The concept of exposure when selecting comparison groups for determining individual susceptibility to addiction to cigarette smoking.

Smoking is a leading cause of preventable death. The effect of tobacco is even more contundent in people with mental illness and, in general, cigarette smoking addiction is influenced by genetic factors. The opioid system is involved in the mesolimbic reward system, which is of great importance in addictive behaviors, such as smoking and is influenced by genes such as the OPRM1. The aim of this study was to evaluate if selecting a comparison group that include light smokers versus people that never smoked impacts the results of genetic association studies. In addition, to evaluate the genetic association in different groups of smokers by analyzing independent covariates such as mental illness and clinical dental data. All subjects were participants of the Dental Registry and DNA Repository project. Genotyping was carried out using TaqMan chemistry for two markers in OPRM1 (rs553202 and rs7755635). Logistic regression analyses were performed as implemented in PLINK. The established value for alpha was 5%, and the Hardy-Weinberg equilibrium was evaluated by the chi-square test with one degree of freedom for each marker. 1,897 patients were included, which were allocated to eight distinct groups, according to the frequency and quantity of cigarettes smoked and mental illness status. There was no significant association between the two markers in OPRM1 and smoking. When mental illness and dental clinical data (tooth loss, dental caries, and periodontitis) were used as covariates, there were associations between heavy smoking and OPRM1, when non-smokers were used as comparison. We did not have diet or microbiome data to consider for these dental analyses and suggest that these kinds of data should be always incorporated in the future. Significant results were found only when the covariables mental illness and oral clinical data were added to the analysis.

Comorbilidad, trastorno psiquiátrico y consumo de sustancias psicoactivas (patología dual) / Comorbility, psichiatric disorder and psychoactive substance consumption (dual pathology)

La patología dual es una problemática en la que se observa la coexistencia de un trastorno psiquiátrico y el consumo de sustancias psicoactivas, simultáneamente. Es de difícil diagnóstico y tratamiento. Se observa en los estados depresivos, los trastornos de ansiedad, la esquizofrenia, el trastorno bipolar y los trastornos de conducta. El abordaje debe ser integral e incluir tratamiento psicofarmacológico, psicoterapéutico cognitivo-conductual, psicoterapia grupal y orientación a la familia, asimismo, lograr un compromiso del paciente, los familiares y los amigos en el cumplimiento estricto del tratamiento. El tratamiento puede realizarse en forma ambulatoria, en hospital de día, con internación breve para la desintoxicación o en comunidades terapéuticas, la elección dependerá del tipo de patología psiquiátrica y del nivel bajo, medio o alto de consumo de sustancias concomitante.

Dual pathology is a problem in which a psychiatric disorder and the consumption of psychoactive substances coexist at the same time. It is difficult to diagnose and to treat. This pathology is observed in depressive states, anxiety disorders, shizophrenia, bipolar disorder and behavior disorders. Its approach should be integral and include psychopharmacological, psychotherapeutic, cognitive-behavioral treatment, group psychotherapy and family guidance, and it should achieve commitment on the part of the patient, relatives and friends, in the strict compliance of such treatment. Treatment can be performed externally, at a day hospital, through brief hospitalization for desintoxication or in therapeutic communities, the choice will depend on the type of psychiatric pathology and on the low, medium or high concomitant level of consumption of substances.

Non-motor function of the midbrain dopaminergic neurons.

The roles of the nigrostriatal pathway are far beyond the simple control of motor functions. The tonic release of dopamine in the dorsal and ventral striatum controls the choice of proper actions toward a given environmental situation. In the striatum, a specific action is triggered by a specific stimulus associated with it. When the subject faces a novel and salient stimulus, the phasic release of dopamine allows synaptic plasticity in the cortico-striatal synapses. Neurons of different regions of cortical areas make synapses that converge to the same medium spine neurons of the striatum. The convergent associations form functional units encoding body parts, objects, locations, and symbolic representations of the subject's world. Such units emerge in the striatum in a repetitive manner, like a mosaic of broken mirrors. The phasic release of dopamine allows the association of units to encode an action of the subject directed to an object or location with the outcome of this action. Reinforced stimulus-action-outcome associations will affect future decision making when the same stimulus (object, location, idea) is presented to the subject in the future. In the absence of a minimal amount of striatal dopamine, no action is initiated as seen in Parkinson's disease subjects. The abnormal and improper association of these units leads to the initiation of unpurposeful and sometimes repetitive actions, as those observed in dyskinetic patients. The association of an excessive reinforcement of some actions, like drug consumption, leads to drug addiction. Improper associations of ideas and unpleasant outcomes may be related to traumatic and depressive symptoms common in many diseases, including Parkinson's disease. The same can be said about the learning and memory impairments observed in demented and nondemented Parkinson's disease patients.