Effects of Trauma Cue Exposure and Posttraumatic Stress Disorder (PTSD) on Affect and Cannabis Craving in Cannabis Users With Trauma Histories: Use of Expressive Writing as an Online Cue-Reactivity Paradigm: Effets de l'exposition aux signaux traumatiques et du SSPT sur l'affect et le besoin de cannabis chez les consommateurs de cannabis ayant des antécédents de traumatismes : utilisation de l'écriture expressive comme paradigme de réactivité en ligne.

OBJECTIVES: Posttraumatic stress disorder (PTSD) and cannabis use disorder (CUD) commonly co-occur. Conditioned associations between psychological trauma cues, distress, cannabis use, and desired relief outcomes may contribute to the comorbidity. These conditioned associations can be studied experimentally by manipulating trauma cue exposure in a cue-reactivity paradigm (CRP) and examining effects on affective and cognitive outcomes in participants with and without PTSD. However, traditional CRPs take place in-lab limiting recruitment/power. We aimed to examine the effects of CRP condition (trauma and neutral) and PTSD group (likely PTSD+ and PTSD-) on affective and craving outcomes using a stand-alone online expressive writing CRP. METHODS: Participants (n = 202; 43.6% male; Mage = 42.94 years, SD = 14.71) with psychological trauma histories and past-month cannabis use completed a measure of PTSD symptoms (PTSD Checklist-5 for DSM-5 [PCL-5]) and were randomized to complete either a trauma or neutral expressive writing task. Then they completed validated measures of affect (Positive and Negative Affect Schedule-Short Form [PANAS-SF]) and cannabis craving (Marijuana Craving Questionnaire-Short Form [MCQ-SF]). RESULTS: Linear mixed models tested the hypothesized main and interactive effects of CRP condition (trauma and neutral) and PTSD group (likely PTSD+ and PTSD-) on negative and positive affect (PANAS-SF) and cannabis craving dimensions (MCQ-SF). The hypothesized main effects of trauma versus neutral expressive writing were found for negative affect and the expectancy dimension of cannabis craving and of PTSD group for negative affect and all cannabis craving dimensions; no interactions were observed. CONCLUSIONS: Expressive writing appears a useful online CRP. Interventions focused on reducing negative affect and expectancy craving to trauma cues may prevent/treat CUD among cannabis users with PTSD. PLAIN LANGUAGE SUMMARY TITLE: The Use of an Online Expressive Writing as a Trauma Cue Exposure: Effects on Craving and Emotions.

People who have gone through trauma sometimes experience both post-traumatic stress disorder (PTSD) and a tendency to use cannabis excessively (cannabis use disorder or CUD). Researchers believe that there's a connection between traumatic memories, emotional distress, cannabis use, and the relief people feel afterward. These associations can be studied experimentally by using a cue-reactivity paradigm (CRP) to examine effects on craving and affective outcomes in those with and without PTSD. This study included 202 participants who had a history of trauma and reported regular cannabis use. They were randomly assigned to write about a traumatic or neutral personal experience. After, they filled out questionnaires about their PTSD symptoms, emotions (both positive and negative), and cravings for cannabis during the task. We expected that the type of writing task (those assigned to the trauma vs. neutral condition) and PTSD status would be associated with increased cannabis craving, negative emotions, and reduced positive emotions. We found that writing about trauma increased negative feelings and positive expectations about using cannabis for relief, especially for those with PTSD. People with PTSD also seemed to have more ongoing negative feelings and cravings for cannabis. The authors suggest that traditional in-lab experiments might be necessary to fully understand how trauma reminders can influence cravings and emotions in individuals with PTSD-CUD.

Do we really need two sessions?: The use of a structured interview as a trauma cue reactivity paradigm.

OBJECTIVES: Derived from classical conditioning theory and rooted in motivational mechanisms, cue reactivity paradigms (CRPs) are used in addictions research to measure participants' propensities for substance-relevant responses (e.g., craving) during exposure to substance-relevant cues (e.g., drug paraphernalia). CRPs are also useful in PTSD-addiction comorbidity research, allowing the study of affective and substance-relevant responses to trauma cues. However, studies using traditional CRPs are time-consuming with high attrition rates due to repeat testing. Thus, we sought to test whether a single session semi-structured trauma interview could serve as a CRP in terms of eliciting theorized cue exposure effects on craving and affect measures. METHOD: Fifty regular cannabis users with trauma histories provided detailed descriptions of their most traumatic lifetime experience, and a neutral experience, according to an established interview protocol. Linear mixed models examined the effect of cue type (trauma vs. neutral) on affective and craving responses. RESULTS: As hypothesized, the trauma interview elicited significantly greater cannabis craving (and alcohol craving among the drinkers), and, greater negative affect among those with more severe PTSD symptoms, compared to the neutral interview. CONCLUSION: Results suggest an established semi-structured interview may function effectively as a CRP for use in trauma and addictions research.

Posttraumatic Stress Disorder Symptoms and Coping Motives are Independently Associated with Cannabis Craving Elicited by Trauma Cues.

Cannabis use is common among individuals with posttraumatic stress disorder (PTSD), although its use can ultimately worsen PTSD outcomes. Cannabis-use coping motives may help explain the PTSD-cannabis relationship. Frequent pairing of trauma cues with substance use to cope with negative affect can lead to conditioned substance craving. For the present cue-reactivity study, we examined if PTSD symptoms were associated with cannabis craving elicited by a personalized trauma cue and explored whether coping motives mediated this hypothesized relationship; enhancement motives were included as a comparison mediator. Participants (N = 51) were trauma-exposed cannabis users who completed validated assessments on PTSD symptom severity and cannabis use motives. They were then exposed to a personalized audiovisual cue based on their own traumatic experience after which they responded to questions on a standardized measure regarding their cannabis craving. The results demonstrated that PTSD symptoms were associated with increased cannabis craving following trauma cue exposure, B = 0.43, p = .004, 95% CI [0.14, 0.72]. However, the results did not support our hypothesis of an indirect effect through general coping motives, indirect effect = .03, SE = .08, 95% CI [-.10, .21]. We found an independent main effect of general coping motives on trauma cue-elicited cannabis craving, B = 1.86, p = .002, 95% CI [0.72, 3.01]. These findings have important clinical implications suggesting that clinicians should target both PTSD symptoms and general coping motives to prevent the development of conditioned cannabis craving to trauma reminders in trauma-exposed cannabis users.

Craving and emotional responses to trauma and cannabis cues in trauma-exposed cannabis users: Influence of PTSD symptom severity.

Conditioned craving to trauma cues and avoidance learning have both been implicated in the high concurrence of trauma-related distress and substance misuse. Using a cue-exposure paradigm involving personalized trauma, cannabis, and neutral cues, we examined if conditioned craving and/or elevated negative affect to trauma cues are mechanisms linking PTSD and cannabis use disorder. Fifty-one trauma-exposed cannabis users were randomly presented the three cue types. Craving and emotional responses were evaluated after each cue using the Marijuana Craving Questionnaire-Short Form (Heishman et al., 2001) and the Positive and Negative Affect Schedule (Watson et al., 1988). Relief cannabis craving (compulsivity and emotionality) was significantly higher after trauma than cannabis and neutral cues (p's < 0.001) and was also higher among those with more severe PTSD symptoms (p's < 0.05). The relationship between PTSD symptom severity and cannabis craving was stronger after trauma than cannabis cues for the compulsivity component of craving (p < .05). Relief craving was also higher after the cannabis cue than after the neutral cue (expectancy and purposefulness; p < .001). Negative affect was significantly higher: after trauma than cannabis and neutral cues (p's < 0.001); and among those with more severe PTSD symptoms (p < . 005). Positive affect was significantly lower after trauma than cannabis cues (p < .05). Trauma cue exposure might promote cannabis misuse through conditioned craving as well as the desire to relieve negative affect. Conditioned cannabis craving involving an uncontrollable compulsion to use cannabis in response to trauma reminders appears particularly likely among cannabis users with more severe PTSD symptoms.

Reasons for Listening to Music Vary by Listeners' Anxiety Sensitivity Levels.

Listening to music aids regulation of emotional arousal and valence (positive vs. negative). Anxiety sensitivity (AS; fear of arousal-related sensations) increases the risk for emotion dysregulation and associated coping behaviors such as substance use and exercise avoidance. The relationship between AS and music listening, however, has received very little attention. This study (1) used exploratory factor analysis of 53 items drawn from three previously validated measures of reasons for music listening to identify the core reasons for listening to music among university students and (2) explored associations between AS and reasons for music listening. Undergraduates (N = 788; 77.7% women; Mage = 19.20, SDage = 2.46) completed the Anxiety Sensitivity Index-3, Motives for Listening to Music Questionnaire, Barcelona Musical Reward Questionnaire, and Brief Music in Mood Regulation Scale. Six core reasons for music listening were identified: Coping, Conformity, Revitalization, Social Enhancement, Connection, and Sensory-Motor. Over and above age and gender, AS was associated with Coping and Conformity-reasons that involve relief from aversive emotions. AS also was associated with listening for Connection reasons. AS was not associated with Revitalization, Social Enhancement, or Sensory-Motor-reasons that involve rewards such as heightened positive emotions. Results suggest that individual differences may influence why people incorporate music listening into their day-to-day lives. Further longitudinal and experimental research is needed to establish directionality and causality in the observed relationship of AS to relief-oriented reasons for music listening. Findings may guide music therapists' efforts to tailor treatment for individuals at risk for anxiety and related mental health problems.

Plasma concentrations of granulocyte colony-stimulating factor (G-CSF) in patients with substance use disorders and comorbid major depressive disorder.

Granulocyte colony-stimulating factor (G-CSF) has raised much interest because of its role in cocaine addiction in preclinical models. We explored the plasma concentrations of G-CSF in patients diagnosed with substance use disorder (SUD) and highly comorbid psychiatric disorders. In particular, we investigated the association between G-CSF concentrations and comorbid major depressive disorder (MDD) in patients with cocaine and alcohol use disorders (CUD and AUD, respectively). Additionally, patients with MDD but not SUD were included in the study. Three hundred and eleven participants were enrolled in this exploratory study: 136 control subjects, 125 patients with SUD (SUD group) from outpatient treatment programs for cocaine (N = 60, cocaine subgroup) and alcohol (N = 65, alcohol subgroup), and 50 patients with MDD but not SUD (MDD group) from primary-care settings. Participants were assessed based on DSM-IV-TR criteria, and a blood sample was collected to examine the plasma concentrations of G-CSF. G-CSF concentrations were negatively correlated with age in the entire sample (r = - 0.233, p < 0.001) but not in the patients with MDD. G-CSF concentrations were lower in patients with SUD than in controls (p < 0.05), specifically in the cocaine subgroup (p < 0.05). Patients with SUD and comorbid MDD had lower G-CSF concentrations than patients with SUD but not comorbid MDD or controls (p < 0.05). In contrast, patients with MDD but not SUD showed no differences compared with their controls. The negative association between G-CSF concentrations and age in the sample was not observed in patients with MDD. G-CSF concentrations were decreased in patients with SUD and comorbid MDD but not in patients with MDD. Therefore, G-CSF may be useful to improve the stratification of patients with dual diagnosis seeking treatment. Further investigation is needed to explore the impact of sex and type of drug on the expression of G-CSF.

Variation in chemokines plasma concentrations in primary care depressed patients associated with Internet-based cognitive-behavioral therapy.

How the presence of inflammation has repercussions for brain function is a topic of active research into depression. Signals released from immune system-related cells, including chemokines, might be indicative of active depression and can, hypothetically, serve as biomarkers of response to interventions, both pharmacological and psychological. The objective of this study is to analyze the peripheral plasma concentrations of CXCL12, CCL11, CX3CL1 and CCL2 in a cohort of depressed primary-care patients, as well as their evolution after an internet-based cognitive-behavioral intervention. The concentrations of those chemokines were measured in 66 primary-care patients with mild and moderate depression, before and after the intervention, as well as 60 controls, using multiplex immunoassays. Concentrations of CXCL12 and CCL2 were significantly higher in the clinical sample in comparison with controls. A stable multivariate discriminative model between both groups was found. Concentrations of all chemokines decreased after the internet-based psychological intervention. These findings support the implication of chemokines in depression, even in a sample of patients with mild and moderate severity. Furthermore, they demonstrate the need for further multidisciplinary research that confirms how biomarkers such as plasma chemokines can serve as a marker for depression and are sensitive to non-pharmacological interventions.

Gender differences in physical activity are partially explained by anxiety sensitivity in post-secondary students.

Objective: Female post-secondary students typically engage in less physical activity than their male counterparts. Given that women have greater anxiety sensitivity (ie, fear of arousal-based body sensations) and anxiety sensitivity is inversely related to physical activity participation, this study sought to determine if anxiety sensitivity mediates gender differences in self-reported physical activity. Participants and methods: A sample of 802 post-secondary students completed the Anxiety Sensitivity Index-3 and a Lifestyles Questionnaire in September 2017. Results: Women reported significantly less physical activity and significantly greater anxiety sensitivity. Anxiety sensitivity was significantly and inversely related to self-reported physical activity. A significant indirect effect of gender on physical activity via anxiety sensitivity was shown (B = 5.56, SE = 2.81, p < .05, 95% CI [1.31, 12.78], PM = .0843). Conclusions: Results suggest that anxiety sensitivity partially explains gender differences in physical activity. Anxiety sensitivity reduction interventions might increase physical activity participation and reduce the existing gender gap.

Cross-cultural selection and validation of instruments to assess patient-reported outcomes in children and adolescents with achondroplasia.

PURPOSE: Achondroplasia, as the most common form of disproportionate short stature, potentially impacts the health-related quality of life (HRQOL) and functioning of people with this condition. Because there are no psychometrically validated patient-reported outcome (PRO) condition-specific instruments for achondroplasia, this study selected and tested available generic, disease-specific and under development questionnaires for possible use in multinational clinical research. METHODS: A three-step approach was applied. First, a literature review and clinician/expert opinions were used to select relevant PRO questionnaires. Second, focus group discussions, including a group cognitive debriefing for piloting of the questionnaires with children/adolescents with achondroplasia and their parents, were performed in Spain and Germany. Third, a field-test study was conducted to test the psychometric properties of these instruments. RESULTS: Six questionnaires were identified as potentially relevant in children with achondroplasia. In each country, five focus groups including a cognitive debriefing were conducted, and the results narrowed the possibilities to three instruments as most appropriate to assess HRQOL (the generic PedsQL, the height-specific QoLISSY, and the achondroplasia-specific APLES). Results of the field study indicate the QoLISSY and the PedsQL questionnaires to be most appropriate for use in clinical research at this time. CONCLUSION: This selection study is a step forward in assessing the impact of achondroplasia on HRQOL. Of the instruments examined, the QoLISSY and the PedsQL both capture items relevant to children with achondroplasia and have met the psychometric validation criteria needed for use in research. The APLES instrument is a promising tool that should be revisited upon psychometric validation.

Bupropion, a possible antidepressant without negative effects on alcohol relapse.

RATIONALE: the role that antidepressants play on alcohol consumption is not well understood. Previous studies have reported that treatment with a Selective Serotonin Reuptake Inhibitor (SSRIs) increases alcohol consumption in an animal model of relapse, however it is unknown whether this effect holds for other antidepressants such as the atypical dopamine/norepinephrine reuptake inhibitors (SNDRI). OBJECTIVES: the main goal of the present study was to compare the effects of two classes of antidepressants drugs, bupropion (SNDRI) and fluoxetine (SSRI), on alcohol consumption during relapse. Since glutamatergic and endocannabinoid signaling systems plays an important role in alcohol abuse and relapse, we also evaluated the effects of both antidepressants onthe expression of the main important genes and proteins of both systems in the prefrontal cortex, a critical brain region in alcohol relapse. METHODS: rats were trained to self-administered alcohol. During abstinence, rats received a 14d-treatment with vehicle, fluoxetine (10 mg/kg) or bupropion (20 mg/kg), and we evaluated alcohol consumption during relapse for 3 weeks. Samples of prefrontal cortex were taken to evaluate the mRNA and protein expression of the different components of glutamatergic and endocannabinoid signaling systems. RESULTS: fluoxetine treatment induced a long-lasting increase in alcohol consumption during relapse, an effect that was not observed in the case of bupropion treatment. The observed increases in alcohol consumption were accompanied by distinct alterations in the glutamate and endocannabinoid systems. CONCLUSIONS: our results suggest that SSRIs can negatively impact alcohol consumption in relapse while SNDRIs have no effects. The observed increase in alcohol consumption are accompanied by functional alterations in the glutamatergic and endocannabinoid systems. This finding could open new strategies for the treatment of depression in patients with alcohol use disorders.

Plasma concentrations of oleoylethanolamide in a primary care sample of depressed patients are increased in those treated with selective serotonin reuptake inhibitor-type antidepressants.

Oleoylethanolamide (OEA) is a non-cannabinoid acylethanolamide with multiple physiological roles that has been proposed to have antidepressant-like activity in preclinical models. OEA shares biosynthetic pathways with anandamide (AEA) a transmitter involved in affective disorders and anxiety in humans. However, although the participation of OEA in depression has been proposed, both, the contribution of OEA to the depressive phenotype and the effect of antidepressant therapy on circulating levels of this and related non-cannabinoid acylethanolamides in humans are basically unknown. The main objective of this study is to compare the plasma concentrations of OEA and related acylethanolamides in a sample of primary care patients with depression (n = 69) with those of healthy non-depressed patients (n = 47). At the time of admission to the study, 22 patients were under selective serotonin reuptake inhibitor (SSRI) antidepressant treatment and 47 patients were not receiving any type of intervention. In addition, plasma concentrations of the endocannabinoid 2-AG and two related monoacylglycerols were monitored. Plasma OEA concentrations were found to be elevated in depressed patients and to correlate with somatic symptoms of depression. Plasma concentrations of both, AEA and 2-AG, were found to be elevated also in depressed patients. Further analysis demonstrated that the elevation observed in the plasma concentrations of both, OEA and 2-AG, was associated to SSRI antidepressant therapy at the time of recruitment. Further clinical research is needed to understand whether SSRI-induced elevations in OEA levels contribute to the response to SSRI in depressed patients as described in preclinical models.

El estudio Andalusian Bipolar Family (ABiF): protocolo y descripción de la muestra / The Andalusian Bipolar Family (ABiF) Study: Protocol and sample description

Introducción: Se presenta la primera descripción del estudio denominado Andalusian Bipolar Family (ABiF). Se trata de una investigación longitudinal con familias procedentes de Andalucía (España), que comenzó en 1997, con el objetivo de dilucidar las causas geneticomoleculares del trastorno afectivo bipolar. Desde entonces, esta cohorte ha contribuido a una serie de hallazgos clave, que han sido publicados en revistas internacionales. Sin embargo, el conocimiento sobre las bases genéticas del trastorno en estas familias sigue siendo limitado. Método: El estudio consta de dos fases: en la fase inicial se reclutaron 100 familias con múltiples afectados de trastorno bipolar y otros trastornos del ánimo. La segunda fase del proyecto, actualmente en curso, comenzó en 2013 con el objetivo de realizar un seguimiento de la cohorte de familias reclutadas originalmente. Los objetivos del estudio de seguimiento son: I) recoger nuevos datos clínicos longitudinales; II) realizar una evaluación neuropsicológica detallada, y III) obtener una extensa colección de biomateriales para futuros estudios moleculares. Resultados: El estudio ABiF, por tanto, generará unos recursos valiosos para futuras investigaciones sobre la etiología del trastorno afectivo bipolar; particularmente con respecto a las causas de la alta carga genética del trastorno en las familias con múltiples afectados. Discusión: Se discute el valor de este enfoque en relación con las nuevas tecnologías para la identificación de factores genéticos de alta penetrancia. Estas nuevas tecnologías incluyen la secuenciación del exoma y del genoma completo, y el uso de células madre pluripotentes inducidas u organismos modelo para la determinación de consecuencias funcionales

Introduction: Here, we present the first description of the Andalusian Bipolar Family (ABiF) Study. This longitudinal investigation of families from Andalusia, Spain commenced in 1997 with the aim of elucidating the molecular genetic causes of bipolar affective disorder. The cohort has since contributed to a number of key genetic findings, as reported in international journals. However, insight into the genetic underpinnings of the disorder in these families remains limited. Method: In the initial 1997-2003 study phase, 100 multiplex bipolar disorder and other mood disorder families were recruited. The ongoing second phase of the project commenced in 2013, and involves follow-up of a subgroup of the originally recruited families. The aim of the follow-up investigation is to generate: I) longitudinal clinical data; II) results from detailed neuropsychological assessments; and III) a more extensive collection of biomaterials for future molecular biological studies. Results: The ABiF Study will thus generate a valuable resource for future investigations into the aetiology of bipolar affective disorder; in particular the causes of high disease loading within multiply affected families. Discussion: We discuss the value of this approach in terms of new technologies for the identification of high-penetrance genetic factors. These new technologies include exome and whole genome sequencing, and the use of induced pluripotent stem cells or model organisms to determine functional consequences

The Andalusian Bipolar Family (ABiF) Study: Protocol and sample description. / El estudio Andalusian Bipolar Family (ABiF): protocolo y descripción de la muestra.

INTRODUCTION: Here, we present the first description of the Andalusian Bipolar Family (ABiF) Study. This longitudinal investigation of families from Andalusia, Spain commenced in 1997 with the aim of elucidating the molecular genetic causes of bipolar affective disorder. The cohort has since contributed to a number of key genetic findings, as reported in international journals. However, insight into the genetic underpinnings of the disorder in these families remains limited. METHOD: In the initial 1997-2003 study phase, 100 multiplex bipolar disorder and other mood disorder families were recruited. The ongoing second phase of the project commenced in 2013, and involves follow-up of a subgroup of the originally recruited families. The aim of the follow-up investigation is to generate: i) longitudinal clinical data; ii) results from detailed neuropsychological assessments; and iii) a more extensive collection of biomaterials for future molecular biological studies. RESULTS: The ABiF Study will thus generate a valuable resource for future investigations into the aetiology of bipolar affective disorder; in particular the causes of high disease loading within multiply affected families. DISCUSSION: We discuss the value of this approach in terms of new technologies for the identification of high-penetrance genetic factors. These new technologies include exome and whole genome sequencing, and the use of induced pluripotent stem cells or model organisms to determine functional consequences.

Decreased plasma concentrations of BDNF and IGF-1 in abstinent patients with alcohol use disorders.

The identification of growth factors as potential biomarkers in alcohol addiction may help to understand underlying mechanisms associated with the pathogenesis of alcohol use disorders (AUDs). Previous studies have linked growth factors to neural plasticity in neurocognitive impairment and mental disorders. In order to further clarify the impact of chronic alcohol consumption on circulating growth factors, a cross-sectional study was performed in abstinent AUD patients (alcohol group, N = 91) and healthy control subjects (control group, N = 55) to examine plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1) and IGF-1 binding protein-3 (IGFBP-3). The association of these plasma peptides with relevant AUD-related variables and psychiatric comorbidity was explored. The alcohol group was diagnosed with severe AUD and showed an average of 13 years of problematic use and 10 months of abstinence at the moment of participating in the study. Regarding common medical conditions associated with AUD, we observed an elevated incidence of alcohol-induced liver and pancreas diseases (18.7%) and psychiatric comorbidity (76.9%). Thus, AUD patients displayed a high prevalence of dual diagnosis (39.3%) [mainly depression (19.9%)] and comorbid substance use disorders (40.7%). Plasma BDNF and IGF-1 concentrations were significantly lower in the alcohol group than in the control group (p<0.001). Remarkably, there was a negative association between IGF-1 concentrations and age in the control group (r = -0.52, p<0.001) that was not found in the alcohol group. Concerning AUD-related variables, AUD patients with liver and pancreas diseases showed even lower concentrations of BDNF (p<0.05). In contrast, the changes in plasma concentrations of these peptides were not associated with abstinence, problematic use, AUD severity or lifetime psychiatric comorbidity. These results suggest that further research is necessary to elucidate the role of BDNF in alcohol-induced toxicity and the biological significance of the lack of correlation between age and plasma IGF-1 levels in abstinent AUD patients.

Evaluation of plasma cytokines in patients with cocaine use disorders in abstinence identifies transforming growth factor alpha (TGFα) as a potential biomarker of consumption and dual diagnosis.

BACKGROUND: Cocaine use disorder (CUD) is a complex health condition, especially when it is accompanied by comorbid psychiatric disorders (dual diagnosis). Dual diagnosis is associated with difficulties in the stratification and treatment of patients. One of the major challenges in clinical practice of addiction psychiatry is the lack of objective biological markers that indicate the degree of consumption, severity of addiction, level of toxicity and response to treatment in patients with CUD. These potential biomarkers would be fundamental players in the diagnosis, stratification, prognosis and therapeutic orientation in addiction. Due to growing evidence of the involvement of the immune system in addiction and psychiatric disorders, we tested the hypothesis that patients with CUD in abstinence might have altered circulating levels of signaling proteins related to systemic inflammation. METHODS: The study was designed as a cross-sectional study of CUD treatment-seeking patients. These patients were recruited from outpatient programs in the province of Malaga (Spain). The study was performed with a total of 160 white Caucasian subjects, who were divided into the following groups: patients diagnosed with CUD in abstinence (N = 79, cocaine group) and matched control subjects (N = 81, control group). Participants were clinically evaluated with the diagnostic interview PRISM according to the DSM-IV-TR, and blood samples were collected for the determination of chemokine C-C motif ligand 11 (CCL11, eotaxin-1), interferon gamma (IFNγ), interleukin-4 (IL-4), interleukin-8 (IL-8), interleukin-17α (IL-17α), macrophage inflammatory protein 1α (MIP-1α) and transforming growth factor α (TGFα) levels in the plasma. Clinical and biochemical data were analyzed in order to find relationships between variables. RESULTS: While 57% of patients with CUD were diagnosed with dual diagnosis, approximately 73% of patients had other substance use disorders. Cocaine patients displayed greater cocaine symptom severity when they were diagnosed with psychiatric comorbidity. Regarding inflammatory factors, we observed significantly lower plasma levels of IL-17α (p < 0.001), MIP-1α (p < 0.001) and TGFα (p < 0.05) in the cocaine group compared with the levels in the control group. Finally, there was a significant primary effect of dual diagnosis on the plasma concentrations of TGFα (p < 0.05) in the cocaine group, and these levels were lower in patients with dual diagnoses. DISCUSSION: IL-17α, MIP-1α and TGFα levels are different between the cocaine and control groups, and TGFα levels facilitate the identification of patients with dual diagnosis. Because TGFα reduction is associated with enhanced responses to cocaine in preclinical models, we propose TGFα as a potential biomarker of complex CUD in humans.

Differences in clinical intrusive thoughts between obsessive-compulsive disorder, generalized anxiety disorder, and hypochondria.

Differences and similarities between intrusive thoughts typical of obsessive-compulsive disorder, generalized anxiety disorder, and hypochondriasis are relevant for their differential diagnosis, formulation, and psychological treatment. Previous research in non-clinical samples pointed out the relevance of some process variables, such as responsibility, guilt, or neutralization strategies. This research is aimed to investigate the differences and similarities between clinical obsessions, worries, and illness intrusions in some of these process variables. A second aim is to identify models based on these variables that could reliably differentiate between them. Three groups of patients with obsessive-compulsive disorder (n = 35; 60% women, mean age 38.57), generalized anxiety disorder (n = 36; 61.1% women, mean age 41.50), and hypochondriasis (n = 34; 70.6% women, mean age 31.59) were evaluated using the Cognitive Intrusions Questionnaire-Transdiagnostic Version (Romero-Sanchiz, Nogueira-Arjona, Godoy-Ávila, Gavino-Lázaro, & Freeston, ). The results showed that some appraisals (e.g., responsibility or egodystonicity), emotions (e.g., guilt or insecurity), neutralization strategies, and other variables (e.g., verbal content or trigger from body sensation) are relevant for the discrimination between obsessions, worries, and illness intrusions. The results also showed 3 stable models based on these variables for the discrimination between these thoughts. The implication of these results in the diagnosis, formulation, and psychological treatment of obsessive-compulsive disorder, generalized anxiety disorder, and hypochondriasis is discussed.

Differences in the Rates of Drug Polyconsumption and Psychiatric Comorbidity among Patients with Cocaine Use Disorders According to the Mental Health Service.

Cocaine continues to be a worldwide public health concern in Europe. To improve prognosis and intervention, it is necessary to understand the characteristics of the patients who depend on the services where they receive care. The objective is to analyze the differences among patients who use cocaine and between ambulatory and residential resources to better adapt treatment. This is a descriptive, observational study of two populations of cocaine users in treatment: the ambulatory therapeutic community (ATC) and the therapeutic community (TC). The PRISM diagnostic interview was used for both groups. An analysis of both populations indicates a high prevalence of cocaine, heroin, cannabis, sedative, psychostimulant, and hallucinogen use disorders in the TC population compared to the ATC. In alcohol use disorder, differences between both mental health services were not observed. The degree of severity of cocaine use disorders (CUD) is greater in the TC population. The prevalence of psychiatric comorbidity is not statistically significant between the two populations, except for primary psychotic disorders, which are more prevalent in the TC population. This difference in the prevalence of psychotic disorders may be related to the high prevalence of cannabis use disorders in TC patients. Differences in the prevalence of substance use disorders, severity of CUD, and psychiatric comorbidity may limit the efficiency of mental health services involved in substance use disorder therapeutics. These results suggest the need for careful and extensive phenotyping of patients to improve intervention and prognosis in a clinical resource-dependent manner.

Economic evaluation of a guided and unguided internet-based CBT intervention for major depression: Results from a multi-center, three-armed randomized controlled trial conducted in primary care.

Depression is one of the most common mental disorders and will become one of the leading causes of disability in the world. Internet-based CBT programs for depression have been classified as "well established" following the American Psychological Association criteria for empirically supported treatments. The aim of this study is to analyze the cost effectiveness at 12-month follow-up of the Internet-based CBT program "Smiling is fun" with (LITG) and without psychotherapist support (TSG) compared to usual care. The perspective used in our analysis is societal. A sample of 296 depressed patients (mean age of 43.04 years; 76% female; BDI-II mean score = 22.37) from primary care services in four Spanish regions were randomized in the RCT. The complete case and intention-to-treat (ITT) perspectives were used for the analyses. The results demonstrated that both Internet-based CBT interventions exhibited cost utility and cost effectiveness compared with a control group. The complete case analyses revealed an incremental cost-effectiveness ratio (ICER) of €-169.50 and an incremental cost-utility ratio (ICUR) of €-11389.66 for the TSG group and an ICER of €-104.63 and an ICUR of €-6380.86 for the LITG group. The ITT analyses found an ICER of €-98.37 and an ICUR of €-5160.40 for the TSG group and an ICER of €-9.91 and an ICUR of €496.72 for the LITG group. In summary, the results of this study indicate that the two Internet-based CBT interventions are appropriate from both economic and clinical perspectives for depressed patients in the Spanish primary care system. These interventions not only help patients to improve clinically but also generate societal savings. TRIAL REGISTRATION: clinicaltrials.gov NCT01611818.

Plasma concentrations of oleoylethanolamide and other acylethanolamides are altered in alcohol-dependent patients: effect of length of abstinence.

Acylethanolamides are a family of endogenous lipid mediators that are involved in physiological and behavioral processes associated with addiction. Recently, oleoylethanolamide (OEA) has been reported to reduce alcohol intake and relapse in rodents but the contribution of OEA and other acylethanolamides in alcohol addiction in humans is unknown. The present study is aimed to characterize the plasma acylethanolamides in alcohol dependence. Seventy-nine abstinent alcohol-dependent subjects (27 women) recruited from outpatient treatment programs and age-/sex-/body mass-matched healthy volunteers (28 women) were clinically assessed with the diagnostic interview PRISM according to the DSM-IV-TR after blood extraction for quantification of acylethanolamide concentrations in the plasma. Our results indicate that all acylethanolamides were significantly increased in alcohol-dependent patients compared with control subjects (p < 0.001). A logistic model based on these acylethanolamides was developed to distinguish alcohol-dependent patients from controls and included OEA, arachidonoylethanolamide (AEA) and docosatetraenoylethanolamide (DEA), providing a high discriminatory power according to area under the curve [AUC = 0.92 (95%CI: 0.87-0.96), p < 0.001]. Additionally, we found a significant effect of the duration of alcohol abstinence on the concentrations of OEA, AEA and DEA using a regression model (p < 0.05, p < 0.01 and p < 0.001, respectively), which was confirmed by a negative correlation (rho = -0.31, -0.40 and -0.44, respectively). However, acylethanolamides were not influenced by the addiction alcohol severity, duration of problematic alcohol use or diagnosis of psychiatric comorbidity. Our results support the preclinical studies and suggest that OEA, AEA and DEA are altered in alcohol-dependence during abstinence and that might act as potential markers for predicting length of alcohol abstinence.

Comorbilidad psiquiátrica y valores plasmáticos de 2-acilgliceroles en consumidores de alcohol en tratamiento ambulatorio. Análisis de las diferencias de género / Psychiatric comorbidity and plasma levels of 2-acyl-glycerols in outpatient treatment alcohol users. Analysis of gender differences

La adicción al alcohol se asocia con una elevada comorbilidad psiquiátrica que complica el tratamiento, siendo necesaria una fenotipación clínica objetiva de estos pacientes para optimizar la atención y mejorar el pronóstico. El presente estudio aborda este problema mediante los siguientes objetivos: a) estimar la prevalencia y tipos de comorbilidad psiquiátrica de una muestra de pacientes que buscan tratamiento por uso de alcohol, b) describir las diferencias de género en su presentación y c) analizar los valores plasmáticos de 2-acilgliceroles (incluyendo el endocannabinoide 2-araquidonilglicerol), estudiando su posible valor como biomarcador de alcoholismo y/o comorbilidad psiquiátrica. Para ello se reclutaron 162 pacientes evaluados con la entrevista semiestructurada PRISM, para evaluar la presencia de comorbilidad y su carácter primario o inducido. Los resultados obtenidos indican que la presencia de psicopatología se asoció a un mayor número de criterios de abuso y dependencia de alcohol Se encontraron diferencias de género tanto en la comorbilidad psiquiátrica, especialmente en trastornos del estado de ánimo. La prevalencia de comorbilidad psiquiátrica encontrada a lo largo de la vida fue del 68,5%, destacando los trastornos del estado ánimo (37%), y seguidos por el trastorno por déficit de atención (24,7%, monitorizado específicamente por la entrevista WURS) y los trastornos de ansiedad (17,9%). Entre los trastornos del estado de ánimo y psicóticos fueron más frecuentes los inducidos, mientras que en los trastornos de ansiedad los primarios fueron más prevalentes. Además, se encontraron concentraciones disminuidas significativamente de 2-acilgliceroles en pacientes con trastornos de ansiedad comórbidos diagnosticados en el último año

Alcohol addiction is associated with high psychiatric comorbidity. Objective stratification of patients is necessary to optimize care and improve prognosis. The present study is designed to gain insights into this challenge by addressing the following objectives: a) to estimate the prevalence of psychiatric comorbidities in a sample of outpatients seeking treatment for alcohol use disorder, b) to describe the existence of gender differences and c) to validate 2-acyl-glycerols as biomarkers of alcohol use disorder and/or psychiatric comorbidity. One hundred and sixty-two patients were recruited and evaluated with the semistructured interview PRISM. The presence of psychopathology was associated with a greater number of criteria for alcohol abuse and dependence according to DSM-IV-TR. We found gender differences in psychiatric comorbidity, e.g., mood disorder, as well as in comorbid substance use disorders. The prevalence of lifetime psychiatric comorbidity was 68.5%, with mood disorders the most frequent (37%), followed by attention deficit disorder (24.7%) and anxiety disorders (17.9%). Substance-induced disorders were more frequent in mood and psychotic disorders, whereas the primary disorders were more prevalent in patients with comorbid anxiety disorders. We found that 2-acyl-glycerols were significantly decreased in comorbid anxiety disorders in alcohol dependent patients in the last year, which makes them a potential biomarker for this psychopathological condition