Temperament and Character Inventory in Bipolar Disorder versus Healthy Controls and Modulatory Effects of 3 Key Functional Gene Variants.

BACKGROUND: Bipolar disorder (BD) has been associated with temperamental and personality traits, although the relationship is still to be fully elucidated. Several studies investigated the genetic basis of temperament and character, identifying catechol-O-methyltransferase (COMT), brain derived neurotrophic factor (BDNF), and serotonin transporter (5-HTT) gene variants as strong candidates. METHODS: In the GECO-BIP study, 125 BD patients and 173 HC were recruited. Subjects underwent to a detailed assessment and the temperament and character inventory 125 items (TCI) was administrated. Three functional genetic variants within key candidate genes (COMT rs4680, BDNF rs6265, and the serotonin-transporter-linked polymorphic region (5-HTTLPR)) were genotyped. Univariate and multivariate analyses were performed. RESULTS: Compared to HC, BD patients showed higher scores in novelty seeking (NS; p = 0.001), harm avoidance (HA; p < 0.001), and self transcendence (St; p < 0.001), and lower scores in self directness (p < 0.001) and cooperativeness (p < 0.001) TCI dimensions. Concerning the genetic analyses, COMT rs4680 was associated with NS in the total sample (p = 0.007) and in the male subsample (p = 0.022). When performing the analysis in the HC and BD samples, the association was confirmed only in HC (p = 0.012), and in the HC male subgroup in particular (p = 0.004). BDNF rs6265 was associated with St in the BD group (p = 0.017). CONCLUSION: COMT rs4680 may modulate NS in males in the general population. This effect was not detected in BD patients, probably because BD alters the neurobiological basis of some TCI dimensions. BDNF rs6265 seems to modulate St TCI dimension only in BD patients, possibly modulating the previously reported association between rs6265 and BD treatment response. Further studies are needed to confirm our findings.

Temperament and character influence on depression treatment outcome.

BACKGROUND: personality features have been repeatedly associated with depression treatment outcome in Major Depressive Disorder (MDD), however conclusive results are still lacking. Moreover, as for Bipolar Disorder (BD), results are only few and preliminary. AIM: the aim of the present study was to perform an exploratory investigation of the influence of personality traits as assessed by the Temperament and Character Inventory (TCI), on principal depression treatment outcomes (non remission, non response and resistance). METHODS: 743 mood disorders patients (455 MDD (61.24%) and 288 BD (38.76%)) were recruited in the context of 6 European studies. Generalized logit models were performed to test the effects of TCI dimensions on treatment outcomes, considering possible confounders such as age, gender and education. Positive results were controlled for comorbidities (anxiety and substance use disorders) as well. RESULTS: MDD Non-Remitters showed high Harm Avoidance (HA) and Self Transcendence (ST) (p = 0.0004, d = 0.40; p = 0.007, d = 0.36 respectively) and low Persistence (P) and Self Directedness (SD) (p = 0.05; d = 0.18; p = 0.002, d = 0.40, respectively); MDD Non-Responders showed a slightly different profile with high HA and low Reward Dependence (RD) and SD; finally, MDD Resistants showed low RD, P and Cooperativeness (C). In BD patients, only higher HA in non response was observed. LIMITATIONS: the retrospective cross-sectional design, the TCI assessment regardless of the mood state and the small number of bipolar patients represent the main limitations. CONCLUSION: specific TCI personality traits are associated with depression treatment outcome in MDD patients. The inclusion of such personality traits, together with other socio-demographic and clinical predictors, could ameliorate the accuracy of the prediction models available to date.

Reversible Valproate Induced Pisa Syndrome and Parkinsonism in a Neuro-Oncology Patient with Depression and Epilepsy.

Neurological and psychiatric conditions frequently overlap in neuro-oncology. This overlapping negatively affects patients' quality of life and decreases the ability of providers to manage specific symptoms by therapy modulation, especially when psychopharmacotherapy needs to be prescribed. We describe here a patient with recurrent brain tumor, symptomatic epilepsy and depression who developed Pisa syndrome and parkinsonism after several months of valproic acid use. An accurate recognition of symptoms and treatment side effect allowed an appropriate clinical approach so as to rapidly improve both movement disorder and depression without increasing the risk of developing seizure. This has improved the autonomy and quality of life in a patient with poor prognosis.

Correlation between neuropsychological and social cognition measures and symptom dimensions in schizophrenic patients.

Neurocognitive and social cognition deficits have been largely reported in Schizophrenia (SKZ) but their association with psychopathology remains uncertain. Our purpose was to explore the relationship between symptom dimensions and neuropsychological performances. We enrolled 35 stabilized schizophrenic outpatients of the Department of Psychiatry of Policlinico Hospital, University of Milan, who completed psychiatric Rating Scales, the Brief Assessment of Cognition in Schizophrenia (BACS) and the Executive and Social Cognition Battery (ESCB). Disorganized dimension seems to have the most significant impact on cognition, being associated with performance in several BACS subtests (verbal memory, working memory, motor speed, symbol coding, Tower of London) and ESCB tasks (MET and Hotel task number of tasks attempted, number of broken MET rules, sum of deviations in Hotel Task). Positive dimension correlated with performance in verbal fluency, negative dimension with IOWA Test results, cognitive dimension with MET number of inefficiencies and Eyes test score. Impulsive-aggressive and depressive dimensions weakly correlated only with Faux Pas test. Our study supports the existence of a specific disorganized dimension in SKZ, separated from cognitive dimension evaluated through clinical instruments (e.g. PANSS), but capable of influencing cognitive abilities. Furthermore, it strengthens the validity of ecological tasks in evaluating cognition in SKZ.

New approaches to the pharmacological management of generalized anxiety disorder.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) and serotonine reuptake Inhibitors (SNRIs) together with pregabalin are actually considered by international guidelines as the first-line choice for generalized anxiety disorder (GAD) treatment. However, 50% of GAD patients have poor response to first-line treatments and different molecules, such as atypical antipsychotics and mood stabilizers, have been used for treating this condition. Purpose of the present article is to provide an overview of the most recent pharmacological approaches for the treatment of GAD and the rationale for their use. AREAS COVERED: A research in the main database sources has been conducted to obtain an overview of the new pharmacological approaches in GAD (anticonvulsants, atypical antipsychotics, agomelatine, memantine, ondansetron and riluzole). EXPERT OPINION: Among unlabelled molecules, quetiapine seems to have the most robust evidence of efficacy in GAD. Valproic acid and agomelatine appear to be effective in GAD patients, but the data are preliminary and need to be confirmed by future studies. Quetiapine is a promising molecule for GAD treatment but its use would be complicated by long-term metabolic side effects. Future research will have the objective to find more targeted molecules for the treatment of this disorder in light of its specific etiology.

White matter metabolism differentiates schizophrenia and bipolar disorder: a preliminary PET study.

Fluorodeoxyglucose-F18 positron emission tomography studies (FDG-PET) have shown similar corticolimbic metabolic dysregulation in bipolar disorder and schizophrenia, with hypoactive prefrontal cortex coupled with hyperactive anterior limbic areas. However, it is not clear whether white matter metabolism connecting these regions is differently affected in the two disorders. Twenty-six patients with schizophrenia (mean age ± S.D.=30.23 ± 9.7 year-old; 19 males; mean weight ± S.D.=71 ± 3 kg) and 26 patients with bipolar disorder (mean age ± S.D.=48.73 ± 13 year-old; 18 males; mean weight ± S.D.=75 ± 15 kg) underwent an FDG-PET scan. Normalized datasets the two groups of patients were compared on a voxel-by-voxel basis using a two-sample t statistic test as implemented in SPM8, and adding age as covariate. Group differences were assessed applying a threshold of p<0.0005. White matter metabolic rates significantly differed between schizophrenia and bipolar disorder, whereas no differences were shown for cortical activity. This is the first FDG-PET, to our best knowledge, directly comparing subjects with schizophrenia to those with bipolar disorder. It reports decreased activity in the center of large fronto-temporal and cerebellar white matter tracts in patients with schizophrenia in respect to those with bipolar disorder. This feature may characterize and differentiate the regional brain metabolism of the two illnesses.