Epidural Hematoma Associated with Red Clover Use After Epidural Injection: A Case Report.

An epidural hematoma is a rare but devastating complication after interventional pain procedures. The etiology is multifactorial, including anatomical variations, inherited coagulation disorders, and consumption of anticoagulants or antiplatelet substances. Specifically, in regard to platelet aggregation, the consumption of herbal medicine is often forgotten as a potential cause for coagulation profile disorders, potentially leading to an epidural hematoma. We present the case of a patient who developed an epidural hematoma after a cervical epidural block, most likely associated with daily "red clover" consumption.

Decision-making dynamics are predicted by arousal and uninstructed movements.

During sensory-guided behavior, an animal's decision-making dynamics unfold through sequences of distinct performance states, even while stimulus-reward contingencies remain static. Little is known about the factors that underlie these changes in task performance. We hypothesize that these decision-making dynamics can be predicted by externally observable measures, such as uninstructed movements and changes in arousal. Here, using computational modeling of visual and auditory task performance data from mice, we uncovered lawful relationships between transitions in strategic task performance states and an animal's arousal and uninstructed movements. Using hidden Markov models applied to behavioral choices during sensory discrimination tasks, we find that animals fluctuate between minutes-long optimal, sub-optimal, and disengaged performance states. Optimal state epochs are predicted by intermediate levels, and reduced variability, of pupil diameter and movement. Our results demonstrate that externally observable uninstructed behaviors can predict optimal performance states and suggest that mice regulate their arousal during optimal performance.

Passive exposure to task-relevant stimuli enhances categorization learning.

Learning to perform a perceptual decision task is generally achieved through sessions of effortful practice with feedback. Here, we investigated how passive exposure to task-relevant stimuli, which is relatively effortless and does not require feedback, influences active learning. First, we trained mice in a sound-categorization task with various schedules combining passive exposure and active training. Mice that received passive exposure exhibited faster learning, regardless of whether this exposure occurred entirely before active training or was interleaved between active sessions. We next trained neural-network models with different architectures and learning rules to perform the task. Networks that use the statistical properties of stimuli to enhance separability of the data via unsupervised learning during passive exposure provided the best account of the behavioral observations. We further found that, during interleaved schedules, there is an increased alignment between weight updates from passive exposure and active training, such that a few interleaved sessions can be as effective as schedules with long periods of passive exposure before active training, consistent with our behavioral observations. These results provide key insights for the design of efficient training schedules that combine active learning and passive exposure in both natural and artificial systems.

Selectivity to acoustic features of human speech in the auditory cortex of the mouse.

A better understanding of the neural mechanisms of speech processing can have a major impact in the development of strategies for language learning and in addressing disorders that affect speech comprehension. Technical limitations in research with human subjects hinder a comprehensive exploration of these processes, making animal models essential for advancing the characterization of how neural circuits make speech perception possible. Here, we investigated the mouse as a model organism for studying speech processing and explored whether distinct regions of the mouse auditory cortex are sensitive to specific acoustic features of speech. We found that mice can learn to categorize frequency-shifted human speech sounds based on differences in formant transitions (FT) and voice onset time (VOT). Moreover, neurons across various auditory cortical regions were selective to these speech features, with a higher proportion of speech-selective neurons in the dorso-posterior region. Last, many of these neurons displayed mixed-selectivity for both features, an attribute that was most common in dorsal regions of the auditory cortex. Our results demonstrate that the mouse serves as a valuable model for studying the detailed mechanisms of speech feature encoding and neural plasticity during speech-sound learning.

Selectivity to acoustic features of human speech in the auditory cortex of the mouse.

A better understanding of the neural mechanisms of speech processing can have a major impact in the development of strategies for language learning and in addressing disorders that affect speech comprehension. Technical limitations in research with human subjects hinder a comprehensive exploration of these processes, making animal models essential for advancing the characterization of how neural circuits make speech perception possible. Here, we investigated the mouse as a model organism for studying speech processing and explored whether distinct regions of the mouse auditory cortex are sensitive to specific acoustic features of speech. We found that mice can learn to categorize frequency-shifted human speech sounds based on differences in formant transitions (FT) and voice onset time (VOT). Moreover, neurons across various auditory cortical regions were selective to these speech features, with a higher proportion of speech-selective neurons in the dorso-posterior region. Last, many of these neurons displayed mixed-selectivity for both features, an attribute that was most common in dorsal regions of the auditory cortex. Our results demonstrate that the mouse serves as a valuable model for studying the detailed mechanisms of speech feature encoding and neural plasticity during speech-sound learning.

Multimodal postoperative analgesia with transdermal buprenorphine is a safe option in arthroscopic rotator cuff repair.

BACKGROUND: Arthroscopic rotator cuff repairs are associated with moderate-to-severe pain. Opioids are not the first line for postsurgical pain control due to their potential misuse and side effects. Transdermal buprenorphine represents an alternative for multimodal postoperative pain control. METHODS: This was a single-centre, prospective longitudinal exploratory study of patients undergoing arthroscopic rotator cuff repairs managed with multimodal analgesia with transdermal buprenorphine. Patients were followed-up by telephone at eight time points, assessing pain levels, rescue analgesics requirement and side effects. FINDINGS: Twenty-five patients with an average age of 63.4 ± 8.2 were included. Fourteen patients were ⩾65 years. Pain levels were similar among age groups at all time points, with no pain or mild pain (visual analogue scale 1-4) in most patients. The most frequent side effects were dizziness and somnolence. CONCLUSION: Transdermal buprenorphine provided a sustained analgesic effect after an arthroscopic rotator cuff repair during the acute postsurgical period. It showed a similar safety profile among younger and older patients.

Passive exposure to task-relevant stimuli enhances categorization learning.

Learning to perform a perceptual decision task is generally achieved through sessions of effortful practice with feedback. Here, we investigated how passive exposure to task-relevant stimuli, which is relatively effortless and does not require feedback, influences active learning. First, we trained mice in a sound-categorization task with various schedules combining passive exposure and active training. Mice that received passive exposure exhibited faster learning, regardless of whether this exposure occurred entirely before active training or was interleaved between active sessions. We next trained neural-network models with different architectures and learning rules to perform the task. Networks that use the statistical properties of stimuli to enhance separability of the data via unsupervised learning during passive exposure provided the best account of the behavioral observations. We further found that, during interleaved schedules, there is an increased alignment between weight updates from passive exposure and active training, such that a few interleaved sessions can be as effective as schedules with long periods of passive exposure before active training, consistent with our behavioral observations. These results provide key insights for the design of efficient training schedules that combine active learning and passive exposure in both natural and artificial systems.

Decision-making dynamics are predicted by arousal and uninstructed movements.

During sensory-guided behavior, an animal's decision-making dynamics unfold through sequences of distinct performance states, even while stimulus-reward contingencies remain static. Little is known about the factors that underlie these changes in task performance. We hypothesize that these decision-making dynamics can be predicted by externally observable measures, such as uninstructed movements and changes in arousal. Here, combining behavioral experiments in mice with computational modeling, we uncovered lawful relationships between transitions in strategic task performance states and an animal's arousal and uninstructed movements. Using hidden Markov models applied to behavioral choices during sensory discrimination tasks, we found that animals fluctuate between minutes-long optimal, sub-optimal and disengaged performance states. Optimal state epochs were predicted by intermediate levels, and reduced variability, of pupil diameter, along with reduced variability in face movements and locomotion. Our results demonstrate that externally observable uninstructed behaviors can predict optimal performance states, and suggest mice regulate their arousal during optimal performance.

Sound-Evoked Responses of Distinct Neuron Classes from the Tail of the Striatum.

Given its inputs from auditory structures and neuromodulatory systems, the posterior tail of the striatum is ideally positioned to influence behavioral responses to acoustic stimuli according to context and previous rewards. Results from previous studies indicate that neurons in this striatal region display selective responses to sounds. However, it is not clear whether different striatal cell classes code for distinct features of sounds or how different striatal output pathways may use acoustic information to guide behavior. Here we compared the sound-evoked responses of posterior striatal neurons that form the striatal direct pathway (and express the dopamine receptor D1) to the responses of neighboring neurons in naive mice. We achieved this via optogenetic photo-identification of D1-expressing neurons during extracellular electrophysiological recordings in awake head-fixed mice of both sexes. We found that the frequency tuning of sound-responsive direct-pathway striatal neurons is comparable with that of their sound-responsive neighbors. Moreover, we found that both populations encode amplitude-modulated sounds in a similar fashion. These results suggest that different classes of neurons in the posterior striatum of naive animals have similar access to acoustic features conveyed by the auditory system even outside the context of an auditory task.

¿Los hijos de pacientes con trastorno bipolar tienen una peor percepción de la calidad de sueño? / Do Children of Patients with Bipolar Disorder have a Worse Perception of Sleep Quality?

RESUMEN Introducción: los Hijos de Padres con Trastorno Bipolar (HPTB) constituyen una población de riesgo ya que pueden heredar el Trastorno Bipolar (TB) como también manifestaciones clínicas tempranas como seria las alteraciones en el sueño. Objetivo: comparar la presencia de trastornos psiquiátricos y las alteraciones en el sueño de los HPTB con los Hijos de Padres Control (HPC). Métodos: Se realizó un estudio analítico de corte transversal, que comparó HPTB versus HPC. Se entrevistaron con instrumentos validados para determinar la existencia de síntomas y trastornos psiquiátricos. Utilizamos las escalas: "Cuestionario de evaluación de sueño" y "Encuesta sobre hábitos de sueño en escolares" para determinarlas características del sueño y factores asociados con el mismo. Adicionalmente se obtuvo el registro de sueño (7-21 días) por medio de un reloj de actígrafia. Resultados: Se reunió una muestra con 42 sujetos (18 HPTB y 24 HPC). Se encontraron diferencias en la presentación de los trastornos psiquiátricos. El grupo de HPTB presento mayor frecuencia del trastorno depresivo mayor (TDM; p = 0,04) y el trastorno disruptivo de la regulación emocional (TDRE, p = 0,04). En el grupo de HPC por su parte se presentó una mayor frecuencia de Trastorno por Déficit de Atención e Hiperactividad (TDAH; p = 0,65) y de Trastorno de Ansiedad por Separación (TAS; p = 0,46). También se encontraron diferencias a nivel del sueño en las medidas subjetivas. En comparación con el HPC, el grupo de HPTB presento una peor percepción de la calidad de sueño (p = 0,02), una mayor presencia de pesadillas (p = 0,01), un menor tiempo total de sueño y una mayor latencia de sueño. Sin embargo, no se encontraron diferencias entre los dos grupos en las mediciones de actigrafías. Conclusiones: el grupo de HPTB presenta mayor frecuencia de trastornos del estado de ánimo, y a su vez una mayor presencia de alteraciones del sueño en las medidas subjetivas. Es posible que exista una asociación entre los síntomas afectivos, las alteraciones en el sueño y el consumo de café. No se encontraron diferencias en el perfil de sueño por actígrafía. © 2020 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España, S.L.U. Todos los derechos reservados. Children

ABSTRACT Introduction: The offspring of bipolar parents (BO) is a high-risk population for inheriting the bipolar disorder (BD) and other early clinical manifestations, such as sleep disturbances. Objective: To compare the presence of psychiatric disorders and sleep disturbances of BO versus offspring of control parents (OCP). Methods: A cross-sectional analytical study was conducted that compared BO versus OCP. The participants were assessed using valid tools to determine the presence of psychiatric symptoms or disorders. The "Sleep Evaluation Questionnaire" and "School Sleep Habits Survey" were used to determine sleep characteristics and associated factors. Sleep records (7-21 days) were also obtained by using an actigraphy watch. Results: A sample of 42 participants (18 BO and 24 OCP) was recruited. Differences were found in the presentation of the psychiatric disorder. The BO group showed a higher frequency of major depression disorder (MDD; P = .04) and Disruptive Mood Dysregulation Disorder (DMDD; P = .04). The OCP group showed a higher frequency of Attention Deficit and Hyperactivity Disorder (ADHD; P = .65), and Separation Anxiety Disorder (SAD; P = .46). Differences were also found in sleep by using subjective measurements. Compared to the OCP group, BO had a worse perception of quality of sleep (P = .02), a higher frequency of nightmares (P = .01), a shorter total sleep time, and a higher sleep latency. Nevertheless, no differences were found between groups in the actigraphy measurements. Conclusions: The BO group had a higher frequency of Mood Disorders, and at the same time a higher number of sleep disturbances in the subjective measurements. It is possible that there is an association between mood symptoms, sleep disturbances, and coffee intake. No differences were found in the sleep profile by using actigraphy. © 2020 Asociación Colombiana de Psiquiatría. Published by Elsevier España, S.L.U. All rights reserved.

Do Children of Patients with Bipolar Disorder have a Worse Perception of Sleep Quality?

INTRODUCTION: The offspring of bipolar parents (BO) is a high-risk population for inheriting the bipolar disorder (BD) and other early clinical manifestations, such as sleep disturbances. OBJECTIVE: To compare the presence of psychiatric disorders and sleep disturbances of BO versus offspring of control parents (OCP). METHODS: A cross-sectional analytical study was conducted that compared BO versus OCP. The participants were assessed using valid tools to determine the presence of psychiatric symptoms or disorders. The "Sleep Evaluation Questionnaire" and "School Sleep Habits Survey" were used to determine sleep characteristics and associated factors. Sleep records (7-21 days) were also obtained by using an actigraphy watch. RESULTS: A sample of 42 participants (18 BO and 24 OCP) was recruited. Differences were found in the presentation of the psychiatric disorder. The BO group showed a higher frequency of major depression disorder (MDD; P = .04) and Disruptive Mood Dysregulation Disorder (DMDD; P = .04). The OCP group showed a higher frequency of Attention Deficit and Hyperactivity Disorder (ADHD; P = .65), and Separation Anxiety Disorder (SAD; P = .46). Differences were also found in sleep by using subjective measurements. Compared to the OCP group, BO had a worse perception of quality of sleep (P = .02), a higher frequency of nightmares (P = .01), a shorter total sleep time, and a higher sleep latency. Nevertheless, no differences were found between groups in the actigraphy measurements. CONCLUSIONS: The BO group had a higher frequency of Mood Disorders, and at the same time a higher number of sleep disturbances in the subjective measurements. It is possible that there is an association between mood symptoms, sleep disturbances, and coffee intake. No differences were found in the sleep profile by using actigraphy.

Contributions of Distinct Auditory Cortical Inhibitory Neuron Types to the Detection of Sounds in Background Noise.

The ability to separate background noise from relevant acoustic signals is essential for appropriate sound-driven behavior in natural environments. Examples of this separation are apparent in the auditory system, where neural responses to behaviorally relevant stimuli become increasingly noise invariant along the ascending auditory pathway. However, the mechanisms that underlie this reduction in responses to background noise are not well understood. To address this gap in knowledge, we first evaluated the effects of auditory cortical inactivation on mice of both sexes trained to perform a simple auditory signal-in-noise detection task and found that outputs from the auditory cortex are important for the detection of auditory stimuli in noisy environments. Next, we evaluated the contributions of the two most common cortical inhibitory cell types, parvalbumin-expressing (PV+) and somatostatin-expressing (SOM+) interneurons, to the perception of masked auditory stimuli. We found that inactivation of either PV+ or SOM+ cells resulted in a reduction in the ability of mice to determine the presence of auditory stimuli masked by noise. These results indicate that a disruption of auditory cortical network dynamics by either of these two types of inhibitory cells is sufficient to impair the ability to separate acoustic signals from noise.

High risk for psychiatric disorders in bipolar offspring. A four years prospective study / Riesgo elevado de trastornos psiquiátricos en hijos de padres con trastorno bipolar. Estudio prospectivo de cuatro años de duración

ABSTRACT Bipolar disorder (BD) has a large hereditary component. It is a disorder that begins in early adulthood, but about which it has been described a premorbid period preceding the onset of BD. During this herald expression psychiatric disorders and symptoms, such as depressive, manic, psychotic, anxious and others, may appear. Objective: To determine the psychopathological profile of a Bipolar Offspring (BO) group compared with the Community Control Offspring (CCO) group, and its evolution over time, including subthreshold symptoms and mental disorders. Methods: We conducted an observational mixed cohort study, with a prospective design. We included subjects from six to 30 years of age, from the region of Antioquia, Colombia. A total of 131 subjects from the risk group BO and 150 subjects from the CCO group were evaluated through validated psychiatric diagnostic interviews (K-SADS-PL and DIGS) at baseline and at 4 years follow up. All interviews were carried out by a staff blind to parent diagnoses. Follow-up assessment were complete in 72% of the offspring. Forty-two subjects were excluded as they surpassed the age of 30 years, and only 46 subjects were not followed (change of address or did not consent to participate). Results: Compared with the CCO group, the BO group had a higher frequency of affective disorder, psychotic disorder, externalizing disorders and use of the psychoactive substances during both assessments at time 1 and 2. The magnitude of the differences between the groups increased when they reach time 2. The BO group had a greater risk for presenting subthreshold symptoms and definitive psychiatric disorders, such as affective disorders, psychotic disorders and externalizing disorders. In addition, the BO group had a younger age of onset for psychoactive substances consumption. Conclusion: During the follow-up period, the BO group had a higher risk of presenting mental disorders compared with the CCO group. The most relevant symptoms and disorders that could precede the onset of BD were depressive, bipolar not otherwise specified, psychotic and substance use.

RESUMEN El trastorno bipolar (TB) tiene un gran componente hereditario. Es un trastorno que comienza en la edad adulta temprana, pero acerca del cual se ha descrito un período premórbido que precede al inicio de TB. Durante esta expresión heraldo, pueden aparecer trastornos y síntomas psiquiátricos, como depresivos, maníacos, psicóticos, ansiosos y otros. Objetivo: Determinar el perfil psicopatológico de un grupo de hijos de padres con TB (BO) en comparación con el grupo de hijos de padres control de la misma comunidad (CCO), y su evolución en el tiempo. Los síntomas subumbrales y los trastornos mentales serán incluidos. Métodos: Nosotros llevamos a cabo un estudio observacional mixto de cohorte, con diseño prospectivo. Incluimos sujetos de seis a 30 anos de edad, de la región de Antioquia, Colombia. Un total de 131 sujetos del grupo de riesgo BO y 150 sujetos del grupo CCO fueron evaluados a través de entrevistas de diagnóstico psiquiátricas validadas (K-SADS-PL y DIGS), al inicio yalos4anos de seguimiento. Todas las entrevistas se llevaron a cabo por personal ciego a los diagnósticos de los padres. La evaluación de seguimiento se completó en el 72% de la descendencia. Cuarenta y dos sujetos fueron excluidos ya que superaron la edad de 30 anos, y solo 46 sujetos no fueron seguidos (cambio de dirección o no dieron su consentimiento para participar). Resultados: En comparación con el grupo CCO, el grupo BO tuvo una mayor frecuencia de trastorno afectivo, el trastorno psicótico, los trastornos de externalización y el uso de las sustancias psicoactivas durante ambas evaluaciones en los tiempos 1 y 2. La magnitud de las diferencias entre los grupos aumentó cuando alcanzaron el tiempo 2. El grupo BO tuvo un mayor riesgo de presentar síntomas subumbrales y trastornos psiquiátricos definitivos, tales como trastornos afectivos, trastornos psicóticos y trastornos de externalización. Además, el grupo BO tuvo una edad de comienzo más baja para el consumo de sustancias psicoactivas. Conclusión: Durante el período de seguimiento, el grupo BO tuvo un mayor riesgo de presentar trastornos mentales en comparación con el grupo CCO. Los síntomas y trastornos más importantes que preceden al inicio del TB fueron: depresivo, bipolar no especificado de otra manera, psicóticos y el uso de sustancias.

High risk for psychiatric disorders in bipolar offspring. A four years prospective study.

Bipolar disorder (BD) has a large hereditary component. It is a disorder that begins in early adulthood, but about which it has been described a premorbid period preceding the onset of BD. During this herald expression psychiatric disorders and symptoms, such as depressive, manic, psychotic, anxious and others, may appear. OBJECTIVE: To determine the psychopathological profile of a Bipolar Offspring (BO) group compared with the Community Control Offspring (CCO) group, and its evolution over time, including subthreshold symptoms and mental disorders. METHODS: We conducted an observational mixed cohort study, with a prospective design. We included subjects from six to 30 years of age, from the region of Antioquia, Colombia. A total of 131 subjects from the risk group BO and 150 subjects from the CCO group were evaluated through validated psychiatric diagnostic interviews (K-SADS-PL and DIGS) at baseline and at 4 years follow up. All interviews were carried out by a staff blind to parent diagnoses. Follow-up assessment were complete in 72% of the offspring. Forty-two subjects were excluded as they surpassed the age of 30 years, and only 46 subjects were not followed (change of address or did not consent to participate). RESULTS: Compared with the CCO group, the BO group had a higher frequency of affective disorder, psychotic disorder, externalizing disorders and use of the psychoactive substances during both assessments at time 1 and 2. The magnitude of the differences between the groups increased when they reach time 2. The BO group had a greater risk for presenting subthreshold symptoms and definitive psychiatric disorders, such as affective disorders, psychotic disorders and externalizing disorders. In addition, the BO group had a younger age of onset for psychoactive substances consumption. CONCLUSION: During the follow-up period, the BO group had a higher risk of presenting mental disorders compared with the CCO group. The most relevant symptoms and disorders that could precede the onset of BD were depressive, bipolar not otherwise specified, psychotic and substance use.

Author Correction: Response outcomes gate the impact of expectations on perceptual decisions.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Somatostatin-Expressing Interneurons in the Auditory Cortex Mediate Sustained Suppression by Spectral Surround.

Sensory systems integrate multiple stimulus features to generate coherent percepts. Spectral surround suppression, the phenomenon by which sound-evoked responses of auditory neurons are suppressed by stimuli outside their receptive field, is an example of this integration taking place in the auditory system. While this form of global integration is commonly observed in auditory cortical neurons, and potentially used by the nervous system to separate signals from noise, the mechanisms that underlie this suppression of activity are not well understood. We evaluated the contributions to spectral surround suppression of the two most common inhibitory cell types in the cortex, parvalbumin-expressing (PV+) and somatostatin-expressing (SOM+) interneurons, in mice of both sexes. We found that inactivating SOM+ cells, but not PV+ cells, significantly reduces sustained spectral surround suppression in excitatory cells, indicating a dominant causal role for SOM+ cells in the integration of information across multiple frequencies. The similarity of these results to those from other sensory cortices provides evidence of common mechanisms across the cerebral cortex for generating global percepts from separate features.SIGNIFICANCE STATEMENT To generate coherent percepts, sensory systems integrate simultaneously occurring features of a stimulus, yet the mechanisms by which this integration occurs are not fully understood. Our results show that neurochemically distinct neuronal subtypes in the primary auditory cortex have different contributions to the integration of different frequency components of an acoustic stimulus. Together with findings from other sensory cortices, our results provide evidence of a common mechanism for cortical computations used for global integration of stimulus features.

Response outcomes gate the impact of expectations on perceptual decisions.

Perceptual decisions are based on sensory information but can also be influenced by expectations built from recent experiences. Can the impact of expectations be flexibly modulated based on the outcome of previous decisions? Here, rats perform an auditory task where the probability to repeat the previous stimulus category is varied in trial-blocks. All rats capitalize on these sequence correlations by exploiting a transition bias: a tendency to repeat or alternate their previous response using an internal estimate of the sequence repeating probability. Surprisingly, this bias is null after error trials. The internal estimate however is not reset and it becomes effective again after the next correct response. This behavior is captured by a generative model, whereby a reward-driven modulatory signal gates the impact of the latent model of the environment on the current decision. These results demonstrate that, based on previous outcomes, rats flexibly modulate how expectations influence their decisions.

High Risk for Psychiatric Disorders in Bipolar Offspring. A Four Years Prospective Study.

Bipolar disorder (BD) has a large hereditary component. It is a disorder that begins in early adulthood, but about which it has been described a premorbid period preceding the onset of BD. During this herald expression psychiatric disorders and symptoms, such as depressive, manic, psychotic, anxious and others, may appear. OBJECTIVE: To determine the psychopathological profile of a Bipolar Offspring (BO) group compared with the Community Control Offspring (CCO) group, and its evolution over time, including subthreshold symptoms and mental disorders. METHODS: We conducted an observational mixed cohort study, with a prospective design. We included subjects from six to 30 years of age, from the region of Antioquia, Colombia. A total of 131 subjects from the risk group BO and 150 subjects from the CCO group were evaluated through validated psychiatric diagnostic interviews (K-SADS-PL and DIGS) at baseline and at 4 years follow up. All interviews were carried out by a staff blind to parent diagnoses. Follow-up assessment were complete in 72% of the offspring. Forty-two subjects were excluded as they surpassed the age of 30 years, and only 46 subjects were not followed (change of address or did not consent to participate). RESULTS: Compared with the CCO group, the BO group had a higher frequency of affective disorder, psychotic disorder, externalizing disorders and use of the psychoactive substances during both assessments at time 1 and 2. The magnitude of the differences between the groups increased when they reach time 2. The BO group had a greater risk for presenting subthreshold symptoms and definitive psychiatric disorders, such as affective disorders, psychotic disorders and externalizing disorders. In addition, the BO group had a younger age of onset for psychoactive substances consumption. CONCLUSION: During the follow-up period, the BO group had a higher risk of presenting mental disorders compared with the CCO group. The most relevant symptoms and disorders that could precede the onset of BD were depressive, bipolar not otherwise specified, psychotic and substance use.