Neuropsychological performance in polyconsumer men under treatment. Influence of age of onset of substance use

Neurocognition is a key factor in the development and maintenance of Substance Use Disorders (SUD). However, there are still several aspects that need to be studied in this area. In this study, we elucidate the influence of age of onset of substance use (OSU) on the clinical course and neuropsychological performance of substance use disorder (SUD) patients, as well as to explore the influence of years of education, duration of drug use and premorbid intelligence quotient (IQ) on the cognitive results obtained. An exhaustive neuropsychological battery was used to assess different cognitive domains in 80 male polyconsumers, 41 with earlier OSU (16 years or before: OSU ≤ 16) and 39 with later OSU (17 years or later: OSU ≥ 17). The patients were under treatment with at least 4 months of abstinence confirmed by urinalysis. The OSU ≤ 16 group presented a worse clinical state, as well as a lower premorbid IQ and worse performance in processing speed, visual perception and planning skills. The duration of drug use may account for the differences in planning and processing speed. In this work we discuss the premorbid or acquired nature of the cognitive deficits found

Circadian Rhythmic Characteristics in Men With Substance Use Disorder Under Treatment. Influence of Age of Onset of Substance Use and Duration of Abstinence

here is evidence of the reciprocal influence between the alteration of circadian rhythms and Substance Use Disorders (SUD), and part of the success of the SUD treatment lays in the patient's rhythmic recovery. We aim to elucidate the effect of the SUD treatment in circadian rhythmicity considering, for the first time, the age of onset of substance use (OSU) and duration of abstinence. We registered the sleep-wake schedules, the chronotype and the distal skin temperature of 114 SUD patients with at least 3 months of abstinence, considering whether they had begun consumption at age 16 or earlier (OSU ≤ 16, n = 56) or at 17 or later (OSU ≥ 17, n = 58), and duration of abstinence as short (SA: 3 to 5 months, n = 38), medium (MA: 6 to 9 months, n = 35) or long (LA: more than 9 months, n = 41). Moreover, we compared the patients' distal skin temperature pattern with a similar sample of healthy controls (HC, n = 103). SUD patients showed a morningness tendency and higher night values, amplitude and stability, a better adjustment to the cosine model and lower minimum temperature and circadianity index in the distal skin temperature rhythm, in contrast to the HC group. The OSU ≥ 17 and LA groups showed a more robust distal skin temperature pattern, as well as milder clinical characteristics when compared to the OSU ≤ 16 and SA groups, respectively. The circadian disturbances associated to substance consumption seem to improve with treatment, although the age of OSU and the duration of abstinence are modulating variables. Our results highlight the need to include chronobiological strategies that boost circadian rhythmicity both in SUD prevention and rehabilitation programs. The measurement of distal skin temperature rhythm, a simple and reliable procedure, could be considered an indicator of response to treatment in SUD patient

Disseny d’un assaig clínic (fase III) per valorar l’eficàcia de la metilzapina en l’esquizofrènia

La metilzapina és un anàleg estructural de l’olanzapina (antipsicòtic atípic de segona generació sintetitzat l’any 1990). Les proves in vitro han determinat que presenta una elevada afinitat pels receptors 5-HT2 serotoninèrgics i pels receptors D3 i D4 dopaminèrgics; una afinitat pels receptors D2 dopaminèrgics mesolímbics elevada i moderada a la resta de vies dopaminèrgiques, i una baixa afinitat pels receptors alfa1 adrenèrgics, els M1 muscarínics colinèrgics i els H1 histaminèrgics

Recerca de nous fàrmacs antipsicòtics

En el camp de la psicofarmacologia, una de les principals àrees de recerca comprèn el desenvolupament de noves substàncies per al tractament, diagnòstic, prevenció o rehabilitació d’un trastorn psicopatològic. Aquests procés és prolongat, costós en temps i diners, i ha de considerar diferents aspectes rellevants per la comercialització i ús del fàrmac (científics, ètics, comercials, legals,...). Hom ha de saber que només una petita quantitat de noves substàncies sintetitzades arriben a ser comercialitzades i moltes d’elles han de ser retirades del mercat degut a l’existència d’efectes adversos. Així mateix, no tots els productes aprovats per al seu ús amb humans són útils. De forma general, el procés de desenvolupament d’un nou fàrmac inclou tres nivells principal de recerca: la síntesi de la substància, els estudis preclínics i els estudis clínics

Executive functioning in men with schizophrenia and substance use disorders. Influence of Lifetime Suicide Attemps

Background: Lifetime suicide attempts in patients with comorbidity between psychotic disorders and Substance Use Disorder (SUD), known as dual diagnosis, was associated with a worse clinical and cognitive state, poor prognosis and premature death. However, to date no previous study has examined the cognitive performance of these patients considering as independent the presence or absence of lifetime suicide attempts. Methods: We explore executive functioning differences between suicide attempters and non-attempters in dual schizophrenia (DS) patients and the possible related factors for both executive performance and current suicide risk. Fifty DS male patients in remission of SUD and clinically stables, 24 with and 26 without lifetime suicide attempts, were evaluated. We considered Z scores for all neuropsychological tests and a composite summary score for both premorbid IQ and executive functioning. Results: DS patients showed low performance in set-shifting, planning and problem solving tasks. Those with suicide attempts presented lower composite summary scores, together with worse problem solving skills and decision-making, compared with non-attempters. However, after controlling for alcohol dependence, only differences in decision-making remained. Executive functioning was related to the premorbid intelligence quotient, and several clinical variables (duration, severity, months of abstinence and relapses of SUD, global functioning and negative symptoms). A relationship between current suicide risk, and first-degree relatives with SUD, insight and positive symptoms was also found. Conclusions: Our results suggest that problem solving and, especially, decision-making tasks might be sensitive to cognitive impairment of DS patients related to presence of lifetime suicide attempts. The assessment of these executive functions and cognitive remediation therapy when necessary could be beneficial for the effectiveness of treatment in patients with DS. However, further research is needed to expand our findings and overcome some limitations of this study

Influencia de la edad de inicio del consumo en el rendimiento cognitivo, ritmicidad circadiana y afrontamiento al tratamiento en pacientes con trastorno por consumo de sustancias

[spa] Los Trastornos por Consumo de Sustancias (TCS) son considerados un problema de salud pública debido a que acarrean graves consecuencias en el plano individual y el comunitario. Además, pese a los avances logrados en su prevención, la incidencia del consumo tanto a nivel mundial como estatal es muy elevada y existe una considerable tasa de recaídas tras el tratamiento. Esto puede ser debido, en gran parte, a que en la etiología de estos trastornos intervienen múltiples factores de riesgo y protección de naturaleza diversa. Ello deriva en una gran heterogeneidad de expresión fenotípica y, en consecuencia, en la respuesta a las intervenciones. En la actualidad es necesario explorar nuevas vías que mejoren el conocimiento de las diferencias individuales en la etiopatogenia de los TCS, así como de sus manifestaciones sintomáticas y las variables asociadas que sean relevantes para su prevención o rehabilitación. En este contexto, el estudio de la edad de inicio del consumo (EIC) tiene un gran interés, puesto que es un importante predictor para el desarrollo de un futuro TCS y su gravedad. Por consiguiente, el principal objetivo de este trabajo consistió en explorar la influencia de la EIC en características que pueden intervenir en el inicio, curso y respuesta clínica de estos trastornos. Para ello se desarrollaron tres estudios con una muestra de entre 80 y 122 hombres con TCS, según el caso. Todos los pacientes estaban abstinentes y en tratamiento, y se clasificaron según si iniciaron el consumo de sustancias a los 16 años o antes (ICS≤16) o a los 17 años o después (ICS≥17). Con ello, nuestro objetivo fue aportar conocimiento que contribuya a explicar factores relacionados con el comienzo del consumo y aplicable tanto al desarrollo de posibles intervenciones preventivas como a vislumbrar estrategias terapéuticas que se adapten a las necesidades de los consumidores de inicio temprano para mejorar su manejo clínico. La investigación consideró cuatro áreas de estudio. En la primera se analizaron las características sociodemográficas y clínicas, permitiendo una aproximación a la realidad actual de los pacientes con TCS que siguen un tratamiento en el estado español. Además, al relacionarlas con otras variables que influyen en el comienzo y progreso de estos trastornos, aportó claves a considerar para prevenir su ocurrencia y favorecer la rehabilitación. La segunda consistió en un exhaustivo estudio del rendimiento cognitivo de los pacientes, puesto que se conoce que ciertas características neurocognitivas infieren mayor vulnerabilidad para desarrollar un TCS, existe la posibilidad de que la EIC temprana influya negativamente en ellas y pueden ser un factor predictivo del éxito del tratamiento. La tercera área exploró diferencias rítmicas circadianas –horarios de sueño-vigilia, cronotipo y distal skin temperature (DST) o temperatura periférica de la piel– según la EIC y la duración de la abstinencia de los pacientes, incluyendo la comparación con un grupo de controles sanos (CS). Existe evidencia de la influencia recíproca entre la alteración de los ritmos circadianos y los TCS, siendo de gran interés evaluar qué parte de la recuperación de los pacientes se basa en la restauración de diversos patrones rítmicos circadianos. Por último, se administró el Inventario de estrategias de afrontamiento (EA) de Tobin para estudiar el modo en el que los pacientes manejaban el malestar relacionado con el tratamiento. Ello es relevante teniendo en cuenta que el empleo de determinadas EA ante estresores puede propiciar el inicio del consumo de sustancias y asociarse con mayores complicaciones clínicas. Los resultados indicaron que los pacientes con ICS≤16 se distinguen de aquellos con ICS≥17 en varios aspectos. Presentaron indicadores de mayor gravedad clínica, como es el uso simultáneo de más tipos de sustancias, más duración del trastorno, mayor tasa de recaídas y de historia familiar de consumo y también la necesidad de seguir un tratamiento más intensivo. A nivel cognitivo, los pacientes con ICS≤16 mostraron menor coeficiente intelectual (CI) verbal y manipulativo, una velocidad de procesamiento de la información más lenta, peor habilidad visuo-perceptiva y mayores dificultades en tareas que implican la habilidad de planificación. También presentaron un patrón rítmico circadiano de la DST menos robusto, con menor activación y mayor somnolencia durante la vigilia. Cabe destacar que la mayoría de los pacientes presentaron un cronotipo matutino, considerado como un factor de protección para los TCS, y sólo aquellos con ICS≥17 y mayor duración de la abstinencia presentaron mejor perfil rítmico de la DST en comparación con los CS. Ello sugiere que el funcionamiento circadiano puede mejorar a medida que se progresa en el tiempo de abstinencia y siguiendo unas pautas horarias terapéuticas, si bien existen diferencias según la EIC. Por último, los pacientes con ICS≤16 afrontaron el tratamiento de un modo más desadaptativo, es decir con más aislamiento, menos búsqueda de soporte emocional en los otros y mayor evitación de las preocupaciones. En el trabajo se discute la naturaleza premórbida o adquirida de las características de los individuos de EIC temprana y cómo distintos factores clínicos (CI premórbido, cantidad de recaídas, gravedad y duración del TCS) modulan los resultados. Nuestros hallazgos tienen distintas implicaciones preventivas y clínicas. Entre ellas, incluir evaluaciones neuropsicológicas, del estado rítmico circadiano y el perfil de EA que se utiliza para manejar el estrés en los programas de prevención de los TCS puede ayudar a detectar individuos con mayor vulnerabilidad y realizar intervenciones específicas para evitar que inicien el consumo, retrasar su EIC o reducir los riesgos asociados. En este sentido, adaptar los tratamientos convencionales a las características de los pacientes con ICS≤16 podría favorecer su adhesión terapéutica, reducir recaídas y favorecer su inclusión social. Para ello, podría ser útil potenciar su rendimiento cognitivo y acomodar las pautas terapéuticas a éste, intensificar las estrategias cronoterapéuticas y aquellas destinadas a fomentar la resolución de problemas y la búsqueda de apoyo emocional en los demás. En conclusión, la EIC se asocia con las características clínicas, cognitivas, de rítmicidad circadiana y relacionadas con el afrontamiento en los pacientes con TCS. Para avanzar en el conocimiento de los endofenotipos de la adicción y sus aplicaciones clínicas se requieren trabajos futuros que indaguen su peso específico en el modelo multifactorial explicativo de inicio y mantenimiento del TCS, siendo recomendable la utilización de diseños longitudinales e incorporar correlatos genéticos y neurobiológicos.[eng] Substance Use Disorders (SUDs) are considered a public health problem since they have serious consequences at the individual and community level. In addition, despite the progress made in their prevention, the incidence of consumption both at the global and the state level is very high and there is a considerable rate of posttreatment relapse. This may be largely due to the complex etiology of these disorders, which involves multiple risk and protection factors of a very diverse nature. This leads to a considerable heterogeneity of phenotypic expression and, consequently, in the response to interventions. At present, it is necessary to explore new ways to enhance our knowledge of individual differences in the pathogenesis of SUDs, as well as their symptomatic manifestations and associated variables that are relevant to their prevention or rehabilitation. In this context, the study of the age of onset of substance use (OSU) is of great interest, as it is an important predictor for the development of a future SUD and its severity. Therefore, the main objective of this work consisted of exploring the influence of the age of OSU on characteristics that may be involved in the onset, course and clinical response of these disorders. For this purpose, three studies were performed with a sample of between 80 and 122 men with SUD, depending on the case. All patients were abstinent and in treatment and were classified according to whether they had initiated substance use at age 16 or earlier (OSU≤16) or at age 17 or later (OSU≥17). Thus, our goal was to provide knowledge that would contribute to explaining the factors related to the onset of consumption and would be applicable both to the development of possible preventive interventions and to the detection of therapeutic strategies that would adapt to the needs of early-onset consumers to improve their clinical management. The research considered four areas of study. In the first one, the sociodemographic and clinical characteristics were analyzed, addressing the current reality of patients with SUD who receive treatment in the Spanish state. In addition, linking them to other variables that influence the onset and progress of these disorders provided the keys to prevent their occurrence and to promote rehabilitation. The second area consisted of an exhaustive study of the patients' cognitive performance because, as certain neurocognitive characteristics are known to lead to greater vulnerability to develop a SUD, early OSU may influence these characteristics negatively and may be a predictor of treatment success. The third area explored circadian rhythmic differences –sleep-wake schedules, chronotype and distal skin temperature (DST)– according to the age of OSU and the duration of the patients' abstinence, including the comparison with a group of healthy controls (HC). There is evidence of the reciprocal influence between the disruption of circadian rhythms and SUDs, and it is very interesting to assess how much of a patient's recovery is based on the restoration of diverse circadian rhythmic patterns. Finally, the Coping Strategies (CS) Inventory developed by Tobin was administered to study how the patients coped with treatment-related distress. This is relevant, taking account that the use of certain stress CS can lead to the onset of substance use and be associated with greater clinical complications. The results indicated that patients with OSU≤16 are different from those with OSU≥17 in several aspects. They presented indicators of greater clinical severity, such as the simultaneous use of more types of substances, longer duration of the disorder, higher rates both relapse and family history of consumption and also the need for more intensive treatment. At the cognitive level, patients with OSU≤16 showed lower verbal and manipulative intelligence quotient (IQ), a slower information-processing speed, poorer visual perceptive ability and greater difficulties in tasks involving the ability to plan. They also presented a less robust circadian rhythmic pattern of the DST, with less activation and increased sleepiness during wakefulness. It should be noted that most of the patients presented a morning chronotype, considered as a protector factor for SUDs, and only patients with OSU≥17 and longer duration of abstinence presented a better rhythmic profile of the DST in comparison with the HC. This suggests that circadian functioning can improve as patients advance in the time of abstinence and if they follow some therapeutic schedule guidelines, although there are differences according to the age of OSU. Finally, patients with OSU≤16 deal with treatment in a more maladaptive way, that is, they were more isolated, sought less emotional support from others and greater avoidance of concerns. The premorbid or acquired nature of the characteristics of the individuals of early OSU is discussed throughout the work and how different clinical factors (premorbid IQ, number of relapses, severity and duration of drug use) modulate the results. Our findings have various preventive and clinical implications. Among them, the inclusion of neuropsychological evaluations, assessment of the circadian rhythmic status and the CS profile used to manage stress in the SUD prevention programs may help to detect individuals with increased vulnerability and to carry out specific interventions to prevent them from beginning to consume, delay their age of OSU or reduce the associated risks. In this sense, adapting the conventional treatments to the characteristics of the patients with OSU≤16 could encourage their therapeutic adherence, reduce relapse and promote their social inclusion. Therefore, it could be useful to enhance their cognitive performance and accommodate the therapeutic guidelines to it, intensify the chrono-therapeutic strategies and those aimed at improving problem solving and the finding emotional support in others. In conclusion, the age of OSU is associated with the clinical, cognitive, circadian rhythmicity and coping characteristics in patients with SUD. In order to advance in the knowledge of the endophenotypes of addiction and their clinical applications, future works are needed that inquire about their specific weight in the multifactorial explanatory model of the onset and maintenance of SUD. The use of longitudinal designs and the incorporation of genetic and neurobiological correlates are recommended

Recerca de nous fàrmacs antipsicòtics

En el camp de la psicofarmacologia, una de les principals àrees de recerca comprèn el desenvolupament de noves substàncies per al tractament, diagnòstic, prevenció o rehabilitació d’un trastorn psicopatològic. Aquests procés és prolongat, costós en temps i diners, i ha de considerar diferents aspectes rellevants per la comercialització i ús del fàrmac (científics, ètics, comercials, legals,...). Hom ha de saber que només una petita quantitat de noves substàncies sintetitzades arriben a ser comercialitzades i moltes d’elles han de ser retirades del mercat degut a l’existència d’efectes adversos. Així mateix, no tots els productes aprovats per al seu ús amb humans són útils. De forma general, el procés de desenvolupament d’un nou fàrmac inclou tres nivells principal de recerca: la síntesi de la substància, els estudis preclínics i els estudis clínics

Executive functioning in men with schizophrenia and substance use disorders. Influence of Lifetime Suicide Attemps

Background: Lifetime suicide attempts in patients with comorbidity between psychotic disorders and Substance Use Disorder (SUD), known as dual diagnosis, was associated with a worse clinical and cognitive state, poor prognosis and premature death. However, to date no previous study has examined the cognitive performance of these patients considering as independent the presence or absence of lifetime suicide attempts. Methods: We explore executive functioning differences between suicide attempters and non-attempters in dual schizophrenia (DS) patients and the possible related factors for both executive performance and current suicide risk. Fifty DS male patients in remission of SUD and clinically stables, 24 with and 26 without lifetime suicide attempts, were evaluated. We considered Z scores for all neuropsychological tests and a composite summary score for both premorbid IQ and executive functioning. Results: DS patients showed low performance in set-shifting, planning and problem solving tasks. Those with suicide attempts presented lower composite summary scores, together with worse problem solving skills and decision-making, compared with non-attempters. However, after controlling for alcohol dependence, only differences in decision-making remained. Executive functioning was related to the premorbid intelligence quotient, and several clinical variables (duration, severity, months of abstinence and relapses of SUD, global functioning and negative symptoms). A relationship between current suicide risk, and first-degree relatives with SUD, insight and positive symptoms was also found. Conclusions: Our results suggest that problem solving and, especially, decision-making tasks might be sensitive to cognitive impairment of DS patients related to presence of lifetime suicide attempts. The assessment of these executive functions and cognitive remediation therapy when necessary could be beneficial for the effectiveness of treatment in patients with DS. However, further research is needed to expand our findings and overcome some limitations of this study