Naira Vassalo Lage

Decision-making impairment is related to serotonin transporter promoter polymorphism in a sample of patients with obsessive-compulsive disorder.

OBJECTIVE Decision-making impairment is an important feature of some psychiatric disorders, such as attention-deficit/hyperactivity disorder and substance-use disorders, and is associated with dysfunction of the fronto-subcortical circuit, mainly the orbitofrontal cortex (OFC). Several data reports support significant correlations between decision-making impairment and the serotonin system. Thus, this neurotransmission system may be a major step in some cognitive features, particularly in OCD because serotonin is associated with this disorder. Therefore, the serotonin transporter promoter polymorphism (5-HTTLPR) may be related to the modulation of these cognitive characteristics. In a sample of Caucasian OCD patients, we explored the link between decision-making and the 5-HTTLPR. METHOD We used the Iowa Gambling Task (IGT) to measure decision-making in 49 OCD patients, according to the DSM-IV criteria. All patients were submitted to Y-BOCS, BDI, BAI, the Raven Progressive Matrices, the Continuous Performance Task, and the Trail Making Test. We grouped S- and/or Lg-carriers in view of the fact that these act in a nearly dominant way. RESULTS On IGT, S- and/or Lg-carriers had significantly lower scores on the third, fourth, and fifth blocks. These findings were confirmed after adjusting for clinical and cognitive variables. DISCUSSION Inconclusive findings about the link between OCD and 5-HTTLPR may be better elucidated by studying OCD subgroups that could be more related in some genetic characteristics. Based on our study, low performance on IGT is associated with S- and/or Lg-carriers. CONCLUSION Our results corroborate the hypothesis that the pattern of neuropsychological functioning observed in previous studies may constitute a biological marker or heritable endophenotype of OCD.

The relationship between the Met allele of the BDNF Val66Met polymorphism and impairments in decision making under ambiguity in patients with obsessive-compulsive disorder.

Brain‐derived neurotrophic factor (BDNF) gene has an important link to neurotransmitter systems, including serotonin, and seems to play a major role in emotional decision making. Impairment of decision making is an important feature of psychiatric disorders such as obsessive–compulsive disorder (OCD). We explore the link between decision making and the BDNF Val66Met polymorphism, which results in a reduction of BDNF activity, in a sample of Caucasian OCD patients. We used the Iowa Gambling Task (IGT) to measure decision making in 122 OCD patients. All patients were assessed using the Yale–Brown Obsessive–Compulsive Scale, the Beck Depression Inventory, the Beck Anxiety Inventory and the Raven Progressive Matrices. Patients also performed the Continuous Performance Task (CPT‐II) and the Trail Making Test (TMT). We grouped Met‐allele carriers because these act in a dominant way. Met‐allele carries exhibited low performance on both halves of the IGT (first half –F = −2.51, df = 120, P = 0.01; second half –F = −2.32, df = 120, P = 0.02). However, logistic regression analyses showed that the influence of the Met allele seemed to be restricted to the first half of the IGT [first half –β = 0.55, df = 1, P < 0.01, odds ratio (OR) = 5.62; second half –β = 0.32, df = 1, P = 0.15, OR = 2.30]. No differences were observed in tests used to evaluate executive functions associated with the dorsolateral prefrontal cortices (TMT and CPT‐II, df = 120, P > 0.05 for both). Met‐allele impairment may only be related to decisions made under ambiguous conditions. The null results involving TMT and CPT‐II are possibly related to the dysfunction of the orbitofrontal cortices that is associated with OCD.

Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder

OBJECTIVE A substantial body of evidence suggests that obsessive-compulsive disorder has a genetic component, and substantial candidate genes for the disorder have been investigated through association analyses. A particular emphasis has been placed on genes related to the serotonergic system, which is likely to play an important role in the pathogenesis of obsessive-compulsive disorder. The gene for tryptophan hydroxylase 2, which is a rate limiting enzyme in serotonin synthesis, is considered an important candidate gene associated with psychiatric disorders. METHOD Our sample consisted of 321 subjects (107 diagnosed with obsessive-compulsive disorder and 214 healthy controls), which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the entire human tryptophan hydroxylase 2 gene. Statistical analyses were performed using UNPHASED, version 3.0.12, and Haploview®. RESULTS Single markers, genotype analysis did not show a significant genetic association with obsessive-compulsive disorder. A significant association between the T-C-T (rs4448731, rs4565946, rs10506645) and C-A-T (rs4565946, rs7955501, rs10506645) haplotypes and obsessive-compulsive disorder was observed, as well as a strong linkage disequilibrium between SNPs rs4448731 and rs4565946, and SNPs rs10506645 and 4760820. DISCUSSION Our research has not demonstrated the existence of associations between the eight SNPs of TPH2 and obsessive-compulsive disorder. However, two LD and two haplotypes areas were demonstrated, thus suggesting that more studies in TPH2 are needed to investigate the role of tryptophan hydroxylase 2 variants in obsessive-compulsive disorder.

Addition of trazodone to sertraline: a probable synergistic action in a case of obsessive-compulsive disorder.

Dear Editor, Despite the considerable advances made with the introduction of the serotonin reuptake inhibitors (SRIs) into clinical practice, 40-60% of the subjects still fail to respond adequately to the initial therapy. Preliminary evidence supports the addition of antipsychotics, mainly atypical, to SRIs in obsessive-compulsive disorder (OCD). These agents combine serotonin-dopamine antagonism with the advantage of being well tolerated, including a low potential for inducing motor side-effects. In contrast, other serotonergic medications do not show satisfactory results as adjuvant treatments in treatment-refractory OCD.

Behavioral disinhibition without persistent mood elevation after high dose citalopram treatment

Dear Editor, This report suggests that emergent behavioral disinhibition during antidepressant treatment may represent milder expression of hypomania. The patient was a 33-year-old, married, Caucasian man with a 2-year history of chronic depression. He was an executive and became disabled due to depression. Laboratory work-up, including complete blood count, creatine kinase level, electrolytes, renal, liver and thyroid function tests, was unremarkable.