[show abstract][hide abstract] ABSTRACT: INTRODUCTION: The structural brain anomalies, present in a high percentage of psychotic patients, might have a progressive course in psychotic patients. The present study aimed to explore possible effects of BDNF Val66Met polymorphism variations on progressive structural brain changes after 3years from a first episode of psychosis. METHOD: Patients were part of a large epidemiological and longitudinal intervention program of first-episode psychosis, carried out at the University Hospital Marqués de Valdecilla, Cantabria, Spain. Eighty first-episode patients and 54 healthy controls were included in the final analyses. Brain magnetic resonance imaging (baseline and 3-year follow-up) and BDNF genotype, and clinical and functional outcome were investigated. RESULTS: We did not detect significant association between brain changes and BDNF Val66Met polymorphism variations in patients and controls (all p›0.060). At baseline, there were no significant associations between brain anomalies and BDNF genotype. Functional deficits were similar in Met-carrier and Val homozygote patients after 3-year follow-up (X(2)=0.66; p=0.564); there was no relationship between significant volume change across time and functional outcome. Otherwise, Met-carrier controls had significant high rates of alcohol-consumption (p=0.019) compared to Val homozygote controls. CONCLUSION: Our findings do not support the notion that BDNF genotype variations may mediate brain macroscopic morphological changes across time.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2013; · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Little is known about how genetic and environmental factors contribute to the association between parental negativity and behavior problems from early childhood to adolescence. The current study fitted a cross-lagged model in a sample consisting of 4,075 twin pairs to explore (a) the role of genetic and environmental factors in the relationship between parental negativity and behavior problems from age 4 to age 12, (b) whether parent-driven and child-driven processes independently explain the association, and (c) whether there are sex differences in this relationship. Both phenotypes showed substantial genetic influence at both ages. The concurrent overlap between them was mainly accounted for by genetic factors. Causal pathways representing stability of the phenotypes and parent-driven and child-driven effects significantly and independently account for the association. Significant but slight differences were found between males and females for parent-driven effects. These results were highly similar when general cognitive ability was added as a covariate. In summary, the longitudinal association between parental negativity and behavior problems seems to be bidirectional and mainly accounted for by genetic factors. Furthermore, child-driven effects were mainly genetically mediated, and parent-driven effects were a function of both genetic and shared-environmental factors.
Development and Psychopathology 05/2013; 25(2):487-500. · 4.40 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: To evaluate, in patients affected by an acute major depressive episode, what predictive value certain baseline psychopathological characteristics have with regard to expected therapeutic remission following biological antidepressant treatment (pharmacological/electroconvulsive; non-psychological). METHODS: Six predefined psychopathological characteristics in acute major depressive episode were evaluated using a logistic regression model through a protocolised antidepressant treatment to assess their predictive value with regard to expected remission rate. RESULTS: The final study sample consisted of 129 subjects affected by an acute major depressive episode. From the baseline evaluation of the anguish/restlessness, reduced emotional reactivity, reduced attention, reduced motor response, feeling of worthlessness, and mood characteristics items, it was possible to correctly classify 88.1% of the sample as remitter/non-remitter with sensitivity of 0.77 and specificity of 0.96. Addition of the 17-item HRSD baseline variable to the regression model increased the capacity for correct classification of the baseline sample by only 0.09%. LIMITATIONS: Protocolised antidepressant treatment was used. The results of this study may not be generalisable to pharmacological treatments not included in this protocol. CONCLUSIONS: The results of this study suggest that certain baseline psychopathological characteristics (and perhaps other clinical variables too) of the acute major depressive episode may be of great use in establishing patient subgroups according to expected clinical remission to the administration of biological antidepressant treatment. This could have considerable consequences for individualised therapeutic decision-making and for future researches (clinical trials included).
Journal of affective disorders 04/2013; · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: The relationship between cannabis and cognitive performance is controversial. While both acute administration and long-term cannabis use impair cognitive performance in healthy subjects, several studies have shown improved cognitive outcomes in patients with schizophrenia spectrum disorders who use cannabis. The aim of this study was to determine the relationship between lifetime cannabis use, as assessed longitudinally over 10 years of follow-up in a sample of 42 patients and 35 of their unaffected siblings, and current cognitive performance. Forty-two healthy control subjects were assessed at follow-up with the same instruments. Stepwise linear regression revealed a negative effect of longitudinal cannabis use on performance in a social cognition task in the patient group. In the sibling group, lifetime cannabis use had a negative effect on processing speed and declarative memory performance. In the control group, cannabis use per se did not predict cognitive performance; however, when adding lifetime tobacco use to the model, we found a negative association between lifetime cannabis and tobacco use and processing speed and social cognition performance. Moreover, a lower IQ associated with current cannabis use predicted worse attentional performance in the control group. The differential pattern of associations between cannabis use and cognitive performance in patients compared with siblings and controls can be explained by the negative impact of illness on cognition.
European Archives of Psychiatry and Clinical Neuroscience 04/2013; · 2.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: The functional variant Val(158)Met in the coding sequence of COMT gene is involved in the modulation of dopamine availability in the prefrontal cortex in both clinical and general population samples. It has been suggested that the interplay between this genotype and early environmental factors could be used to predict the observed variation in cognitive flexibility. However, other genetic variants and environmental factors may confound the association and produce the inconsistent results commonly found in the literature. In the present study we aimed at testing putative interaction mechanisms between childhood maltreatment and COMT genotypic variability that might explain a proportion of the observed variability of cognitive flexibility in the population. Our design was based on a sample of adult monozygotic twins, which allowed us to test these effects free from potential genetic and shared-environmental confounding factors. Results showed that unique environmental effects of childhood maltreatment significantly impacted cognitive performance among Met/Met subjects. Interestingly, the direction of the association indicated that exposure to early stressful experiences was associated with enhanced cognitive flexibility in this genotype group. These results suggest that COMT may operate as a plasticity gene that provides differential cognitive capacity to respond to environmental stressors.
Journal of psychiatric research 03/2013; · 3.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: The influence of genetic and/or environmental factors on the volumetric brain changes observed in subjects affected by anxiety and depression disorders remains unclear. The current study aimed to investigate whether genetic and environmental liabilities make different contributions to abnormalities in gray matter volume (GMV) in anxiety and depression using a concordant and discordant MZ twin pairs design. METHODS: Fifty-three magnetic resonance imaging (3T) brain scans were obtained from monozygotic (MZ) twins concordant (6 pairs) and discordant (10 pairs) for lifetime anxiety and depression disorders and from healthy twins (21 subjects). We applied voxel-based morphometry to analyse GMV differences. Concordant affected twins were compared to healthy twins and within-pairs comparisons were performed in the discordant group. RESULTS: GMV reductions in bilateral fusiform gyrus and amygdala were observed in concordant affected twins for anxiety and depression compared to healthy twins. No intrapair differences were found in GMV between discordant affected twins and their healthy co-twins. LIMITATIONS: The sample size was modest. This might explain why no intrapair differences were found in the discordant MZ twin group. CONCLUSIONS: As concordant affected MZ twins are believed to have a particularly high genetic liability for the disorder, our findings suggest that fusiform gyrus and amygdala gray matter reductions are related to a genetic risk for anxiety and depression. Discrepancies in regard to brain abnormalities in anxiety and depression may be related to the admixture of patients with GMV abnormalities mainly accounted for by genetic factors with patients presenting GMV mainly accounted for by environmental factors.
Journal of affective disorders 02/2013; · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: RATIONALE: The endocannabinoid system has been implicated in the pathogenesis of major depression (MD) as well as in the mediation of antidepressant drug effects. OBJECTIVES: To analyze CNR1 gene variants in MD and clinical response to citalopram (selective serotonin re-uptake inhibitors [SSRI]). METHODS: The role of CNR1 gene (rs806368, rs1049353, rs806371, rs806377 and rs1535255) was investigated in 319 outpatients with MD and 150 healthy individuals. A subsample of 155 depressive patients were treated with citalopram and evaluated for response (fourth week) and remission (12th week) by the 21-item Hamilton Depression Rating Scale (HDRS). RESULTS: We observed a higher frequency of rs806371 G carriers in MD patients with both presence of melancholia (p = 0.018) and psychotic symptoms (p = 0.007) than in controls. Haplotype frequency distributions between MD sample and controls showed a significant difference for Block 1 (rs806368-rs1049353-rs806371) (p = 0.008). This haplotype finding was consistent when we compared controls with MD subsample stratified by melancholia (p = 0.0009) and psychotic symptoms (p = 0.014). The TT homozygous of the rs806368 and rs806371 presented more risk of no Remission than the C carriers (p = 0.008 and 0.012, respectively). Haplotype frequency distributions according to Remission status showed a significant difference for Block 1 (p = 0.032). Also, we observed significant effect of time-sex-genotype interaction for the rs806368, showing that the C carrier men presented a better response to antidepressant treatment throughout the follow-up than TT homozygous men and women group (p = 0.026). CONCLUSIONS: These results suggest an effect of CNR1 gene in the etiology of MD and clinical response to citalopram.
[show abstract][hide abstract] ABSTRACT: Executive dysfunction represents a core deficit that is associated with schizophrenia spectrum disorders (SSDs). However, the longitudinal course of executive deficits in SSDs is still controversial. The aim of this study was to examine the executive performance of 34 SSD patients in relation to 34 of their unaffected siblings over a period of 10years. Both groups completed psychopathological and executive assessments. Thirteen healthy controls were assessed using the same instruments. At baseline, the SSD patients differed significantly from siblings and controls in their performance on the Trail Making Test-B (TMT-B) and the number of categories in which they succeeded in the Wisconsin Card Sorting Test (WCST). They also differed significantly from the controls in the total number of errors in the WCST. The siblings did not differ in executive functioning from the controls over the follow-up. Longitudinally, the patients demonstrated significant improvement only for the TMT-B. However, only 14.71% of the patients showed reliable and clinically significant improvements for the TMT-B, and 8.82% made more errors on the WCST at the follow-up evaluation. Less than 3% of the patients showed either improved or worse results on the remaining measures of the WCST. A stabilisation pattern for the WCST was observed in the three groups. The patients performed worse than their siblings and controls on both executive tests. Some patients exhibited significant improvements in the TMT-B over time, but this improvement was reliable and clinically significant for less than 15% of the sample. Thus, we conclude that the patients exhibited stable impairments over time in the executive functions assessed.
Schizophrenia Research 12/2012; · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: Serotonergic genes have been widely investigated regarding antidepressant response in major depressive disorder (MDD) but results are still not univocal. Methods: 159 MDD patients treated with citalopram were genotyped and evaluated by the 21-item Hamilton Depression Rating Scale at the beginning and every 4 weeks during the 12-week follow-up. Four serotonin-related genetic variants were tested for association with treatment outcome: tryptophane hydroxylase 1 (TPH1) rs1800532, monoamine oxidase A µVNTR, serotonin 2A receptor rs6311 and serotonin 2C receptor rs6318. The effect of these polymorphisms was tested both in the whole sample and in depressive subtypes with usually higher clinical severity: psychotic and melancholic MDD. Results: No effect on response, remission and symptom improvement was found for the four polymorphisms. However, rs1800532 was found to affect the outcome depending on the MDD subtype: the A allele predicted worse response both in MDD with psychotic (F((6, 378)) = 2.90; p = 0.009) and melancholic (F((6, 381)) = 2.86; p = 0.0097) features. Conclusions: The A allele at TPH1 rs1800532 may be associated with citalopram efficacy only in melancholic and psychotic MDD. These results suggest the usefulness of investigating the effect of genetic variants in conjunction with specific clinical features.
[show abstract][hide abstract] ABSTRACT: Childhood maltreatment and low socioeconomic status (SES) are considered stressful environmental events with lasting detrimental effects on adult mental health and associated cognitive performance, such as memory. However, the association between childhood maltreatment and low SES remains unclear, probably due to design limitations and putative confounding factors. Particular concerns have been raised on genetic influences, as genetic background may modulate the effects of environmental stressors. The aim of the present study was to examine the effect of childhood maltreatment on adult memory in low- and high-SES subjects, free of confounding due to other environmental and genetic influences. A monozygotic twin design based on 188 healthy adult subjects (94 twin pairs) from the general population was conducted. This design based on genetically identical individuals allowed disentangling the unique environmental effects of childhood maltreatment on memory, which was explored in low and high SES. Results showed that the unique environmental effects of childhood maltreatment were only evident in the high-SES group (β = -0.22; SE = 0.08; p < 0.01; 95 % CI = -0.375 to -0.066). By contrast, no evidence for this effect could be detected in the more stressful low-SES group. These results suggest that enriched environments may provide a more stable context where early stressful experiences can influence cognitive processes. This study provides preliminary support for the inclusion of environmental enrichment in studies addressing the impact of childhood maltreatment on adult cognition and psychiatric disorders.
European Archives of Psychiatry and Clinical Neuroscience 11/2012; · 2.75 Impact Factor
[show abstract][hide abstract] ABSTRACT: First line treatment of major depression is based on selective serotonin re-uptake inhibitors (SSRIs) that enhance serotonergic neurotransmission by blocking the serotonin transporter. However, clinical response is a complex phenomenon in which other systems such as the endocannabinoid system could be involved. Given the evidence for the role of the endocannabinoid system in the pathogenesis of depression as well as in the mediation of antidepressant drug effects, the aim of this study was to analyze genetic variability in the endocannabinoid system genes (CNR1, CNR2 and FAAH genes) and their role in clinical response (at week 4) and remission (at week 12) in SSRI (citalopram) treatment in a sample of 154 depressive outpatients, all of Spanish origin. All patients were treated with citalopram and followed over 12 weeks. Severity of depressive symptomatology was evaluated by means of the 21-item Hamilton Depression Rating Score (HDRS). No differences were found in any of the genotype distributions according to response or remission. The longitudinal study showed that (i) the CNR1 rs1049353-GG genotype conferred a better response to citalopram treatment in the subgroup of male patients and (ii) G allele carriers (CNR2 rs2501431) presented higher HDRS scores in the follow-up than AA homozygous allele carriers. Our results seem to suggest the involvement of CNR1 and CNR2 genes in clinical responses to citalopram treatment.
Journal of Psychopharmacology 07/2012; 26(10):1391-8. · 3.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: Despite extensive research, our knowledge of structural or functional pathology of severe mental disorders such as schizophrenia and major affective disorders is limited. The only etiological factor with reasonably firm foundation is inheritance, as evidenced by family, twin and adoption studies, however, the molecular basis of this heritability is not established yet. In the absence of clear knowledge about the biological substrate for these psychiatric disorders all the genes expressed in the human brain are potential candidate genes. Association studies analyze genetic variants (polymorphisms) in genes with presumed functional significance in the pathophysiology of the disease (candidate genes). These genetic studies compare the frequency of the hypothetical risk variant in people affected by the disease and in healthy control representatives of the same population. Also, simplex families with an affected child (trios) or with discordant affected offspring (quadruplets), can be used in the association studies. This strategy constitutes a tool to identify the small and moderate effects of genes in these complex phenotypes. Likewise, these kinds of studies could be useful to explain the effect of genes in some specific traits and symptoms present in functional psychoses. Some of our own results on serotoninergic system genes and major depression are included in this chapter as an example of case-control association developed studies in mental disorders.
Neurotoxicity Research 04/2012; 4(5-6):523-30. · 2.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: Only little information is available on prevalence of tardive dyskinesia (TD) in schizophrenia patients from developing countries like India. Present research was undertaken to study prevalence of TD in schizophrenia patients in Indian population. Our second objective was to compare occurrence of TD in subjects on atypical antipsychotics with those on typical antipsychotics and to identify possible factors causing risk of TD. Methods: A total of 160 outpatients fulfilling the DSM-IV TR criteria for schizophrenia and who received antipsychotics for at least one year were included in the study. Data pertaining demographic and clinical factors (on-set of illness, duration of illness, smoking history; use of anti-Parkinsonism agents, antidepressants, mood-stabilizers; antipsychotics, doses, duration of therapy, route of administration; past history of antipsychotic drug use and compliance with therapy) were collected. Among 160 patients, 90 received atypical antipsychotics and rest typical antipsychotics. These patients were assessed for dyskinetic movements with Abnormal Involuntary Movement Scale (AIMS) and Tardive Dyskinesia Rating Scale (TDRS). Schooler and Kane's criteria for TD was used to diagnose TD. Subjects with TD were compared with those without TD. Logistic regression analyses were used to examine relationship between TD and clinical risk factors. Results: The prevalence rate for probable TD was 26.4%. The study find-ings revealed occurrence of TD among atypical group as 20% and among typical group as 31.4%. The occurrence of TD with atypical antipsychotics was statistically significantly lower comparing occurrence of TD in typical antipsychotics. On univariate analysis, age, duration of treatment, duration of illness, past history of extrapyramidal symptoms, anticholergic use and intermittent treatment were found as important factors to predict TD. After controlling covariates using logistic regressions, total cumulative antipsy-chotic dose (in Chlorpromazine equivalence) and intermittent treatment were the factors which predicted TD. Age, gender, anticholergic use and nicotine abuse did not predict TD on regression analysis. Discussion: Prevalence of TD in schizophrenia in India is similar to preva-lence rates elsewhere in the world. The use of atypical antipsychotic was associated with significantly lower risk of tardive dyskinesia compared with typical antipsychotics. More systematic prospective studies are required to compare rates of TD in different atypical antipsychotics in drug-naïve schizophrenia patients to know the exact risk. This study corroborates re-lationship between TD and Cumulative antipsychotic dose and intermittent neuroleptic treatment. Background: Recent studies have shown that both childhood trauma and
Schizophrenia Research 01/2012; 136(1):1-375. · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Val158Met catechol-O-methyl transferase functional polymorphism has been repeatedly associated to differences in performing the Wisconsin Card Sorting Test in both, patients with schizophrenia and healthy individuals. However, this association has not been consistently replicated for the Trail Making Test part-B (TMT-B). In a sample of 89 patients suffering from a functional psychotic disorder and their healthy siblings we aim (i) to explore if there is any difference completing the TMT-B between both groups and among the different psychotic categories, and (ii) to investigate the association between the catechol-O-methyl transferase genotype and the TMT-B performance. Psychotic patients executed the TMT-B worse than the siblings group (P≤0.006). The patients (P=0.001) and the siblings (P=0.006) with the Val/Val genotype used more time to execute the test than those who carried the Met allele.
[show abstract][hide abstract] ABSTRACT: Abstract Objectives. Early-onset schizophrenia is considered to be neurobiologically similar to adult-onset forms, although it represents a more severe expression of the disorder. In the present study, we explored putative larger familial vulnerability of intellectual impairments in early-onset schizophrenia spectrum disorders (EOS) when compared to adult-onset (AOS) families. Methods. A sample of 340 subjects including schizophrenia spectrum disorder patients, their first degree relatives and age-matched healthy controls was assessed on intelligence quotient (IQ). We used linear regression analysis and intraclass correlation coefficients (ICC) to explore familial aggregation of IQ across age at onset groups. Results. The relationship between IQ level of patients and their first-degree relatives showed positive linear association (β = 0.43, P < 0.01). High significant familial aggregation was found for intelligence quotient in EOS families (ICC = 0.618, P < 0.01), while AOS families responded to lower estimates (ICC = 0.204, P = 0.26; between ICC comparison z = 1.993, P < 0.05). Conclusions. High aggregation of intellectual performance in the EOS group suggests larger familial vulnerability in early-onset forms of the disease when cognitive functions are considered. Within a continuum of psychopathology in schizophrenia spectrum disorders, specific genetic effects are discussed for distinct onset forms that might be in line with a neurodevelopmental model of the disease.
The World Journal of Biological Psychiatry 08/2011; 13(7):493-500. · 3.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: The well-established relationship between childhood adversity and psychosis is likely to involve other factors such as genetic variants that can help us to understand why not everyone exposed to adverse events develops psychotic symptoms later in life.
We investigated the influence of childhood abuse and neglect on positive and negative psychotic-like experiences in adulthood and the potential moderating effect of the BDNF-Val66Met polymorphism.
Psychotic-like experiences and childhood adversity were assessed in 533 individuals from the general population.
Childhood abuse showed a strong independent effect on the positive dimension of psychotic-like experiences (β = 0.16, s.e. = 0.05, P = 0.002). Furthermore, this association was moderated by the BDNF-Val66Met polymorphism (β = 0.27, s.e. = 0.10, P = 0.004).
Individuals exposed to childhood abuse are more likely to report positive psychotic-like experiences. Met carriers reported more positive psychotic-like experiences when exposed to childhood abuse than did individuals carrying the Val/Val genotype. Therefore, the observed gene-environment interaction effect may be partially responsible for individual variation in response to childhood abuse.
The British journal of psychiatry: the journal of mental science 07/2011; 199(1):38-42. · 6.62 Impact Factor
[show abstract][hide abstract] ABSTRACT: Dysbindin-1 is a relatively ubiquitous protein in the brain which is involved in the modulation of synaptic homeostasis. The dysbindin-1 gene (DTNBP1) has been associated with schizophrenia and bipolar disorder diagnoses. However, its contribution to the severity of the clinical and neurocognitive expression of these disorders remains controversial. We aimed to explore the association between DTNBP1 and the phenotypes which are more directly linked with the underlying biology, such as age at onset and neurocognitive impairment. The present family sample comprised 894 Caucasian individuals: 268 patients affected by functional psychosis [58% with illness onset before 18 years, mean age at onset (SD): 14.71 (2.10)], 483 parents and 143 siblings. Ten DTNBP1 single nucleotide polymorphisms were genotyped in all individuals and their transmission disequilibrium was tested in relation to: (i) the risk for psychosis; (ii) patients' age at onset; and (iii) familial neurocognitive performance (including IQ estimation and executive functioning). In early-onset families a 5-marker haplotype encompassing exons 2-4 and the surrounding introns was significantly over-transmitted to cases, while in adult-onset families two haplotypes corresponding to the region between introns 4 and 7 were over-transmitted to cases. Estimated IQ was associated with the rs760666 marker in the whole sample, whereas a significant association between executive functioning and the rs2619522 marker appeared in early-onset families. Our findings confirm the role of the dysbindin-1 gene in the risk for functional psychosis and show a differential haplotypic risk pattern in families with early as opposed to adult onset in the affected offspring.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 02/2011; 156B(3):322-33. · 3.23 Impact Factor
[show abstract][hide abstract] ABSTRACT: Abnormalities in white matter (WM) volumes and integrity in schizophrenia, together with post-mortem studies showing reduced expression of oligodendrocyte/myelination genes and apoptotic processes taking place in oligodendrocytes, suggest the interest of major regulators of apoptosis as candidate genes for some features related to myelin integrity in schizophrenia. Protein p53, encoded by TP53 gene, has a central role in the control of apoptosis and is involved in oligodendrocyte development. TP53 gene polymorphisms may account for variability in WM features, metabolic activity and biochemical markers of neuronal integrity and membrane turnover. Pro72Arg and Ins16bp polymorphisms at TP53 gene were analyzed in 20 DSM-IV schizophrenia patients. T1/T2-weighted sequences of these patients were acquired using a 1.5T Philips Gyroscan system. Scans were transformed into Talairach space and segmented into gray matter (GM), WM and cerebrospinal fluid (CSF) using Statistical Parametric Mapping under a ROI approach. Likewise dorsolateral prefrontal cortex (DLPFC) metabolic activity was measured using a procedure based on MRI/PET image fusion. In 13 of these patients proton magnetic resonance spectroscopy was used to examine N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) levels in dorsolateral-medial prefrontal cortex (DLMPFC). MRI data were adjusted for age and brain volume using regression parameters from a healthy control group (n=45). Patients Pro/Arg heterozygous (Pro72Arg polymorphism) showed a generalized deficit in whole-brain WM that was especially prominent in frontal lobe and a lower metabolic activity in the DLPFC as compared to Pro/Pro homozygous. Pro/Arg subjects also showed decreased NAA/Cho and increased Cho/Cr ratios in right DLMPFC. TP53 genetic variability influences WM volumes in frontal lobes and it seems to modulate the metabolic activity in this region. Our results suggest that TP53 might influence aspects of myelin and white matter integrity which may account for some of the frontal dysfunction features commonly described in these patients.
[show abstract][hide abstract] ABSTRACT: Neuroplastic processes are thought to be involved in the pathophysiology of major depression. It has been reported that serum brain-derived neurotrophic factor (BDNF) is decreased in depressed patients.
Compare BDNF levels in depressed patients and healthy controls in platelet poor plasma and in washed platelets. Observe the effects of 8- and 24-week treatment with S-citalopram on these levels.
We assessed the levels of BDNF in platelet poor plasma and in washed platelets from 18 major depression patients, and compared them with 14 healthy controls. Blood samples were obtained from patients before and during treatment (8 and 24 weeks) with a selective serotonin reuptake inhibitor, S-citalopram.
A significant decrease in severity of depressive symptoms was observed from the first month of treatment with S-citalopram, and symptoms continued decreasing until the 6th month. Plasma BDNF levels in untreated patients appeared significantly increased (p<0.01) but reached values similar to those of controls at the 24th week. In contrast, levels of platelet BDNF appeared significantly decreased (p<0.05), but treatment also normalized levels so that values obtained were equivalent to those of controls.
Untreated depressed patients showed increased plasma BDNF levels and decreased platelet BDNF levels, as compared with control subjects, and tend to normalize during treatment with S-citalopram for 24 weeks, with BDNF reaching levels similar to those in healthy controls at the 24th week in both samples. We observed that improvement in depressive symptoms was accompanied by normalization of plasma and platelet BDNF levels.