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Background: The global increasing prevalence of obsessive-compulsive disorders and symptoms among various age groups and nationalities is considered a great clinical challenge. However, limited data are available on this topic in the Middle East and Gulf Council Countries. This study aimed to raise awareness of obsessive-compulsive symptoms among adults in Bahrain by determining its prevalence and risk factors among patients attending primary healthcare centers. Materials and Methods: A cross-sectional study was conducted among adult patients attending primary healthcare centers in Bahrain. A self-administered online questionnaire using Google form, a free online survey-creating website, was distributed through WhatsApp messages. A snowball sampling technique was used. The questionnaire consisted of three parts: the socio-demographic data of participants, the Maudsley Obsessional-Compulsive Inventory, and the Yale-Brown Obsessive-Compulsive Scale. Descriptive and inferential analyses were conducted. Results: A total of 614 participants were included with a mean age of 30.04 ± 13.04 years. Most participants were females (82.5%) and single (n = 347, 56.5%). The estimated prevalence of obsessive-compulsive symptoms among the participants was 15%; most of them reported mild symptoms (85%). Significantly higher obsession and compulsion symptoms were found among non-Bahraini (P < 0.001 and P < 0.002), single (P < 0.001 and P < 0.033), and student participants (P < 0.001 and P = 0.002) compared to their counterparts, respectively. In addition, undergraduates reported higher obsessions compared to other participants (P = 0.005). Conclusions: Approximately, one in every eight people in Bahrain were found to suffer from obsessive-compulsive symptoms, especially single, students, and non-Bahraini participants. These findings highlight the need for raising awareness of obsessive-compulsive disorder and its symptoms as well as the importance of early detection and management of obsessive-compulsive disorder.

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Randomized controlled trials have reported psychoanalytic psychotherapy to improve longer-term post-treatment outcomes in patients with treatment-resistant depression. In this case study, we examine the therapy process of a female trial participant diagnosed with treatment-resistant depression. Structured clinical assessments indicated that the patient's level of depression remained unchanged during and after treatment. Over the course of the therapy, she repeatedly broke away from important others and finally also from the therapy itself, which we linked to the impact of earlier experiences of abandonment on her internal world. In the discussion, we present a variety of reflections that were put forward by the authors during a series of case discussion meetings. Some of these reflections relate to how the inner world of this patient might have triggered a negative therapeutic reaction and a destructive pattern of repetition. The interpretative stance, in which the therapist interpreted this reaction as indicative of a psychic conflict and linked this conflict to the therapeutic relationship, seemed to be experienced by the patient as unhelpful and persecutory. Other elements that were brought up include basic distrust, lack of symbolization and trauma in the patient, as well as the constraints of the research context.

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Heinz et al. (2024) recently criticised habit/compulsion theory of human addiction but nevertheless concluded that 'habit formation plays a significant role in drug addiction'. To challenge this causal claim, the current article develops four further methodological criticisms, that publications supporting the habit/compulsion account of human addiction: (1) under-report contradictory observations; (2) exaggerate the process purity of positive observations; (3) under-emphasise the low quality of epidemiological support for a causal hypothesis; (4) recapitulate the social injustice of racial intelligence era by prematurely attributing lower task performance to drug user group membership (endophenotype) without having adequately tested social, psychological, economic and environmental inequalities. Methodological guidelines are recommended to address each concern, which should raise evidence standards, incorporate social justice and improve accuracy of estimating any specific effect of addiction history on task performance. Given that construing drug users as intellectually impaired could promote stigma and reduce their recovery potential, it is recommended that scientific discourse about habit/compulsive endophenotypes underpinning addiction is avoided until these higher evidence standards are met.

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The author presents a long analysis of a patient, Giulia, whose obstinate will to achieve evokes the workings of alchemical sulphur at its fieriest and a dread of its coniunctio with alchemical salt. Jung's description of these symbols in Mysterium Coniunctionis offers a useful imaginal perspective to clinical work in the area of compulsion and its possible transformations. Right from the start, the analytic relationship appeared to be mirrored and affected by this alchemical perspective. However, it was only after much time, uncertainty and emotional endurance that a fuller psychological experience of sulphur and salt could be accessed, allowing the analysis to take a more imaginative and mercurial turn. In the course of his work with Giulia the author has witnessed and experienced a range of intense affects-the many colours that the combustion of sulphur can generate-whether on the verge of unstoppable creation or ruthless destruction, often of archetypal intensity. This experience has been lived through and has undergone a transformative relation with salt, which until then had lived a dissociated existence in the fixed trauma of the compulsion and in a nocturnal underworld of tears.

L'auteur présente la longue analyse d'une patiente, Giulia, dont la volonté obstinée de réussir fait penser à l'activité du soufre alchimique à son point le plus ardent et à la crainte terrible de son coniunctio avec le sel alchimique. La description que fait Jung de ces symboles dans Mysterium Coniunctionis fournit une perspective imaginale qui est utile pour le travail clinique dans le domaine de la compulsion et de ses transformations possibles. Dès le début, la relation analytique semblait être reflétée et affectée par cette perspective alchimique. Cependant, ce fut seulement après beaucoup de temps, d'incertitude et d'endurance émotionnelle qu'une expérience psychologique plus complète du soufre et du sel a pu être atteinte, ce qui a permis à l'analyse de prendre une tournure plus imaginative et plus mercurienne. Durant son travail avec Giulia l'auteur a été témoin et a éprouvé un éventail d'affects intenses ­ les multiples couleurs que la combustion du souffre peut générer ­ que ce soit au bord d'une création irrésistible ou d'une destruction impitoyable, souvent d'une intensité archétypale. Cette expérience a été traversée et a subi une relation transformative avec le sel, qui jusqu'alors avait vécu une existence dissociée dans le traumatisme figé de la compulsion et dans les enfers nocturnes des larmes.

El autor presenta un largo análisis de una paciente, Giulia, cuya obstinada voluntad de logro evoca el funcionamiento del azufre alquímico en su forma más ardiente y el temor a su coniunctio con la sal alquímica. La descripción que Jung hace de estos símbolos en Mysterium Coniunctionis ofrece una perspectiva imaginal útil para el trabajo clínico en el ámbito de la compulsión y sus posibles transformaciones. Desde el principio, la relación analítica pareció reflejarse y verse afectada por esta perspectiva alquímica. Sin embargo, fue sólo después de mucho tiempo, incertidumbre y resistencia emocional que pudo accederse a una más plena experiencia psicológica de azufre y sal, lo cual permitió que el análisis tomara un giro más imaginativo y mercurial. En el transcurso de su trabajo con Giulia, el autor ha sido testigo y ha experimentado una gama de intensas emociones ­los múltiples colores que puede generar la combustión del azufre­, ya sea al borde de una creación imparable o de una destrucción despiadada, a menudo de intensidad arquetípica. Esta experiencia pudo ser atravesada y ha experimentado una relación transformadora con la sal, la cual hasta entonces había vivido una existencia disociada en la fijeza compulsiva del trauma y en un submundo nocturno de lágrimas.

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Background: Exercise dependence (ED) is characterised by behavioural and psychological symptoms that resemble those of substance use disorders. However, it remains inconclusive whether ED is accompanied by similar brain alterations as seen in substance use disorders. Therefore, we investigated brain alterations in individuals with ED and inactive control participants. Methods: In this cross-sectional neuroimaging investigation, 29 individuals with ED as assessed with the Exercise Dependence Scale (EDS) and 28 inactive control participants (max one hour exercising per week) underwent structural and functional resting-state magnetic resonance imaging (MRI). Group differences were explored using voxel-based morphometry and functional connectivity analyses. Analyses were restricted to the striatum, amygdala, and inferior frontal gyrus (IFG). Exploratory analyses tested whether relationships between brain structure and function were differently related to EDS subscales among groups. Results: No structural differences were found between the two groups. However, right IFG and bilateral putamen volumes were differently related to the EDS subscales "time" and "tolerance", respectively, between the two groups. Resting-state functional connectivity was increased from right IFG to right superior parietal lobule in individuals with ED compared to inactive control participants. Furthermore, functional connectivity of the angular gyrus to the left IFG and bilateral caudate showed divergent relationships to the EDS subscale "tolerance" among groups. Discussion: The findings suggest that ED may be accompanied by alterations in cognition-related brain structures, but also functional changes that may drive compulsive habitual behaviour. Further prospective studies are needed to disentangle beneficial and detrimental brain effects of ED.

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Stimulants are the first-line pharmacological treatment for attention deficit hyperactivity disorder (ADHD). We present the unique case of a patient who developed a chewing compulsion when taking mixed amphetamine salts (MAS). A 32-year-old female patient with a past medical history of gastroesophageal reflux disease (GERD), gastroparesis, and migraines was seen for initial psychiatric assessment due to concerns for irritability. She was diagnosed with post-traumatic stress disorder (PTSD); generalized anxiety disorder; ADHD, inattentive type; and unspecified bipolar disorder. Lamotrigine was started and titrated to 25mg twice per day, with improved mood stability. MAS immediate-release (IR) was started at 2.5mg and titrated to 5mg daily for ADHD. She then experienced an uncontrollable urge to chew, finding relief when chewing on a child's teething necklace, which provided satisfaction and a reduction in anxiety. She denied jaw tightness or teeth grinding. The dose of MAS IR was reduced to 2.5mg daily with improvement in symptoms and later increased again to 5mg daily, which she was then able to tolerate. Stereotyped biting behaviors have been observed in rats with the use of amphetamines, and the onset of compulsive behavior has emerged in children with the use of dextroamphetamine. However, this is the first known case of compulsive chewing or biting movements reported in humans with MAS use. This case highlights the need to assess patients for adverse events, such as compulsive biting and chewing movements or other oral facial stereotypies, after commencement of stimulants, including MAS.

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Obsessive-compulsive disorder (OCD) is a prevalent and debilitating mental health condition. This literature review examines the latest strategies in managing and treating OCD, with an emphasis on psychotherapy, pharmacological interventions, and neurosurgical options. A comprehensive literature search utilizing PubMed, Google Scholar, ClinicalKey, and Embase databases was conducted. Utilizing chosen keywords, the resulting articles were filtered based on inclusion and exclusion criteria. Included articles were used to discuss current research regarding OCD treatment and management. Findings reveal the efficacy and obstacles of treatments such as cognitive-behavioral therapy, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and evidence-based neurosurgical methods, offering a broad perspective on OCD management. We discuss the limitations of these established treatments and examine the innovative response of neurosurgery in treating patients with OCD. This review highlights the importance of individualized treatment plans and areas for future research.

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Background The COVID-19 pandemic and subsequent guidelines have had a substantial effect on social norms. This likely affected self-report assessment of psychopathology, namely those that assess obsessive-compulsive tendencies routinely used to screen for obsessive-compulsive disorder (OCD). It was hypothesized that self-report assessment of OCD likely produces inflated, non-discriminating scale scores. Methods Data collection occurred prior to the COVID-19 pandemic with the aim of validating a new psychological test; however, data collection was abruptly halted in March 2020. Data collection was allowed to resume in the latter half of the year. Both groups were racio-ethnically and gender diverse. Results Self-report measures of OCD yielded inflated scores. For instance, the total obsessive-compulsive inventory-revised (OCI-R) average score of all participants went from normative levels prior to COVID-19 (M = 13.69, SD = 10.32) to an average score that was above the clinical cut-off on the OCI-R (M = 32.89; SD = 12.95) during the pandemic (t(135) = 9.66, p < 0.001, Cohen's d = 1.66). Conclusions OCD-related scale scores likely produced false positives in research and practice due to COVID-19 health guidelines put in place to protect against infection that may otherwise be considered contamination fears on OCD measures.

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The direction of time is often defined by describing asymmetries between past and future events, referred to as "time-arrows." Two important time-arrows are the mutability time-arrow, which specifies that the past is unalterable, while the future is not; and the causal time-arrow, which stipulates that past events may cause future events, but not vice versa. The author argues that the unconscious conception of causation expressed in both the oedipal myth and certain oedipal wishes negates the mutability and causal time-arrows. The author suggests, therefore, distinguishing between oedipal phantasies that undermine the ordinary conceptions of causation and time (such as the wish of being one's own parent), and classical content that is in line with our time perception (such as sexual and aggressive wishes toward parents). Analyzing clinical examples suggests that some patients' oedipal phantasies are combined with unconscious sexual satisfaction from the asymmetric conception of time. When this sexual satisfaction is analyzed, they might expose the oedipal phantasies founded on the symmetric conception of time.

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BACKGROUND: Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) are two common and impairing neurodevelopmental conditions with partial symptomatic overlap. The aim of this study is to systematically and meta-analytically examine the following: (i) the prevalence of an OCD diagnosis among young people with ASD, (ii) the prevalence of an ASD diagnosis among young people with OCD, and (iii) the clinical and therapeutic implications of such comorbidity. METHOD: A multistep literature search was performed from database inception until 17 November 2023. This PRISMA/MOOSE-compliant systematic review, registered in PROSPERO (CRD42023480543), identified studies reporting on the prevalence, sociodemographic, psychopathologic, prognostic, and therapeutic correlates of OCD and ASD concurrence in children and adolescents. A quantitative meta-analysis with random effects was conducted to analyse the pooled prevalence of OCD among samples with a mean age of < 18 years old with ASD and the prevalence of ASD among individuals under 18 with OCD. Sensitivity analyses were performed to investigate the effect of diagnostic criteria and different continents. Meta-regression analyses were conducted to examine the effect of gender, age, IQ, and OCD severity scores. A narrative review of the clinical and therapeutical implications of the comorbidity was provided. RESULTS: 42 studies were selected for the systematic review (SR), and 31 of them were also included in one of the meta-analyses. The pooled prevalence of OCD among ASD youth samples (n = 8916, mean age = 10.6 ± 1.6; 16.4% female) was 11.6% (95% confidence intervals [CI] = 6.9%; 18.8%), and the pooled prevalence of ASD among OCD children and adolescent samples (n = 6209, mean age = 14.1 ± 1.4; 45.7% female) was 9.5% (95% CI = 6.0%; 14.7%). Meta-regressions found a statistically higher prevalence of ASD among samples with a lower prevalence of females (ß = -4.7; 95%CI = -8.6; -0.8). Children with both OCD and ASD present higher rates of functional impairment, psychopathology, and other comorbidities, compared to youth with either of the disorders alone. CONCLUSIONS: OCD and ASD are highly concurrent conditions in youth, with symptomatic, prognostic, severity, and therapeutic implications. Future research should focus on conducting longitudinal cohort studies prospectively to determine development trajectories, along with randomized controlled trials to assess the efficacy of specific therapeutic interventions.

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Alcohol use disorder is a substantial social and economic burden. During the last years, the number of women with drinking problems has been increasing, and one main concern is that they are particularly more vulnerable to negative consequences of alcohol. However, little is known about female-specific response patterns for alcohol, and potential underlying differences in brain mechanisms, including for compulsion-like alcohol drinking (when intake persists despite adverse consequences). We used lickometry to assess behavioral microstructure in adult Wistar male and female rats (n = 28-30) during alcohol-only drinking or moderate- or higher-challenge alcohol compulsion (10 or 60 mg/l quinine in alcohol, respectively). Estrous stages were determined and related to drinking levels and patterns of responding to alcohol, as was ovariectomy. Our findings showed that females (where we didn't determine estrus stage) had similar total licks in a session as males, but significantly longer licking bouts under alcohol-only and moderate-challenge, suggesting greater persistence. Further, greater intake under alcohol-only and moderate-challenge was related to faster licking in males, while female consumption was not related to licking speed. Thus, females could have increased persistence without greater vigor, unlike males. However, under higher-challenge, faster licking did predict higher intake in females, similar to males. To better understand female higher-challenge responding, we examined drinking in relation to phases of the estrous cycle. Higher-challenge had longer bouts only in late diestrus. In addition, ovariectomy led to longer bouts only under higher-challenge, suggesting that conditions with reduced hormone levels could increase female persistence for alcohol under higher-challenge. However, ovariectomy also reduced alcohol-only and moderate-challenge drinking but did not reduce bout length. Thus, intake level and response strategy could be regulated somewhat differently by ovarian hormones. Finally, moderate-challenge licking speed was less variable during early diestrus, and we previously showed more stereotyped responding specifically under moderate-challenge in males. By combining behavioral microstructure and sex- and estrus-related changes in drinking patterns, our results suggest that females have greater persistence for alcohol under lower-challenge drinking, while late diestrus and ovariectomy unmasked greater persistence under higher-challenge. Together, our novel insights could help develop more effective and personalized treatments for problematic alcohol use.

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BACKGROUND: A significant proportion of people with clozapine-treated schizophrenia develop 'checking' compulsions, a phenomenon yet to be understood. AIMS: To use habit formation models developed in cognitive neuroscience to investigate the dynamic interplay between psychosis, clozapine dose and obsessive-compulsive symptoms (OCS). METHOD: Using the anonymised electronic records of a cohort of clozapine-treated patients, including longitudinal assessments of OCS and psychosis, we performed longitudinal multi-level mediation and multi-level moderation analyses to explore associations of psychosis with obsessiveness and excessive checking. Classic bivariate correlation tests were used to assess clozapine load and checking compulsions. The influence of specific genetic variants was tested in a subsample. RESULTS: A total of 196 clozapine-treated individuals and 459 face-to-face assessments were included. We found significant OCS to be common (37.9%), with checking being the most prevalent symptom. In mediation models, psychosis severity mediated checking behaviour indirectly by inducing obsessions (r = 0.07, 95% CI 0.04-0.09; P < 0.001). No direct effect of psychosis on checking was identified (r = -0.28, 95% CI -0.09 to 0.03; P = 0.340). After psychosis remission (n = 65), checking compulsions correlated with both clozapine plasma levels (r = 0.35; P = 0.004) and dose (r = 0.38; P = 0.002). None of the glutamatergic and serotonergic genetic variants were found to moderate the effect of psychosis on obsession and compulsion (SLC6A4, SLC1A1 and HTR2C) survived the multiple comparisons correction. CONCLUSIONS: We elucidated different phases of the complex interplay of psychosis and compulsions, which may inform clinicians' therapeutic decisions.

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By revisiting the last years of a long psychoanalytic treatment of a female patient, a psychoanalyst reflects on her own development as a clinician and on the changes in her experience of psychoanalytic generativity. An increasing ability to understand patient's shifts between creativity and destructiveness brings about a different understanding of the process of mourning, while the shared aging of the analytic dyad highlights the difficulty of ending an analysis that has become a way of life.

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Problem alcohol drinking continues to be a substantial cost and burden. In addition, alcohol consumption in women has increased in recent decades, and women can have greater alcohol problems and comorbidities. Thus, there is a significant need for novel therapeutics to enhance sex-specific, individualized treatment. Heart rate (HR) and HR variability (HRV) are of broad interest because they may be both biomarkers for and drivers of pathological states. HRV reflects the dynamic balance between sympathetic (SNS, 'fight or flight') and parasympathetic (PNS, 'rest and digest') systems. Evidence from human studies suggest PNS predominance in women and SNS in men during autonomic regulation, indicating the possibility of sex differences in risk factors and physiological drivers of problem drinking. To better understand the association between HRV sex differences and alcohol drinking, we examined whether alcohol consumption levels correlated with time domain HRV measures (SDNN and rMSSD) at baseline, at alcohol drinking onset, and across 10 min of drinking, in adult female and male Wistar rats. In particular, we compared both HRV and HR measures under alcohol-only and compulsion-like conditions (alcohol + 10 mg/L quinine), because compulsion can often be a significant barrier to treatment of alcohol misuse. Importantly, previous work supports the possibility that different HRV measures could be interpreted to reflect PNS versus SNS influences. Here, we show that females with higher putative PNS indicators at baseline and at drinking onset had greater alcohol consumption. In contrast, male intake levels related to increased potential SNS measures at drinking onset. Once alcohol was consumed, HR predicted intake level in females, perhaps a pharmacological effect of alcohol. However, HRV changes were greater during compulsion-like intake versus alcohol-only, suggesting HRV changes (reduced SNS in females, reduced PNS and increased HR in males) specifically related to aversion-resistant intake. We find novel and likely clinically relevant autonomic differences associated with biological sex and alcohol drinking, suggesting that different autonomic mechanisms may promote differing aspects of female and male alcohol consumption.

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BACKGROUND:  COVID-19 caused unforeseen global burden, although vaccine strategy rapidly stalled transmission and protected those at risk. Many governments made vaccination mandatory for public space access. AIM:  This study aimed to elucidate perception of Nigerian civil servants towards mandatory COVID-19 vaccination and elicited their recommendations. SETTING:  This study was conducted in twelve purposively selected states in the six geopolitical zones and the Federal Capital Territory (FCT), Nigeria. Relevant ministries, departments and agencies were selected within the study sites. METHODS:  It was a qualitative study that interviewed consenting civil servants. Ethical approval was obtained from the National Health Research Ethics Committee. Interviews were conducted in person, following a pre-test. Data was analysed using NVivo software version 12. RESULTS:  Most participants were willing to take the vaccine if their safety was assured. However, enforcement to do so was a hindrance. Most participants commended the government for the effort to curb COVID-19 transmission and create awareness but were displeased with planning and handling of misconceptions. They recommended a more committed approach to vaccine production and funding by the government. CONCLUSION:  Participants were willing to take the COVID-19 vaccines because the gains of protection outweighed the risks. They suggested a less involuntary approach through reinforcing awareness creation and avoiding threats.Contribution: There is limited qualitative research on perception of Nigerian civil servants regarding mandatory COVID-19 vaccination. Being the main driving force of Nigeria's public service, their views are invaluable. Findings could contribute to future policies in times of emergency.

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BACKGROUND: For individuals with severe mental illness, involuntary assessment and/or treatment (hereafter detention) can be a necessary intervention to support recovery and may even be lifesaving. Despite this, little is known about how often these interventions are used for children and adolescents. METHODS: This global scoping review set out to: (1) map the current evidence around mental health detentions of children and adolescents (< 18 years); (2) identify the clinical, sociodemographic, and behavioural factors associated with detention; and (3) document the views of professionals and young people on the implementation of mental health legislation. RESULTS: After searching databases of peer-reviewed literature and citation chaining, 42 articles from 15 jurisdictions were included. About one fifth of psychiatric admissions in national register data were detentions, however trends were only available for a few high-income Western countries. The circumstances justifying detention and the criteria authorising detention varied between studies, with a mix of clinical factors and observed behaviours reported as the reason(s) warranting/precipitating a detention. Particular groups were more likely to experience detention, such as children and adolescents from minority ethnic communities and those with a documented history of abuse. There was a notable absence of qualitative research exploring the views of professionals or children and adolescents on detention. CONCLUSION: Further research is needed to explore the impact of detention on those aged < 18 years, including national register-based studies and qualitative studies. This is particularly relevant in nations currently undergoing legislative reform.

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Much remains unknown about the etiology of compulsion-like alcohol drinking, where consumption persists despite adverse consequences. The role of the anterior insula (AIC) in emotion, motivation, and interoception makes this brain region a likely candidate to drive challenge-resistant behavior, including compulsive drinking. Indeed, subcortical projections from the AIC promote compulsion-like intake in rats and are recruited in heavy-drinking humans during compulsion for alcohol, highlighting the importance of and need for more information about AIC activity patterns that support aversion-resistant responding. Single-unit activity was recorded in the AIC from 15 male rats during alcohol-only and compulsion-like consumption. We found three sustained firing phenotypes, sustained-increase, sustained-decrease, and drinking-onset cells, as well as several firing patterns synchronized with licking. While many AIC neurons had session-long activity changes, only neurons with firing increases at drinking onset had greater activity under compulsion-like conditions. Further, only cells with persistent firing increases maintained activity during pauses in licking, suggesting roles in maintaining drive for alcohol during breaks. AIC firing was not elevated during saccharin drinking, similar to lack of effect of AIC inhibition on sweet fluid intake in many studies. In addition, we observed subsecond changes in AIC neural activity tightly entrained to licking. One lick-synched firing pattern (determined for all licks in a session) predicted compulsion-like drinking, while a separate lick-associated pattern correlated with greater consumption across alcohol intake conditions. Collectively, these data provide a more integrated model for the role of AIC firing in compulsion-like drinking, with important relevance for how the AIC promotes sustained motivated responding more generally.

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BACKGROUND: Obsessive-compulsive disorder (OCD) is a classic disorder on the compulsivity spectrum, with diverse comorbidities. In the current study, we sought to understand OCD from a dimensional perspective by identifying multimodal neuroimaging patterns correlated with multiple phenotypic characteristics within the striatum-based circuits known to be affected by OCD. METHODS: Neuroimaging measurements of local functional and structural features and clinical information were collected from 110 subjects, including 51 patients with OCD and 59 healthy control subjects. Linked independent component analysis (LICA) and correlation analysis were applied to identify associations between local neuroimaging patterns across modalities (including gray matter volume, white matter integrity, and spontaneous functional activity) and clinical factors. RESULTS: LICA identified eight multimodal neuroimaging patterns related to phenotypic variations, including three related to symptoms and diagnosis. One imaging pattern (IC9) that included both the amplitude of low-frequency fluctuation measure of spontaneous functional activity and white matter integrity measures correlated negatively with OCD diagnosis and diagnostic scales. Two imaging patterns (IC10 and IC27) correlated with compulsion symptoms: IC10 included primarily anatomical measures and IC27 included primarily functional measures. In addition, we identified imaging patterns associated with age, gender, and emotional expression across subjects. CONCLUSIONS: We established that data fusion techniques can identify local multimodal neuroimaging patterns associated with OCD phenotypes. The results inform our understanding of the neurobiological underpinnings of compulsive behaviors and OCD diagnosis.

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Background: Many features of self-administration behavior may be explained by reference to the properties of schedules of reinforcement. Schedules alter the probability of a behavior being reinforced and thereby increase, or decrease, the frequency of the behavior and fixed ratio (FR) magnitude reportedly alters the rate of responding to cocaine. A pharmacokinetic/pharmacodynamic interaction theory states that lever-pressing behavior is induced only when cocaine levels in the body are above the priming/remission threshold and below the satiety threshold-a range termed the compulsion zone. This theory successfully explains cocaine self-administration in rats on a progressive ratio and the FR1 schedule. Objectives: To determine the effects of high FR magnitude on the rate of self-administration of cocaine and the rate of lever-pressing behavior when cocaine levels are within the compulsion zone. Methods: Rats acquired cocaine self-administration on an FR1 schedule and then were switched to sessions that started with FR1 and then FR 5, 10, 20, or 50. An only FR1 session was run each week between FR1/FR50 sessions and then only FR1 sessions were conducted for several weeks. Results: Interinjection intervals at a unit dose of 3 µmol/kg were regular at both FR1 and FR50 but were longer by the time required to complete the 50 presses. When responding by rats was maintained under an FR50 schedule of cocaine presentations, compared to baseline FR1 sessions, dramatic increases in the number of lever-presses were observed after access to cocaine was terminated, a previously unreported finding. However, lever-pressing occurred only when cocaine levels were in the compulsion zone, and this duration was unchanged. The increase in lever-pressing persisted for weeks. Interinjection intervals at FR1 were not altered after exposure to FR50. Conclusions: Although previously considered key to understanding the regulation of cocaine self-administration behavior, FR magnitude simply increased interinjection intervals by the time required to complete 50 lever-presses. The dramatic increase in the rate of lever-pressing was caused by the high FR schedule rather than cocaine. The utility of the schedule-induced increase in the rate of lever-pressing is unclear. The compulsion zone theory provides a rational pharmacological basis for understanding cocaine self-administration behavior.

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