The safety of serotonin-noradrenaline reuptake inhibitors (SNRIs) in pregnancy and breastfeeding: a comprehensive review.

OBJECTIVE: The present study provides a comprehensive review of the existing literature on the safety of serotonin-noradrenaline reuptake inhibitors (SNRIs) in pregnancy and lactation. METHODS: Studies published in English, reporting the use of SNRIs in pregnant and/or breastfeeding women, were identified by searching MEDLINE/Pubmed, PsycINFO, and EMBASE. RESULTS: Twenty-nine studies were included in the review. Altogether, the initial evidence coming from the reviewed studies suggests a lack of association between SNRIs and an increased risk of major congenital malformations. Conversely, exposure to SNRIs seems to be significantly associated with an increased risk of some perinatal complications. No neonatal adverse events emerged, so far, in the few studies concerning the safety of SNRIs during breastfeeding. CONCLUSIONS: Available data suggest that venlafaxine is relatively safe during pregnancy, in particular as far as major malformations are concerned, whereas considering the small number of studies published, no definitive conclusions can be drawn on its safety during breastfeeding. Because of the few studies so far published, the safety of duloxetine during pregnancy and breastfeeding remains to be well established.

The Mini Questionnaire of Personal Organization (MQPO): preliminary validation of a new post-rationalist personality questionnaire.

BACKGROUND: The Mini Questionnaire of Personal Organization (MQPO) has been constructed in order to comply with the inward/outward Personal Meaning Organization's (PMO) theory. According to Nardi's Adaptive Post-Rationalist approach, predictable and invariable caregivers' behaviours allow inward focus and a physical sight of reciprocity; non-predictable and variable caregivers' behaviours allow outward focus and a semantic sight of reciprocity. METHODS: The 20 items of MQPO have been selected from 29 intermediate (n = 160) and 40 initial items (n = 204). Psychometric validation has been conducted (n = 296), including Internal Validity (Item-Total Correlation; Factor Analysis), Internal Coherence by Factor Analysis, two analyses in Discriminant Validity (n = 132 and n = 80) and Reliability by Test-Retest Analysis (n = 49). All subjects have been given their written informed consent before beginning the test. RESULTS: The validation of the MQPO shows that the ultimate version is consistent with its post-rationalist paradigm. Four different factors have been found, one for each PMO. Validity of the construct and the internal reliability index are satisfying (Alpha = 0.73). Moreover, the results obtained are constant (from r = 0.80 to r = 0.89). There is an adequate agreement between the MQPO scales and the clinical evaluations (72.5%), as well as an excellent agreement (80.0%) between the scores of the MQPO and those of the Personal Meaning Questionnaire. CONCLUSION: The MQPO is a tool able to study personality as a process by focusing on the relationships between personality and developmental process axes, which are the bases of the PMO's theory, according to the APR approach.

[Is the cognitive-behavioural therapy an effective strategy also in the prevention of post partum depression? a critical review]. / La terapia cognitivo-comportamentale è una strategia efficace anche nella prevenzione della depressione post partum? Una revisione critica.

OBJECTIVE: The aim of this study was to evaluate the efficacy of cognitive-behavioural therapy (CBT) in the prevention of post partum depression (PPD) in pregnant women at risk. METHODS: PubMed, Medline, PsychInfo, Embase, and the Cochrane Library databases were searched from January 1991 to June 2011 to review studies on the efficacy of CBT in the prevention of PD. RESULTS: The literature analyzed recommends that depression in pregnancy requires an efficient management to provide mother's symptoms relief as well as to prevent PD. While several studies demonstrated the efficacy of CBT in the treatment of PD, only a few controlled studies focused on its efficacy in the prevention of PD in women identified at risk during pregnancy. The efficacy of CBT in preventing PD in pregnant women at risk is supported by only a few studies, presenting some methodological flaws. DISCUSSION: Better designed trials are needed to strongly support the efficacy of such psychotherapeutic preventive strategy in women at risk for PD.

Bioinformatic analyses to select phenotype affecting polymorphisms in HTR2C gene.

OBJECTIVE: Single nucleotide polymorphisms (SNPs) in serotonin related genes influence mental disorders, responses to pharmacological and psychotherapeutic treatments. In planning association studies, researchers that want to investigate new SNPs have to select some among a large number of candidates. Our aim is to guide researchers in the selection of the most likely phenotype affecting polymorphisms. Here, we studied serotonin receptor 2C (HTR2C) SNPs because, till now, only relatively few of about 2000 are investigated. METHODS: We used the most updated and assessed bioinformatic tools to predict which variations can give rise to biological effects among 2450 HTR2C SNPs. RESULTS: We suggest 48 SNPs that are worth considering in future association studies in the field of psychiatry, psychology and pharmacogenomics. Moreover, our analyses point out the biological level probably affected, such as transcription, splicing, miRNA regulation and protein structure, thus allowing to suggest future molecular investigations. CONCLUSIONS: Although few association studies are available in literature, their results are in agreement with our predictions, showing that our selection methods can help to guide future association studies.

An improved in silico selection of phenotype affecting polymorphisms in SLC6A4, HTR1A and HTR2A genes.

OBJECTIVE: Among the experimentally assessed DNA variations in serotonin related genes, some influence physiological expression of personality and mental disorders, others alter the responses to pharmacological and/or psychotherapeutic treatments. Because of the huge number of polymorphisms lying in genes and of the great length of time necessary to perform association studies, a selection of the variations being studied is a necessary and crucial step. METHODS: In this work we used the most updated and assessed bioinformatic tools to predict the phenotype affecting polymorphisms of the human HTR1A, HTR2A and SLC6A4 serotonin related genes. Moreover, we carried out a literature search to collect information about the recent association studies to compare it versus our prediction data. RESULTS: Gene polymorphism analysis indicated the variations that are worth considering in the association studies in the field of psychiatry, psychology and pharmacogenomics. The literature revision allowed to show both the few well and the most not enough investigated polymorphisms. CONCLUSIONS: Our data can be useful to select polymorphisms for new association studies, especially those not yet investigated that can be related to behaviour, mental disorders and individual treatment response.

[Neuropsychological modifications at high altitude: from Pamir to Karakorum]. / Modificazioni neuropsicologiche da alta quota: dal Pamir al Karakorum.

AIM: Neuropsychological modifications and acclimatization processes at over 8000 without auxiliary oxygen were investigated in two climbers, evaluating attentive abilities and matching their performances. METHOD: During rest in base-camp (4800 m), at other three Resorts - Resort I (5800 m), Resort II (6400 m), Resort III (7200 m) -, and four months after the return at low altitude, were administered: Temporal Orientation Test (TOT), Trail Making Test (TMT), Animal Naming (AN), Verbal Fluency Test (VFT), Arithmetical Judgment Test (AJT), and Drawing Test (DT). Results. At TOT and at AJT, both the climbers demonstrated scores at higher normal levels (Eq = 4) in all the Resorts in which they were performed. They showed an impairment at AN test, especially at Resort III, showing sensitivity of animal naming to hypoxia. At the DT, human figures were reduced in their dimensions and details, as consequence of the tendency to self closure and introversion that occurs at higher altitudes. DISCUSSION: Neuropsychological functions concerning verbal fluency showed sensitivity to hypoxia, especially at higher altitudes. TMT demonstrated that attentive ability can be preserved if acclimatization is good. Sensitivity to hypoxia and acclimatization processes showed a significant subjective variability. CONCLUSIONS: The results of this study show that exposure to high altitude produces some significant neuropsychological changes.

[Depression in pregnancy: focus on the safety of antidepressant drugs.] / Depressione in gravidanza: focus sulla sicurezza dei farmaci antidepressivi.

Antepartum depression, frequently in comorbidity with anxiety disorders, is a severe psychopathological condition frequently reported in pregnancy and in many cases associated with obstetric and neonatal complications and potential negative consequences on child neurodevelopment. However, the pharmacological treatment of depression, during pregnancy generates a lot of concerns about the risks of such treatment for the fetus development and the neonatal health. The aim of this review is to present a selection of the latest international literature including recent original studies, systematic reviews, meta-analyses and recommendations from the guidelines, both on the risks of an untreated depressive disorders and on the risk of antidepressant therapy during gestation with drugs belonging to the SSRI and SNRI (SRI) class. An updated information of the recent risk-benefit data of these drug treatments in women with affective disorders in pregnancy may actually enable better and more conscious management of these disorders, not only for those working in the mental health field but also for general practitioners and those of other medical specialties.

Effectiveness of group CBT in treating adolescents with depression symptoms: a critical review.

Depression is among the most common psychological disorders of adolescents. Its management is based on pharmacological treatment, psychological therapy, or a combination thereof. Cognitive behavioral therapy (CBT) is the most extensively tested intervention for adolescent depression. A PubMed search was conducted for randomized controlled trials (RCT) of the efficacy of CBT in treating adolescents with depressive symptoms published in 2005-2015. Keywords were "cognitive behavioral therapy", "group therapy", "depression" and "adolescent". Of the 23 papers that were retrieved, only six met all inclusion criteria. Three of them reported a significant reduction in depressive symptom severity after either individual or group (G)-CBT compared with the control group, even with a small number of CBT sessions (six rather than 10-12), with a medium or medium-to-large effect size. One study reported improved self-awareness and a significantly greater increase in perceived friend social support compared with bibliotherapy and check with brochure. Two studies reported clinical symptom reduction without significant differences compared with the control group (activity contrast). This review highlighted primarily that very few RCT have applied CBT in adolescents; moreover, it confirmed the effectiveness of G-CBT, especially as psychotherapy, although it was not always superior to other interventions (e.g. other activities in prevention programs). Comparison showed that G-CBT and group interpersonal psychotherapy were both effective in reducing depressive symptoms. Successful G-CBT outcomes were related to the presence of peers, who were an important source of feedback and support to observe, learn, and practice new skills to manage depressive symptoms and improve social-relational skills.

[Aripiprazole in pregnancy: a review of literature]. / Aripiprazolo in gravidanza: una rassegna della letteratura internazionale.

AIM: Data on tolerability and safety of aripiprazolo during pregnancy and in childbirth are so far limited. Aim of the present study is to provide a review of the literature on the safety profile of aripiprazole during pregnancy and on maternal and neonatal outcomes, including two cases coming from our database (www.degradatabase.it). METHODS: Medline database was searched for English language articles by using the following keywords: "aripiprazole", "atypical antipsychotic", "major malformations", "perinatal complications", "pregnancy". We reported 2 cases of women treated with aripiprazole during their pregnancy at the Clinic of Affective Disorders in Pregnancy and Postpartum of the United Hospital of Ancona (DEGRA Center - www.depressionegravidanza.it). RESULTS: The data available in the literature did not provide clear evidence about the safety and potential risks related to this drug during pregnancy. Data coming from our database did not detected any malformations and perinatal complications after exposure to aripiprazole in 2 newborns beyond the first trimester of pregnancy. DISCUSSION AND CONCLUSION: From the evidence available, aripiprazole seems to be an antipsychotic effective and well tolerated in the treatment of women with psychotic disorders in pregnancy. However, further studies are needed to better establish the safety of aripiprazole during pregnancy, particularly as the risk of major malformtions and perinatal complications is concerned.

How much do we know about the coupling of G-proteins to serotonin receptors?

Serotonin receptors are G-protein-coupled receptors (GPCRs) involved in a variety of psychiatric disorders. G-proteins, heterotrimeric complexes that couple to multiple receptors, are activated when their receptor is bound by the appropriate ligand. Activation triggers a cascade of further signalling events that ultimately result in cell function changes. Each of the several known G-protein types can activate multiple pathways. Interestingly, since several G-proteins can couple to the same serotonin receptor type, receptor activation can result in induction of different pathways. To reach a better understanding of the role, interactions and expression of G-proteins a literature search was performed in order to list all the known heterotrimeric combinations and serotonin receptor complexes. Public databases were analysed to collect transcript and protein expression data relating to G-proteins in neural tissues. Only a very small number of heterotrimeric combinations and G-protein-receptor complexes out of the possible thousands suggested by expression data analysis have been examined experimentally. In addition this has mostly been obtained using insect, hamster, rat and, to a lesser extent, human cell lines. Besides highlighting which interactions have not been explored, our findings suggest additional possible interactions that should be examined based on our expression data analysis.

Role of 5-HTTLPR polymorphism in the development of the inward/outward personality organization: a genetic association study.

Reciprocity with primary caregivers affects subjects' adaptive abilities toward the construction of the most useful personal meaning organization (PMO) with respect to their developmental environment. Within cognitive theory the post-rationalist approach has outlined two basic categories of identity construction and of regulation of cognitive and emotional processes: the Outward and the Inward PMO. The presence of different, consistent clinical patterns in Inward and Outward subjects is paralleled by differences in cerebral activation during emotional tasks on fMRI and by different expression of some polymorphisms in serotonin pathways. Since several lines of evidence support a role for the 5-HTTLPR polymorphism in mediating individual susceptibility to environmental emotional stimuli, this study was conducted to investigate its influence in the development of the Inward/Outward PMO. PMO was assessed and the 5-HTTLPR polymorphism investigated in 124 healthy subjects who were subdivided into an Inward (n = 52) and an Outward (n = 72) group. Case-control comparisons of short allele (S) frequencies showed significant differences between Inwards and Outwards (p = 0.036, χ2 test; p = 0.026, exact test). Genotype frequencies were not significantly different although values slightly exceeded p ≤ 0.05 (p = 0.056, χ2 test; p = 0.059, exact test). Analysis of the 5-HTTLPR genotypes according to the recessive inheritance model showed that the S/S genotype increased the likelihood of developing an Outward PMO (p = 0.0178, χ2 test; p = 0.0143, exact test; OR = 3.43, CI (95%) = 1.188-9.925). A logistic regression analysis confirmed the association between short allele and S/S genotypes with the Outward PMO also when gender and age were considered. However none of the differences remained significant after correction for multiple testing, even though using the recessive model they approach significance. Overall our data seem to suggest a putative genetic basis for interindividual differences in PMO development.

Is the cognitive-behavioral therapy an effective intervention to prevent the postnatal depression? A critical review.

OBJECTIVE: The aim of this article is to review and discuss the efficacy of the Cognitive-Behavioral Therapy (CBT), in the prevention of postnatal depression (PD) in pregnant women at risk. METHOD: PubMed, Medline, PsychInfo, Embase, and the Cochrane Library databases were searched from February 1991 to February 2011. RESULTS: Eight Randomized Controlled Trials (RCT) on the prevention of PD with the CBT were selected and their data were analyzed. The literature analyzed recommends that depression in pregnancy requires an efficient management to provide mother's symptoms relief as well as to prevent the PD. While several studies demonstrated the efficacy of the CBT in the treatment of PD, the efficacy of the CBT in preventing PD in pregnant women at risk has been investigated only by a few studies, presenting a number of methodological flaws. CONCLUSIONS: Better designed RCT are needed to support the efficacy of such psychotherapeutic preventive strategy in women at risk for PD.

Evaluación de la calidad de vida en mujeres con vaginismo primario mediante el WHOQOL-BREF / Evaluation of the quality of life in women with primary vaginismus by WHOQOL-BREF

Antecedentes: El vaginismo es una disfunción sexual que impide Ia penetración y que afecta a cerca de un 5 por ciento de las mujeres y que les genera malestar tanto a ellas como a sus parejas. Objetivo: Conocer la calidad de vida de mujeres con vaginismo primario y comparar con un grupo control. Método: Aplicación presencial del WHOQOL-BREF a 50 mujeres con vaginismo primario y a 47 mujeres sin patología, socio-demográficamente similares. Resultados: El nivel de calidad de vida en las mujeres con vaginismo fue menor a aquella del grupo de comparación respecto a la calidad general de la vida y la salud, y en tres de los cuatro dominios del WHOQOL-BREF. Conclusión: El vaginismo es una condición que afecta la calidad de vida de las mujeres con ese diagnóstico.

Background: Vaginismus is a sexual dysfunction that prevents the penetration and affects about 5 percent of women and makes them feel upset both them and their partners. Objective: Determine the quality of life of women with primary vaginismus and compared with a control group. Method: Application of the WHOQOL-BREF to 50 women with primary vaginismus and 47 women without pathology and similar demographically status. Results: The level of quality of life in women with vaginismus was lower than that of the comparison group regarding the overall quality of life and health, and in three of the four domains of the WHOQOL-BREF. Conclusion: Vaginismus is a condition that affects the quality of life of women with this diagnosis.

Eficacia de la terapia cognitivo conductual en la prevención de la depresión posparto / Efficacy of cognitive-behavioral therapy in the prevention of postnatal depression

Objetivo: Evaluar la eficacia de la terapia cognitivo conductual (TCC) en la prevención de la depresión posparto (DPP) en mujeres embarazadas consideradas en riesgo de padecerla. Método: Revisión bibliográfica en PubMed, Medline, PsychInfo, Embase y de la Cochrane Library de publicaciones efectuadas entre enero de 1991 y junio de 2012 respecto de investigaciones sobre la eficacia de la TCC en la prevención de la DPP. Resultados: De la literatura analizada se concluye que la depresión en el embarazo requiere de un manejo eficiente tanto para tratar los síntomas de la depresión preparto (DAP), como de prevenir la DPP. Mientras diversos estudios han demostrado la eficacia de la TCC en el tratamiento de la DPP, sólo pocos estudios controlados se han centrado sobre su eficacia en la prevención de la DPP. La eficacia en la prevención de la DPP en mujeres en riesgo durante el embarazo ha sido apoyada sólo por pocos estudios, los cuales presentan algunas limitaciones metodológicas. Conclusión: Resultan necesarios estudios clínicos para confirmar la eficacia de tal estrategia de prevención psicoterapéutica en las mujeres en riesgo de DPP.

Aims: To evaluate the efficacy of cognitive-behavioral therapy (CBT) in the prevention of postnatal depression (PD) in pregnant women at risk. Methods: PubMed, Medline, PsychInfo, Embase, and the Cochrane Library data bases were searched from January 1991 to June 2011 to review studies on the efficacy of CBT in the prevention of PD. Results: The literature analyzed recommends that depression in pregnancy requires an efficient management to provide mother's symptoms relief as well as to prevent PD. While several studies demonstrated the efficacy of CBT in the treatment of PD, only a few controlled studies focused on its efficacy in the prevention of PD in women identified at risk during pregnancy. The efficacy of CBT in preventing PD in pregnant women at risk is supported by only a few studies, presenting some methodological flaws. Conclusion: Better designed trials are needed to strongly support the efficacy of such psychotherapeutic preventive strategy in women at risk for PD.

Estudio mediante imagen funcional de resonancia magnética (fMRI) de las activaciones emotivas correlacionadas a la presentación de rostros extraños o del propio rostro en sujetos con personalidad inward y outward / Functional magnetic resonance imaging (fMRI) study of emotional expressions correlated to strange face expressions or of the itself in subjects with inward or outward personality

Introduction: Due to patterns ofreciprocity based on steady and coherent behaviours or, on the contrary, on articúlate and changing behaviours, attachment relationships produce personal meaning organizations respectively centred on inward or outward focus. In inward organizations, emotions are more distinct and reciprocity is more based on physical distance (protection, loneliness); in outward organizations, emotions are more blurred and reciprocity is more based on a semantic sight of relations (approval, rules). Thanks to the modern technologies of neuroimaging (especially functional magnetic resonance, flMR), a scientific, Uve study ofwhat happens when an emotion starts is now possible. Method: We studied in 10 healthy subjects the amygdala and other nervous system structures activations when the subject perceives emotional expressions by seeing an unknown face and his/her own face. Results were also matched with inward/outward organization (studied with clinical approach and MMPI2, QSP, MQOP). Results and Discussion: Our results proved that an unknown face produces higher activation on the subjects than their own face (surprise effect); the anger mostly activates the right amygdala, while the joy activates both the amygdalas or the left one (it produces a semantic decoding). Outward subjects, with respect to the inward ones, respond to the anger with a less intense and univocal pattern, actívate more cortical ßreas, not always respond to their own facial expressions and respond to the joy with an higher involvement ofthe left verbal hemisphere.

Introducción: Patrones de reciprocidad estable y coherente o, al contrario, no unívocos y cambiantes, permiten desarrollar organizaciones de significado personal con enfoque de la experiencia a lo interno (inward) o externo (outward). En los inward las emociones son más definidas y la reciprocidad es primordialmente física (protección, soledad); en los outward las emociones son más difuminadas y la reciprocidad es prevalentemente semántica (confirmación, reglas). Las modernas tecnologías de imágenes funcionales han permitido estudiar en vivo qué sucede cuando se experimenta una emoción. Método: Hemos estudiado, mediante imagen funcional de resonancia magnética (fMRI), las activaciones de la amígdalay de otras estructuras del SNCproducidas, en 10 voluntarios sanos, por estímulos emocionales externos estandarizados, tanto cuando el sujeto percibe expresiones emotivas relativas a un rostro extraño (tercera persona), como relativas al rostro propio (primera persona). Resultados y Discusión: Los resultados obtenidos han sido confrontados con las modalidades de enfoque inward o outward, atribuibles al funcionamiento de base de la personalidad individual. Tales modalidades han sido comprobadas mediante MMPI2, QSPyMQOP asociados a una evaluación clínica realizada por un psicoterapeuta experto. Los resultados indican que un rostro extraño produce activaciones mayores respecto al propio (efecto sorpresa), que la rabia activa mayormente la amígdala derecha, mientras que la alegría activa ambas amígdalas o la izquierda. Los outward, respecto a los inward, responden a la rabia de manera menos intensa y unívoca, activan más áreas corticales, pueden no responder a las emociones propias y tienen una mayor implicación del hemisferio verbal en la alegría.