Uncovering the Genetic and Molecular Features of Huntington's Disease in Northern Colombia.

Huntington's disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene. Juan de Acosta, Atlántico, a city located on the Caribbean coast of Colombia, is home to the world's second-largest HD pedigree. Here, we include 291 descendants of this pedigree with at least one family member with HD. Blood samples were collected, and genomic DNA was extracted. We quantified the HTT CAG expansion using an amplicon sequencing protocol. The genetic heterogeneity was measured as the ratio of the mosaicism allele's read peak and the slippage ratio of the allele's read peak from our sequence data. The statistical and bioinformatic analyses were performed with a significance threshold of p < 0.05. We found that the average HTT CAG repeat length in all participants was 21.91 (SD = 8.92). Of the 291 participants, 33 (11.3%, 18 females) had a positive molecular diagnosis for HD. Most affected individuals were adults, and the most common primary and secondary alleles were 17/7 (CAG/CCG) and 17/10 (CAG/CCG), respectively. The mosaicism increased with age in the participants with HD, while the slippage analyses revealed differences by the HD allele type only for the secondary allele. The slippage tended to increase with the HTT CAG repeat length in the participants with HD, but the increase was not statistically significant. This study analyzed the genetic and molecular features of 291 participants, including 33 with HD. We found that the mosaicism increased with age in the participants with HD, particularly for the secondary allele. The most common haplotype was 17/7_17/10. The slippage for the secondary allele varied by the HD allele type, but there was no significant difference in the slippage by sex. Our findings offer valuable insights into HD and could have implications for future research and clinical management.

Theory of Mind in Huntington's Disease: A Systematic Review of 20 Years of Research.

Background: People with Huntington's disease (HD) exhibit neurocognitive alterations throughout the disease, including deficits in social cognitive processes such as Theory of Mind (ToM). Objective: The aim is to identify methodologies and ToM instruments employed in HD, alongside relevant findings, within the scientific literature of the past two decades. Methods: We conducted a comprehensive search for relevant papers in the SCOPUS, PubMed, APA-PsyArticles, Web of Science, Redalyc, and SciELO databases. In the selection process, we specifically focused on studies that included individuals with a confirmed genetic status of HD and investigated ToM functioning in patients with and without motor symptoms. The systematic review followed the PRISMA protocol. Results: A total of 27 papers were selected for this systematic review, covering the period from 2003 to 2023. The findings consistently indicate that ToM is globally affected in patients with manifest motor symptoms. In individuals without motor symptoms, impairments are focused on the affective dimensions of ToM. Conclusions: Based on our analysis, affective ToM could be considered a potential biomarker for HD. Therefore, it is recommended that ToM assessment be included as part of neuropsychological evaluation protocols in clinical settings. Suchinclusion could aid in the identification of early stages of the disease and provide new opportunities for treatment, particularly with emerging drugs like antisense oligomers. The Prospero registration number for this review is CRD42020209769.

ADGRL3, FGF1 and DRD4: Linkage and Association with Working Memory and Perceptual Organization Candidate Endophenotypes in ADHD.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurobehavioral disorder that affects children worldwide, with detrimental long-term consequences in affected individuals. ADHD-affected patients display visual-motor and visuospatial abilities and skills that depart from those exhibited by non-affected individuals and struggle with perceptual organization, which might partially explain impulsive responses. Endophenotypes (quantifiable or dimensional constructs that are closely related to the root cause of the disease) might provide a more powerful and objective framework for dissecting the underlying neurobiology of ADHD than that of categories offered by the syndromic classification. In here, we explore the potential presence of the linkage and association of single-nucleotide polymorphisms (SNPs), harbored in genes implicated in the etiology of ADHD (ADGRL3, DRD4, and FGF1), with cognitive endophenotypes related to working memory and perceptual organization in 113 nuclear families. These families were ascertained from a geographical area of the Caribbean coast, in the north of Colombia, where the community is characterized by its ethnic diversity and differential gene pool. We found a significant association and linkage of markers ADGRL3-rs1565902, DRD4-rs916457 and FGF1-rs2282794 to neuropsychological tasks outlining working memory and perceptual organization such as performance in the digits forward and backward, arithmetic, similarities, the completion of figures and the assembly of objects. Our results provide strong support to understand ADHD as a combination of working memory and perceptual organization deficits and highlight the importance of the genetic background shaping the neurobiology, clinical complexity, and physiopathology of ADHD. Further, this study supplements new information regarding an ethnically diverse community with a vast African American contribution, where ADHD studies are scarce.

Impulsive and Omission Errors: Potential Temporal Processing Endophenotypes in ADHD.

Temporal processing (TP) is associated with functions such as perception, verbal skills, temporal perspective, and future planning, and is intercorrelated with working memory, attention, and inhibitory control, which are highly impaired in individuals with attention deficit hyperactivity disorder (ADHD). Here we evaluate TP measures as potential endophenotypes in Caribbean families ascertained from probands affected by ADHD. A total of 232 individuals were recruited and clinically evaluated using an extensive battery of neuropsychological tasks and reaction time (RT)-based task paradigms. Further, the heritability (genetic variance underpinning phenotype) was estimated as a measure of the genetics apportionment. A predictive framework for ADHD diagnosis was derived using these tasks. We found that individuals with ADHD differed from controls in neuropsychological tasks assessing mental control, visual-verbal memory, verbal fluency, verbal, and semantic fluency. In addition, TP measures such as RT, errors, and variability were also affected in individuals with ADHD. Moreover, we determined that only omission and commission errors had significant heritability. In conclusion, we have disentangled omission and commission errors as possible TP endophenotypes in ADHD, which can be suitable to assess the neurobiological and genetic basis of ADHD. A predictive model using these endophenotypes led to remarkable sensitivity, specificity, precision and classification rate for ADHD diagnosis, and may be a useful tool for patients' diagnosis, follow-up, and longitudinal assessment in the clinical setting.

Genetic Variation Underpinning ADHD Risk in a Caribbean Community.

Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and prevalent neurodevelopmental disorder that frequently persists into adulthood. Strong evidence from genetic studies indicates that single nucleotide polymorphisms (SNPs) harboured in the ADGRL3 (LPHN3), SNAP25, FGF1, DRD4, and SLC6A2 genes are associated with ADHD. We genotyped 26 SNPs harboured in genes previously reported to be associated with ADHD and evaluated their potential association in 386 individuals belonging to 113 nuclear families from a Caribbean community in Barranquilla, Colombia, using family-based association tests. SNPs rs362990-SNAP25 (T allele; p = 2.46 × 10-4), rs2282794-FGF1 (A allele; p = 1.33 × 10-2), rs2122642-ADGRL3 (C allele, p = 3.5 × 10-2), and ADGRL3 haplotype CCC (markers rs1565902-rs10001410-rs2122642, OR = 1.74, Ppermuted = 0.021) were significantly associated with ADHD. Our results confirm the susceptibility to ADHD conferred by SNAP25, FGF1, and ADGRL3 variants in a community with a significant African American component, and provide evidence supporting the existence of specific patterns of genetic stratification underpinning the susceptibility to ADHD. Knowledge of population genetics is crucial to define risk and predict susceptibility to disease.

ADGRL3 (LPHN3) variants predict substance use disorder.

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we assembled recursive-partitioning frameworks (classification tree analyses) with clinical, demographic, and ADGRL3 genetic information to predict SUD susceptibility. Our results indicate that SUD can be efficiently and robustly predicted in ADHD participants. The genetic models used remained highly efficient in predicting SUD in a large sample of individuals with severe SUD from a psychiatric institution that were not ascertained on the basis of ADHD diagnosis, thus identifying ADGRL3 as a risk gene for SUD. Recursive-partitioning analyses revealed that rs4860437 was the predominant predictive variant. This new methodological approach offers novel insights into higher order predictive interactions and offers a unique opportunity for translational application in the clinical assessment of patients at high risk for SUD.

The role of neuropsychologic tests in the diagnosis of attention deficit hyperactivity disorder.

Attention, memory, executive function, language, and visual-motor skills were evaluated in a sample of 621 children, 6 to 11 years old, to assess the discriminant validity of neuropsychologic testing. Attention deficit hyperactivity disorder cases (249) and controls (372) were identified and tested. Analysis of covariance, nonparametric comparison tests, effect sizes, discriminant function, factor analyses, and receiver-operator characteristics curve analyses were used to establish the best diagnostic cutoff points for each variable. Statistically significant differences were found on cognitive effort, auditory skills, continuous performance test, working memory, visual-motor skills, verbal comprehension, and executive function measures (P < 0.05); however, the effect of group sizes was low to modest (0.24 to 0.54). Receiver-operator characteristics curve analysis showed modest sensitivity and low specificity, demonstrating that an important proportion of the variance in test scores was overlapping. Factor analysis of neuropsychologic testing results revealed a structure of six factors each for attention deficit hyperactivity disorder, control, and combined samples. The latent variables produced one discriminant function with a total correct classification accuracy of 61.9%. Neuropsychologic tests should be used as Attention Deficit Hyperactivity Disorder diagnostic tools with caution, but they hold promise for identifying core cognitive deficits and processes that can aid prevention and intervention.

Evaluating empathy in Colombian ex-combatants: Examination of the internal structure of the Interpersonal Reactivity Index (IRI) in Spanish.

The Republic of Colombia has a long-standing history of internal armed conflict, further complicated by the ideological assumptions underlying their war. In recent years, its government designed the Program for Reincorporation to Civilian Life (Programa para la Reincorporación a la Vida Civil, PRVC), aiming demobilization of thousands of insurgents who were involved in guerilla and paramilitary forces. One PRVC goal involves the psychological characterization of its reincorporated members, aiming the informed design of effective and efficacious interventions to improve their adjustment. We are interested in the examination of empathy in this population. Empathy refers to the ability to predict, understand, and experience other's feelings. Empathy appears to have an effect on level of aggressive behavior. The Interpersonal Reactivity Index (IRI; Davis, 1980, 1983) is a well-established 28-item self-report tool for the assessment of empathy, including 4 scales: Perspective Taking, Fantasy, Empathic Concern, and Personal Distress. Versions in Spanish were validated in Spain and Chile, but no norms for Colombians exist. We examined the factorial structure of the IRI in a sample of 548 (83.4% males) members of the PRVC. Ten items with low factor loadings were eliminated following a series of confirmatory factor analyses (CFA). The final 4-factor model (Model 2) reached an acceptable fit (e.g., CFI = .898). A second-order CFA demonstrated that empathic concern correlated too high with a common "empathy" latent factor. With these results at hand, our 18-item IRI version in Spanish achieved a factorial structure comparable to that previously validated for Spanish speakers from other countries. (PsycINFO Database Record

Social Cognitive Training Improves Emotional Processing and Reduces Aggressive Attitudes in Ex-combatants.

Emotional processing (EP) is a complex cognitive function necessary to successfully adjust to social environments where we need to interpret and respond to cues that convey threat or reward signals. Ex-combatants have consistently shown atypical EP as well as poor social interactions. Available reintegration programs aim to facilitate the re-adaptation of ex-combatants to their communities. However, they do not incorporate actions to improve EP and to enhance cognitive-emotional regulation. The present study was aimed at evaluating the usefulness of an intervention focused on Social Cognitive Training (SCT), which was designed to equip ex-combatants enrolled in the Social Reintegration Route with EP and social cognition skills. A group of 31 ex-combatants (mean age of 37.2, 29 men) from Colombian illegal armed groups were recruited into this study. Of these, 16 were invited to take part in a SCT and the other continued with the conventional reintegration intervention. Both groups underwent 12 training sessions in a period 12-14 weeks. They were assessed with a comprehensive protocol which included Psychosocial, Behavioral, and Emotion Processing instruments. The scores on these instruments prior to and after the intervention were compared within and between groups. Both groups were matched at baseline. Ex-combatants receiving the SCT experienced significant improvements in EP and a reduction in aggressive attitudes, effects not observed in those continuing the conventional reintegration intervention. This is the first study that achieves such outcomes in such a population using SCT intervention. We discuss the implications of such results toward better social reintegration strategies.

Atypical Modulations of N170 Component during Emotional Processing and Their Links to Social Behaviors in Ex-combatants.

Emotional processing (EP) is crucial for the elaboration and implementation of adaptive social strategies. EP is also necessary for the expression of social cognition and behavior (SCB) patterns. It is well-known that war contexts induce socio-emotional atypical functioning, in particular for those who participate in combats. Thus, ex-combatants represent an ideal non-clinical population to explore EP modulation and to evaluate its relation with SCB. The aim of this study was to explore EP and its relation with SCB dimensions such as empathy, theory of mind and social skills in a sample of 50 subjects, of which 30 were ex-combatants from illegally armed groups in Colombia, and 20 controls without combat experience. We adapted an Emotional Recognition Task for faces and words and synchronized it with electroencephalographic recording. Ex-combatants presented with higher assertion skills and showed more pronounced brain responses to faces than Controls. They did not show the bias toward anger observed in control participants whereby the latter group was more likely to misclassify neutral faces as angry. However, ex-combatants showed an atypical word valence processing. That is, words with different emotions yielded no differences in N170 modulations. SCB variables were successfully predicted by neurocognitive variables. Our results suggest that in ex-combatants the links between EP and SCB functions are reorganized. This may reflect neurocognitive modulations associated to chronic exposure to war experiences.

Prepotent response inhibition and reaction times in children with attention deficit/hyperactivity disorder from a Caribbean community.

Impairment in inhibitory control has been postulated as an underlying hallmark of attention deficit/hyperactivity disorder (ADHD), which can be utilized as a quantitative trait for genetic studies. Here, we evaluate whether inhibitory control, measured by simple automatized prepotent response (PR) inhibition variables, is a robust discriminant function for the diagnosis of ADHD in children and can be used as an endophenotype for future genetic studies. One hundred fifty-two school children (30.9% female, 67.8% with ADHD) were recruited. The ADHD checklist was used as the screening tool, whilst the DSM-IV Mini International Neuropsychiatry Interview, neurologic interview and neurologic examination, and the WISC III FSIQ test were administered as the gold standard procedure to assert ADHD diagnosis. A Go/No-Go task using a naturalistic and automatized visual signal was administered. A linear multifactor model (MANOVA) was fitted to compare groups including ADHD status, age, and gender as multiple independent factors. Linear discriminant analysis and the receiver operating characteristic curve were used to assess the predictive performance of PR inhibition variables for ADHD diagnosis. We found that four variables of prepotent response reaction time- and prepotent response inhibition established statistically significant differences between children with and without ADHD. Furthermore, these variables generated a strong discriminant function with a total classification capability of 73, 84% specificity, 68% sensitivity, and 90% positive predictive value for ADHD diagnosis, which support reaction times as a candidate endophenotype that could potentially be used in future ADHD genetic research.

Screening for conduct disorder in an adolescent male sample from Colombia.

This study assessed the validity, reliability, and utility of a screening measure for detecting the signs or symptoms of Conduct Disorder in male adolescents from schools in Medellín, Colombia. A first study examined the differences between 70 male offender adolescents (aged 12-16 years) attending alternative education institutions, and 68 (sex, age, and socioeconomic status (SES)-matched) adolescent controls attending regular schools. A CD checklist (CD-CL) was constructed to be used by mothers (CD-CL-M) and for self-report by adolescents (CD-CL-SR). The validity of the screener for CD diagnosis was supported by significant differences between groups (ANOVA, p<.001). The CD-CL-SR had better sensitivity/specificity with a diagnostic cut-off point of 5 (sensitivity=95.3% and specificity=90.5%) than the CD-CL-M. A second study used the CD-CLSR with a random sample of 190 male adolescents (aged 12 to 16 years) from schools of low, middle and high SES. Reliability as assessed by Cronbach's alpha was 0.86. An epidemiological cut point of 5 classified 35.5% of the adolescents assessed as probable CD cases. A psychometric cut point at T score>59 (85th percentile) estimated 16.8% of the sample as probable CD cases. A psychometric cut point at T score>64 (90th percentile) revealed that 10.5% of the sample would be severe CD cases. Some significant differences (p<0.001) in proportions of CD adolescents were found between age and SES groups. It was concluded that such a high frequency of conduct problems in adolescence argues for the need for preventive programs in Colombian schools.

Validation of two rating scales for attention-deficit hyperactivity disorder diagnosis in Colombian children.

This study assesses the validity of the Behavioral Assessment System for Children-parent and teacher questionnaires for attention-deficit hyperactivity disorder diagnosis in a randomized sample of 344 Colombian children (145 cases, 199 controls), males and females, ages 6 to 11, with an estimated Wechsler Full Scale Intelligence Quotient over 70. The assessment protocol for both groups included psychiatric, neurologic, and psychological interviews, parent and teacher rating forms, and an Attention-Deficit Hyperactivity Disorder Checklist. All Behavioral Assessment System for Children-parent and teacher dimensions, except withdrawal and somatization, significantly differentiated cases and controls. Parents and teachers rated attention-deficit hyperactivity disorder combined type children as significantly more aggressive. Both questionnaires had good discriminant accuracy for detecting cases and control children, but accuracy for discriminating between attention-deficit hyperactivity disorder subtypes was poor. The Behavioral Assessment System for Children-parent and teacher questionnaires for 6- to 11-year-olds may be useful tools for diagnosing the presence of attention-deficit hyperactivity disorder. Additional assessment methods will be needed to discriminate between the subtypes.

Cross-cultural validation of a behavioral screener for executive functions: Guidelines for clinical use among Colombian children with and without ADHD.

Garcia-Barrera, Kamphaus, and Bandalos (2011) derived a 25-item executive functioning screener from the Behavior Assessment System for Children (BASC), measuring 4 latent executive constructs: problem solving, attentional control, behavioral control, and emotional control. The current study included a cross-cultural examination of this screener in Colombian children with and without attention-deficit/hyperactivity disorder (ADHD). BASC teacher ratings were collected for Colombian children ages 6-11 years (848 healthy children [53% boys] and 155 children with ADHD [76% boys]). To examine the psychometric properties of the screener, a multistep procedure was implemented, including (a) confirmatory factor analysis (CFA) and factorial invariance testing across gender, age group (6-8 years, 9-11 years), and ADHD status to replicate and extend the original derivation; (b) item response theory (IRT) analysis to evaluate the information provided by individual items; and (c) given IRT results, a repeated CFA and invariance testing after the exclusion of 1 item from the problem-solving factor. The 24-item 4-factor model fit was adequate for controls and for ADHD participants. Results support the use of the 24-item executive functioning screener in a cross-cultural context. In turn, in supplemental material, normative data for the Colombian sample are reported along with bilingual guidelines (i.e., Spanish/English) for implementing the screener in clinical practice. Even though the screener is useful when examining executive functions, it was not designed as a diagnostic measure for developmental disorders such as ADHD; as such, it should only inform about status of executive functioning.

Attention-deficit/hyperactivity disorder and comorbidities in 18 Paisa Colombian multigenerational families.

OBJECTIVE: Eighteen extended multigenerational families were recruited from the genetically isolated Paisa community in Colombia to conduct genetic studies of attention-deficit/hyperactivity disorder (ADHD). This report describes the inclusion strategy and clinical features of participants to facilitate comparisons with other data sets. METHOD: Families were selected through a fixed-sampling scheme beginning with child probands referred for clinical evaluation for ADHD. Direct structured psychiatric interviews were conducted with 433 informative individuals, including 92 children aged 4 to 11, 57 adolescents aged 12 to 17, and 284 adults. Best estimate ADHD diagnoses were established for each informative pedigree member. RESULTS: These families contained a high proportion of individuals affected with ADHD (32.8%), which was highly comorbid with conduct disorder (50%; odds ratio 11.5, 95% confidence interval = 6.4-20.9), oppositional defiant disorder (25.4%; odds ratio 2.7, confidence interval = 1.5-4.8), and associated conditions including nicotine dependence and alcohol abuse and/or dependence. CONCLUSIONS: ADHD in these extended Paisa families is highly comorbid with conduct and oppositional defiant disorders. This pattern of comorbidity, as well as the large dense pedigrees of the sample, suggests that it will be particularly useful for molecular genetic studies that are currently under way.

Statistical analyses of structural magnetic resonance imaging of the head of the caudate nucleus in Colombian children with attention-deficit hyperactivity disorder.

Magnetic resonance imaging (MRI) studies of the caudate nucleus have reported reversal asymmetry and alterations of its size, suggesting a striate cortical disorder related to attention-deficit hyperactivity disorder (ADHD). The objective was to evaluate whether alterations of the asymmetry and size of the caudate nucleus head exist in a sample of well-controlled 7- to 11-year-old Colombian children, with different types of ADHD. Two groups of cases-ADHD of the combined type and ADHD of the inattentive type-and one control group, were selected. Multiple methods for assessing ADHD (rating scales, psychologic.interview, neurologic history and examination, and neuropsychologic evaluation) were used to confirm the diagnoses. Participants with a history of language disorder, learning disabilities, depression, and other major neurologic and psychiatric conditions were excluded. Finally all groups had 15 children, matched by sex (7 male, 8 female), age, socioeconomic status, and grade. Height, weight, head circumference, and encephalic index were statistically controlled. Three T1-weighted volumetric (three-dimensional) MRI slides of the caudate nucleus head were obtained with a 1.5-Tesla Gyroscan apparatus. The control group had a significantly higher Wechsler Full-Scale IQ than the groups with ADHD of the combined type and ADHD of the inattentive type (P < .001). Volumes from the left caudate nucleus head were significantly larger than volumes from the right in all groups (P < .001). There were no group differences when volumes were compared between groups. All of the groups had left caudate nucleus head volumes significantly higher than right, although there were no between-group differences. The results in relation to previous studies are discussed.

[Dimensions of Empathy in Ex-Combatants of the Colombian Armed Conflict Using a Standardized Scale]. / Dimensiones de la empatía en excombatientes del conflicto armado colombiano utilizando una escala estandarizada.

INTRODUCTION: Empathy is one of the main concepts of in social neurosciences. It is defined as a trait with multiple dimensions allowing individuals to place themselves in the emotional states of others. Colombia has an irregular, internal and long-lasting armed conflict which has been increasing its cruelty levels. OBJECTIVES: to assess the empathy dimensions of 285 ex-combatants from the internal Colombian conflict, using the Interpersonal Reactivity Index(IRI) in Spanish. METHODOLOGY AND SUBJECTS: a sample of 285 male ex-combatants, 241 (84, 6%) males: 85,3% paramilitaries, and 14,7% guerillas. The 28 Item IRI questionnaires were administered. 3 exploratory factor analyses (EFA) were performed. Confirmatory factor analyses (CFA) were developed using structural equation procedures. RESULTS: The first EFA obtained 9 factors (KMO=0,74, variance 54,7% and internal consistency (IC): 0,22 - 0,63). The second EFA produced 20 items with burdens above 0,4 and showed a 6-factor structure (KMO=0,70, variance 50,3%, IC: 0,37 - 0,63). The third EFA forced the 4 original IRI dimensions (KMO=0,74, variance 33,77, IC: 0,44 - 0,77. CFAs showed goodness of adjustment indexes adequate for the three models. The 4-factor model obtained the lowest value, while the 6-factor model obtained the highest. The 4- factor model showed the best IC. CONCLUSION: The Spanish IRI administered to ex-combatants of the Colombian conflict has possible structures of 4, 6 and 9 factors. The best adjustment was for the 6-fctor. The 4-factor model exhibited the best IC.

Trombólisis con activador recombinante del plasminógeno tisular (rt-PA) para el ataque cerebro vascular agudo: la experiencia colombiana / Thrombolysis with rt-PA for acute stroke: Colombian experience

RESUMEN El tratamiento con activador recombinante del plasminógeno tisular (sigla en inglés rt-PA), aplicado por vía intravenosa (VIV) es el procedimiento de primera línea en casos de ataque cerebrovascular agudo (ACVA) en una ventana de 4,5 horas. En Colombia hay una experiencia publicada del uso exitoso de este medicamento. En el número actual se publica una nueva experiencia del uso de rt-PA en el caribe colombiano, de gran utilidad para reseñar los artículos publicados en Colombia acerca del tema.

ABSTRACT Treatment with intravenous recombinant tissue plasminogen activator (rt-PA) for acute stroke (AS) is the first line procedure for patients in 4,5 hours window. In Colombia there is a published experience about the successful use of this medication. In the currently issue a new experience from Colombian Caribbean is presented, which it is taken in advantage for briefly reviewing the published papers about the theme in our country.

[Diagnostic validity of attention deficit/hyperactivity disorder: from phenomenology to neurobiology (II)]. / Validez del diagnostico de trastorno por deficit de atencion/hiperactividad: de lo fenomenologico a lo neurobiologico (II).

The diagnostic criteria for the attention deficit/hyperactivity disorder (ADHD) were defined by the American Psychiatric Association in the Diagnostic and Statistical Manual of Mental Disorders, fourth version. ADHD is a neuro-psychiatric disorder associated with impairments in everyday life and behavioral dysregulation (i.e. inattention, hyper-activity and impulsivity), and it has showed empirical evidence from clinical, pharmacological, and psychometric studies. Nevertheless, the role of neurobiological impairments in the presentation of the symptoms remains unclear. For this paper, the authors reviewed Spanish and English literature that support the neurobiological validity of the disorder, aimed to present evidence associated with its cognitive and behavioral phenotype (e.g. in: neuropsychology, electrophysiology, structural and functional magnetic resonance imaging, neurochemistry and genetics). Additionally, an integrative theoretical clinical and scientific proposal is presented. Finally, the introduction of neurobiological marker as part of the definitive diagnosis is suggested, as a started point for the identification of therapeutic targets.

Analysis of brain metabolism by proton magnetic resonance spectroscopy (1H-MRS) in attention-deficit/hyperactivity disorder suggests a generalized differential ontogenic pattern from controls.

Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder of childhood. Preliminary studies with proton magnetic resonance spectroscopy ((1)H-MRS) of the brain have reported differences in brain metabolite concentration-to-Cr ratios between individuals with ADHD and unaffected controls in several frontal brain regions including anterior cingulate cortex. Using multivoxel (1)H-MRS, we compared 14 individuals affected with ADHD to 20 individuals without ADHD from the same genetic isolate. After controlling by sex, age, and multiple testing, we found significant differences at the right posterior cingulate of the Glx/Cr ratio density distribution function between ADHD cases and controls (P < 0.05). Furthermore, we found several interactions of metabolite concentration-to-Cr ratio, age, and ADHD status: Ins/Cr and Glx/Cr ratios at the left posterior cingulate, and NAA/Cr at the splenius, right posterior cingulate, and at the left posterior cingulate. We also found a differential metabolite ratio interaction between ADHD cases and controls for Ins/Cr and NAA/Cr at the right striatum. These results show that: (1) NAA/Cr, Glx/Cr, and Ins/Cr ratios, as reported in other studies, exhibit significant differences between ADHD cases and controls; (2) differences of these metabolite ratios between ADHD cases and controls evolve in specific and recognizable patterns throughout age, a finding that replicates previous results obtained by structural MRI, where is demonstrated that brain ontogeny follows a different program in ADHD cases and controls; (3) Ins/Cr and NAA/Cr ratios, at the right striatum, interact in a differential way between ADHD cases and controls. As a whole, these results replicate previous 1H-MRS findings and add new intriguing differential metabolic and ontogeny patterns between ADHD cases and controls that warrant further pursue.