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Our study aims at replicating our previous finding of an association between COMT rs4680 G/A polymorphism and early onset major depression (MD). We included 462 MD, 147 bipolar disorders (BD) subjects and 295 healthy controls. We could partially replicate previous findings. In particular, rs4680 GG + AG genotypes were more represented in the subgroup of early onset MD patients (p = 0.04). Additionally, we observed an association between rs737865 alleles and early onset MD (p = 0.04). Rs4680 genotype was associated with early onset BD as well (p = 0.01). In conclusion, we partially replicated our previous findings confirming a possible influence of COMT variants in MD and BD, particularly in early onset subjects, though not with the same risk genotypes. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real-life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness-related variables, personal resources and context-related factors. Some of these variables were never investigated before in relationship with real-life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real-life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real-life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real-life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real-life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia. In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real-life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness-related variables, personal resources and context-related factors. Some of these variables were never investigated before in relationship with real-life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real-life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real-life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real-life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real-life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.

Background The high comorbidity between Eating Disorders (EDs) and Obsessive-Compulsive disorder (OCD) is well known, as well as its implications in terms of worse outcome and need to adapt treatment. Estimates of OCD comorbidities in EDs are variable in different studies and poorly informative for clinical purposes. In this study, we sought to derive more consistent estimates, taking into account potential methodological and sampling confounding factors. Methods We searched published studies reporting lifetime and current rates of comorbid OCD in ED samples based on recent diagnostic criteria. Comorbidity rates were meta-analyzed using a binary random effects model. Heterogeneity among the studies and publication bias were systematically checked. Potential confounding factors were tested by meta-regression analysis and adjusted by sensitivity analysis. Results Globally, respectively 18% and 15% of all patients with an ED had a lifetime and current comorbidity with OCD. Rates were slightly higher in anorexia (19% and 14%) than in bulimia nervosa (13% and 9%), although only the current comorbid OCD was significantly higher in anorexia than in bulimia. Prospective follow-up studies provided considerably higher lifetime estimates (EDs 38%, anorexia 44%, bulimia 19%). Limitations Temporal/causal relationship between ED and OCD could not be defined. Conclusions OCD comorbidity in EDs is a relevant phenomenon, affecting almost one fifth of the patients in cross-sectional observations and up to nearly 40% in prospective follow-up studies. These data indicate the need for focused attention to non-food or body-shape related OCD symptoms, for better diagnostic and prognostic accuracy, and targeted treatment.

Background: Social adjustment is impaired in depressed patients. The difficulty to adjust to social circumstances has been hypothesized to be one of the causes of depression, as well as a consequence of the disorder. Genetic variation in the serotonin transporter gene has been previously associated with social adjustment levels in patients with mood disorders. Methods: We investigated whether variations on the HTR1A (rs6295) and HTR2A (rs7997012) genes were associated with levels of social adjustment using the Social Adjustment Scale in two samples of depressed patients (total n=156). Results: Patients carrying the GG genotype of the HTR2A-rs7997012 showed better social adjustment in areas of work and family unit bonding. Limitations: These findings did not survive correction for multiple testing and should be interpreted with caution. Conclusion: Our finding is in line with previous observations that have associated the G allele of the HTR2A-rs7997012 with higher rate of antidepressant response. The HTR2A-rs7997012 is worthy of further investigation in studies examining factors that are related to depression course and outcome. (C) 2013 Elsevier B.V. All rights reserved

MAOA and, to a lesser extent, MAOB poly- morphisms have been related to aggression traits and suicidality. We aimed to investigate the role of MAOA and MAOB in suicidal versus non-suicidal participants and interactions between genetic variation and suicidal status on aggression and anger-related traits. The sample was com- posed of three groups: one group of suicide attempters (n = 171, males 35.1 %), one group of suicide completers (n = 90, males 57.8 %) and a healthy control group (n = 317, males 43.8 %). We examined the following markers: MAOA rs909525, rs6323, and rs2064070, and MAOB rs1799836. Anger traits were measured with the state-trait anger expression inventory (STAXI) and aggression traits with the questionnaire for measuring fac- tors of aggression (FAF). Associations were separately examined for males and females. Variation in the three MAOA variants was associated with higher levels of anger expressed outwards (STAXI ''anger-out'' subscale) in male suicidal patients compared to controls (p \ 0.001). In females, the C allele of rs6323 showed higher scores on the same subscale (''anger out'') (p = 0.002). Allele frequen- cies of the MAOA rs909525 were associated with suici- dality (p \ 0.007). Our findings show an association between genetic variation in three polymorphisms of the MAOA and anger traits in suicidal males and one replication for the functional variant rs6323 in females. This relation- ship was stronger than a direct genetic association with suicide status. Future studies incorporating endophenotypic measures of anger and aggression in suicidal participants are warranted.

In the present study, aimed at investigating whether a set of single nucleotide polymorphisms (SNPs) within PTGS2 gene (rs4648276, rs2066826 and rs689466) could be associated with antidepressant response, remission and treatment resistance in a sample of major depression patients, we did not find evidence supporting any of such associations. © 2010 Elsevier Ltd.

Aim: The aim of the present review is to summarize available evidence about the efficacy and side effects of novel antidepressants for the treatment of panic disorder. Methods: A literature search was undertaken using MEDLINE, ISI web of knowledge and references of retrieved articles. The search included articles published in English up to September 2009. Both controlled and uncontrolled trials were included. The quality of the reviewed articles was also assessed. Results: Fourteen mainly poor-quality studies were included. Mirtazapine showed some efficacy in reducing the number and the severity of panic symptoms in many uncontrolled studies and was comparable to selective serotonin reputake inhibitors (SSRIs) in direct-comparison studies. Reboxetine was significantly more efficacious than placebo but less effective than SSRIs. Further uncontrolled studies suggested preliminary evidence for the use of milnacipran and duloxetine as well. All drugs were usually well tolerated. Discussion: Current studies do not yet provide convincing evidence supporting the efficacy of mirtazapine, reboxetine, milnacipran and duloxetine for the treatment of panic disorder patients. However, on account of positive preliminary results, further research is warranted.

Cytochrome P450 genes are involved in the metabolism of antidepressants and could influence treatment response. The aim of this study was to investigate the role of allelic variations of the cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes in antidepressant treatment response and remission rates. Two hundred and seventy-eight patients affected by major depression, responders (N=81) and nonresponders (N=197) to at least one adequate antidepressant treatment, were recruited with a multicentre design for resistant depression and genotyped for all relevant variations. None of the considered metabolic profiles (e.g. poor, intermediate, extensive and ultrarapid metabolizers) was found to be associated with either response or remission rates. In conclusion, the investigated cytochrome genes do not seem to play a major role in antidepressant response in the present sample of depressive patients. Nevertheless, methodological and sample size limitations of this study do not allow definitive conclusions. Int Clin Psychopharmacol 24:250-256 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Several studies investigated possible associations between single nucleotide polymorphisms and the temperament and character inventory (TCI) scores. The possible association between TCI scores and the estrogen receptors 1 (ESR1) polymorphisms, which are expressed in cerebral regions that are involved in the development of temperament and character, has not been investigated yet. The aim of the present study is to investigate possible associations between specific ESR1 polymorphisms and TCI scores. Two hundred eighty-nine healthy subjects and I I I suicide attempters were enrolled in the study. All subjects compiled TCL Rs827421, rs1913474, rs1801132, rs722207, rs974276, and rs910416 in ESR1 were genotyped. Rs722207 was associated with Harm Avoidance (HA) in the healthy sample (P = 0.003). Further associations have been found for two HA subscales, HA2 and HA3, in the healthy sample. Additionally, the haplotype rs722207-rs974276 showed an association with HA (P = 0.0003) and HA2 (P = 0.0002) in the global sample and in healthy volunteers and HA3 showed an association in the global sample. Our study showed a moderate association between ESR1 variants and TCI scores. The main finding concerns the association between rs722207 and HA in the healthy sample. Further research is needed to replicate our findings and to investigate further ESR1 polymorphisms. (C) 2008 Wiley-Liss, Inc

The heritability of human personality traits is by now well established. However, since the first reports on associations between specific genetic variants and personality traits, only modest progress has been made in identifying loci that robustly support these associations. The aim of this study was to provide a summary of literature data on association studies focused on the genetic modulation of personality, according to the Cloninger, Eysenck and Costa and McCrae models. PubMed was searched for papers investigating the association between any gene variant and personality traits, which were grouped into five clusters: (a) anxiety, (b) impulsivity, (c) determination-activity, (d) socialization and (e) spirituality, in healthy individuals, populations and psychiatric patients. A total of 369 studies were included. No clear consensus on the role of any individual gene variant in personality modulation emerged, although SLC6A4 haplotypes and the DRD4 rs1800955 promoter variant seemed to be more reliably related to anxiety and impulsivity-related traits, respectively. Because conflicting results emerged from the literature, plausibly as a result of the combined influence of many loci of small effects on personality, larger sample sizes and more narrow and specific phenotype will be the minimum requirements for future genetic studies on personality. Moreover, genexgene and genexenvironment interaction studies deserve further attention. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Available evidence concerning the side effects experienced by bipolar disorder (BD) patients under naturalistic conditions has been poorly investigated. The aim of this study was therefore to investigate side effects related to major psychotropic drugs in two independent samples of BD patients naturalistically treated with mood stabilizers, antidepressants, antipsychotics and/or anxiolytics. Overall, 3654 patients from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) sample and 282 patients from the Clinical Outcome and Psycho-Education for Bipolar Disorder (COPE-BD) sample were included. The primary outcome measure was the influence of each class of psychotropic drugs under investigation on the emergence of any side effect, as measured with the monitoring form in the STEP-BD study and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale in the COPE-BD study. Secondary outcome measures included the effects of such drugs on psychic, neurologic, autonomic and other side effects. Mood stabilizers and antipsychotics were associated with high rates of side effects in both samples. Furthermore, antipsychotics were specifically associated with psychic side effects, whereas mood stabilizers were specifically associated with neurologic side effects. Our results largely confirm in a naturalistic setting results previously observed in randomized controlled trials focusing on BD patients.

Background: Depression is common in the elderly and in the last few years this led to a significant increase in antidepressant prescription rates. However, little is known about antidepressant efficacy profile in relation with socio-demographic and clinical features in this population. The aim of the present study was to define the most suitable socio-demographic and clinical profile for the use of antidepressant treatments in late-life depression. Methods: MEDLINE, EMBASE and PsycINFO were searched for randomized controlled trials (RCTs) focused on efficacy of antidepressants of all classes in major depressed elderly subjects (> 60 years old). Reviews and meta-analyses focusing on this topic have been considered as well. Thirty-four RCTs were included and socio-demographic and clinical features were investigated via meta-regression analysis as moderators of efficacy measures (standardized mean difference based on Hamilton Depressive Rating Scale and Montgomery-Asberg Depression Rating Scale). Results: A lower rate of response to antidepressants of all classes was found in patients of male gender, of older age, and with a longer mean duration of the current episode. On the contrary, a higher rate of response was found in patients with a higher baseline severity and at their first episode of illness. Subsamples treated with selective serotonin reuptake inhibitors alone yielded similar results. Limitations: RCTs only have been included. Conclusions: A number of socio-demographic and clinical features have been found to moderate antidepressant efficacy in elderly population. Those variables could help clinicians for a more individualized treatment. (C) 2012 Elsevier B.V. All rights reserved.

The extent to which a family history of mood disorders and suicide could impact on clinical features of patients suffering from major depression (MD) and bipolar disorder (BD) has received relatively little attention so far. The aim of the present work is, therefore, to assess the clinical implications of the presence of at least one first- and/or second-degree relative with a history of MD, BD and suicide in a large sample of patients with MD or BD. One thousand one hundred and fifty-seven subjects with MD and 686 subjects with BD were recruited within the context of two large projects. The impact of a family history of MD, BD, and suicide-considered both separately and together-on clinical and socio-demographic variables was investigated. A family history of MD, BD, and suicide was more common in BD patients than in MD patients. A positive family history of mood disorders and/or suicide as well as a positive family history of MD and BD separately considered, but not a positive history of suicide alone, were significantly associated with a comorbidity with several anxiety disorders and inversely associated with age of onset. The clinical implications as well as the limitations of our findings are discussed. The extent to which a family history of mood disorders and suicide could impact on clinical features of patients suffering from major depression (MD) and bipolar disorder (BD) has received relatively little attention so far. The aim of the present work is, therefore, to assess the clinical implications of the presence of at least one first- and/or second-degree relative with a history of MD, BD and suicide in a large sample of patients with MD or BD. One thousand one hundred and fifty-seven subjects with MD and 686 subjects with BD were recruited within the context of two large projects. The impact of a family history of MD, BD, and suicide - considered both separately and together - on clinical and socio-demographic variables was investigated. A family history of MD, BD, and suicide was more common in BD patients than in MD patients. A positive family history of mood disorders and/or suicide as well as a positive family history of MD and BD separately considered, but not a positive history of suicide alone, were significantly associated with a comorbidity with several anxiety disorders and inversely associated with age of onset. The clinical implications as well as the limitations of our findings are discussed. © 2012 Springer-Verlag.

Background: Little is known about the extent to which a family history of major depression (MD) affects residual depressive symptoms in responder and non-responder patients suffering from MD. Methods: Nine hundred eighty-six patients with MD were recruited within the context of a large multicenter project. Information about the family history of MD, as well as about total depressive symptoms and specific depressive clusters, was collected and analyzed. Results: No significant difference was observed in overall depressive symptoms between patients with and those without a family history of MD. However, non-responder patients with a family history of MD showed significantly higher scores in core symptoms as compared with responder patients without a family history of MD. Conclusions: Non-responder MD patients with a positive family history of MD could represent a slightly different sub-group of MD patients with more consistent core depressive symptoms as compared with responder patients without a family history of MD. However, taking into account the retrospective assessment of data, the use of positive or negative family history as a dichotomous indicator of familial loading and the cross-sectional design of the present study, further research is needed to draw more definitive conclusions. (C) 2014 Elsevier Inc. All rights reserved.

In the present study, we aimed to confirm the previous finding of an association between GRIK4 and GNB3 variants (rs195478 and rs5443) and remission and treatment resistance in major depression, using a multicenter sample of 223 patients. We did not find any supporting evidence for such associations. These conflicting data may result from difficulties in the replication of candidate gene association studies.

Background: The transcription factor Cyclic adenosine monophosphate Response Element Binding (CREB) protein has been repeatedly involved in the aetiology and pharmacotherapy of major depression (MD). The aim of this study was to investigate the potential association of a set of single nucleotide polymorphisms (SNPs) in CREB1 gene and both MD and response, remission and treatment resistance to antidepressants. Methods: One hundred-ninety MD patients collected in the context of a resistant depression study and treated with antidepressants for at least 4 weeks were genotyped for 5 CREB1 SNPs (rs2709376, rs2253206, rs7569963, rs7594560, and rs4675690). Response, remission and treatment resistance were recorded. Results: An allele of rs7569963 as well as rs2253206-rs7569963 A-A and rs7569963-rs4675690 A-C haplotypes were associated with the status of treatment resistance. Additionally, rs7569963 GG genotype was positively associated with remission. No further significant associations were observed. Limitations: Limitations of the present study include a relatively small sample size and the incomplete ascertainment of data which could influence the outcome. Conclusions: Our results preliminary suggest that some genetic polymorphisms in CREB1 could be associated to treatment resistance. Although such finding needs to be replicated in larger samples, it increases current knowledge about the genetic predictors of response to antidepressants that will probably lead to enhance treatment outcomes by addressing each individual to the most appropriate treatment strategy in the early stages of treatment. (C) 2010 Elsevier B.V. All rights reserved.

Objective: Eating disorders are influenced by both environmental factors and genes. The 5-HTTLPR polymorphism of serotonin transporter gene has been suggested as a good candidate. This meta-analysis was undertaken: (1) to investigate the association between 5-HTTLPR and eating disorders considered as a whole, including anorexia (AN), bulimia (BN), and binge eating disorder (BED); (2) to extend recently reported findings on the association between 5-HTTLPR and AN-BN. Method: PubMed, ISI, and PsycINFO databases were searched for studies published until October 2009. Fifteen studies have been included. Data were analyzed with the Cochrane Collaboration Review Manager Software. Quality of studies and publication bias were assessed. Results: An association between S allele and eating disorders, in particular AN, has been found. Discussion: To be carrier of the 5-HTTLPR S allele seem to represent a risk factor for eating disorders, especially for AN. However, considering the reported high between-study heterogeneity, future studies should focus on more homogeneous endophenotype. (C) 2010 by Wiley Periodicals, Inc

Suicide is one of the leading causes of death among young adults. Both genetic and personality factors plausibly have a role on suicidal behavior. We focused on the catechol-O-methyltransferase gene (COMT) and we performed: a review of studies investigating the association between COMT and both suicidal behavior and personality; a meta-analysis of studies investigating the association between suicidal behavior and COMT rs4680 polymorphism; an association study investigating the link between seven COMT polymorphisms (rs737865, rs5844402, rs5993883, rs4680, rs4633, rs165599 and rs9332377) and both personality traits and suicidal behavior. For the review and the meta-analysis we performed an electronic search to identify studies focused on the association between COMT and both suicidal behavior and personality. The sample of the association study was composed of three groups: 289 German healthy controls, 111 German suicide attempters and 70 Italian mood disorder patients. From the review, the meta-analysis and the association study no relationship emerged between COMT and suicidal behavior. Nevertheless, from both review and association study several links were found between COMT and personality traits. In particular, in the association study we found a significant correlation between rs4633 and Reward Dependence (Temperament and Character Inventory). As secondary results we found an association between rs737865 and Angry Reaction (State-Trait Anger Expression Inventory) and between rs9332377 and Irritability (Questionnaire for Measuring Factors of Aggression). Our findings suggested that COMT variants may not be directly implicated in suicidal behavior, however evidence of a COMT role in the modulation of personality traits has been found.

Excessive daytime sleepiness (EDS) is a symptom with high public health importance. Within psychiatric settings, depression is the most significant risk factor for EDS; however, this relationship has not been clearly detailed. The aim of this study was to describe the quality of sleep of depressed patients with and without EDS and to investigate the association between EDS and depression severity. A cross-sectional study with 78 female depressed outpatients (34.17 ± 11.37. years; range 18-60) was performed. The Epworth Sleepiness Scale, the Athens Insomnia Scale, the Pittsburgh Sleep Quality Index, and the Hamilton Rating Scale for Depression (HRSD) were administered. Patients were classified in two groups: with (43.5%) and without (56.5%) EDS. There were no differences with regard to comorbidity, socio-demographic (except for employment), or HRSD variables. The two groups were homogeneous in sleep patterns, with no difference in quality or sleep efficiency. EDS was not associated with reduced sleep efficiency or severity of depressive symptoms. Limitations of the present study include the small sample size and the use of self-report measurements. These results offer valuable information to clinicians in the sense of the need to deeply investigate the etiology of EDS before attributing it to bad sleep quality or depression severity. © 2009 Elsevier Ireland Ltd.

Purpose. The issue of defence mechanisms is of great importance in clinical practice. The aim of this meta-analysis is to compare different defence styles (Mature, Neurotic, and Immature), assessed using the three-factor defence style questionnaire (DSQ), in major depressive disorder (MDD), and panic disorder (PD) in order to evaluate potential differences in defence profiles among these disorders. Methods. We assessed all publications listed in PubMed, PsycINFO, ISI, and Lilacs databases focusing on DSQ defence styles in MDD and PD. To be included studies had to be published in English, to include psychiatric patients, to provide defence style mean scores, and to employ the three-factor DSQ versions. Data were entered into the Cochrane Collaboration Review Manager Software and analysed by RevMan version 4.2. Results. MDD patients reported significantly lower scores in Mature style and both MDDandPDpatients reported significantly higher scores inNeurotic and Immature styles. Conclusions. A dissimilarity between depressive and anxious profiles emerged, since the former profile was characterized by low Mature and high Neurotic and Immature scores while the latter by high Neurotic and Immature scores only. These results could indicate the use of specific strategies in clinical and psychotherapeutic management of patients with these diagnoses. Nevertheless, present results should be considered with caution because of the high heterogeneity of the studies and some weaknesses in the psychometric properties of the DSQ. © The British Psychological Society.

Sleep patterns, frequently altered in depression, have been hypothesized to be under genetic control. The circadian locomotor output cycles kaput (CLOCK) T3111C variant has been studied in association with sleep disturbances in depressed patients. The aim of this study was to investigate possible effects of T3111C CLOCK on insomnia, daytime sleepiness, sleep quality, and depression severity in a sample of 100 major depressive disorder patients. Inclusion criteria were: major depressive disorder, drug-free for any antidepressant and/or benzodiazepines for at least four weeks previously to the study, and a minimum score of > 17 on the Hamilton Rating Scale for Depression. The Morningness-Eveningness Questionnaire, Epworth Sleepiness Scale, Athens Insomnia Scale, and Pittsburgh Sleep Quality Index were applied. No significant difference was found concerning genotype or allele groups and Hamilton Rating Scale for Depression items or clusters. No difference was found between genotypes and comorbidity, chronotype distribution, Epworth Sleepiness Scale, Athens Insomnia Scale, or Pittsburgh Sleep Quality Index total scores. Overall, the present findings did not support the hypothesis of an effect of the T3111C CLOCK variant on sleep disturbances in major depressive disorder. Further analysis of clock machinery will clarify the contribution of clock genes to the maintenance of mental health. (Author correspondence: alessandro.serretti@unibo.it). Sleep patterns, frequently altered in depression, have been hypothesized to be under genetic control. The circadian locomotor output cycles kaput (CLOCK) T3111C variant has been studied in association with sleep disturbances in depressed patients. The aim of this study was to investigate possible effects of T3111C CLOCK on insomnia, daytime sleepiness, sleep quality, and depression severity in a sample of 100 major depressive disorder patients. Inclusion criteria were: major depressive disorder, drug-free for any antidepressant andor benzodiazepines for at least four weeks previously to the study, and a minimum score of >17 on the Hamilton Rating Scale for Depression. The Morningness-Eveningness Questionnaire, Epworth Sleepiness Scale, Athens Insomnia Scale, and Pittsburgh Sleep Quality Index were applied. No significant difference was found concerning genotype or allele groups and Hamilton Rating Scale for Depression items or clusters. No difference was found between genotypes and comorbidity, chronotype distribution, Epworth Sleepiness Scale, Athens Insomnia Scale, or Pittsburgh Sleep Quality Index total scores. Overall, the present findings did not support the hypothesis of an effect of the T3111C CLOCK variant on sleep disturbances in major depressive disorder. Further analysis of clock machinery will clarify the contribution of clock genes to the maintenance of mental health. © Informa UK Ltd.

A wide debate is ongoing regarding whether antidepressant effects should be considered a general property of these agents or whether they exclusively belong to the context of target symptoms. The aim of the present review is to summarize findings on antidepressant influences on healthy volunteers, focusing on changes in psychological and cognitive functions. Differences have been detected between acute and chronic treatments. Acute treatment has been found to lead to positive bias in emotion processing and facilitation in negative emotion recognition. Chronic treatments have been found to stabilise some changes induced by acute treatment, such as increased social behaviours. Regarding antidepressant modulation of affective symptomatology contrasting results have been reported suggesting that the link between action on cognitive processes and mood may be not direct. In fact, meta-analyzing data on mood and anxiety symptoms no difference was detected between subjects receiving placebo and SSRIs. However, meta-analyzing data on negative affects, a significant decrease was detected in subjects receiving SSRIs in comparison with subjects receiving placebo. In summary, antidepressants seem to exert a detectable influence also in healthy subjects. (C) 2009 Elsevier B.V. and ECNP. All rights reserved.

Personality influences several characteristics of normal and pathologic behaviors and it is associated with neurotransmitter systems that are under genetic control. The dopaminergic system has been proposed to play a role in the modulation of personality traits. In the present study, variants of the tyrosine hydroxylase (TH) and DOPA decarboxylase (DDC) genes (for TH: rs3842727, rs6356; for DDC: rs1451371, rs1470750, rs998850) were investigated in 111 suicide attempters and 289 healthy subjects to assess the involvement of the dopaminergic synthesis pathway in personality traits. No strong evidence was found for the associations between personality and TH or DDC in overall tests. An interaction effect of genotype and diagnosis was present, with TH and DDC SNPs having a greater effect on the respective personality dimensions in the group of suicide attempters. Because of the risk of false positives, these findings should be interpreted with highest caution. Direct replication attempts within independent groups of suicide attempters will help to resolve this question. Copyright (C) 2009 S. Karger AG, Basel

Background: Rhythm disturbances are a frequent clinical manifestation of depression. In recent years a possible relationship between depression and chronotypes has emerged. Specifically eveningness has been proposed as vulnerability factor. The aim of this study was to describe sleep features of depressed patients according to chronotypes and to explore possible associations with the clinical features of depressive episodes. Methods: 100 patients diagnosed with Major Depressive Disorder according to the Mini International Neuropsychiatric Interview (MINI) were included (age: 34 +/- 11.74, range: 18-60 years; female/male:79/21). At admission the Hamilton Rating Scale for Depression (HRSD) was administered. Patients were also administered the Morningness-Eveningness Questionnaire (MEQ), the Epworth Sleepiness Scale, the Athens Insomnia Scale and the Pittsburgh Sleep Quality Index. Results: According to MEQ scores patients were classified in three groups: a) eveningness (n = 18), b) neither (n = 61) and c) morningness type (n = 21). The age was different among chronotypes, being morningness-type patients older. The eveningness-type group showed higher scores in suicidal thoughts, more impaired work and activities, higher paranoid symptoms, higher scores on the anxiety cluster (HRSD), while the morningness-type group showed lower proportion of melancholic symptoms (MINI). We did not find association between sleep parameters and specific chronotypes. Limitations: The relatively small sample size and the concurrent assessment of chronotypes and depression may have biased our findings. Conclusions: Our data suggest the idea that chronotypes have an impact on depressive episodes features, with higher severity for the eveningness-type. (C) 2009 Elsevier B.V. All rights reserved

The 5-HT2A receptor is a key modulator of the serotonin pathway. We previously observed a marginal association between 5-HT2A gene variants and antidepressant efficacy in Japanese and Italian population but in the opposite direction. In the present report, we hypothesize that discrepant findings on 5-HT2A gene variants could be due to both the effect of ethnicity and a possible specific effect on some symptom improvement. The sample comprised 203 patients affected by mood disorders and treated for major depression with paroxetine or fluvoxamine. The total depressive scores for all patients were analyzed in previous reports, but symptomatologic clusters were not examined previously. The 21-item Hamilton Rating Scale for Depression (HAM-D) was administered to evaluate depressive symptoms at baseline and bi-weekly over 6 weeks of treatment. All patients were genotyped for the 5-HT2A T102C polymorphism. Compared with patients with the 5-HT2A T and C variants, in the Japanese sample T allele carriers showed selective and slower score reductions than C allele carriers in delusion and activity symptoms; on the other hand, in the Italian sample, C allele carriers showed a slower and selective score reduction compared with T allele carriers in Somatic anxiety, while they did not differ from other patients on the other scores. Despite the limitations of the small sample size and modest significance levels, these findings suggest that response to SSRIs is not a unitary phenomenon and discrepant findings across ethnic groups may be due to differential effects of gene variants. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

The aim of this study is to summarize available knowledge about common genetic, clinical, demographic and psychosocial predictors of response to pharmacotherapy in mood and anxiety disorders. A literature search was carried out by using MEDLINE and references of selected articles. The search included articles published up to March 2008. The main genetic finding concerns the serotonin transporter gene promoter polymorphisms, the long variant of which seems to be related to a positive response to therapy in mood disorders and could also have a role in the treatment of anxiety disorders. Among other predictors, the main factors common to both classes of disorder are comorbid axis II disorders and early onset of illness, which are related to a worse response to therapy and concomitant good physical conditions, absence of earlier treatments, early administration and response to therapies, and higher self-directedness, which is related to a better outcome. Many common predictors have been identified and these seem to be related to features covering the totality of patients that go beyond specific characteristics of single disorders. Possible limitations and suggestions for future research based on a more integrated vision of human complexity are discussed. Int Clin Psychopharmacol 24:1-18 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Temperamental features are strongly associated with suicidal behaviors both in general population and clinical samples. In the present study we considered the association between personality traits, measured by Temperament and Character Inventory (TCI), and suicidal behavior. We analyzed five samples: a German control sample of 1148 healthy individuals; 144 German suicide attempters affected by Mood (n = 101), Schizophrenia spectrum (it = 20) and Borderline Personality (n = 23) Disorders; 46 Italian suicide attempters affected by Mood Disorders (UP= 15; BP = 3 1); 76 German non-suicide Mood Disorder patients; 147 Italian non-suicide Mood Disorder patients. Suicide attempters showed higher scores in Harm Avoidance (HA) and lower scores in Self- Directedness (SD) and Cooperativeness (C), when compared to controls. Nevertheless, comparing the German and the Italian suicide attempter groups with the non-suicide Mood Disorder patient groups, no differences were detected. This could be due to the effect of Mood Disorder on personality. In conclusion, the present Study reveals the difficulty to disentangle the personality profile of suicide attempters from their psychopathology. Those findings may be useful for cautions in further dissecting this complex phenotype. (C) 2007 Elsevier Ltd. All rights reserved.

Clinicians face everyday the complexity of depression. Available pharmacotherapies and psychotherapies improve patients suffering in a large part of subjects, however up to half of patients do not respond to treatment. Clinicians may forecast to a good extent if a given patient will respond or not, based on a number of data and sensations that emerge from face to face assessment. Conversely, clinical predictors of non response emerging from literature are largely unsatisfactory. Here we try to fill this gap, suggesting a comprehensive assessment of patients that may overcome the limitation of standardized assessments and detecting the factors that plausibly contribute to so marked differences in depressive disorders outcome. For this aim we present and discuss two clinical cases. Mr. A was an industrial manager who came to psychiatric evaluation with a severe depressive episode. His employment was demanding and the depressive episode undermined his capacity to manage it. Based on standardized assessment, Mr. A condition appeared severe and potentially dramatic. Mrs. B was a housewife who came to psychiatric evaluation with a moderate depressive episode. Literature predictors would suggest Mrs. B state as associated with a more favourable outcome. However the clinician impression was not converging with the standardized assessment and in fact the outcome will reverse the prediction based on the initial formal standard evaluation. Although the present report is based on two clinical cases and no generalizability is possible, a more detailed analysis of personality, temperament, defense mechanisms, self esteem, intelligence and social adjustment may allow to formalize the clinical impressions used by clinicians for biologic and pharmacologic studies. Clinicians face everyday the complexity of depression. Available pharmacotherapies andpsychotherapies improve patients suffering in a large part of subjects, however up to half ofpatients do not respond to treatment. Clinicians may forecast to a good extent if a given patientwill respond or not, based on a number of data and sensations that emerge from face to faceassessment. Conversely, clinical predictors of non response emerging from literature are largelyunsatisfactory.Here we try to fill this gap, suggesting a comprehensive assessment of patients that mayovercome the limitation of standardized assessments and detecting the factors that plausiblycontribute to so marked differences in depressive disorders outcome.For this aim we present and discuss two clinical cases. Mr. A was an industrial manager who cameto psychiatric evaluation with a severe depressive episode. His employment was demanding andthe depressive episode undermined his capacity to manage it. Based on standardized assessment,Mr. A condition appeared severe and potentially dramatic. Mrs. B was a housewife who came topsychiatric evaluation with a moderate depressive episode. Literature predictors would suggestMrs. B state as associated with a more favourable outcome.However the clinician impression was not converging with the standardized assessment and infact the outcome will reverse the prediction based on the initial formal standard evaluation.Although the present report is based on two clinical cases and no generalizability is possible, amore detailed analysis of personality, temperament, defense mechanisms, self esteem,intelligence and social adjustment may allow to formalize the clinical impressions used byclinicians for biologic and pharmacologic studies

Introduction: Irritable mood (IM) and subthreshold hypomanic symptoms are reported in half and two-fifths of major depressed subjects respectively, but their clinical and prognostic meanings remain unclear. The aim of this study was to test the clinical usefulness of 2 specifiers in DSM-IV major depressive disorder (MDD): IM occurring during an index episode (IM+) and lifetime episodes of elated mood or IM with at least 2 concurrent hypomanic symptoms (subthreshold hypomanic episodes [SHEs]). Method: We included 482 outpatients with MDD participating in the Combining Medications to Enhance Depression Outcome study (mean age 43.14 ± 12.46 years, 144 males – 30%). The main aim of the original study was to test whether 2 different medications when given in combination as the first treatment step, compared to 1 medication, would improve antidepressant response. Results: IM + subjects (N = 349; 70%) were younger and more often females, with a more severe depression, a more marked social impairment, and more psychiatric comorbidities. The IM + group was also characterized by higher levels of suicidal ideation and more cases of emotional abuse. The combination of IM+ and SHEs was associated with an even more severe clinical picture. Limitations include the post hoc method, incomplete assessment of bipolar validators (e.g., family history of bipolar illness), personality disorders and suicide attempts. Conclusions: The presence of IM and SHEs in MDD correlate with an overall more severe clinical condition.

Introduction The aims of this systematic review and meta-analysis are to provide a summary of the current literature concerning compulsory treatments in patients with eating disorders (ED) and to understand whether compulsorily and involuntarily treated patients differ in terms of baseline characteristics and treatment outcomes. Methods Relevant articles were identified following the PRISMA guidelines by searching the following terms: “treatment refusal”, “forced feeding”, “compulsory/coercive/involuntary/forced treatment/admission”, “eating disorders”, “feeding and eating disorders”, “anorexia nervosa”, “bulimia nervosa”. Research was restricted to articles concerning humans and published between 1975 and 2020 in English. Results Out of 905 articles retrieved, nine were included for the analyses allowing the comparisons between 242 compulsorily and 738 voluntarily treated patients. Mean body mass index (BMI) was slightly lower in patients compelled to treatments. Mean illness duration, BMI at discharge and BMI variation showed no significant differences between the two groups. Average length of hospitalization was 3 weeks longer among compulsory-treated patients, but this did not result in a higher increase in BMI. No significant risk difference on mortality was estimated (three studies). Conclusions Compulsory treatments are usually intended for patients having worse baseline conditions than voluntary ones. Those patients are unlikely to engage in treatments without being compelled but, after the treatments, albeit with longer hospitalisations, they do achieve similar outcomes. Therefore, we can conclude that forcing patients to treatment is a conceivable option. Level of evidence Level I, systematic review and meta-analysis.

Social withdrawal is an early manifestation of several neuropsychiatric disorders, and it is characterised by a gradual disengagement from social interactions, potentially leading to complete isolation. This study investigated the association between social withdrawal at baseline and short-term symptom remission in five independent cohorts, including patients with major depressive disorder (MDD), bipolar spectrum disorders, and schizophrenia. Measures of social withdrawal were derived in each study, and clinical remission was estimated based on the psychopathological severity assessed after short-term psychopharmacological treatment (12weeks). Logistic regression was performed in each sample, adjusting for age and baseline psychopathological severity residualised for social withdrawal. Results were then meta-analysed across samples within a random-effect framework. A total of 4461 patients were included in the analyses (3195 patients with MDD, 655 with bipolar spectrum disorders and 611 with schizophrenia). The meta-analysis showed that higher baseline levels of social withdrawal were associated with a decreased likelihood of short-term remission (ORadj=0.67, 95% CI, 0.58-0.79, P=5.28×10−7), with the strongest effect in patients with schizophrenia. Overall, our study highlighted the need to address social withdrawal in the early phases of the disease to promote symptom remission in patients with major psychiatric disorders. Understanding the neurobiology underlying social withdrawal may aid the development of medications that can specifically reverse social impairment, thereby fostering clinical remission. Int Clin Psychopharmacol 37: 38-45 Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Gastrointestinal side effects (SEs) are frequently observed in patients with major depressive disorder (MDD) while taking antidepressants and may lead to treatment discontinuation. The aim of this meta-analysis is to provide quantitative measures on short-term rates of gastrointestinal SEs in MDD patients treated with second-generation antidepressants. An electronic search of the literature was conducted by using MEDLINE, ISI Web of Science – Web of Science Core Collection, and Cochrane Library databases. Eligible studies had to focus on the use of at least one of 15 antidepressants commonly used in MDD (i.e., agomelatine, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, mirtazapine, paroxetine, reboxetine, sertraline, venlafaxine, and vortioxetine) and report data on treatment-emergent gastrointestinal SEs (i.e. nausea/vomiting, diarrhoea, constipation, abdominal pain, dyspepsia, anorexia, increased appetite and dry mouth) within 12 weeks of treatment. Overall, 304 studies were included in the meta-analyses. All the considered antidepressants showed higher rates of gastrointestinal SEs than placebo. Escitalopram and sertraline were shown to be the least tolerated antidepressants on the gastrointestinal tract, being associated with all the considered SEs with the exception of constipation and increased appetite, while mirtazapine was shown to be the antidepressant with fewer side effects on the gut, being only associated with increased appetite. In conclusion, commonly used antidepressants showed different profiles of gastrointestinal SEs, possibly related to their mechanisms of action. The specific tolerability profile of each compound should be considered by clinicians when prescribing antidepressants in order to improve adherence to treatment and increase positive outcomes in patients with MDD.

Anorexia Nervosa (AN) is a severe eating disorder which typically develops in younger females. Many studies focus on this specific population, a majority of which will eventually partially or fully recover. A minority will become chronic despite extensive treatment. These patients are treatment-resistant and may not necessarily benefit from usual treatment. In this article we will reflect on possible mechanisms which may explain the maintenance of disease, and especially on the possible role of affective and anxiety disturbances. We will use, due to the lack of large-scale studies, data from risk and prognostic factors, treatment options and neurobiological correlates in chronic AN patients. Lastly, we will propose how these elements may advise further research and treatments.

Background: Major Depressive Disorder(MDD) and its frequent partial response to antidepressants are a major health concern and therefore an important focus of research. Despite the efforts, MDD pathogenesis and the mechanisms of antidepressant action are only partially understood. In the last few years, the need of rethinking the classification of depressive disorders and psychiatric disorders, in general, has been suggested, in order to provide a nosology that reflects more closely the biological background associated with disease pathogenesis and its role/significance in treatment. The classification proposed by the National Institute of Mental Health (NIMH), namely the research domain criteria (RDoC), may represent a key framework to guide research in this direction. Methods: A literature search was performed on PubMed and Google Scholar databases in order to retrieve data regarding Antidepressants effects on specific RDoC constructs. Further, the targets of drugs of interest were identified through the Drug bank database, and their possible function within RDoC constructs was discussed. Discussion: In this review, we summarize and discuss the significance of the results of pre-clinical and clinical studies investigating specific RDoC paradigms relevant to depressive phenotypes and antidepressant effects. Conclusion: The RDoC framework may facilitate a more specific use of antidepressants based on the individual’s spectrum of symptoms and the development of new compounds that target specific depressive symptoms.

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD+P). AD+P affects ∼50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD-P). Although the estimated heritability of AD+P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5,445 AD+P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p=1.26×10−8) and one spanning the 3’-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56-0.76), p=3.24×10−8), had genome-wide significant associations with AD+P. Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4. AD+P demonstrated negative genetic correlations with cognitive and educational attainment and positive genetic correlation with depressive symptoms. We previously observed a negative genetic correlation with schizophrenia; instead, we now found a stronger negative correlation with the related phenotype of bipolar disorder. Analysis of polygenic risk scores supported this genetic correlation and documented a positive genetic correlation with risk variation for AD, beyond the effect of ε4. We also document a small set of SNPs likely to affect risk for AD+P and AD or schizophrenia. These findings provide the first unbiased identification of the association of psychosis in AD with common genetic variation and provide insights into its genetic architecture.

A systematic review was implemented according to PRISMA guidelines on Pubmed, Psychinfo, Medline, Embase to fill the existing literature gap on the effectiveness of using Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) in Anorexia Nervosa (AN), Bulimia Nervosa (BN) and Binge Eating Disorder (BED). Twenty-two articles were included. Four studies reported an increased density in 5-hydroxytryptamine receptor (5-HT1A) in fronto-temporo-parietal regions in both affected and recovered AN as well as in BN. The 5-HT transporter (5-HTT) binding was increased or diminished in different specific cortical areas and in relation to Eating Disorder (ED) subtypes. Some evidences of blunted Dopamine (DA) release in the putamen in BN patients suggest that their DA function might be impaired as in addictive behaviours. Studies estimating the regional Cerebral Blood Flow (rCBF) with SPECT demonstrated that temporal areas seem to play a key role in ED corroborating the hypothesis of a cingulate-temporal cortical dysfunction in AN. In addition, alterations of both parietal and prefrontal cortex provide a possible common neural substrate in AN. Studies included in this review are heterogeneous preventing robust conclusions, however, our findings add knowledge on some of the neurotransmitters involved in ED.

Interstitial pneumonia was the first manifestation to be recognized as caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, in just a few weeks, it became clear that the coronavirus disease-2019 (COVID-19) overrun tissues and more body organs than just the lungs, so much so that it could be considered a systemic pathology. Several studies reported the involvement of the conjunctiva, the gut, the heart and its pace, and vascular injuries such as thromboembolic complications and Kawasaki disease in children and toddlers were also described. More recently, it was reported that in a sample of 214 SARS-CoV-2 positive patients, 36.4% complained of neurological symptoms ranging from non-specific manifestations (dizziness, headache, and seizures), to more specific symptoms such hyposmia or hypogeusia, and stroke. Older individuals, especially males with comorbidities, appear to be at the highest risk of developing such severe complications related to the Central Nervous System (CNS) involvement. Neuropsychiatric manifestations in COVID-19 appear to develop in patients with and without pre-existing neurological disorders. Growing evidence suggests that SARS-CoV-2 binds to the human Angiotensin-Converting Enzyme 2 (ACE2) for the attachment and entrance inside host cells. By describing ACE2 and the whole Renin Angiotensin Aldosterone System (RAAS) we may better understand whether specific cell types may be affected by SARS-CoV-2 and whether their functioning can be disrupted in case of an infection. Since clear evidences of neurological interest have already been shown, by clarifying the topographical distribution and density of ACE2, we will be able to speculate how SARS-CoV-2 may affect the CNS and what is the pathogenetic mechanism by which it contributes to the specific clinical manifestations of the disease. Based on such evidences, we finally hypothesize the process of SARS-CoV-2 invasion of the CNS and provide a possible explanation for the onset or the exacerbation of some common neuropsychiatric disorders in the elderly including cognitive impairment and Alzheimer disease.

About 20–30% of patients with major depressive disorder (MDD) develop treatment-resistant depression (TRD) and finding new effective treatments for TRD has been a challenge. This study aimed to identify new possible pharmacological options for TRD. Genes in pathways included in predictive models of TRD in a previous whole exome sequence study were compared with those coding for targets of drugs in any phase of development, nutraceuticals, proteins and peptides from Drug repurposing Hub, Drug-Gene Interaction database and DrugBank database. We tested if known gene targets were enriched in TRD-associated genes by a hypergeometric test. Compounds enriched in TRD-associated genes after false-discovery rate (FDR) correction were annotated and compared with those showing enrichment in genes associated with MDD in the last Psychiatric Genomics Consortium genome-wide association study. Among a total of 15,475 compounds, 542 were enriched in TRD-associated genes (FDR p < .05). Significant results included drugs which are currently used in TRD (e.g. lithium and ketamine), confirming the rationale of this approach. Interesting molecules included modulators of inflammation, renin-angiotensin system, proliferator-activated receptor agonists, glycogen synthase kinase 3 beta inhibitors and the rho associated kinase inhibitor fasudil. Nutraceuticals, mostly antioxidant polyphenols, were also identified. Drugs showing enrichment for TRD-associated genes had a higher probability of enrichment for MDD-associated genes compared to those having no TRD-genes enrichment (p = 6.21e-55). This study suggested new potential treatments for TRD using a in silico approach. These analyses are exploratory only but can contribute to the identification of drugs to study in future clinical trials.

Patients suffering from major depression and related pathologies (feeding and eating disorders, obsessive-compulsive disorder, post-traumatic stress disorder, anxiety disorders, etc.) are usually treated with antidepressant agents belonging to several pharmacological and chemical classes; the most recent of these agents are collectively known as “new-generation antidepressants”. In these patients, therapeutic drug monitoring (TDM) with the determination of drug and metabolite blood levels is one of the most useful procedures to optimise and personalise the treatment, enhancing both effectiveness and safety. A new approach is proposed in this study, based on microsampling of both blood and oral fluid by means of volumetric absorptive microsampling (VAMS). This approach makes sampling and storage much simpler and even self- and at-home-sampling possible, while retaining reliability, vastly increasing analyte stability and reducing overall expenses. The microsamples were pretreated by means of microextraction by packed sorbent (MEPS) on C2 sorbent and analysed by liquid chromatography with sequential spectrophotometric and spectrofluorimetric detection (HPLC-UV-FL). Method validation results were satisfactory (extraction yield >84%, precision RSD < 8.9%, stability>85.0% after 3 months). Application to blood and oral fluid VAMS from patients treated with four possible different antidepressants (sertraline, fluoxetine, citalopram and vortioxetine) provided results always in good agreement with those obtained from the corresponding fluid matrices, including the levels of drug metabolites.

Objective: The present study aims at exploring associations between a continuous measure of distorted thought contents and a set of demographic and clinical features in a sample of unipolar/bipolar depressed patients. Methods: Our sample included 1,833 depressed subjects. Severity of mood symptoms was assessed by the 21 items Hamilton Depression Rating Scale (HAM-D). The continuous outcome measure was represented by a delusion (DEL) factor, extracted from HAM-D items and including items: 2 ("Feelings of guilt"), 15 (" Hypochondriasis"), and 20 ("Paranoid symptoms"). Each socio-demographic and clinical variable was tested by a generalized linear model test, having depressive severity (HAM-D score-DEL score) as the covariate. Results: A family history of major depressive disorder (MDD; p=0.0006), a diagnosis of bipolar disorder, type I (p=0.0003), a comorbid general anxiety disorder (p, SCOPUS: ar.j, info:eu-repo/semantics/published

Second-generation antipsychotics (SGA) have been associated with risk of stroke in elderly patients, but the molecular and genetic background under this association has been poorly investigated. The aim of the present study was to prioritize a list of genes with an SGA altered expression in order to characterize the genetic background of the SGA-associated stroke risk. Genes with evidence of an altered expression after SGA treatments in genome-wide investigations, both in animals and men, were identified. The Genetic Association Database (GAD) served to verify which of these genes had a proven positive association with an increased stroke risk, and along with it each evidence was tested and recorded. Seven hundred and forty five genes had evidence of a change of their expression profile after SGA administration in various studies. Nine out of them have also been significantly related to an increased strokes risk. We identified and described nine genes as potential candidates for future genetic studies aimed at identifying the genetic background of the SGA-related stroke risk. Further, we identify the molecular pathways in which these genes operate in order to provide a molecular framework to understand on which basis SGA may enhance the risk for stroke.

Early antidepressant response (2nd week) has been reported as the result of a true antidepressant effect and a predictor of subsequent stable response. With the purpose to study the clinical profile of early response/remission (2nd week) compared to late response/remission (4th-6th weeks), two independent major depressive disorder (MDD) samples (the Sequenced Treatment Alternatives to Relieve Depression or STAR*D n=1922 and an Italian sample n=171) were investigated. Patients were treated with citalopram in the STAR*D while in a naturalistic setting in the Italian sample. Depressive symptomatology was assessed by the Hamilton Depressive Rating Scale weekly in the Italian sample and biweekly by the Quick Inventory of Depressive Symptomatology Clinician Rated in the STAR*D. Logistic regression was used to investigate possible predictors of early response and the Bonferroni correction was applied. In the STAR*D, higher levels of baseline core depressive symptoms (Bech subscale) were associated with early response (p=0.00017), as well as lower baseline insomnia (p=0.003) and higher work and social functioning (p=0.001). In the Italian sample none of these variables were associated with the phenotype, but a non significant trend of lower baseline quality of life (p=0.078) was observed in late remitters. In the STAR*D late responders reported higher levels of antidepressant induced side effects, especially difficulty in sleeping (p=5.68e-13), with a non significant trend in the same direction in the Italian sample (p=0.09). The identification of late versus early antidepressant responders at the beginning of the treatment may be useful to guide therapeutic choices in clinical settings.

We previously investigated a sample of psychotic patients acutely ill and acutely treated with haloperidol in the search for genetic predictors of response at PANSS scores during the first month of treatment. In the present work we extend the analysis to a wider panel of genetic variations including SNPs harbored by genes whose products are involved in molecular pathways consistent with the latest results of genome-wide association studies (GWAS) of antipsychotic efficacy. 96 Patients were investigated. The results were replicated in an independent sample of bipolar manic patients treated with antipsychotics (n tot=470, the sample was retrieved from the STEP-BD). Outcomes were the PANSS variation through time in the first sample, and changes of mania symptomatology at any two consecutive observations in the public available STEP-BD replication sample. A list of variations harbored by AKAP13, CACNA1, GRIK4 and GRIA1 were found to be significantly associated with outcome in both samples (different set of variations for each sample). Results did not survived multiple testing in the original sample but were replicated in both samples. This finding stresses the relevance of the glutamatergic system and regulatory molecular cascades in antipsychotic response. Nonetheless, the level of significance and the indirect and incomplete replication mandate cautiousness and further replication.

OBJECTIVE: The aim of this literature review was to assess the effects of Animal-Assisted Interventions (AAI) on elderly patients with dementia or various psychiatric disorders. METHODS: We conducted a comprehensive literature search using the online PubMed network of the US National Library of Medicine & National Institutes of Health, Embase, PsycINFO, with the purpose of investigating AAI effects on cognitive functions, mood, and behaviour. RESULTS: A total of 18 articles on dementia and 5 on psychiatric disorders were included in the present review. AAI were found to have positive influences on demented patients by reducing degree of agitation and by improving degree and quality of social interaction. Few studies have assessed the effects of AAI on mood, and even fewer have assessed its consequences on cognitive functions. The results that are available indicate a positive effect on communication and coping ability, but none on cognitive performance. A substitute pet robot yielded encouraging results, but its use requires further investigation. The few studies conducted for elderly patients presenting a variety of psychiatric diagnoses produced controversial findings. CONCLUSIONS: In spite of the encouraging results of AAI, much more research examining the issue of optimal AAI duration, frequency of sessions, and suitable target group is needed.

none 28 no BACKGROUND: The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. METHOD: A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. RESULTS: We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (⩾14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI

Alzheimer's disease (AD) has been associated with up-regulation of pro-inflammatory cytokines (e.g., specific gene variants for TNF-alpha; IL-6; IFN-gamma) and low plasma levels of cyanocobalamin (vitamin B12). Our goal was to relate B12 levels to AD symptoms and to expression of pro-inflammatory cytokines. Clinical manifestations were investigated for a case series of fifty-five outpatients using the MMSE, Neuropsychiatric Inventory (NPI) and Cornell Scale for Depression in Dementia (CDDS). Plasma B12 levels were measured by radioligand binding assay. Basal and PMA-stimulated levels of IFN-gamma, TNF-alpha, and IL-6 were measured by ELISPOT (PBMC culture supernatant). 47 patients were genotyped for APOE. Ten patients (18%) had their B12 levels below < 250 pg/ml. They did not statistically differ from those 45 who had normal levels in most demographic and clinical features; their MMSE scores were lower (14.7 vs 19.6 p=0.03) but not after adjustment for disease duration. A greater basal production of IL-6 was reported in patients who had low B12 levels compared to normal B12 subjects (1333 pg/ml vs 976 p< 0.01); this association was confirmed after controlling for age of onset and APOE genotype. In conclusion, low B12 level is associated with greater production of IL-6 in peripheral blood mononuclear cells. Further research is warranted to elucidate whether this neuroinflammatory effect of cobalamin is implicated in the pathophysiology of AD.

Response to pharmacological treatments is moderated by both genetic and environmental factors. The contribution of such factors is relatively small and complex interactions are likely to be involved. Serotonin transporter gene (SLC6A4) is a major candidate gene associated to response to antidepressant treatment. Moreover, the 5-HTTLPR polymorphism has been associated with anxiety-related traits such as neuroticism and harm avoidance (HA), which are known to influence the risk to develop mood disorders and response to treatments. In the present study we aimed to investigate the interaction between 3 SLC6A4 variants and HA on medium term antidepressant response in a sample of depressed bipolar-spectrum patients followed for 12 months. Contrary to expectations, SLC6A4 variants did significantly influence neither the course of depressive symptoms nor HA scores. However, a significant interaction was observed between HA and 5-HTTLPR genotype. Indeed, a high HA impaired outcome in patients carrying the L(G)/S or the S/S genotype more than in L(A)/L(A) patients. Though a number of limitations characterize the present study, our results indicate HA as a potential moderator of the effect of 5-HTTLPR on the outcome of depression. Given that many factors may influence response to pharmacological treatments, studies that consider personality and other individual characteristics are warranted also in pharmacogenetic investigations.

We assessed a set of biological (HDL, LDL, SGOT, SGPT, GGT, HTc, Hb and T levels) and psychometric variables (investigated through HAM-D, HAM-A, GAS, Liebowitz Social Anxiety Scale, Mark & Mathews Scale, Leyton scale, and Pilowski scale) in a sample of 64 alcohol dependent patients, at baseline and after a detoxification treatment. Moreover, we recruited 47 non-consanguineous relatives who did not suffer alcohol related disorders and underwent the same tests. In both groups we genotyped 11 genetic variations (rs1800587; rs3087258; rs1799724; 5-HTTLPR; rs1386493; rs1386494; rs1487275; rs1843809; rs4570625; rs2129575; rs6313) located in genes whose impact on alcohol related behaviors and disorders has been hypothesized (IL1A, IL1B, TNF, 5-HTTLPR, TPH2 and HTR2A). We analyzed the epistasis of these genetic variations upon the biological and psychological dimensions in the cases and their relatives. Further on, we analyzed the effects of the combined genetic variations on the short - term detoxification treatment efficacy. Finally, being the only not yet investigated variation within this sample, we analyzed the impact of the rs6313 alone on baseline assessment and treatment efficacy. We detected the following results: the couple rs6313 + rs2129575 affected the Leyton -Trait at admission (p = 0.01) (obsessive-compulsive trait), whilst rs1800587 + 5-HTTLPR impacted the Pilowski test at admission (p = 0.01) (hypochondriac symptoms). These results did not survive Bonferroni correction (p < or = 0.004). This lack of association may depend on the incomplete gene coverage or on the small sample size which limited the power of the study. On the other hand, it may reflect a substantial absence of relevance of the genotype variants toward the alcohol related investigated dimensions. Nonetheless, the marginal significance we detected could witness an informative correlation worth investigating in larger samples.