comparison to eight in the remainder of the sample and five in the rest of the atypicals. The age of onset of depression was lower. DST, SPECT, EOG and PR-VEPs findings were similar between groups. The only significant finding concerned the latency of the bs wave of the scotopic ERG (P < 0.01), but even in this, patients with positive history did not differ from the rest of the atypical patients. CONCLUSION: The present study provided limited data connecting atypical features of depression, personality traits, psychological stressors, hypercortisolaemia and family history of dementia. Further research with larger samples is essential. ( Int J Psych Clin Pract 2000; 4: 215 - 222).

Changes in pupil reaction to light in melancholic patients.

The aim of the current study was to compare the pupil reaction to light in depressed patients and normal control subjects. Seven depressed patients with melancholic features according to DSM-IV criteria and 14 age- and gender-matched control subjects took part in the study. All were free of any medication for at least 2 weeks. All were aged between 25 and 50 years. An optical method was used to assess the pupil reaction to a single flash. Depressed patients manifested shorter latency for constriction than control subjects, and a marginal difference in the total work produced by acetylcholine. The results of the current study support the theory that there is a norepinephrine hypoactivity in melancholic depression, with less affected acetylcholine activity.