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 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'.

Higher than recommended dosages of antipsychotics in male patients with schizophrenia are associated with increased depression but no major neurocognitive side effects: Results of a cross-sectional pilot naturalistic study.

INTRODUCTION: The current small pilot naturalistic cross-sectional study assesses whether higher dosages of antipsychotics are related to a satisfactory outcome concerning symptoms of schizophrenia but also to a worse outcome in terms of adverse events and neurocognitive function. MATERIAL AND METHODS: 41 male stabilized hospitalized schizophrenic patients were assessed by PANSS, Calgary Depression Rating Scale, UKU and Simpson-Angus Scale and a battery of neurocognitive tests. Medication and dosage was prescribed according to clinical judgement of the therapist. RESULTS: Clinical variables and adverse events did not differ between patients in the recommended vs high dosage groups. Higher dosage correlated with depressive symptoms but there was no correlation with neurocognitive measures except for impaired concentration. DISCUSSION: Results suggest that it is possible to achieve a good clinical response in refractory patients by exceeding recommended antipsychotic dosages at the price of depression and possible mild isolated concentration deficits but not other neurocognitive or extrapyramidal adverse events. Currently clinicians prefer first-generation antipsychotics when high dosages are prescribed, but considering the more favorable adverse effects profile of newer agents, it is important to study higher dosages of these agents and to test whether they should be preferably given when high dosages are necessary.

Could PANSS be a useful tool in the determining of the stages of schizophrenia? A clinically operational approach.

Staging in schizophrenia might be an important approach for the better treatment and rehabilitation of patients. The purpose of this study was to empirically devise a staging approach in a sample of stabilized patients with schizophrenia. One hundred and seventy patients aged ≥18 years (mean = 40.7, SD = 11.6) diagnosed by DSM-5 criteria were evaluated with the Positive and Negative Syndrome Scale (PANSS). Principal components analysis (PCA) with varimax rotation was used. The model was examined in the total sample and separately across a hypothesized stage of illness based on three age groups and between the two sexes. The PCA revealed a six factor structure for the total sample: 1) Negative, 2) Positive, 3) Depression and anxiety, 4) Excitement and Hostility, 5) Neurocognition and 6) Disorganization. The separate PCAs by stage of illness and sex revealed different patterns and quality of symptomatology. The Negative and Positive factors were stable across all examined groups. The models corresponding to different stages differed mainly in terms of neurocognition and disorganization and their interplay. Catatonic features appear more prominent in males while in females neurocognition takes two forms; one with disorganization and one with stereotype thinking with delusions. This study suggests that the three arbitrary defined stages of illness (on the basis of age) seem to reflect a progress from a preserved insight and more coherent mental functioning to disorganization and eventually neurocognitive impairment. Sexes differ in terms of the relationship of psychotic features with neurocognition. These results might have significant research and clinical implications.

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.

Is antiepileptic-induced suicidality a data-based class effect or an exaggeration? A comment on the literature.

A few years ago the Food and Drug Administration, based on a meta-analysis, issued a warning stating that antiepileptic drugs (AEDs) are associated with an increased risk of suicidal ideation, suicide attempts, and completed suicide. This warning generated significant concern about the use of AEDs, especially in patients with epilepsy and affective disorders. Following the FDA report, several studies addressed this issue but only served to generate further concern and confusion. There seems to be no convincing data concerning a "class effect" of AEDs in inducing any type of suicide-related behaviors. Some data suggest a possible association of lamotrigine, levetiracetam, and topiramate with suicidality, but further research is needed. In any case, clinicians need to carefully assess suicidality in all patients treated with AEDs and inform them and their families on the possible increased risk of suicidality, though preferably in a way that keeps open the continuing use of AEDs.

Standardization of the TEMPS-A in the Greek general population.

BACKGROUND: The current study evaluates the reliability and factor-structure replicability of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A) in its Greek Version. METHODS: The TEMPS-A was administered to a convenient sample of 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 analysis included the calculation of Chronbach's alpha, the calculation of the threshold to define dominant temperaments (+2 standard deviations or 95th percentile), confirmatory factor analysis and the calculation of Pearson correlation coefficients between the temperament scales scores. Analysis of Covariance with age as covariate and post-hoc t-test was used to search for differences in temperament scores between males and females. Also a table of percentile values corresponding to a raw score was created. RESULTS: Internal consistency was excellent for the various temperaments (0.72-0.88). The factor analysis confirmed the five factor solution as the best factor solution. All TEMPS items were included in the final version of the scale in the Greek language. LIMITATIONS: The study sample included subjects from the general population, but it is a convenient and not representative sample. Although the authors tried to select them on the basis of being mentally healthy and without a psychiatric history, there is always a degree of uncertainty. There is also always the possibility some of them to manifest a mental disorder in the future, thus being currently in a premorbid state. CONCLUSION: The Greek version of the TEMPS-A, has good internal consistency and factor structure similar to what was found in other translations. Overall our results are in accord with the literature and in line with theoretical considerations as well as with empirical evidence.

Burning issues in the meta-analysis of pharmaceutical trials for depression.

During the last decade a number of meta-analytic studies have been published and they triggered a debate on the true clinical usefulness of antidepressants. The current article comments on problems within the randomized controlled trials design, the study samples, the psychometric scales, the methods of meta-analysis, the interpretation of the results, and the reporting of conflicts of interest. Although the meta-analyses published so far agree that medication works in severe depression, they question its efficacy in mild cases. However, several methodological issues should be clarified before conclusions are definite. Different methods give different results and similar results seem to entertain a variety of interpretations. In the future it is important to address all of these problems, and to improve methodology on the basis of clinically informed choices. Otherwise, meta-analysis risks alienation from clinical reality and thus risks becoming the 21(st) century psychoanalysis.

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.

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.

Star-crossed? The association of the 5-HTTLPR s allele with season of birth in a healthy female population, and possible consequences for temperament, depression and suicide.

BACKGROUND: Birth season has well-known effects on neuropsychiatric disorders, and may also influence genotype distribution by possibly influencing chance of conception via parental idiosyncratic conception patterns or survival of foetuses or infants. The 5-HTTLPR is associated with phenomena including affective temperaments or suicide which are also associated with birth season. Our aim was to investigate the association of 5-HTTLPR genotype and birth season in a healthy female population. METHODS: Birth date and 5-HTTLPR genotype was determined for 327 psychiatrically healthy women. The association between presence of s allele and time of birth was analysed using generalized linear models. RESULTS: A significant association between s allele frequency and time of birth was detected. S allele carrier frequency was marginally significantly higher in July borns and significantly lower in autumn borns. LIMITATIONS: We investigated an adult sample so genotype frequency data do not reflect birth frequencies. Our sample consisted exclusively of females. CONCLUSIONS: There is no clear explanation for the observed association, although idiosyncratic parental conception patterns, the association of 5-HTTLPR with sudden infant/intrauterine death, or other s allele-mediated behaviours may play a role. Our results are strikingly parallel with earlier data reporting a higher risk of completed suicide in July borns, and higher scores of July borns and lower scores of autumn borns on certain affective temperament scales, both of which are also associated with the s allele of 5-HTTLPR. Thus our results may add to the growing body of evidence regarding the etiological background of affective disorders.

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

BACKGROUND: Suicide and suicide attempts are significant and costly public health problems. In order to prevent suicidal and other self-injurious behaviors, 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 items describing suicide-related behavior itself rather than strongly related clinical features on the basis of a general population study. METHODS: 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. RESULTS: 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. LIMITATION: The findings need replication in clinical and epidemiologic studies. CONCLUSION: 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.