Rosa Catalán

5-HTTLPR polymorphism of the serotonin transporter gene predicts non-remission in major depression patients treated with citalopram in a 12-weeks follow up study.

In the context of a long term follow-up study, we analysed the possible implication of the 5-HTTLPR polymorphism at the serotonin transporter gene in clinical response and remission of major depressive patients treated with citalopram. The sample consisted of 131 patients, all of Spanish origin, diagnosed according to DSM-IV criteria. A 21-item Hamilton Depression Rating Scale (HDRS) was used to evaluate severity of the symptoms during the follow-up and to determine clinical response and remission condition of the patients at 4th and 12th week, respectively. Our results showed that S/S genotype of the 5-HTTLPR polymorphism was associated with the non-Remission condition at 12th week (χ2 = 8.7, P = 0.013). Moreover, homozygous for the allele S presented three times more risk for non reaching remission of depressive episode after citalopram treatment than patients with any other 5-HTTLPR genotype combination (χ2: 7.29, P = 0.006; OR = 3.23 [95%CI: 1.24–8.5]). In conclusion, our results show that genetic variation of serotonin transporter is involved in clinical remission of major depressive episodes after twelve weeks of citalopram treatment.

Executive function and nonverbal memory in obsessive-compulsive disorder

It has been suggested that memory impairments found in obsessive-compulsive disorder (OCD) are mediated by organizational problems in encoding that are caused by primary executive dysfunction. Performance on different nonverbal memory and executive skills was tested in 68 subjects (35 non-depressed OCD sufferers and 33 healthy controls). Multiple regression models were performed to analyze the role of different cognitive variables, especially organizational encoding strategies in nonverbal memory. OCD patients performed significantly worse than controls in immediate nonverbal memory [Rey-Osterrieth Complex Figure Test (RCFT)] and on all the executive functions such as interference control (Stroop test), mental set shifting (Trail-Making Test), and organizational strategies (copy organization). As no differences were found in the memory of faces, where organizational strategies are minimal, it is possible to speculate that immediate nonverbal memory problems in OCD appear only when organizational strategies mediate the recalling process. Thus, memory deficits appear to have less to do with memory, per se, and more to do with the degree of organization necessary to effectively complete the task. Statistical analyses of mediation models showed the highest explanatory power for the organizational approach and demonstrated the mediation effect of organizational strategies in nonverbal impairment.

Cognitive Remediation Therapy for outpatients with chronic schizophrenia: A controlled and randomized study

Cognitive Remediation Therapy (CRT) is a novel rehabilitation approach designed to improve neurocognitive abilities such as attention, memory and executive functioning. The aim of the present study is to evaluate the effect of CRT on neurocognition, and secondarily on symptomatology and psychosocial functioning. Cognitive Behavioural Therapy (CBT) was used as a control condition because it aims to improve emotional problems and positive symptoms, focusing on modification of maladaptive beliefs and schemas, but neurocognition is not targeted. A total of 40 chronic patients with DSM-IV schizophrenia disorder were randomly assigned for 4 months to one of two treatment groups: CRT or CBT. Repeated assessments were conducted before and after the treatments and at the end of a follow-up period of 6 months. Additionally, a method to establish reliable change was calculated from a separate sample of 20 schizophrenic patients who were under standard medication without any kind of psychological treatment. Results showed that CRT produced an overall improvement on neurocognition (Mean effect size=0.5), particularly in verbal and nonverbal memory, and executive function. CBT showed the expected treatment effect on general psychopathology (anxiety and depression) but produced only a slight non-specific improvement in neurocognition (Working Memory). Furthermore, patients receiving CRT showed improvement in social functioning, demonstrating that cognitive improvements are clinically meaningful. These gains were still present at the 6 month follow-up.

Brain Effects of Cognitive Remediation Therapy in Schizophrenia: A Structural and Functional Neuroimaging Study

BACKGROUND Cognitive remediation therapy positively affects cognition and daily functioning in patients with schizophrenia. However, studies on the underlying neurobiological mechanisms of this treatment are scarce. The aim of the current study was to investigate functional and structural connectivity brain changes in schizophrenia patients after cognitive remediation therapy using a whole-brain approach that combined functional magnetic resonance imaging and diffusion tensor imaging. METHODS A randomized controlled trial with 30 schizophrenia outpatients and 15 healthy volunteers. A strategy-learning-based treatment was used as a cognitive remediation therapy. A social skills training that provides useful information about illness management was used as an active control. We investigated changes in the pattern of functional connectivity assessed during an n-back task by tensorial independent component analysis as implemented in the multivariate exploratory linear decomposition into independent components and in the fractional anisotropy index of white matter integrity using tract-based spatial statistics. RESULTS Brain networks activation pattern significantly changed in patients exposed to the cognitive treatment in the sense of normalizing toward the patterns observed in healthy control subjects. Additionally, in white matter, they showed an increase in fractional anisotropy index in the anterior part of the genu of the corpus callosum. Cognitive improvement, functional, and also structural changes showed statistically significant correlations. CONCLUSIONS Improvement in brain functioning detected after cognitive remediation therapy in schizophrenia patients might be based on an increase of the interhemispheric information transfer between the bilateral prefrontal cortexes via the corpus callosum.

Evidence for a combined genetic effect of the 5-HT1A receptor and serotonin transporter genes in the clinical outcome of major depressive patients treated with citalopram

In the context of a long-term follow-up study, we analysed the possible implication of the 5-HT1A receptor gene (HTR1A) -1018C/G polymorphism in the clinical outcome of major depressive patients treated with citalopram. We had previously reported an association between variation on the SERT gene (SLC6A4) and clinical remission after citalopram treatment. In the present 12-week follow-up study, the combined effect of HTR1A and SLC6A4 genes in clinical outcome and response to citalopram was also evaluated. The sample consisted of 130 patients, all of Spanish origin, who were diagnosed as having a current major depressive episode according to DSM-IV criteria. A 21-item Hamilton Depression Rating Scale was used to assess severity of symptoms at the beginning and during the follow-up to determine the outcome and remission status at week 12. Patients were genotyped for HTR1A gene and, in addition, for two polymorphisms at the CYP2C19 gene, which together account for the 87% of the Caucasian poor metabolizer phenotype. Data were analysed adjusting for the effect of poor metabolizers in clinical response. No independent effect was found for the 5-HT1A receptor gene in relation to clinical outcome or remission after citalopram treatment. However, a combined genetic effect of HTR1A and SLC6A4 genes was found to influence the clinical outcome of patients [F(4,102) = 2.89, p= 0.02]. When considering the remission status, an increase of patients carrying the risk genotype combination (S/S-G/G) was found among those subjects who did not reach remission (Fisher’s exact test = 0.009). Our results suggest that the combined effect of the serotonin transporter and the 5-HT1A receptor genes could be related to the clinical outcome of depressive patients treated with citalopram.

Association analysis between a functional polymorphism in the monoamine oxidase A gene promoter and severe mood disorders.

Monoamine oxidase A (MAOA) has been suggested to be involved in human behaviour and physiology due to its key role in the metabolism of several different biological amines including the neurotransmitters serotonin, norepinephrin and dopamine. Recently, a 30 bp repeat in the MAOA gene promoter (uMAOA) has been demonstrated to be polymorphic and to affect transcriptional activity. In the context of an association case–control study design, we analysed the uMAOA polymorphism in 389 unrelated patients affected by severe mood disorders (88 bipolar subjects and 301 major depressive individuals) and in 156 controls. No association was found between the uMAOA locus and bipolar disorder or major depression. However, an increase of high-activity uMAOA alleles was found in major depression female patients presenting a seasonal pattern (χ2=3.013, P=0.05) or psychotic symptoms in their episodes (χ2=2.679, P=0.07). In female bipolar disorder patients, long alleles were associated with longest times of admission (F=4.604, P=0.037). A trend for association with seasonal pattern was also defined in this group (data not corrected for multiple testing). Our results suggest that MAOA gene variation may modulate the expression of some clinical aspects of severe mood disorders, especially in females, and support the existence of a genetic and aetiologic heterogeneity underlying the diagnoses of bipolar disorder and major depression.

Cognitive mechanisms, psychosocial functioning, and neurocognitive rehabilitation in schizophrenia

The aim of the present study is to test Brenners model of cognitive functioning in schizophrenia. It is assumed that elementary cognitive disorders (attention and encoding) and complex cognitive disorders (recall, concept formation) reinforce each other. Cognitive disorders are supposed to cause detrimental effects on functional outcome. We used cognitive rehabilitation as a strategy to induce cognitive changes in 27 patients assigned to treatment groups following the cognitive modules of the Integrated Psychological Treatment (IPT). Ten schizophrenic patients without cognitive impairments worked as a control group. With only one minor conceptual change (replacing concept formation with executive function, a more comprehensive construct), we found that our data fitted with Brenners model. A relationship has been found between neuropsychological improvements and higher levels of autonomy and social functioning. These findings have important implications not only for cognitive assessment but also for selecting targets in cognitive rehabilitation.

Cognitive dysfunctions in recovered melancholic patients

Cognitive dysfunctions were studied in symptom-free patients suffering from Recurrent Depressive Disorder with melancholia. Their performances on a standard neuropsychological battery were compared with those of a healthy sample matched for age and educational level. Statistically significant differences were found in Immediate Visual Memory, Delayed Logical and Visual Memory, Paired Learning and Block Design. Results seem to indicate that the cognitive disfunctions are not likely to be only mnesic. All these data suggest that these disfunctions found in some melancholic depressives could not be state-dependent.

Executive function needs to be targeted to improve social functioning with Cognitive Remediation Therapy (CRT) in schizophrenia.

While the role of impaired cognition in accounting for functional outcome in schizophrenia is generally established, the relationship between cognitive and functional change in the context of treatments is far from clear. The current paper tries to identify which cognitive changes lead to improvements in daily functioning among persons with chronic schizophrenia who had current negative symptoms and evidenced neuropsychological impairments. In a previous work, Cognitive Remediation Therapy (CRT) was compared with a control therapy, involving similar length of therapist contact but different targets. At the end of treatment, CRT conferred a benefit to people with schizophrenia in cognition and functioning [Schizophrenia Research, 87 (2006) 323-331]. Subsequently, analyses of covariance (ANCOVA) were conducted with baseline and cognitive change scores as covariates to test whether cognitive change predicted change in functioning. Additionally, statistical tests to establish the mediation path with significant variables were performed. Although verbal memory, but not executive functioning, was associated with functioning at baseline, it was the improvement in executive functioning that predicted improved daily functioning. Verbal memory played a mediator role in the change process. Consequently, in order to improve daily functioning with CRT, executive function still needs to be targeted in despite of multiple cognitive impairments being present.

Analysis of structural polymorphisms and C-1018G promoter variant of the 5-HT 1A receptor gene as putative risk factors in major depression

Analysis of structural polymorphisms and C-1018G promoter variant of the 5-HT 1A receptor gene as putative risk factors in major depression