Emotional Alterations Research Articles

Long-term cognitive, emotional and neurogenic alterations induced by alcohol and methamphetamine exposure in adolescent rats

A high proportion of young methamphetamine (MA) users simultaneously consume alcohol. However, the potential neurological and behavioural alterations induced by such a drug combination have not been systematically examined. We studied in adolescent rats the long-term effects of alcohol, MA, and alcohol and MA combined on anxiety-like behaviour, memory, and neurogenesis in the adult hippocampus. Rats received saline, ethanol (ETOH, 1.5g/kg), MA (MA, 2mg/kg), or ethanol and MA combined (ETHOH-MA, 1.5g/kg ethanol plus 2mg/kg MA) via oral gavage, once daily for 5 consecutive days. Open field (OF), elevated plus maze (EPM) and radial arm maze (RAM) tests were conducted following a 15-day withdrawal period. The results showed alterations in exploratory behaviour in the OF in the MA and ETOH-MA groups, and anxiety-like effects in the EPM in all three drug treatment groups. All three drug groups exhibited reference memory deficits in the RAM, but only the combination treatment group displayed alterations in working memory. Both MA and ETOH-MA treatments increased the length of doublecortin (DCX)-void gaps in the dentate gyrus but only ETOH-MA treatment increased the number of such gaps. An increased number and length of DCX-void gaps correlated with decreased exploratory activity in the OF, and impaired working memory in the RAM was associated with an augmented number of gaps. These findings suggest that alterations in adult hippocampal neurogenesis are linked to the persistent cognitive and behavioural deficits produced by alcohol and MA exposure.

Association of alcohol use with problematic mobile phone use and depressive symptoms among college students in Anhui, China

Aim Problematic mobile phone use (PMPU) is defined as an inability to regulate one’s use of the mobile phone, including excessive use, gradual increase in use to get the gratification, interference with school and other personal activities, and the need to avoid emotional alterations when mobile phone use is impeded. The potential health risks of PMPU have attracted increasing research attention. This study investigated the proportion of PMPU and the interactive effect of PMPU and depressive symptoms with alcohol use among college students in Anhui Province, China.

Abstract # 1806 Effect of an omega-3 and antioxidants supplemented diet on emotional and cognitive alterations and neuroinflammatory processes associated with obesity

Obesity is a metabolic and inflammatory disorder that represents a major risk factor for development of comorbidities such as cardiovascular diseases or diabetes. Obese patients also often experience mood and cognitive dysfunctions, which drastically worsen obesity. Reducing their development may therefore allow improving health and quality of life of obese patients. Converging studies suggested that inflammation, which is a key component of severe obesity, might contribute to development of neuropsychiatric alterations, especially when it occurs in brain areas controlling mood and cognition such as the hippocampus. Nutrients such as n-3 polyunsaturated fatty acids (n-3 PUFAs) or antioxidants (AO) are known to improve emotional and cognitive alterations in other medical conditions, particularly by modulating neuroinflammation. However, their effect in obesity still remains poorly understood. Thus, we aimed here to evaluate if a n-3 PUFAs/AO supplemented diet improved mood and cognition in a genetic mouse model of obesity, and to identify the underlying mechanisms. Chronic supplemented diet consumption did not improve anxiety-like behavior, but reversed spatial memory deficits associated with obesity. This improvement, which occurs independently of any normalization of increased inflammation, may rather involve modulation of hippocampal neuronal plasticity. These findings suggest dissociation between the neurobiological mechanisms respectively underlying mood and cognitive alterations associated with obesity. They may help indentifying new targets for nutritional interventions aiming to improve health and quality of life of obese patients.

Age-related individual variability in memory performance is associated with amygdala-hippocampal circuit function and emotional pattern separation

While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional information in older adults with and without age-related memory impairment (characterized by performance on a word-list learning task: low performers: LP vs. high performers: HP). We found signals consistent with emotional pattern separation in hippocampal dentate (DG)/CA3 in HP but not in LP individuals, suggesting a deficit in emotional pattern separation. During false recognition, we found increased DG/CA3 activity in LP individuals, suggesting that hyperactivity may be associated with overgeneralization. We additionally observed a selective deficit in basolateral amygdala—lateral entorhinal cortex—DG/CA3 functional connectivity in LP individuals during pattern separation of negative information. During negative false recognition, LP individuals showed increased medial temporal lobe functional connectivity, consistent with overgeneralization. Overall, these results suggest a novel mechanistic account of individual differences in emotional memory alterations exhibited in aging.

No praise, please: Depressive symptoms, reactivity to positive social interaction, and fear of positive evaluation

BackgroundDepression is characterized by depressed mood and loss of interest or pleasure. Resulting alterations in emotional reactivity have been explained by three different accounts: ‘positive attenuation’, ‘negative potentiation’, and ‘emotion context insensitivity’. Despite the importance of depression-related emotional alteration in social interactions, research with naturalistic interpersonal stimuli is scarce and underlying mechanisms largely unknown. MethodsHence, the present study examined subjective emotional reactivity to brief negative, positive, and neutral social-evaluative videos as a function of depressive symptoms in an adult sample (N = 84). Fear of positive evaluation (FPE) and fear of negative evaluation (FNE), often conceptualized as cognitive components of social anxiety, were examined as possible mediators. ResultsResults revealed that more depression symptoms were related to diminished pleasantness responses to both positive and neutral videos. When considering all three video conditions simultaneously, only responses to positive videos remained significantly related to depression scores, supporting the ‘positive attenuation’ account. Moreover, FPE was found to uniquely mediate the relationship between depressive symptoms and pleasantness responses to positive videos. ConclusionsResults indicate that emotional reactivity to positive interpersonal stimuli is relevant for theoretical and clinical considerations of depression. This research underlines the importance of FPE not only for understanding social anxiety but also depression.

Positivity effect specific to older adults with subclinical memory impairment

Numerous studies have suggested that older adults preferentially remember positive information (“positivity effect”), however others have reported mixed results. One potential source of conflict is that aging is not a unitary phenomenon and individual differences exist. We modified a standard neuropsychological test to vary emotional content and tested memory at three time points (immediate/20 min/1 wk). Cognitively normal older adults were stratified into those with and without subclinical memory impairment. We found that the positivity effect was limited to those with subclinical memory impairment, suggesting that consideration of subclinical memory impairment is necessary for understanding age-related emotional memory alterations.

Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine

Only a portion of the population exposed to trauma will develop persistent emotional alterations characteristic of posttraumatic stress disorder (PTSD), which illustrates the necessity for identifying vulnerability factors and novel pharmacotherapeutic alternatives. Interestingly, clinical evidence suggests that novelty seeking is a good predictor for vulnerability to the development of excessive and persistent fear. Here, we first tested this hypothesis by analyzing contextual and cued fear responses of rats selected for their high (high responders, HR) or low (low responders, LR) exploration of a novel environment, indicator of novelty seeking. While HR and LR rats exhibited similar sensitivity to the shock and cued fear memory retention, fewer extinction sessions were required in HR than LR animals to reach extinction, indicating faster contextual and cued memory extinction. In a second part, we found an effective disruption of contextual fear reconsolidation by the N-methyl-d-aspartate receptor antagonist ketamine, associated with a down-regulation of early growth response 1 (Egr1) in the hippocampal CA1 area, and up-regulation of brain-derived neurotrophic factor (Bdnf) mRNA levels in the prelimbic and infralimbic cortices. Altogether, these data demonstrate a link between novelty seeking and conditioned fear extinction, and highlight a promising novel role of ketamine in affecting established fear memory.

Effects of DA-Phen, a dopamine-aminoacidic conjugate, on alcohol intake and forced abstinence

The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator.This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation.For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior during acute abstinence were evaluated. A characterization of DA-Phen CNS targeting by its quantification in the brain was also carried out. Our findings showed that DA-Phen administration was able to reduce relapse in alcohol drinking by 50% and reversed the alterations in behavioral reactivity and emotionality observed during acute abstinence.In conclusion, DA-Phen can reduce reinstatement of alcohol drinking in an operant-drinking paradigm following deprivation periods and reverse abstinence-induced behavioral phenotype. DA-Phen activity seems to be mediated by the modulation of the DAergic transmission. However further studies are needed to characterize DA-Phen pharmacodynamic and pharmacokinetic properties, and its potential therapeutic profile in alcohol addiction.

Indoleamine-2,3-dioxygenase mediates neurobehavioral alterations induced by an intracerebroventricular injection of amyloid-β1-42 peptide in mice

Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by a progressive cognitive decline along with various neuropsychiatric symptoms, including depression and anxiety. Increasing evidence has been proposed the activation of the tryptophan-degrading indoleamine-2,3-dyoxigenase (IDO), the rate-limiting enzyme of kynurerine pathway (KP), as a pathogenic factor of amyloid-beta (Aβ)-related inflammation in AD. In the current study, the effects of an intracerebroventricular (i.c.v.) injection of Aβ1-42 peptide (400pmol/mice; 3μl/site) on the regulation of KP biomarkers (IDO activity, tryptophan and kynurerine levels) and the impact of Aβ1-42 on neurotrophic factors levels were investigated as potential mechanisms linking neuroinflammation to cognitive/emotional disturbances in mice. Our results demonstrated that Aβ1-42 induced memory impairment in the object recognition test. Aβ1-42 also induced emotional alterations, such as depressive and anxiety-like behaviors, as evaluated in the tail suspension and elevated-plus maze tests, respectively. We observed an increase in levels of proinflammatory cytokines in the Aβ1-42-treated mice, which led to an increase in IDO activity in the prefrontal cortex (PFC) and the hippocampus (HC). The IDO activation subsequently increased kynurerine production and the kynurenine/tryptophan ratio and decreased the levels of neurotrophic factors in the PFC and HC, which contributed to Aβ-associated behavioral disturbances. The inhibition of IDO activation by IDO inhibitor 1-methyltryptophan (1-MT), prevented the development of behavioral and neurochemical alterations. These data demonstrate that brain IDO activation plays a key role in mediating the memory and emotional disturbances in an experimental model based on Aβ-induced neuroinflammation.

Evaluation of Xerostomia in Different Psychological Disorders: An Observational Study.

Psychiatric diseases like anxiety, depression, schizophrenia and bipolar disorders are increasing at an alarming rate. These diseases can affect the quantity and quality of saliva leading to multiple oral diseases. Although many researchers have evaluated xerostomia in general population, its prevalence is not been assessed in patients suffering from different psychological disorders. To investigate the prevalence of xerostomia and to assess the correlation between xerostomia and dryness of lip and mucosa in different psychological disorders. A cross-sectional observational study was conducted over a period of six months in Department of Psychiatry and Department of Oral Medicine. Patients with anxiety, depression, schizophrenia and bipolar disorder, as diagnosed by an experienced psychiatrist, were given a questionnaire to evaluate the xerostomia. Patients with symptoms of xerostomia were subjected to oral examination by a skilled oral diagnostician to check for dryness of lips and mucosa. One hundred patients from each group of psychiatric diseases were included in the study using a consecutive sampling technique. An equal number of healthy individuals reporting to oral medicine department for routine oral screening were included as control group after initial psychiatric evaluation. In this study statistically significant increase in the xerostomia in psychiatric patients was recorded when compared to the control group (p<0.01). Xerostomia was significantly higher in anxiety patients (51%) followed by depression (47%), bipolar disorder (41%), schizophrenia (39%) and control group (27%). The majority of the psychiatric patients had 'moderate' to 'severe' xerostomia whereas the control group had 'mild' xerostomia. Xerostomia was significantly higher in younger age group (18-49 years) than in older age group and females patients had higher xerostomia than male patients. Psychiatric patients had significantly more dryness of lip and mucosa than healthy controls. A moderate to strong spearman correlation (r=0.72) was observed between xerostomia and psychological alterations. A positive association was established between psychological alterations and xerostomia and dryness of lip and mucosa. Emotional alterations may act as a precipitating factor that could influence the salivary secretion resulting in multiple oral diseases. Psychiatrists can screen for xerostomia and collaborate with dentists for comprehensive management of xerostomia in psychiatric patients.

Inventario de síntomas prefrontales (ISP): validez ecológica y convergencia con medidas neuropsicológicas

The Prefrontal Symptoms Inventory (PSI) is a self-reported questionnaire, created in Spain, which asks about cognitive, emotional and behavioural alterations in activities of daily living and which can be applied in both the general population and in multiple clinical populations. There is a shorter 20-item version (PSI-20) with excellent psychomotor properties for screening. To study the convergent and divergent validity of the PSI and PSI-20, by analysing how their scales reflect the day-to-day consequences of real deficits found in neurological assessment performed by means of performance tests. A sample of 52 persons undergoing treatment for substance addiction (31 males and 21 females) were administered the PSI together with an abbreviated neuropsychological examination battery focused on describing attentional, mnemonic and executive processes. Both versions of the PSI present optimal psychometric properties (0.78 > alpha > 0.94 for the complete 46-item version and 0.7 > alpha > 0.89 for the abbreviated 20-item version). The results confirm the hypotheses regarding their validity: the performance problems scale is related with the capacity to resolve tests that supposedly rate the executive functions of a prefrontal origin (convergent validity), whereas the scales of problems in emotional control and problems with social behaviour are not related with those cognitive capabilities (discriminant validity). The PSI is a test that is clinically useful, psychometrically valid and applicable in multiple clinical populations.

Nutritional Omega-3 Deficiency Alters Glucocorticoid Receptor-Signaling Pathway and Neuronal Morphology in Regionally Distinct Brain Structures Associated with Emotional Deficits.

Extensive evidence suggests that long term dietary n-3 polyunsaturated fatty acids (PUFAs) deficiency results in altered emotional behaviour. We have recently demonstrated that n-3 PUFAs deficiency induces emotional alterations through abnormal corticosterone secretion which leads to altered dendritic arborisation in the prefrontal cortex (PFC). Here we show that hypothalamic-pituitary-adrenal (HPA) axis feedback inhibition was not compromised in n-3 deficient mice. Rather, glucocorticoid receptor (GR) signaling pathway was inactivated in the PFC but not in the hippocampus of n-3 deficient mice. Consequently, only dendritic arborisation in PFC was affected by dietary n-3 PUFAs deficiency. In addition, occlusion experiment with GR blockade altered GR signaling in the PFC of control mice, with no further alterations in n-3 deficient mice. In conclusion, n-3 PUFAs deficiency compromised PFC, leading to dendritic atrophy, but did not change hippocampal GR function and dendritic arborisation. We argue that this GR sensitivity contributes to n-3 PUFAs deficiency-related emotional behaviour deficits.

Indicadores de síntomas ADHD en el contexto de aprendizaje virtual, utilizando técnicas de aprendizaje automático

Rev.esc.adm.negEste artículo presenta un proceso de modelado de usuario, específicamente un modelado de estudiante, en un ambiente virtual de aprendizaje, que permite inferir la presencia o no de síntomas del Déficit de Atención e Hiperactividad (TDAH). El modelo de usuario es construido teniendo en cuenta tres características del estudiante: Conducta de comportamiento (BC), Rendimiento de funciones ejecutivas (EFP), y estado emocional (ES). Para inferir si un estudiante puede tener un perfil asintomático de TDAH, se usa un grupo de reglas de clasificación que usan los resultados obtenidos en cada característica como datos de entrada para su funcionamiento. Basados en las pruebas del modelo propuesto, se obtiene un grupo de entrenamiento que es usado para preparar un algoritmo de aprendizaje automático, el cual podrá realizar y mejorar la tarea de crear el perfil para cada estudiante de acuerdo a si presenta o no síntomas del TDAH o problemas de atención. Esto, puede ser el primer paso para ofrecer recursos de aprendizajesadaptados a las necesidades educativas de estudiantes que presenten este trastorno.

Altered social behavior and ultrasonic communication in the dystrophin-deficient mdx mouse model of Duchenne muscular dystrophy.

BackgroundThe Duchenne and Becker muscular dystrophies (DMD, BMD) show significant comorbid diagnosis for autism, and the genomic sequences encoding the proteins responsible for these diseases, the dystrophin and associated proteins, have been proposed as new candidate risk loci for autism. Dystrophin is expressed not only in muscles but also in central inhibitory synapses in the cerebellum, hippocampus, amygdala, and cerebral cortex, where it contributes to the organization of autism-associated trans-synaptic neurexin-neuroligin complexes and to the clustering of synaptic gamma-aminobutyric acid (GABA)A receptors. While brain defects due to dystrophin loss are associated with deficits in cognitive and executive functions, communication skills and social behavior, only a subpopulation of DMD patients meet the criteria for autism, suggesting that mutations in the dystrophin gene may confer a vulnerability to autism. The loss of dystrophin in the mdx mouse model of DMD has been associated with cognitive and emotional alterations, but social behavior and communication abilities have never been studied in this model.MethodsHere, we carried out the first in-depth analysis of social behavior and ultrasonic communication in dystrophin-deficient mdx mice, using a range of socially relevant paradigms involving various degrees of executive and cognitive demands, from simple presentation of sexual olfactory stimuli to social choice situations and direct encounters with female and male mice of various genotypes.ResultsWe identified context-specific alterations in social behavior and ultrasonic vocal communication in mdx mice during direct encounters in novel environments. Social behavior disturbances depended on intruders’ genotype and behavior, suggesting alterations in executive functions and adaptive behaviors, and were associated with selective alterations of the development, rate, acoustic properties, and use of the ultrasonic vocal repertoire.ConclusionsThis first evidence that a mutation impeding expression of brain dystrophin affects social behavior and communication sheds new light on critical cognitive, emotional, and conative factors contributing to the development of autistic-like traits in this disease model.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0053-9) contains supplementary material, which is available to authorized users.

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse.

Adaptation of the nervous system to different chemical and physiologic conditions is important for the homeostasis of brain processes and for learning and remembering appropriate responses to challenges. Although processes such as tolerance and dependence to various drugs of abuse have been known for a long time, it was recently discovered that even a single pharmacologically relevant dose of various drugs of abuse induces neuroplasticity in selected neuronal populations, such as the dopamine neurons of the ventral tegmental area, which persist long after the drug has been excreted. Prolonged (self-) administration of drugs induces gene expression, neurochemical, neurophysiological, and structural changes in many brain cell populations. These region-specific changes correlate with addiction, drug intake, and conditioned drugs effects, such as cue- or stress-induced reinstatement of drug seeking. In rodents, adolescent drug exposure often causes significantly more behavioral changes later in adulthood than a corresponding exposure in adults. Clinically the most impairing and devastating effects on the brain are produced by alcohol during fetal development. In adult recreational drug users or in medicated patients, it has been difficult to find persistent functional or behavioral changes, suggesting that heavy exposure to drugs of abuse is needed for neurotoxicity and for persistent emotional and cognitive alterations. This review describes recent advances in this important area of research, which harbors the aim of translating this knowledge to better treatments for addictions and related neuropsychiatric illnesses.

Has bioscience reconciled mind and body?

The aim of this discursive paper is to explore the question 'has biological science reconciled mind and body?'. This paper has been inspired by the recognition that bioscience has a historical reputation for privileging the body over the mind. The disregard for the mind (emotions and behaviour) cast bioscience within a 'mind-body problem' paradigm. It has also led to inherent limitations in its capacity to contribute to understanding the complex nature of health. This is a discursive paper. Literature from the history and sociology of science and psychoneuroimmunology (1975-2015) inform the arguments in this paper. The historical and sociological literature provides the basis for a socio-cultural debate on mind-body considerations in science since the 1970s. The psychoneuroimmunology literature draws on mind-body bioscientific theory as a way to demonstrate how science is reconciling mind and body and advancing its understanding of the interconnections between emotions, behaviour and health. Using sociological and biological evidence, this paper demonstrates how bioscience is embracing and advancing its understanding of mind-body interconnectedness. It does this by demonstrating the emotional and behavioural alterations that are caused by two common phenomena; prolonged, chronic peripheral inflammation and prolonged psychological stress. The evidence and arguments provided has global currency that advances understanding of the inter-relationship between emotions, behaviour and health. This paper shows how bioscience has reconciled mind and body. In doing so, it has advanced an understanding of science's contribution to the inter-relationship between emotions, behaviour and health. The biological evidence supporting mind-body science has relevance to clinical practice for nurses and other healthcare professions. This paper discusses how this evidence can inform and enhance clinical practice directly and through research, education and policy.

Maternal separation induces neuroinflammation and long-lasting emotional alterations in mice

Early life experiences play a key role in brain function and behaviour. Adverse events during childhood are therefore a risk factor for psychiatric disease during adulthood, such as mood disorders. Maternal separation is a validated mouse model for maternal neglect, producing negative early life experiences that result in subsequent emotional alteration. Mood disorders have been found to be associated with neurochemical changes and neurotransmitter deficits such as reduced availability of monoamines in discrete brain areas. Emotional alterations like depression result in reduced serotonin availability and enhanced kynurenine metabolism through the action of indoleamine 2, 3-dioxygenase in response to neuroinflammatory factors. This mechanism involves regulation of the neurotransmitter system by neuroinflammatory agents, linking mood regulation to neuroinmunological reactions. In this context, the aim of this study was to investigate the effects of maternal separation with early weaning on emotional behaviour in mice. We investigated neuroinflammatory responses and the state of the tryptophan–kynurenine metabolic pathway in discrete brain areas following maternal separation. We show that adverse events during early life increase risk of long-lasting emotional alterations during adolescence and adulthood. These emotional alterations are particularly severe in females. Behavioural impairments were associated with microglia activation and disturbed tryptophan–kynurenine metabolism in brain areas related to emotional control. This finding supports the preeminent role of neuroinflammation in emotional disorders.

Alteración emocional en atención primaria y urgencias pediátricas. ¿Se enfadan los padres durante la atención pediátrica?

A study was conducted in order to determine the presence of anxiety and anger in paediatric health care, exploring possible differences between primary health care and paediatric emergencies. The study also sought to determine which of the variables studied better predict anxiety in the sample of parents studied. A total of 1.517 parents whose children had been attended in paediatric department participated in this study. The method was based on a cross-sectional descriptive study using a questionnaire, where all the participants answered the State-Trait Anger Expression Inventory and the Spielberger State-Trait Anxiety Inventory. The results indicate a significant association between anxiety and both the considered dimensions of anger and the level of severity perceived by parents in the child's health status. From the anger dimensions considered, anger as a feeling is the most predictive expression of parental anxiety. Emotional alterations in paediatric health care settings should be prevented, detected when they occur, and effectively treated to avoid different negative consequences.

Role of neuroinflammation in the emotional and cognitive alterations displayed by animal models of obesity.

Obesity is associated with a high prevalence of mood disorders and cognitive dysfunctions in addition to being a significant risk factor for important health complications such as cardiovascular diseases and type 2 diabetes. Identifying the pathophysiological mechanisms underlying these health issues is a major public health challenge. Based on recent findings, from studies conducted on animal models of obesity, it has been proposed that inflammatory processes may participate in both the peripheral and brain disorders associated with the obesity condition including the development of emotional and cognitive alterations. This is supported by the fact that obesity is characterized by peripheral low-grade inflammation, originating from increased adipose tissue mass and/or dysbiosis (changes in gut microbiota environment), both of which contribute to increased susceptibility to immune-mediated diseases. In this review, we provide converging evidence showing that obesity is associated with exacerbated neuroinflammation leading to dysfunction in vulnerable brain regions associated with mood regulation, learning, and memory such as the hippocampus. These findings give new insights to the pathophysiological mechanisms contributing to the development of brain disorders in the context of obesity and provide valuable data for introducing new therapeutic strategies for the treatment of neuropsychiatric complications often reported in obese patients.

Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain.

In this study, we investigated the role of the endocannabinoid system (ECS) in the emotional and cognitive alterations associated with osteoarthritis pain. The monosodium iodoacetate model was used to evaluate the affective and cognitive manifestations of osteoarthritis pain in type 1 (CB1R) and type 2 (CB2R) cannabinoid receptor knockout and wild-type mice and the ability of CB1R (ACEA) and CB2R (JWH133) selective agonists to improve these manifestations during a 3-week time period. The levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured in plasma and brain areas involved in the control of these manifestations. Patients with knee osteoarthritis and healthy controls were recruited to evaluate pain, affective, and cognitive symptoms, as well as plasma endocannabinoid levels and cannabinoid receptor gene expression in peripheral blood lymphocytes. The affective manifestations of osteoarthritis were enhanced in CB1R knockout mice and absent in CB2R knockouts. Interestingly, both ACEA and JWH133 ameliorated the nociceptive and affective alterations, whereas ACEA also improved the associated memory impairment. An increase of 2-AG levels in prefrontal cortex and plasma was observed in this mouse model of osteoarthritis. In agreement, an increase of 2-AG plasmatic levels and an upregulation of CB1R and CB2R gene expression in peripheral blood lymphocytes were observed in patients with osteoarthritis compared with healthy subjects. Changes found in these biomarkers of the ECS correlated with pain, affective, and cognitive symptoms in these patients. The ECS plays a crucial role in osteoarthritis and represents an interesting pharmacological target and biomarker of this disease.