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Although cerebellar involvement across a wide range of cognitive and neuropsychiatric phenotypes is increasingly being recognized, previous large-scale studies in schizophrenia (SZ) have primarily focused on supratentorial structures. Hence, the across-sample reproducibility, regional distribution, associations with cerebrocortical morphology and effect sizes of cerebellar relative to cerebral morphological differences in SZ are unknown. We addressed these questions in 983 patients with SZ spectrum disorders and 1349 healthy controls (HCs) from 14 international samples, using state-of-the-art image analysis pipelines optimized for both the cerebellum and the cerebrum. Results showed that total cerebellar grey matter volume was robustly reduced in SZ relative to HCs (Cohens's d=-0.35), with the strongest effects in cerebellar regions showing functional connectivity with frontoparietal cortices (d=-0.40). Effect sizes for cerebellar volumes were similar to the most consistently reported cerebral structural changes in SZ (e.g., hippocampus volume and frontotemporal cortical thickness), and were highly consistent across samples. Within groups, we further observed positive correlations between cerebellar volume and cerebral cortical thickness in frontotemporal regions (i.e., overlapping with areas that also showed reductions in SZ). This cerebellocerebral structural covariance was strongest in SZ, suggesting common underlying disease processes jointly affecting the cerebellum and the cerebrum. Finally, cerebellar volume reduction in SZ was highly consistent across the included age span (16-66 years) and present already in the youngest patients, a finding that is more consistent with neurodevelopmental than neurodegenerative etiology. Taken together, these novel findings establish the cerebellum as a key node in the distributed brain networks underlying SZ.

Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn. Here, we examined 16 drug-naive, first-episode psychosis patients and 16 healthy controls using PET and the TSPO radioligand [ 11 C]PBR28. Gray matter (GM) volume of distribution ( V T ) derived from a two-tissue compartmental analysis with arterial input function was the main outcome measure. Statistical analyses were performed controlling for both TSPO genotype, which is known to affect [ 11 C]PBR28 binding, and gender. There was a significant reduction of [ 11 C]PBR28 V T in patients compared with healthy controls in GM as well as in secondary regions of interest. No correlation was observed between GM V T and clinical or cognitive measures after correction for multiple comparisons. The observed decrease in TSPO binding suggests reduced numbers or altered function of immune cells in brain in early-stage schizophrenia.

Schizophrenia is characterized by a multiplicity of symptoms arising from almost all domains of mental function. γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain and is increasingly recognized to have a significant role in the pathophysiology of the disorder. In the present study, cerebrospinal fluid (CSF) concentrations of GABA were analyzed in 41 first-episode psychosis (FEP) patients and 21 age- and sex-matched healthy volunteers by high-performance liquid chromatography. We found lower CSF GABA concentration in FEP patients compared with that in the healthy volunteers, a condition that was unrelated to antipsychotic and/or anxiolytic medication. Moreover, lower CSF GABA levels were associated with total and general score of Positive and Negative Syndrome Scale, illness severity and probably with a poor performance in a test of attention. This study offers clinical in vivo evidence for a potential role of GABA in early-stage schizophrenia.

Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

Infertility affects 30% to 50% of women with endometriosis. Women with endometriosis are at risk of decreased ovarian reserve, both because of the pathophysiology of the disease and iatrogenic injury resulting from surgical intervention. Fertility preservation must occur at multiple levels, including careful selection of surgical candidates, avoidance of repeat procedures, and meticulous surgical technique. Fertility preservation with oocyte or ovarian tissue cryopreservation may be considered on an individual basis for women with endometriosis, particularly those at risk of bilateral ovarian injury, such as women with bilateral endometriomas.

To our knowledge, there is no consensus regarding when individuals who repeatedly self-harm and are at risk of suicide should be hospitalized. To evaluate a new alternative, we examined the effects of brief admission (BA) to hospital by self-referral. To determine the effects of BA on inpatient service use and on secondary outcomes of daily life functioning, nonsuicidal self-injuries, and attempted suicide among individuals who self-harm and are at risk of suicide. The single-masked Brief Admission Skåne Randomized Clinical Trial was conducted from September 2015 to June 2018 at 4 psychiatric health care facilities in southern Sweden. Data were collected 6 months retrospectively at baseline and at 6-month and 12-month follow-ups. Participants were randomized to either BA and treatment as usual (BA group) or treatment as usual (control group). The sample was a referral population, with the most important inclusion criteria being current episodes of self-harm and/or recurrent suicidality, at least 3 diagnostic criteria for borderline personality disorder, and hospitalization in the last 6 months. Self-referred BA was offered for 12 months, with standard limits for duration and frequency, after the negotiation of a contract outlining the intervention. Prespecified main outcome measures were days admitted to the hospital, including voluntary admission, BA, and compulsory admission. The 125 participants had a mean (SD) age of 32.0 (9.4) years, 106 (84.8%) were women, and 63 were randomized to the BA group and 62 to the control group. No significant advantage was observed in the number of days in the hospital for the BA group compared with the control group. Within-group analyses demonstrated significant decreases in both groups regarding days admitted to the hospital (BA group: χ2 = 22.71; P < .001; control group: χ2 = 23.01; P < .001) and visits to the emergency department (BA group: χ2 = 13.95; P < .001; control group: χ2 = 21.61; P < .001), but only the BA group showed a reduction in days with compulsory admission (χ2 = 7.67; P = .02) and nonsuicidal self-injuries (χ2 = 6.13; P = .047). The BA group showed significantly greater improvements in the mobility domain of daily life functioning (z = -2.39; P = .02) and significant within-group improvements in 3 other domains (cognition: F = 9.02; P < .001; domestic responsibilities: F = 3.23; P = .049; and participation: F = 3.79; P = .03). Brief admission appears no more efficacious in reducing use of inpatient services than usual care for individuals who self-harm and are at risk of suicide. Future studies should explore other possible beneficial effects. ClinicalTrials.gov identifier: NCT02985047.

PurposeObstructive sleep apnea (OSA) is associated with polycystic ovarian syndrome (PCOS), a common cause of infertility. Understanding predictors and outcomes of OSA in women with infertility may guide treatment.MethodsA descriptive cross-sectional survey was performed to assess OSA in women presenting to an infertility clinic using validated sleep questionnaires to assess sleep and fertility outcomes. An Infertile-C group (controls with male or tubal factors) and an Infertile-S group (unknown/other infertile causes) were analyzed to assess OSA risk and other sleep disorders (e.g., restless legs syndrome (RLS) and insomnia) with fertility outcomes (time to pregnancy, PCOS, irregular menstruation, and miscarriage).ResultsIn 258 women, occurrences of OSA diagnosis (6%) and RLS (10%) were reported similar to women of child-bearing age in the general population. PCOS was unassociated with OSA risk. Predictors of OSA risk were BMI, insomnia symptoms, and sleep aid use. Obese women with high OSA risk were more likely to have other comorbidities (e.g., depression). In adjusted models, prior clinical OSA diagnosis was associated with miscarriage (odds ratio: 6.17 (1.24, 30.62), p = 0.026). RLS was associated with irregular menstruation (odds ratio: 3.73 (1.21, 11.53), p = 0.022).ConclusionsSimilar to other populations, women with infertility and OSA risk have more health comorbidities and higher BMI and may present with insomnia symptoms. While the data are limited, this study supports the potential associations of OSA and miscarriage. Further work is needed to evaluate OSA in female infertility.

PurposeTo compare growth factor and cytokine profiles in the endometrial secretions of patients with and without endometriosis to determine whether a particular protein profile is predictive of the disease.MethodsPatients undergoing laparoscopic gynecologic surgery for benign indications were recruited for this prospective cohort study. Prior to surgery, endometrial fluid was aspirated and multiplex immunoassay was used to quantify 7 cytokines and growth factors. During surgery, each patient was staged according to the ASRM staging system for endometriosis. Cytokines and growth factors were evaluated using the Mann-Whitney and Kruskal-Wallis tests. Combinations of cytokines were evaluated using logistic regression analysis, and ROC curves were generated to evaluate the predictive capacity of the assay.ResultsEndometrial secretions were analyzed from 60 patients. Nineteen had stage 3–4 endometriosis, 19 had stage 1–2 disease, and 22 had no endometriosis. There were no significant differences between controls and stage 1–2 endometriosis; however, levels of IL-1α and IL-6 were significantly increased in women with moderate-to-severe disease. A combination of IL-1α, IL-1β, and IL-6 in endometrial secretions predicts stage 3–4 endometriosis with an AUC of 0.78. A threshold value of 118 pg/mL yields a sensitivity of 75% and specificity of 70%.ConclusionAspiration of endometrial fluid is a safe and effective approach for evaluating the endometrial profile of women with endometriosis. Women with moderate-to-severe endometriosis demonstrate a distinct cytokine profile compared to controls. A combination of IL-1α, IL-1β, and IL-6 in the endometrial secretions is predictive of stage 3–4 endometriosis, but is not predictive of minimal-to-mild disease.

As oncologic therapy continues to advance, survivorship care has widened the realm of possibilities for quality-of-life improvements, including fertility preservation and restoration. We aim to summarize the current and future directions of fertility preservation techniques for patients facing gonadotoxic medical therapies who desire pregnancy after their condition is treated. This review of both ovarian and uterine transposition highlights the present roles, techniques, and fertility outcomes of the two fertility preservation treatment modalities designed to protect reproductive organs from harmful pelvic radiation. Current evidence shows that ovarian transposition preserves ovarian function for patients with localized pelvic radiation demonstrating the most successful return of fertility. Uterine transposition holds great promise for patients desiring to conceive and carry a full-term pregnancy after radiation therapy. With ongoing advancements in oncologic treatments leading to increased survival rates, fertility is increasingly becoming a key survivorship issue. Patients can anticipate counseling about these fertility preservation surgical techniques that protect both the ovaries as well as the uterus from harmful pelvic radiation.

Uterus transplantation is a surgical treatment for women with congenital or acquired uterine factor infertility. While uterus transplantation is a life-enhancing transplant that is commonly categorized as a vascular composite allograft (e.g., face or hand), it is similar to many solid organ transplants (e.g., kidney) in that both living donors (LDs) and deceased donors (DDs) can be utilized for organ procurement. While many endpoints appear to be similar for LD and DD transplants (including graft survival, time to menses, livebirth rates), there are key medical, technical, ethical, and logistical differences between these modalities. Primary considerations in favor of a LD model include thorough screening of donors, enhanced logistics, and greater donor availability. The primary consideration in favor of a DD model is the lack of physical or psychological harm to a living donor. Other important factors, that may not clearly favor one approach over the other, are important to include in discussions of LD vs. DD models. We favor a stepwise approach to uterus transplantation, one in which programs first begin with DD procurement before attempting LD procurement to maximize successful organ recovery and to minimize potential harms to a living donor.