A case-control study of paternal and maternal age as risk factors in mood disorders.

Objective: Advanced parental age might constitute a risk factor for various disorders. We tested whether this concerns also mood disorder patients. Methods: The study included 314 subjects (42 bipolar-BD patients; 21 manics and 21 depressives, 68 unipolar-UD, and 204 normal controls-NC). Analysis of Covariance (ANCOVA) and the calculation of the Relative Risk (RR) and the Odds Ratio (OR) were used for the analysis. Results: Paternal age differed between NC and UD patients (29.42 ± 6.07 vs. 32.12 ± 5.54; p = .01) and manics (29.42 ± 6.07 vs. 35.00 ± 5.75; p = .001) and maternal age between NC and manics (25.46 ± 4.52 vs. 31.43 ± 4.75; p < .001) and manic and UD (31.43 ± 4.75 vs. 26.75 ± 6.03; p = .002). The RR and OR values suggested that advanced parental age constitutes a risk factor for the development of mood disorders. Conclusions: In a non-dose dependent and gender-independent, advanced parental age constitutes a risk factor for the development of BD with index episode of mania (probably manic predominant polarity); only advanced paternal age constitutes a risk factor for the development of UD and BD with index episode of depression (probably depressive predominant polarity). This is the first study suggesting differential effect of advanced parental age depending on predominant polarity of BD.

Paternal and maternal age as risk factors for schizophrenia: a case-control study.

OBJECTIVE: Advanced parental age might constitute a generic risk factor for mental and somatic disorders. The current study tested whether this concerns also patients with schizophrenia. METHODS: A total of 231 schizophrenic, 56 other severe mental disorders patients and 204 controls were diagnosed according to DSM-IV-TR. Data were tested with ANOVA models including relative risk and odds ratios. RESULTS: Patients with schizophrenia manifested higher paternal (32.55 ± 6.35 vs. 29.42 ± 6.07, p < .001) and maternal age (27.66 ± 5.57 vs. 25.46 ± 4.52, p < .001). Patients with other mental disorders had higher paternal (33.29 ± 8.35; p = .001) but not maternal age (26.69 ± 5.89; p = .296) compared to controls. There was no difference between the two patient groups concerning either paternal or maternal age (p > .05). There seems to be a higher risk for the development of schizophrenia in offspring with paternal age above 25 years and maternal age above 22 years at delivery. CONCLUSIONS: The current study provides further support for the suggestion that advanced paternal age constitutes a risk factor (in a non-dose dependent and gender-independent way) for the development of schizophrenia but also for other mental disorders. In contrast, advanced maternal age characterises schizophrenia specifically. The higher risk is evident after 25 years of paternal and 22 years of maternal age, respectively.

Mood Symptoms in Stabilized Patients with Schizophrenia: A Bipolar Type with Predominant Psychotic Features?

BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) are traditionally distinguished on the basis of progressive deterioration and long-term outcome, but a more dimensional approach is warranted. There are limited data on the occurrence of manic symptoms in patients with schizophrenia. The aim of the current study was to search for patterns in the clinical symptomatology, which may suggest the presence of one or several mood disorders under the label of schizophrenia. SUBJECTS AND METHODS: Hundred-seventy-five patients diagnosed with schizophrenia according to DSM-5 were included in the study. The psychometric assessment included the Positive and Negative Syndrome Scale, Young Mania Rating Scale, The Montgomery-Åsberg Depression Rating Scale and the Calgary Depression Scale. The statistical analysis included MANOVA, Pearson Correlation coefficient and principal components analysis. RESULTS: Significant subthreshold manic symptoms were present in 25.14% of patients. Mood symptoms correlated with positive symptoms. The PCA revealed a complex structure with 15 factors (one positive, negative, somatic, anxiety, neurocognitive, disorganization and manic, five depressive and three psychomotor/excitement/hostility/violence). CONCLUSION: Psychotic mood disorders are often phenotypically indistinguishable from schizophrenia, so it is likely that psychotic affective patients have been misdiagnosed with schizophrenia. The current study suggests that there seem to be patients with mania misdiagnosed as 'schizophrenics' because of the presence of psychotic features, a condition better described as 'schizophreniform bipolar disorder'.

Standardization and normative data of the Greek version of the temperament and character inventory (TCI).

BACKGROUND: Robert Cloninger's psychobiological model of temperament and character is a dimensional approach to personality assessment and gave birth to the temperament and character inventory (TCI). The aim of the present report is to examine the psychometric properties of the Greek version of the TCI, and to replicate its postulated structure and provide preliminary normative data for the Greek population. METHODS: The study sample included 734 subjects from the general Greek population (436 females; 59.4 % and 298 males; 40.6 %). Their mean age was 40.80 ± 11.48 years (range 25-67 years). The mean age for females was 39.43 ± 10.87 years (range 25-65 years), while the mean age for males was 42.82 ± 12.06 years (range 25-67 years). Descriptive statistics tables concerning age, gender and occupational status distribution in the sample were created. The analysis included the calculation of Cronbach's alpha, factor analysis with promax rotation and the calculation of Pearson correlation coefficients between the subscales scores. Analysis of Covariance with age as covariate and t test and Cohen's d as post hoc tests was used to search for differences in subscales scores between males and females. RESULTS: The overall psychometric properties of the Greek version of the TCI proved to be satisfactory, with acceptable consistencies of the subscales. The factor analysis of temperament identified four factors which together explained 58.56 % of total variance, while the factor analysis of the three-factor solution of the character explained 52.24 % of total variance. The TCI scales correlate significantly but weakly between each other and with age. DISCUSSION: The Greek version of the TCI exhibits psychometric properties similar to its original English counterpart and to other national translations and it is suitable for use in research and clinical practice.

Standardization of the NEO-PI-3 in the Greek general population.

BACKGROUND: The revised NEO Personality Inventory (NEO-PI-3) includes 240 items corresponding to the Big Five personality traits (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness to Experience) and subordinate dimensions (facets). It is suitable for use with adolescents and adults (12 years or older). The aim of the current study was to validate the Greek translation of the NEO-PI-3 in the general Greek population. MATERIAL AND METHODS: The study sample included 734 subjects from the general Greek population of whom 59.4% were females and 40.6% males aged 40.80 ± 11.48. The NEO-PI-3 was translated into Greek and back-translated into English, and the accuracy of the translation was confirmed and established. The statistical analysis included descriptive statistics, confirmatory factorial analysis (CFA), the calculation of Cronbach's alpha, and the calculation of Pearson product-moment correlations. Sociodemographics groups were compared by ANOVA. RESULTS: Most facets had Cronbach's alpha above 0.60. Confirmatory factor analysis showed acceptable loading of the facets on their own hypothesized factors and very good estimations of Cronbach's alphas for the hypothesized factors, so it was partially supportive of the five-factor structure of the NEO-PI-3.The factors extracted with Procrustes rotation analysis can be considered reasonably homologous to the factors of the American normative sample. Correlations between dimensions were as expected and similar to those reported in the literature. DISCUSSION: The literature suggests that overall, the psychometric properties of NEO-PI-3 scales have been found to generalize across ages, cultures, and methods of measurement. In accord with this, the results of the current study confirm the reliability of the Greek translation and adaptation of the NEO-PI-3. The inventory has comparable psychometric properties in its Greek version in comparison to the original and other national translations, and it is suitable for clinical as well as research use.

A systematic review on the role of anticonvulsants in the treatment of acute bipolar depression.

Despite the high morbidity and mortality associated with bipolar depression, the optimal treatment for this phase is still a matter of debate. The aim of the current review was to provide updated evidence about the efficacy and tolerability of anticonvulsants in the treatment of acute bipolar depression. A comprehensive review of randomized controlled trials (RCTs) evaluating the use of anticonvulsants for the treatment of acute bipolar depression up to June 2011 was conducted by means of the PubMed-Medline database. Eligibility criteria included active comparator-controlled or placebo-controlled randomized studies involving monotherapy or combination therapy. A total of 18 RCTs fulfilled the inclusion criteria. Studies supported the efficacy of divalproex as monotherapy in acute bipolar depression but small sample size was a common methodological limitation. Findings were inconclusive for lamotrigine and carbamazepine although overall lamotrigine may have a beneficial but modest effect. Negative results were found for levetiracetam and gabapentin but the evidence base on these agents is scant. All anticonvulsants were generally well tolerated. No double-blind RCTs were found for the use of other anticonvulsants such as oxcarbazepine, licarbazepine, zonisamide, retigabine, pregabalin, tiagabine, felbamate and vigabatrine in the acute treatment of bipolar depression. To sum up, taking into consideration the efficacy and tolerability profiles of anticonvulsants, current evidence supports the use of divalproex and lamotrigine in the treatment of acute bipolar depression. However, available data for most other anticonvulsants are inconclusive and further RCTs with larger sample sizes are needed before drawing firm conclusions.

Trends in suicidality amid the economic crisis in Greece.

For the decade 2000-2010, suicidal rates appear to be both low and stable in Greece and unrelated to the socioeconomic environment. It is highly possible that the recent crisis caused a significant increase in dysphoria, stress, depression and maybe suicidal ideation in the general population, but completed suicides do not seem to have increased so far. Measures are needed to make sure there will be no increase in completed suicides in the near future, since historically, periods of socioeconomic instability might be related to increased suicidality. Community interventions reduce stigma and enhance help-seeking. However, only those including the creation of social support networks are essential in the fight against suicidality.

No role for initial severity on the efficacy of antidepressants: results of a multi-meta-analysis.

INTRODUCTION: During the last decade, a number of meta-analyses questioned the clinically relevant efficacy of antidepressants. Part of the debate concerned the method used in each of these meta-analyses as well as the quality of the data set. MATERIALS AND METHODS: The Kirsch data set was analysed with a number of different methods, and eight key questions were tackled. We fit random effects models in both Bayesian and frequentist statistical frameworks using raw mean difference and standardised mean difference scales. We also compare between-study heterogeneity estimates and produce treatment rank probabilities for all antidepressants. The role of the initial severity is further examined using meta-regression methods. RESULTS: The results suggest that antidepressants have a standardised effect size equal to 0.34 which is lower but comparable to the effect of antipsychotics in schizophrenia and acute mania. The raw HDRS difference from placebo is 2.82 with the value of 3 included in the confidence interval (2.21-3.44). No role of initial severity was found after partially controlling for the effect of structural (mathematical) coupling. Although data are not definite, even after controlling for baseline severity, there is a strong possibility that venlafaxine is superior to fluoxetine, with the other two agents positioned in the middle. The decrease in the difference between the agent and placebo in more recent studies in comparison to older ones is attributed to baseline severity alone. DISCUSSION: The results reported here conclude the debate on the efficacy of antidepressants and suggest that antidepressants are clearly superior to placebo. They also suggest that baseline severity cannot be utilized to dictate whether the treatment should include medication or not. Suggestions like this, proposed by guidelines or institutions (e.g. the NICE), should be considered mistaken.

Treatment of mixed bipolar states.

Mixed bipolar states are associated with more severe symptoms and outcome. Our aim is to review the literature examining their treatment. We conducted a literature search of randomized clinical studies and post-hoc analyses on mixed bipolar states' treatment. Remarkably, there is only one double-blind, placebo-controlled trial, recruiting a mixed episode cohort, and one post-hoc analysis of this trial, while most data come from post-hoc analyses of trials including both manic and mixed patients. Improvement of manic symptoms in mixed episodes is similar to that seen in pure manic episodes and independent of baseline depressive features. The magnitude of response to manic symptoms' treatment probably exceeds that of depressive symptoms, which appear to resolve later. Valproate and carbamazepine are effective in acute mixed episodes, but the efficacy of lithium appears questionable. Atypical antipsychotic monotherapy improves both manic and depressive symptoms. Mood-stabilizer-atypical antipsychotic combination increases this effect. Atypical antipsychotic-antidepressant combination against acute mixed depression does not increase the risk for mania, although its superior efficacy vs. atypical antipsychotic monotherapy cannot be supported by current data. As regards prophylaxis, atypical antipsychotic monotherapy is associated with a lower incidence of and a longer time to relapse of any kind. The augmentation of lithium or divalproex with atypical antipsychotics increases prophylactic efficacy. Lithium or divalproex monotherapy have not been associated with significant prophylactic benefits following mixed mania. New, randomized prospective trials involving homogeneous cohorts of mixed bipolar patients are needed in order to delineate the appropriate pharmacological treatment of mixed states.

Anodal transcranial direct current stimulation sustainably increases EEG alpha activity in patients with schizophrenia.

AIMS: Transcranial direct current stimulation (tDCS) applied to the prefrontal cortex has been frequently used to elicit behavioral changes in patients with schizophrenia. However, the interaction between prefrontal tDCS and electrophysiological changes remains largely uncharted. The present study aimed to investigate cortical electrophysiological changes induced by tDCS in frontal areas by means of repeated electroencephalography (EEG) in patients with schizophrenia. METHODS: In total, 20 patients with schizophrenia received 13 minutes of anodal tDCS (1 mA) applied to the left dorsolateral prefrontal cortex (DLPFC). Repeated resting EEG was recorded before (once) and following (at five follow-up time-bins) tDCS to trace post-tDCS effects. We used sLORETA for source reconstruction to preserve the localization of brain signals with a low variance and to analyze frequency changes. RESULTS: We observed significant changes after the stimulation in areas highly connected with the stimulated DLPFC areas. The alpha 1 (8.5-10.0 Hz) activity showed a highly significant, long-lasting, increase for up to 1 hour after the stimulation in the postcentral gyrus (Brodmann area 2, 3, and 40). Significant yet unstable changes were also seen in the alpha-2 frequency band precentral at 10 minutes, in the beta-1 frequency band occipital at 20 minutes, and in the beta-3 frequency band temporal at 40 minutes. CONCLUSION: We were able to show that anodal tDCS can induce stable EEG changes in patients with schizophrenia. The results underline the potential of tDCS to induce long-lasting neurophysiological changes in patients with schizophrenia showing the possibility to induce brain excitability changes in this population.

A standardized scoring method for the copy of cube test, developed to be suitable for use in psychiatric populations.

BACKGROUND: Although the 'copy of cube test', a version of which is included in the Short Test of Mental Status (STMS), has existed for years, little has been done to standardize it in detail. The aim of the current study was to develop a novel and detailed standardized method of administration and scoring this test. METHODS: The study sample included 93 healthy control subjects (53 women and 40 men) aged 35.87 ± 12.62 and 127 patients suffering from schizophrenia (54 women and 73 men) aged 34.07 ± 9.83 years. The psychometric assessment included the Positive and Negative Symptoms Scale (PANSS) the Young Mania Rating Scale (YMRS), and the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: A scoring method was developed based on the frequencies of responses of healthy controls. Cronbach's α was equal to 0.75 and inter-rater reliability was 0.90. Three indices and five subscales of the Standardized Copy of the Cube Test (SCCT) were eventually developed. They included the Deficit Index (DcI), which includes the Missing Elements (ME) Mirror Image (M) subscales, the Deformation Index (DfI) which includes the Deformation (D) and the Rotation (R) subscales and the Closing-In Index (CiI). DISCUSSION: The SCCT seems to be a reliable, valid and sensitive to change instrument for the testing of psychiatric patients. The great advantage of this instrument is the fact that it only requires paper and a pencil, and is this easily administered and brief. Further research is necessary to test its usefulness as a neuropsychological test.

The standardised copy of pentagons test.

BACKGROUND: The 'double-diamond copy' task is a simple paper and pencil test part of the Bender-Gestalt Test and the Mini Mental State Examination (MMSE). Although it is a widely used test, its method of scoring is crude and its psychometric properties are not adequately known. The aim of the present study was to develop a sensitive and reliable method of administration and scoring. METHODS: The study sample included 93 normal control subjects (53 women and 40 men) aged 35.87 ± 12.62 and 127 patients suffering from schizophrenia (54 women and 73 men) aged 34.07 ± 9.83. RESULTS: The scoring method was based on the frequencies of responses of healthy controls and proved to be relatively reliable with Cronbach's α equal to 0.61, test-retest correlation coefficient equal to 0.41 and inter-rater reliability equal to 0.52. The factor analysis produced two indices and six subscales of the Standardised Copy of Pentagons Test (SCPT). The total score as well as most of the individual items and subscales distinguished between controls and patients. The discriminant function correctly classified 63.44% of controls and 75.59% of patients. DISCUSSION: The SCPT seems to be a satisfactory, reliable and valid instrument, which is easy to administer, suitable for use in non-organic psychiatric patients and demands minimal time. Further research is necessary to test its psychometric properties and its usefulness and applications as a neuropsychological test.

Obesity and smoking in patients with schizophrenia and normal controls: a case-control study.

Cardiovascular risk factors, especially obesity and smoking are highly prevalent in patients with schizophrenia. Central obesity and the metabolic syndrome are conditions mostly attributed to the use of antipsychotic medication and lifestyle habits, and they constitute a significant health concern. Our study sample included 105 patients suffering from schizophrenia aged 36.25+/-10.03 and 156 normal control subjects aged 36.03+/-11.33. All patients were in- or out-patients of a private hospital. Clinical diagnosis was made according to DSM-IV-TR criteria. Height, weight, waist circumference and number of cigarettes smoked daily were recorded. Duration of illness was calculated based on records concerning the age of first onset of psychotic symptoms. Body Surface Area (BSA) and Body Mass Index (BMI) were calculated as well as % body fat, with the use of LifeWise Body Fat Analyzers No 63-1525. The results of analysis of variance suggested a significant main effect regarding diagnosis and sex as well as for their interaction. There were significant differences between patients and controls regarding body weight, waist circumference, BMI, BSA and % body fat, with patients, especially females, being more obese than controls. The results of the present study corroborate the increased prevalence of obesity in schizophrenia. The interpretation of this finding remains unclear.

Psychotherapeutic intervention and suicide risk reduction in bipolar disorder: a review of the evidence.

BACKGROUND: 25-50% of bipolar patients attempt suicide at least once in their lifetime and completed suicide in this population is about 1% annually, about 60 times the rate of the general population. Psychotherapy may be an effective adjunctive option in preventing suicide in bipolar patients. It has been suggested that interpersonal, cognitive and behavioural techniques may be effective in controlling mood shifts, increasing compliance with pharmacotherapy, and maintaining morale in the face of therapeutic adversity and incomplete response. The aim of our study was to systematically review the literature concerning the efficacy of psychosocial interventions in reducing the risk for attempting or committing suicide. METHODS: We searched MEDLINE with the combination of the key words 'psychotherapy' or 'psychoeducation' or 'cognitive therapy' or 'behavio(u)ral therapy', 'cognitive-behavio(u)ral' or 'family therapy' or 'social rhythm' or 'rhythm' with 'suicide' and 'bipolar', limited to English language papers published between 1990 and January 2008. Papers were selected based on the criterium that they provided definite data on the role of psychotherapy in suicide prevention, and specifically in bipolar disorder. RESULTS: Our search returned 481 references, of which 17 were selected based on the above criteria. The selected papers were classified according to the area of suicide prevention they were dealing with as 1. Psychosocial and demographic factors, 2. Psychological profile and 3. Efficacy of psychotherapies. DISCUSSION: Our paper summarizes specific features and correlates of suicide in bipolar patients and possible targets of psychosocial intervention in the prevention of suicide in bipolar patients. Although studies researching the effect of psychosocial interventions on suicidal behaviour are virtually non-existent, hard data concerning the effectiveness of psychosocial interventions in bipolar disorder are emerging, but still suffer from methodological drawbacks.

Preliminary data concerning the reliability and psychometric properties of the Greek translation of the 20-item Subjective Well-Being Under Neuroleptic Treatment Scale (SWN-20).

BACKGROUND: The 20-item Subjective Well-Being Under Neuroleptic Treatment Scale (SWN-20) is a self-report scale developed in order to assess the well-being of patients receiving antipsychotic medication independent of the improvement in their psychotic symptoms. The current study reports on the reliability and the psychometric properties of the Greek translation of the SWN-20. METHODS: A total of 100 inpatients or outpatients with schizophrenia (79 males and 21 females, aged 42.6 +/- 11.35 years old) from 3 different facilities were assessed with the Positive and Negative Symptoms Scale (PANSS), the Calgary Depression Scale and the Simpson-Angus Scale, and completed the SWN-20. The statistical analysis included the calculation of Pearson product moment correlation coefficient, the Cronbach alpha and factor analysis with Varimax normalised rotation. RESULTS: The SWN-20 had an alpha value equal to 0.79 and all the items were equal. The factor analysis revealed the presence of seven factors explaining 66% of total variance. The correlation matrix revealed a moderate relationship of the SWN-20 and its factors with the PANSS-Negative (PANSS-N), PANSS-General Psychopathology (PANSS-G), the Simpson-Angus and the Calgary scales, and no relationship to age, education and income class. DISCUSSION: The Greek translation of the SWN-20 is reliable, with psychometric properties close to the original scale.

Development of a standardized scoring method for the Graphic Sequence Test suitable for use in psychiatric populations.

Although the graphic version of the Alternating Sequences Test which was introduced by Luria exists for years little has been done to standardize it. The aim of the current study was to develop a novel and detailed standardized method of administration and scoring. The study sample included 93 normal control subjects (53 women and 40 men) aged 35.87+/-12.62 and 127 patients suffering from schizophrenia (54 women and 73 men) aged 34.07+/-9.83. The psychometric assessment included the Positive and Negative Symptoms Scale the Young Mania Rating Scale, and the Montgomery-Asberg Depression Rating Scale. A scoring method was developed and was based on the frequencies of responses of healthy controls. Cronbach alpha and test-retest and interrater reliability were very good. Two indices and 6 subscales of the Standardized Graphic Sequence Test were eventually developed. The Standardized Graphic Sequence Test seems to be a reliable, valid, and sensitive to change instrument based on Luria's graphic sequence test. The great advantage of this instrument is the fact that it is paper and pencil, easily administered and little time consuming. Further research is necessary to test its usefulness as a neuropsychologic test.

Late-life depression, religiosity, cerebrovascular disease, cognitive impairment and attitudes towards death in the elderly: interpreting the data.

Geriatric depression is considered to be a major health problem in the elderly. Passing the age, the speed of mental process is decreasing and personality obtains more mature functioning (better coping) while most of its traits remain stable. Empirical studies have shown that fear of death is most prominent during midlife and not late-life. Neuroimaging studies led to the "vascular depression" hypothesis. Depression was found to be a strong predictive factor leading to stroke, while religiosity seemed to be a 'protective' factor. A possible interpretation of these reports could consider late-life depression to be an early symptomatology of an undergoing vascular disease. Religiosity could be interpreted as absence of depression, and therefore, mainly as absence of vascular lesions. The above have profound implications in the understanding of late-life depression and to the therapeutic design, especially in the primary care setting.