Cannabis Dependence is Associated with Reduced Hippocampal Subregion Volumes Independently of Sex: Findings from an ENIGMA Addiction Working Group Multi-Country Study.

Background: Males and females who consume cannabis can experience different mental health and cognitive problems. Neuroscientific theories of addiction postulate that dependence is underscored by neuroadaptations, but do not account for the contribution of distinct sexes. Further, there is little evidence for sex differences in the neurobiology of cannabis dependence as most neuroimaging studies have been conducted in largely male samples in which cannabis dependence, as opposed to use, is often not ascertained. Methods: We examined subregional hippocampus and amygdala volumetry in a sample of 206 people recruited from the ENIGMA Addiction Working Group. They included 59 people with cannabis dependence (17 females), 49 cannabis users without cannabis dependence (20 females), and 98 controls (33 females). Results: We found no group-by-sex effect on subregional volumetry. The left hippocampal cornu ammonis subfield 1 (CA1) volumes were lower in dependent cannabis users compared with non-dependent cannabis users (p<0.001, d=0.32) and with controls (p=0.022, d=0.18). Further, the left cornu ammonis subfield 3 (CA3) and left dentate gyrus volumes were lower in dependent versus non-dependent cannabis users but not versus controls (p=0.002, d=0.37, and p=0.002, d=0.31, respectively). All models controlled for age, intelligence quotient (IQ), alcohol and tobacco use, and intracranial volume. Amygdala volumetry was not affected by group or group-by-sex, but was smaller in females than males. Conclusions: Our findings suggest that the relationship between cannabis dependence and subregional volumetry was not moderated by sex. Specifically, dependent (rather than non-dependent) cannabis use may be associated with alterations in selected hippocampus subfields high in cannabinoid type 1 (CB1) receptors and implicated in addictive behavior. As these data are cross-sectional, it is plausible that differences predate cannabis dependence onset and contribute to the initiation of cannabis dependence. Longitudinal neuroimaging work is required to examine the time-course of the onset of subregional hippocampal alterations in cannabis dependence, and their progression as cannabis dependence exacerbates or recovers over time.

Sex and dependence related neuroanatomical differences in regular cannabis users: findings from the ENIGMA Addiction Working Group.

Males and females show different patterns of cannabis use and related psychosocial outcomes. However, the neuroanatomical substrates underlying such differences are poorly understood. The aim of this study was to map sex differences in the neurobiology (as indexed by brain volumes) of dependent and recreational cannabis use. We compared the volume of a priori regions of interest (i.e., amygdala, hippocampus, nucleus accumbens, insula, orbitofrontal cortex (OFC), anterior cingulate cortex and cerebellum) between 129 regular cannabis users (of whom 70 were recreational users and 59 cannabis dependent) and 114 controls recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age, IQ, and alcohol and tobacco use. Dependent cannabis users, particularly females, had (marginally significant) smaller volumes of the lateral OFC and cerebellar white matter than recreational users and controls. In dependent (but not recreational) cannabis users, there was a significant association between female sex and smaller volumes of the cerebellar white matter and OFC. Volume of the OFC was also predicted by monthly standard drinks. No significant effects emerged the other brain regions of interest. Our findings warrant future multimodal studies that examine if sex and cannabis dependence are specific key drivers of neurobiological alterations in cannabis users. This, in turn, could help to identify neural pathways specifically involved in vulnerable cannabis users (e.g., females with cannabis dependence) and inform individually tailored neurobiological targets for treatment.

Structural neuroimaging of somatoform disorders: A systematic review.

Although there has been an increment in neuroimaging research in somatoform disorders (SD), to date little is known about the neural correlates of these diseases. Therefore, in this systematic, review we aimed at summarizing the existing evidence of structural brain alterations in SD as per DSM-IV and DSM-5 criteria. Three electronic databases (Scopus, PubMed and Web of Science) were searched. Only case-control studies using structural neuroimaging were included. Forty-five out of 369 articles fulfilled inclusion criteria and were reviewed. Compared to controls, subjects with SD showed morphological alterations encompassing motor, limbic and somatosensory circuits. Although far from being conclusive, the results suggested that SD are characterized by selective alterations of large-scale brain networks implicated in cognitive control, emotion regulation and processing, stress and somatic-visceral perception. This review highlights the need for further multimodal neuroimaging studies with longitudinal designs, in larger and better-characterized samples, to elucidate the temporal and causal relationship between neuroanatomical changes and SD, which is paramount for informing tailored treatments.

The Neuroanatomy of Somatoform Disorders: A Magnetic Resonance Imaging Study.

BACKGROUND: Somatoform disorders (SDs) are a heterogeneous group of psychiatric syndromes characterized by common symptoms, which may mimic a physical condition but they are not explained by a medical condition. Although the biologic nature of this disorder has been widely accepted, the neuroanatomical correlates characterizing SDs are still inconclusive. OBJECTIVE: This study aims to explore gray matter (GM) volume alterations in SD patients compared to healthy controls and their possible association with clinical and cognitive measures. METHOD: We used voxel-based morphometry to examine regional GM volumes in 20 inpatients with SDs and 24-matched healthy controls. Only for SD patients, we employed multiple instruments to assess psychopathology and cognitive functioning, which were then used to explore their association with GM volume deficits. RESULTS: Compared to healthy controls, SD patients showed GM volume reductions in the hypothalamus, left fusiform gyrus, right cuneus, left inferior frontal gyrus, left posterior cingulate, and right amygdala (p < 0.05, cluster Family Wise Error corrected). Additionally, in SD, Symptom Checklist-90-Phobia and Hamilton Depressive Rating Scale scores negatively correlated with specific fronto-temporoparietal regions whereas Symptom Checklist-90-Sleep scores positively correlated with anterior cingulate cortex. Lastly, the Boston Naming Test negatively correlated with fronto-temporoparietal and striatal volumes whereas Free and Cued Selective Reminding Test and Stroop scores positively correlated with superior temporal gyrus and cuneus, respectively (all p < 0.05, cluster Family Wise Error corrected). CONCLUSION: Our results suggest that SDs might be characterized by selective impairments in specific cortico-limbic regions associated to two overlapping circuits, the neuromatrix of pain and the emotion regulation system.