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Hormonal contraceptives (HCs) are one of the most highly prescribed classes of drugs in the world used for both contraceptive and noncontraceptive purposes. Despite their prevalent use, the impact of HCs on the brain remains inadequately explored. This review synthesizes recent findings on the neuroscience of HCs, with a focus on human structural neuroimaging as well as translational, nonhuman animal studies investigating the cellular, molecular, and behavioral effects of HCs. Additionally, we consider data linking HCs to mood disorders and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and stress response as a potential mediator. The review also addresses the unique sensitivity of the adolescent brain to HCs, noting significant changes in brain structure and function when HCs are used during this developmental period. Finally, we discuss potential effects of HCs in combination with smoking-derived nicotine on outcomes of ischemic brain damage. Methodological challenges, such as the variability in HC formulations and user-specific factors, are acknowledged, emphasizing the need for precise and individualized research approaches. Overall, this review underscores the necessity for continued interdisciplinary research to elucidate the neurobiological mechanisms of HCs, aiming to optimize their use and improve women’s health. [ABSTRACT FROM AUTHOR]

Background: Intimate partner violence (IPV) perpetration is highly prevalent among veterans. Suggested risk factors of IPV perpetration include combat exposure, post-traumatic stress disorder (PTSD), depression, alcohol use, and mild traumatic brain injury (mTBI). While the underlying brain pathophysiological characteristics associated with IPV perpetration remain largely unknown, previous studies have linked aggression and violence to alterations of the limbic system. Here, we investigate whether IPV perpetration is associated with limbic microstructural abnormalities in military veterans. Further, we test the effect of potential risk factors (i.e., PTSD, depression, substance use disorder, mTBI, and war zone-related stress) on the prevalence of IPV perpetration. Methods: Structural and diffusion-weighted magnetic resonance imaging (dMRI) data were acquired from 49 male veterans of the Iraq and Afghanistan wars (Operation Enduring Freedom/Operation Iraqi Freedom; OEF/OIF) of the Translational Research Center for TBI and Stress Disorders (TRACTS) study. IPV perpetration was assessed using the psychological aggression and physical assault sub-scales of the Revised Conflict Tactics Scales (CTS2). Odds ratios were calculated to assess the likelihood of IPV perpetration in veterans with either of the following diagnoses: PTSD, depression, substance use disorder, or mTBI. Fractional anisotropy tissue (FA) measures were calculated for limbic gray matter structures (amygdala-hippocampus complex, cingulate, parahippocampal gyrus, entorhinal cortex). Partial correlations were calculated between IPV perpetration, neuropsychiatric symptoms, and FA. Results: Veterans with a diagnosis of PTSD, depression, substance use disorder, or mTBI had higher odds of perpetrating IPV. Greater war zone-related stress, and symptom severity of PTSD, depression, and mTBI were significantly associated with IPV perpetration. CTS2 (psychological aggression), a measure of IPV perpetration, was associated with higher FA in the right amygdala-hippocampus complex (r  =  0.400, p  =  0.005). Conclusion: Veterans with psychiatric disorders and/or mTBI exhibit higher odds of engaging in IPV perpetration. Further, the more severe the symptoms of PTSD, depression, or TBI, and the greater the war zone-related stress, the greater the frequency of IPV perpetration. Moreover, we report a significant association between psychological aggression against an intimate partner and microstructural alterations in the right amygdala-hippocampus complex. These findings suggest the possibility of a structural brain correlate underlying IPV perpetration that requires further research. [ABSTRACT FROM AUTHOR]

Background: Cognitive decline is considered a fundamental component in schizophrenia. Abnormalities in fronto-striatal-thalamic (FST) sub-circuits are present in schizophrenia and are associated with cognitive impairments. However, it remains unknown whether abnormalities in FST sub-circuits are present before psychosis onset. This may be elucidated by investigating young adults with 22q11.2 deletion syndrome (22q11DS), of whom 30% will develop schizophrenia in adulthood. In 22q11DS, cognitive decline, most pronounced in Verbal IQ (VIQ), precedes the onset of psychosis and those who develop psychosis diverge more strongly from a typical cognitive trajectory. Based on these findings, studies of young adults with 22q11DS without overt psychosis but with prodromal symptoms may increase our understanding of cognitive manifestations and early pathology in FST subcircuits in schizophrenia. Here we examined white matter (WM) tracts in FST sub-circuits, especially those involving dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC), and their associations with VIQ in young adults with 22q11DS with and without prodromal symptoms. Methods: We compared Fractional Anisotropy (FA), Axial Diffusivity (AD), and Radial Diffusivity (RD) in tracts of the FST sub-circuits in 21 individuals with 22q11DS with prodromal symptoms (age: M=21.43) and 30 individuals without prodromal symptoms (age: M=20.73) to 30 healthy controls (age: M=20.89). Two-tensor tractography was applied to reconstruct WM fiber tracts of the whole brain, followed by applying the White Matter Query Language (WMQL) method to select tracts between striatum and thalamus, with the rostral middle frontal gyrus (rMFG) and inferior frontal gyrus (IFG), representing DLPFC and VLPFC. This yielded four tracts of interest: thalamus-rMFG, thalamus-IFG, striatum-rMFG, and striatum-IFG tracts. Additionally, correlations between the dMRI measures and scores on VIQ were performed. Results: FA was significantly increased, while RD was significantly decreased in most WM tracts in both 22q11DS groups when compared to healthy controls. In the whole 22q11DS group, VIQ correlated negatively with FA in the right thalamus-IFG tract (r=-0.336, p=.018), while RD correlated positively with VIQ in the right thalamus-IFG tract (r=0.290, p=.043) in individuals with 22q11DS, such that increased FA and decreased RD were associated with a lower VIQ. We followed up on the results in individuals with 22q11DS with prodromal symptoms to determine whether the presence of prodromal symptoms drove the correlations. VIQ correlated significantly with FA (r=-0.491, p=0.024, FDR-adjusted=0.048) and significantly at trend level with RD (r=0.487, p=0.025, FDR-adjusted=0.050) in the right thalamus-IFG tract in individuals with 22q11DS with prodromal symptoms. Discussion: Microstructural abnormalities in brain WM tracts connecting the thalamus and the striatum with prefrontal cortices are present in young adults with 22q11DS with and without prodromal symptoms compared to healthy controls. These abnormalities are associated with the individuals’ cognitive performance in VIQ in individuals with 22q11DS with prodromal symptoms and therefore emphasize the potential involvement of the FST sub-circuits in schizophrenia. While changes in FST circuitry have been reported in patients with schizophrenia, we observed that changes in FST circuitry are also present in young adults with 22q11DS at risk for but without psychotic symptoms. Our results suggest that psychosis onset in 22q11DS may be associated with a complex pattern of WM alterations. Furthermore, cognitive abnormalities, especially in VIQ, present an important preclinical risk factor for psychosis in 22q11DS. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SCZ) is a severe and chronic brain disorder that affects about 1% of the world population. It is among the most burdensome illnesses with a serious impact on patients, their families and society. To this day, a lot remains unknown about the neuropathological cause and etiology of SCZ. The prominent two-hit theory postulates that early neurodevelopmental abnormalities interact with a later “second hit” which occurs around symptom onset. Recent research points towards the role of inflammation in pathophysiology of schizophrenia. Matrix metalloproteinase-9 (MMP-9) was recently suggested as a potential key player in both first and second “hit” in the pathology of SCZ. It is considered to not only regulate brain development and synaptic plasticity, but to also mediate neuroinflammation. A point of interest for interaction with neuroinflammatory pathways is the Choroid Plexus (ChP). MMP-9 has been reported to be upregulated in ChP in SCZ. Since ChP regulates CSF production and permeability of the blood-CSF-barrier, MMP-9 upregulation in ChP might lead to its enlargement, as well as enlargement of the lateral ventricles and increased extracellular water volume, all found previously in SCZ. We investigate, for the first time, the relationship between MMP-9 blood plasma concentration and volume of ChP in patients with SCZ compared to healthy controls (HC). Methods: We included 66 subjects (25 female = 38%, 41 male = 62%, mean age 32.59 +/- 9.14 years); 32 were patients with SCZ, 34 were HC. ELISA analysis was performed to measure MMP-9 blood concentrations in patients and HC. A whole brain, high-resolution three-dimensional T1-weighted magnetization prepared rapid gradient echo (MPRAGE) sequence scan was used to collect 240 sagittal slices, field of view = 224 x 224 mm2, 1 mm3 isotropic voxel, TR = 2.3 s, TE = 2.33 ms, flip angle = 8° on a 3T Siemens Magnetom Prisma. Structural T1 images underwent visual quality control, were realigned and parcellated into 176 gray and white matter regions using FreeSurfer software. Preliminary analyses were conducted comparing 1) MMP-9 levels between groups and 2) relating MMP-9 levels to ChP volume utilizing regression analyses. Results: Patients with SCZ showed a strong upregulation of MMP-9 compared to HC (patients: 120 ± 60 ng/ml; HC: 60 ± 40 ng/ml; p < 0.0001). Furthermore, linear regression analyses - corrected for age and sex - demonstrated a positive association between concentration of MMP-9 and ChP volumes (left: R2 = .095, p < .01; right: R2 = .084, p < .02). Discussion: To our knowledge, our study is the first to present preliminary evidence of an association between brain structure and MMP-9 peripheral upregulation in SCZ. Advanced evaluation of MMP-9 might enhance our understanding of illness cause, enable outcome predictions and paint the way for more individualized psychopharmacotherapy, as MMP-9 might serve as potential pharmacological target. However, further analyses are needed to validate our findings using as neuroanatomically precise methods as possible and to develop MMP-9 biomarkers that would capture central, as opposed to peripheral levels of MMP-9. [ABSTRACT FROM AUTHOR]