Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia.

Background: One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.

How do genes exert their role? Period 3 gene variants and possible influences on mood disorder phenotypes.

The action of multiple liability genes is responsible for complex phenotypes at the same time, a single gene, could control several phenotypic features. This is the case of human period 3 gene (hper3), mainly involved in the setting of the biologic clock. Some variants of this gene, besides being associated with the Delayed Sleep Phase Syndrome, showed a key role in determining evening preference rather than morning one.

Further evidence of MAO-A gene variants associated with bipolar disorder.

The aim of this study was to investigate MAOA gene variants in bipolar disorder by using a family-based association approach. The first sample included 331 nuclear families from Western and Central Canada with at least 1 offspring affected with bipolar disorder comprising a total of 1,044 individuals. All subjects were genotyped for MAOA-941T > G and -uVNTR gene variants using PCR techniques.

Serotonin transporter gene-linked polymorphic region: possible pharmacogenetic implications of rare variants.

A functional insertion/deletion (*l/*s) repeat polymorphism within the promoter region of the serotonin transporter (5-HTTLPR) has been described. An association between *l variant and a better and faster response to serotonin selective reuptake inhibitors in depressed patients was reported in Caucasians. The value of the explained variance due to the 5-HTTLPR, however, was 7% only, and different *l and *s variants were reported according to the nucleotide sequence of repeats.

Genes involved in Alzheimer's disease, a survey of possible candidates.

Alzheimer's disease (AD) is the major cause of dementia in the elderly. It is characterized by a progressive deterioration in memory and cognitive functions, but also behavioral symptoms are common. Many different genes are possibly involved in Alzheimer's Disease: four genetic factors were confirmed in different studies, while at least 50 additional genes were tested with contrasting results.

Polymorphisms of heat shock protein 70 gene (HSPA1A, HSPA1B and HSPA1L) and schizophrenia.

The heat shock protein 70 (HSP70) is believed to be involved in the pathogenesis of schizophrenia with regards to neurodevelopment. An aberration in the HSP70 has been proposed in schizophrenia patients, suggesting that it is a candidate gene for schizophrenia. This study aimed to investigate the association between the three polymorphisms of HSP70-1 (HSPA1A), HSP70-hom (HSPA1L) and HSP70-2 (HSPA1B) and schizophrenia.

No evidence for interaction between 5-HT2A receptor and serotonin transporter genes in schizophrenia.

This study was to aim at investigating the potential interaction for the serotonin receptor gene (5-HTR) 2A and serotonin transporter gene (5-HTTLPR) polymorphisms in the development of schizophrenia, as well as the interaction of the two polymorphisms in relation with symptomatology, family history, age of onset and antipsychotic response. Genomic DNA analysis with polymerase chain reaction (PCR) was used for the genotyping. One hundred and eleven (111) patients with schizophrenia and 172 normal controls participated in the study.

Pharmacogenetics in the treatment of depression: pharmacodynamic studies.

The pharmacological treatment of mood disorders has reduced their morbidity and improved mental health for millions of individuals worldwide, favouring a considerable reduction of the direct and indirect costs caused by these common pathologies. Unfortunately, not all individuals benefit, and 30-40% of patients do not show a complete response to treatment. Efficient clinical predictors are not available, although genetic factors are thought to play a substantial (but complex) role in the antidepressant response.

Pharmacogenetics of selective serotonin reuptake inhibitor response: a 6-month follow-up.

Background: We previously reported the association between some genetic factors and short-term antidepressant outcome. In the present paper we investigated the same gene variants in a prospective 6-months naturalistic follow-up.

Methods: The sample included 185 inpatients affected by recurrent major depression consecutively admitted to the Psychiatric Inpatient Unit of San Raffaele Hospital from 1998 to 2003 and prospectively followed for 6 months after their recovery.

The C(-1019)G polymorphism of the 5-HT1A gene promoter and antidepressant response in mood disorders: preliminary findings.

Several studies have demonstrated the involvement of 5-HT1A receptors in the pathogenesis of depression and in the antidepressant response to SSRIs. A functional new variant in the promoter region of the 5-HT1A gene was recently reported (-1019 C>G). The aim of this study is to investigate a possible association between this 5-HT1A receptor variant and antidepressant response to fluvoxamine in a sample of 262 mood-disorder subjects (151 major depressed and 111 bipolars) treated with fluvoxamine for 6 wk.

Further evidence of a combined effect of SERTPR and TPH on SSRIs response in mood disorders.

We reported an independent association of the short variant of the serotonin transporter gene-linked polymorphic region (SERTPR) and tryptophan hydroxylase (TPH) genes with antidepressant response to selective serotonin reuptake inhibitors (SSRIs). The aim of the present study was to confirm the effect of the SERTPR and TPH gene variants on the SSRIs antidepressant activity in a new sample of major and bipolar depressives. Two hundred and twenty one inpatients (major depressives = 128, bipolar disorder = 93) were treated with SSRIs (fluvoxamine or paroxetine) for 6 weeks; the severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression (HAMD).

Genetic features of antidepressant induced mania and hypo-mania in bipolar disorder.

Rationale And Objectives: The present study investigated possible genetic association between some polymorphisms possibly involved in antidepressant response and the occurrence of manic or hypo-manic switches during antidepressant treatment.

Methods: We retrospectively examined 169 individuals with a diagnosis of bipolar disorder (BP) type I ( n=103) and II ( n=66), who presented at least one sudden manic or hypo-manic episode (according to DSM IV criteria) during antidepressant therapy, that occurred within a period of 3 weeks from the beginning of the treatment and without any interposed period of well being ("manic switch"). They were compared with a sex, age, and ethnicity-matched group of 247 subjects, randomly selected from our pool of bipolar subjects, who never showed switches.

From molecular biology to pharmacogenetics: a review of the literature on antidepressant treatment and suggestions of possible candidate genes.

Pharmacogenetic studies in mood disorders are raising increasing interest, after the first findings of a significant association between antidepressant response and a functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR). However, the results of published studies are not unequivocal. The reasons of these discordances could be various: the small samples, which could affect the power to detect a good effect size, the use of different and often not comparable scales and methodologies to assess the response rates.

The 5-HT2C receptor as a target for mood disorders.

The serotonin (5-hydroxytryptamine2C [5-HT2C]) receptor is one of the 5-HT receptors with a G-protein-coupled intracellular signalling pathway. A large number of compounds showing antidepressive, antipsychotic and anxiolytic properties, and affecting sleep patterns, feeding behaviour and neuroendocrine functions, target this subtype of receptor. The potential use of 5-HT2C receptor ligands in psychiatry has been suggested as a result of a number of observations from animal and in vitro experiments.

Clinical features of antidepressant associated manic and hypomanic switches in bipolar disorder.

The present study investigated possible clinical differences between bipolar patients with and without manic or hypomanic switch during antidepressant (AD) treatment. The authors undertook a retrospective assessment of 169 individuals affected by bipolar disorder type I (BP I: n=96) and II (BP II: n=73) who experienced at least one manic or hypomanic episode following depression without any interposed normothymic period ("manic switch") during AD therapy. They were compared with a sex, age (+/-5 years), and ethnicity-matched group of 247 subjects, randomly selected from our pool of bipolar subjects who have never had manic switches.

[Microsporogenesis y microgametogenesis de annatto (Bixa orellana L.)].

A series of buds of increasing maturity were individually sampled in order to examine cytological events of annatto (Bixa orellana L.), genotype Portuguesa. They were fixed in Carnoy II at 12:30 am, time of the highest rate of meiotic division.

Predicting response to lithium in mood disorders: role of genetic polymorphisms.

Lithium is considered to be the first choice mood stabilizer in recurrent mood disorders. Its widespread and large-scale use is the result of its proven efficacy. In spite of this fact, patients have been observed to show a variable response to lithium treatment: in some cases it is completely effective in preventing manic or depressive relapses, while in other cases it appears to show no influence on the disease course.