Dysconnectivity between the anterior insula and the dorsal anterior cingulate cortex during an emotion go/nogo paradigm is associated with aggressive behaviors in male schizophrenia patients.

This study aimed to investigate the association between past-reported violent/aggressive behaviors and brain functional connectivity in male patients suffering from schizophrenia using a task modeling the interaction between negative emotion processing and response inhibition. Forty-four male patients with schizophrenia and twenty-two healthy male controls performed an emotional go/no-go task using angry and neutral faces during a functional magnetic resonance imaging session. Generalized psycho-physiological interaction was conducted to explore task-based functional connectivity and a negative binomial regression was used to evaluate the relationship between neural alterations and violent/aggressive behaviors. Regions involved in response inhibition and emotion regulation, such as the anterior insula, dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (DLPFC), were used as seed regions. During emotion-related response inhibition, patients with schizophrenia displayed altered connectivity between the anterior insula and amygdala, the DLPFC and lateral orbitofrontal cortex (OFC), as well as the anterior insula and the dACC when compared to healthy individuals. The latter was negatively associated with aggressive behaviors in participants with schizophrenia (Wald χ2 = 9.51; p < 0.05, p-FDR corrected). Our results highlight alterations in functional connectivity in brain regions involved in cognitive control and emotion processing which are associated with aggressive behaviors in schizophrenia.

Changes in brain structure and function following chronic exposure to inhaled vaporised cannabis during periadolescence in female and male mice: A multimodal MRI study.

BACKGROUND AND AIMS: Social norms and legality surrounding the use of medical and recreational cannabis are changing rapidly. The prevalence of cannabis use in adolescence is increasing. The aim of this study was to assess any sex-based neurobiological effects of chronically inhaled, vaporised cannabis on adolescent female and male mice. METHODS: Female and male mice were exposed daily to vaporised cannabis (10.3% Δ-9-tetrahydrocannabinol [THC] and 0.05% cannabidiol [CBD]) or placebo from postnatal day 23 to day 51. Following cessation of treatment, mice were examined for changes in brain structure and function using noninvasive multimodal magnetic resonance imaging (MRI). Data from voxel-based morphometry, diffusion weighted imaging and rest state functional connectivity were registered to and analysed with a 3D mouse atlas with 139 brain areas. Following imaging, mice were tested for their preference for a novel object. RESULTS: The effects were sexually dimorphic with females showing a unique distribution and inverse correlation between measures of fractional anisotropy and apparent diffusion coefficient localised to the forebrain and hindbrain. In contrast males displayed significant increased functional coupling with the thalamus, hypothalamus and brainstem reticular activating system as compared with controls. Cannabis males also presented with altered hippocampal coupling and deficits in cognitive function. CONCLUSION: Chronic exposure to inhaled vaporised cannabis had significant effects on brain structure and function in early adulthood corroborating much of the literature. Females presented with changes in grey matter microarchitecture, while males showed altered functional connectivity in hippocampal circuitry and deficits in object recognition.

Increased cingulo-orbital connectivity is associated with violent behaviours in schizophrenia.

OBJECTIVE: Although schizophrenia patients are at a heightened risk of exhibiting violent behaviours compared to the general population, few functional neuroimaging studies have explored the aberrant neurocircuitry underpinning such behaviours. This study aimed to identify disrupted resting-state activity and functional connectivity in schizophrenia patients with a history of violence. METHODS: Resting state functional magnetic resonance imaging data was collected from 62 schizophrenia patients and 25 healthy controls. Voxel-wise analyses of fractional amplitude of low frequency fluctuations (fALFF) were implemented to investigate disrupted regional patterns of spontaneous brain activity. Brain regions which yielded significant differences between groups were subsequently used as data-driven seeds for functional connectivity analyses. Finally, significant alterations (activity and connectivity) were correlated with lifetime violent behaviours. RESULTS: When compared to healthy controls, schizophrenia patients exhibited reduced fALFF in multiple brain regions including the (subgenual) anterior cingulate cortex (ACC), posterior cingulate cortex, precuneus cortex and left lateral orbitofrontal cortex (OFC). Seed-to-voxel analyses yielded significantly enhanced connectivity between the ACC and left OFC. The heightened functional connectivity between the latter two regions predicted the number of violent behaviours reported by schizophrenia patients. CONCLUSION: The current study demonstrated that the functional connectivity of brain regions associated with emotion regulation is impaired in schizophrenia and associated with violent antecedents among patients. This result is consistent with predominant theoretical models proposing that the OFC plays a critical role in the neurobiology of violence.

The clouded debate: A systematic review of comparative longitudinal studies examining the impact of recreational cannabis legalization on key public health outcomes.

Background: Ineffective cannabis regulatory frameworks such as prohibition have sparked interest in alternative solutions to reduce individual and societal harms. While it has been suggested that the recreational legalization process has yielded early successes, the relatively recent implementation of the novel policies has provided a modest time frame for a truly thorough establishment and assessment of key population-level indicators. The following systematic review focuses on identifying the downstream public health sequelae of cannabis legalization policies, including parameters such as cannabis consumption rates, hospitalization rates, vehicular accidents and fatalities, criminal activity, and suicidal behaviors, as well as other substance use trends. Methods: An exhaustive search of the MEDLINE and Google Scholar databases were performed to identify high-quality (1) longitudinal studies, which (2) compared key public health outcomes between regions which had and had not implemented recreational cannabis legalization (RML) policies, (3) using distinct databases and/or time frames. Thirty-two original research articles were retained for review. Results: Adult past-month cannabis consumption (26+ years) seems to have significantly increased following RML, whereas young adult (18-26 years) and adolescent (12-17 years) populations do not show a significant rise in past-month cannabis use. RML shows preliminary trends in increasing service use (such as hospitalizations, emergency department visits, or poisonings) or vehicular traffic fatalities. Preliminary evidence suggests that RML is related to potential increases in serious/violent crimes, and heterogeneous effects on suicidal behaviors. While the research does not illustrate that RML is linked to changing consumptions patterns of cigarette, stimulant, or opioid use, alcohol use may be on the rise, and opioid prescribing patterns are shown to be significantly correlated with RML. Conclusion: The current data supports the notion that RML is correlated with altered cannabis consumption in adults, potentially increased criminal activity, and a decline in opioid quantities and prescriptions provided to patients. Future work should address additional knowledge gaps for vulnerable populations, such as individuals with mental health problems or persons consuming cannabis frequently/at higher THC doses. The effects of varying legalization models should also be evaluated for their potentially differing impacts on population-level outcomes.

A systematic review of longitudinal studies investigating the impact of cannabis use in patients with psychotic disorders.

Introduction: Research has established a link between cannabis use and adverse psychotic outcomes in psychosis patients. However, we have yet to determine if this relationship is maintained when controlling for important confounding variables. The following systematic review aims to investigate if the association between cannabis use and psychotic outcomes is preserved when accounting for important confounders, and if discontinued use mitigates any potential negative impacts.Areas covered: The authors conducted an exhaustive search of the MEDLINE database and Google Scholar to identify articles pertaining to the systematic review. Thirty-three articles were retained for meeting the eligibility criteria.Expert opinion: The evidence confirms an overarching pattern of negative psychotic outcomes of cannabis intake in psychosis populations, even when accounting for crucial confounders. Psychosis patients should be informed with evidence-based health information regarding the effects of cannabis use. Clinicians should systematically evaluate cannabis intake patterns in psychosis patients and offer intervention services geared toward reducing problematic consumption. Researchers should record confounding factors in a more systematic manner in future longitudinal investigations while paying careful attention to the potency and dose-response effects of the ingested cannabis. Deciders will need to investigate the impact of cannabis regulations on psychosis populations.

The processing of angry faces in schizophrenia patients with a history of suicide: An fMRI study examining brain activity and connectivity.

BACKGROUND: The high rate of suicidal behaviours (SBs) in psychiatric populations remain an important preoccupation to address. The literature reveals emotional instability as an important risk factor for SBs. However, the neural mechanisms underpinning this risk factor have never been investigated in schizophrenia patients with SBs. The following study implemented a task-based emotional processing functional magnetic resonance imaging (fMRI) paradigm to evaluate the activation and connectivity differences exhibited by schizophrenia patients with a history of suicide attempt (SA). METHOD: A sample of 62 schizophrenia patients with and without SA and 22 controls completed an fMRI emotional processing task, which included the visualization of dynamic angry facial expressions. Task-based connectivity was assessed using generalized psychophysical interaction analyses. RESULTS: During the processing of angry faces, suicidal schizophrenia patients displayed increased activation of the left median cingulate gyrus, left middle frontal gyrus, and left precuneus when compared to nonsuicidal schizophrenia patients and healthy controls. Whole-brain connectivity analyses yielded an increased coupling of the right amygdala and right superior frontal gyrus, as well as between the left precuneus and median cingulate gyrus, in suicidal schizophrenia patients. Schizophrenia patients' hostility scores on the Positive and Negative Symptom Scale (PANSS) were significantly and positively correlated with the activity of the left median cingulate gyrus. CONCLUSION: When exposed to angry faces, suicidal schizophrenia patients demonstrate elevated activation of brain regions associated to executive functioning and self-processing, as well as aberrant fronto-limbic connectivity involved in emotion regulation. Our results highlight the neglected role of anger when investigating the neural alterations underpinning SBs in schizophrenia.

Violence and Cannabis Use: A Focused Review of a Forgotten Aspect in the Era of Liberalizing Cannabis.

There has been a shift surrounding societal and legal perspectives on cannabis reflecting changing public attitudes towards the perceived safety and social acceptability of cannabis use. With cannabis liberalization internationally, the focus of most cannabis-related harms has been on effects with users themselves. Harm-to-others including injuries from violence have nevertheless been unfortunately largely overlooked. While studies remain heterogeneous, there is meta-analytical evidence pointing towards an association. The aims of this focused review are two-fold: (I) review the evidence from meta-analyses on the association between cannabis and violence; and (II) provide an overview of possible mechanisms relating cannabis use to violence. First, evidence from meta-analytical studies in youths, intimate partners, and individuals with severe mental disorders have shown that there is a global moderate association between cannabis use and violence, which is stronger in the latter more at-risk population. Preliminary data has even highlighted a potential dose-response relationship with larger effects in more frequent users. Although of importance, this subject has remained essentially forgotten as a public health concern. While literature remains inconclusive, data has suggested potential increases in cannabis use following liberalization policies. This may increase violent outcomes if the effect is directly related to the use of cannabis by means of its psychophysiological modifications. However, for the moment, the mechanisms associating cannabis use and violence remain to be clearly resolved. Considering the recency of policy changes on cannabis, further methodologically sound research using longitudinal designs should examine the effects that cannabis use may have on different forms of violence and the trends that emerge, while evaluating the effects of possible confounding factors (e.g. other substance use). In addition, as evidence-based research from meta-analyses have shown that cannabis use is associated with violence, measures must be taken to mitigate the risks.

Oxytocin and object preferences in the male prairie vole.

The neuropeptide oxytocin has been previously associated with social attachment behaviors in various species. Studies in socially monogamous prairie voles (Microtus ochrogaster) and other species have implicated oxytocin in partner preferences and other social behaviors. In the present study male prairie voles were injected intraperitoneally with either oxytocin or the selective oxytocin antagonist, L-368,899, and were assessed for object preference (for small inanimate toys) 30-min after injection. Object preferences were assessed in animals tested alone or in the presence of their sibling cage mate. Saline-treated controls displayed preferences for the novel object, both when tested alone and in pairs, while oxytocin-treated voles did not demonstrate an object preference, regardless of whether tested alone or in pairs. Finally, oxytocin antagonist treated voles showed preference for the novel object, but only when tested in pairs. These data support a possible involvement of oxytocin and oxytocin receptors in object preference.

Centrally-administered oxytocin promotes preference for familiar objects at a short delay in ovariectomized female rats.

Oxytocin has been previously associated with social attachment behaviors in various species, however, most studies focused on partner preference in the socially-monogamous prairie vole. In these, oxytocin treatment was shown to promote partner preference, such that females receiving either central or pulsatile peripheral administration would spend more time with a familiar male. This behavioral outcome was blocked by oxytocin receptor antagonist treatment. The aim of the current study was to further explore the preference-inducing properties of oxytocin by examining its effects on object preference on ovariectomized female rats. In other words, we assessed whether these effects would apply to objects and if they would be persistent across species. Eight rats were infused with oxytocin into the left ventricle and object preference was assessed at two delays: 30min and 4h. At the 30min delay, oxytocin-treated animals showed preference for the familiar object, whereas saline-treated controls exhibited preference for the novel object. At the 4h delay, both groups showed novel-object preference. Our findings show that oxytocin modulates object preference in the female rat at a shorter delay, similar to the findings from partner-preference studies in the prairie vole, suggesting that the mechanisms driving object preference might be in part similar to those responsible for partner preference.

Bronchobiliary fistulae due to echinococcosis.

OBJECTIVE: A bronchobiliary fistula (BBF) is a rare complication of echinococcosis due to rupture of hydatid cysts located at the upper surface of the liver to the bronchial tree. We present our experience in treating this uncommon and dangerous entity. MATERIAL: During the last 20 years, 21 patients, ten men and 11 women ranging in age from 26 to 83 years with a BBF were treated in our department. They presented dyspnea, biloptysis, cough or fever. Diagnostic imaging studies have been very helpful in identifying the communication and in delineating its location. The disease was limited to the liver in 11 cases, whereas in the rest ten cases, both liver and lung were involved. RESULTS: Right thoracotomy was the approach of choice. Our strategy consisted of adequate evacuation of the intrahepatic cysts, obliteration of the cyst space, freeing the adherent lung, dissection and closure of the BBF. Two deaths occurred due to anaphylactic shock and cardiac insufficiency. Follow up at 7-12 years did not reveal any recurrence. CONCLUSION: Although the incidence of echinococcosis has been decreased, the BBF still remains a serious complication with a high morbidity and mortality. Early diagnosis and management of septic associated complications are essential.