Frontal-striatal connectivity and positive symptoms of schizophrenia: implications for the mechanistic basis of prefrontal rTMS.

Repetitive transcranial magnetic stimulation (rTMS), when applied to left dorsolateral prefrontal cortex (LDLPFC), reduces negative symptoms of schizophrenia, but has no effect on positive symptoms. In a small number of cases, it appears to worsen the severity of positive symptoms. It has been hypothesized that high-frequency rTMS of the LDLPFC might increase the dopaminergic neurotransmission by driving the activity of the left striatum in the basal ganglia (LSTR)-increasing striatal dopaminergic activity. This hypothesis relies on the assumption that either the frontal-striatal connection or the intrinsic frontal and/or striatal connections covary with the severity of positive symptoms. The current work aimed to evaluate this assumption by studying the association between positive and negative symptoms severity and the effective connectivity within the frontal and striatal network using dynamic causal modeling of resting state fMRI in a sample of 19 first episode psychosis subjects. We found that the total score of positive symptoms of schizophrenia is strongly associated with the frontostriatal circuitry. Stronger intrinsic inhibitory tone of LDLPFC and LSTR, as well as decreased bidirectional excitatory influence between the LDLPFC and the LSTR is related to the severity of positive symptoms, especially delusions. We interpret that an increase in striatal dopaminergic tone that underlies positive symptoms is likely associated with increased prefrontal inhibitory tone, strengthening the frontostriatal 'brake'. Furthermore, based on our model, we propose that lessening of positive symptoms could be achieved by means of continuous theta-burst or low-frequency (1 Hz) rTMS of the prefrontal area.

Lateral Tarsoconjunctival Flap Suspension Treatment of Post Blepharoplasty Lower Eyelid Retraction.

PURPOSE: To describe and evaluate the use of a lateral tarsoconjunctival suspension flap (TCSF) for the management of post blepharoplasty lower eyelid retraction. METHODS: Two-center, retrospective chart review of patients who received a lateral TCSF between 2010 and 2018 for correction of post blepharoplasty lower eyelid retraction. The postoperative follow-up was a minimum of 3 months. Pre- and postoperative lower eyelid position (margin reflex distance 2 on standard photographs), degree of ocular surface disease, symptoms, complications, and need for further intervention were recorded. Pre- and postoperative photographs were scored using an objective grading system for cosmetic surgical results (MDACS). RESULTS: Forty-eight eyelids from 30 patients met inclusion criteria for this study. Twenty (67%) of the patients were female. Age ranged from 55 to 89 (mean, 73.2). After the TCSF, ocular surface exposure improved in all cases. Lower eyelid retraction (average margin reflex distance 2 pre- vs. postintervention) improved in 98% of cases. Objective scoring of appearance improved; the mean MDACS score was 8 pre- and 3 post-TCSFs (p < 0.0001). One patient required midface lift and lateral canthoplasty 7 months later for undercorrected eyelid retraction. Another case required partial resection due to visibility of the flap in the interpalpebral zone. Postoperative pyogenic granulomas were noted in 8% (4/48) of eyelids. CONCLUSIONS: The lateral TCSF was safe and effective in improving both functional and esthetic parameters in this series of post blepharoplasty eyelid retraction patients.

Giant Bilateral Cysts of the Accessory Lacrimal Glands of Wolfring in a Child.

Ductal cysts of the accessory lacrimal glands of Wolfring are rare clinical entities. They typically present as mobile and translucent lesions on the superior or inferior tarsal borders. Here, the authors describe a 7-year-old male child presenting with giant bilateral cysts of Wolfring. Management of such cysts is primarily surgical and the preferred route for excision is transconjunctival. To the best of the authors' knowledge, this is the first report of a bilateral Wolfring dacryops affecting a child.Cysts of the accessory lacrimal glands of Wolfring are rare clinical entities. To the authors' knowledge, here the authors describe the first report of a bilateral Wolfring dacryops affecting a child.

Orbital Bone Decompression for Non-Thyroid Eye Disease Proptosis.

PURPOSE: To report a multicenter large case series of orbital decompression for non-thyroid eye disease proptosis. METHODS: Retrospective chart review of cases of orbital decompression performed by 9 experienced orbital surgeons from different countries from 2014 to 2017 for non-thyroid eye disease proptosis. Patients were divided into 3 groups: 1) negative vector (high axial length or shallow orbit), 2) inflammatory, and 3) tumor. Types of orbital decompression and Hertel exophthalmometry (preoperative and minimum 6 months postoperative) were recorded. Charts were also assessed for serious complications. The amount of exophthalmometry improvement was recorded according to the above groups. RESULTS: The analysis included 41 orbits of 29 patients (14 women and 15 men) with a mean age of 38.9 years (ranging from 9 to 74; standard deviation (SD) 15.66). There were 17 orbits of 11 patients in the negative vector group, 16 orbits of 10 patients in the inflammatory group, and 8 orbits of 8 patients in the tumor group. The mean reduction of proptosis was 2.95 mm in the negative vector group, 2.54 mm in the inflammatory group, and 5.75 mm in the tumor group. There were no serious complications. CONCLUSIONS: Orbital decompression was safe and effective in reducing proptosis for non-thyroid eye disease indications in this series. The amount of exophthalmometry improvement was less in the inflammatory orbitopathy group compared with other proptosis etiology groups.Orbital decompression may have a role in improving proptosis in non-thyroid eye disease entities.

A comparative study of modified transcanalicular diode laser dacryocystorhinostomy versus conventional transcanalicular diode laser dacryocystorhinostomy.

External dacryocystorhinostomy (DCR) is the gold standard surgical technique for the treatment of primary acquired nasolacrimal duct obstruction (PANDO). However, new techniques such as endoscopic DCR and transcanalicular dacryocystorhinostomy (T-DCR) are being studied in an attempt to reduce surgical time, avoid external scarring and preserve the lacrimal pump while achieving the same efficacy. The purpose of this study was to compare the efficacy between conventional T-DCR and modified transcanalicular dacryocystorhinostomy (MT-DCR) in patients with PANDO. MT-DCR is performed to remove nasal mucosa prior to laser osteotomy. This is a comparative, prospective, interventionist and randomized study. Patients with PANDO were selected to undergo MT-DCR or T-DCR by blocked randomization. PANDO was diagnosed based on clinical presentation, dye disappearance test and dacryocystography. All of the procedures were performed by the same surgery team members. Anatomical success outcome was defined as positive lacrimal syringing and functional success outcome was defined as the absence or improvement of epiphora. A total of 44 surgical procedures were performed (22 MT-DCR and 22 T-DCR). In the case of MT-DCR, the anatomical and functional success rates after 12 months were 90 and 86%, respectively. After T-DCR, these rates were 77 and 72%, respectively (p = 0.162). MT-DCR and T-DCR are both safe and fast procedures with low morbidity and well-tolerated.

Complications and Management of Polymethylmethacrylate (PMMA) Injections to the Midface.

BACKGROUND: Polymethylmethacrylate (PMMA) has been used as an injectable filler to treat hollows and reduce rhytids. PMMA injections have been associated with several side effects, however, the literature is scarce on periorbital complications and their treatments. OBJECTIVES: The purpose of this study is to report a series of complications after periorbital PMMA injections to the midface and to describe their management. METHODS: Retrospective chart review, including photography and histopathology when available. RESULTS: The authors identified 11 cases of complications of PMMA injections to the midface. Patient ages ranged from 36 to 62 years (mean, 47 years; median, 44 years). Two (18%) were males and 9 (82%) were females. Adverse effects began between 2 to 24 months after injection (mean, 7.2 months; median, 6 months). All patients had edema, erythema, and contour irregularity. Seven (64%) patients had nodules, 4 (36%) had yellow, xanthomatous skin changes, and 2 (18%) had eyelid malposition. Histopathology demonstrated a giant cell inflammation in 5 of 6 cases. Corticosteroid injection was tried in 6 cases but was associated with minimal clinical improvement. Surgical debulking of the implanted material was performed in 9 (82%) cases and was effective in improving edema, erythema, and nodularity. CONCLUSIONS: PMMA injection to the midface may be associated with chronic inflammation, fibrotic nodules, yellowing of the skin, and eyelid malposition. Intralesional corticosteroid injections yielded minimal or no improvement; surgical debulking achieved favorable results. LEVEL OF EVIDENCE 4: Therapeutic.

Long-term outcomes of modified transcanalicular diode laser dacryocystorhinostomy.

PURPOSE: The purpose of this study is to assess the long-term outcomes of modified transcanalicular diode laser dacryocystorhinostomy in a large cohort of patients affected by primary acquired nasolacrimal duct obstruction. METHODS: This study, conducted from January 17 to June 2022, encompassed 141 patients (159 procedures) who underwent modified transcanalicular diode laser dacryocystorhinostomy (MT-DCR). The procedure employed an 810-nm diode laser. Patients were monitored for at least a year after the intervention. Anatomical success was determined by ostium patency upon irrigation, while functional success referred to epiphora resolution. Parameters studied included patient demographics, procedure duration, complications, and both anatomical and functional success. Statistical analysis was performed using the Statistical Package for the Social Sciences software, with results considered significant at a 95% confidence interval (p≤0.05). RESULTS: A total of 159 lacrimal drainage systems (141 patients: 112 women and 29 men) were included in this study. Among them, 18 underwent bilateral procedures. The average patient age was 58 years (range: 34-91 years), and the average surgical duration was 24 minutes (range: 18-35 minutes). One year after the surgery, MT-DCR exhibited anatomical and functional success rates of 84.9% (135/159) and 83% (132/159), respectively. CONCLUSION: MT-DCR achieved an anatomical success rate of 84.9%, reflecting an excellent outcome. However, further extensive studies with larger sample sizes and longer follow-up periods are necessary to substantiate these findings.

Temporal prediction errors modulate cingulate-insular coupling.

Prediction error (i.e., the difference between the expected and the actual event's outcome) mediates adaptive behavior. Activity in the anterior mid-cingulate cortex (aMCC) and in the anterior insula (aINS) is associated with the commission of prediction errors under uncertainty. We propose a dynamic causal model of effective connectivity (i.e., neuronal coupling) between the aMCC, the aINS, and the striatum in which the task context drives activity in the aINS and the temporal prediction errors modulate extrinsic cingulate-insular connections. With functional magnetic resonance imaging, we scanned 15 participants when they performed a temporal prediction task. They observed visual animations and predicted when a stationary ball began moving after being contacted by another moving ball. To induced uncertainty-driven prediction errors, we introduced spatial gaps and temporal delays between the balls. Classical and Bayesian fMRI analyses provided evidence to support that the aMCC-aINS system along with the striatum not only responds when humans predict whether a dynamic event occurs but also when it occurs. Our results reveal that the insula is the entry port of a three-region pathway involved in the processing of temporal predictions. Moreover, prediction errors rather than attentional demands, task difficulty, or task duration exert an influence in the aMCC-aINS system. Prediction errors debilitate the effect of the aMCC on the aINS. Finally, our computational model provides a way forward to characterize the physiological parallel of temporal prediction errors elicited in dynamic tasks.

Language network self-inhibition and semantic similarity in first-episode schizophrenia: A computational-linguistic and effective connectivity approach.

INTRODUCTION: A central feature of schizophrenia is the disorganization and impoverishment of language. Recently, we observed higher semantic similarity in first-episode-schizophrenia (FES) patients. In this study, we investigate if this aberrant similarity relates to the 'causal' connectivity between two key nodes of the word production system: inferior frontal gyrus (IFG) and the semantic-hub at the ventral anterior temporal lobe (vATL). METHODS: Resting-state fMRI scans were collected from 60 participants (30 untreated FES and 30 healthy controls). The semantic distance was measured with the CoVec semantic tool based on GloVe. A spectral dynamic causal model with Parametrical Empirical Bayes was constructed modelling the intrinsic self-inhibitory and extrinsic-excitatory connections within the brain regions. We estimated the parameters of a fully connected model with the semantic distance as a covariate. RESULTS: FES patients chose words with higher semantic similarity when describing the pictures compared to the HC group. Among patients, an increased semantic similarity was related with an increase in intrinsic connections within both the vATL and IFG, suggesting that reduced 'synaptic gain' in these regions likely contribute to aberrant sampling of the semantic space during discourse in schizophrenia. CONCLUSIONS: Lexical impoverishment relates to increased self-inhibition in both the IFG and vATL. The associated reduction in synaptic gain may relate to reduced precision of locally generated neural activity, forcing the choice of words that are already 'activated' in a lexical network. One approach to improve word sampling may be via promoting synaptic gain via supra-physiological stimulation within the Broca's-vATL network; this proposal needs verification.

Active Inference, Epistemic Value, and Uncertainty in Conceptual Disorganization in First-Episode Schizophrenia.

BACKGROUND AND HYPOTHESIS: Active inference has become an influential concept in psychopathology. We apply active inference to investigate conceptual disorganization in first-episode schizophrenia. We conceptualize speech production as a decision-making process affected by the latent "conceptual organization"-as a special case of uncertainty about the causes of sensory information. Uncertainty is both minimized via speech production-in which function words index conceptual organization in terms of analytic thinking-and tracked by a domain-general salience network. We hypothesize that analytic thinking depends on conceptual organization. Therefore, conceptual disorganization in schizophrenia would be both indexed by low conceptual organization and reflected in the effective connectivity within the salience network. STUDY DESIGN: With 1-minute speech samples from a picture description task and resting state fMRI from 30 patients and 30 healthy subjects, we employed dynamic causal and probabilistic graphical models to investigate if the effective connectivity of the salience network underwrites conceptual organization. STUDY RESULTS: Low analytic thinking scores index low conceptual organization which affects diagnostic status. The influence of the anterior insula on the anterior cingulate cortex and the self-inhibition within the anterior cingulate cortex are elevated given low conceptual organization (ie, conceptual disorganization). CONCLUSIONS: Conceptual organization, a construct that explains formal thought disorder, can be modeled in an active inference framework and studied in relation to putative neural substrates of disrupted language in schizophrenia. This provides a critical advance to move away from rating-scale scores to deeper constructs in the pursuit of the pathophysiology of formal thought disorder.

Three-Dimensional Analysis of Tear Trough Volume After Lower Blepharoplasty with Midface Lift.

Background: This study aims to evaluate three-dimensional stereophotogrammetry measured volume changes in the tear trough area after lower blepharoplasty with midface lift with or without orbital fat manipulation. Objective: Among patients undergoing midface lift surgery, volume change by three-dimensional photography in the tear trough region was compared between those having no orbital fat manipulation, fat transposition, or fat resection. Methods: This is a prospective study of 260 eyelids of 130 patients who underwent cosmetic midface surgery. All patients had an external skin muscle flap midface lift. During the procedure, medial inferior orbital fat was resected, repositioned to a preperiosteal dissection pocket, or not manipulated. Forty-six patients (35.4%) had no fat manipulation, 42 patients (32.3%) had fat preservation with repositioning to the preperiosteal pockets on the medial inferior orbital rim, and 42 patients (32.3%) had fat resection without repositioning. Results: All patients had volume gain in tear trough volume. The amount was not statistically significantly different between fat treatment groups. Mean follow-up time was 12 months (range 6-20 months). Conclusions: Midface lifting improved tear trough volume irrespective of how fat was manipulated.

Syntactic complexity of spoken language in the diagnosis of schizophrenia: A probabilistic Bayes network model.

In the clinical linguistics of schizophrenia, syntactic complexity has received much attention. In this study, we address whether syntactic complexity deteriorates within the six months following the first episode of psychosis in those who develop a diagnosis of schizophrenia. We collected data from a cohort of twenty-six first-episode psychosis and 12 healthy control subjects using the Thought and Language Index interview in response to three pictures from the Thematic Apperception Test at first assessment and after six months (the time of consensus diagnosis). An automated labeling (part-of-speech tagging) for specific syntactic elements calculated large and granular syntactic complexity indices with a focus on clause complexity as a particular case from this spoken language data. Probabilistic reasoning leveraging the conditional independence properties of Bayes networks revealed that consensus diagnosis of schizophrenia predicted a decrease in nominal subjects per clause among individuals with first episode psychosis. From the entire sample, we estimate a 95.4 % probability that a 50 % decrease in mean nominal subjects per clause after six months is explained by the presence of first episode psychosis. Among those with psychosis, a 30 % decrease in this clause-complexity index after six months of experiencing the first episode predicted with 95 % probability a consensus diagnosis of schizophrenia, representing a conditional relationship between a longitudinal decrease in syntactic complexity and a diagnosis of schizophrenia. We conclude that an early drift towards linguistic disorganization/impoverishment of clause complexity-at the granular level of nominal subject per clause-is a distinctive feature of schizophrenia that decreases longitudinally, thus differentiating schizophrenia from other psychotic illnesses with shared phenomenology.

More than words: Speech production in first-episode psychosis predicts later social and vocational functioning.

Background: Several disturbances in speech are present in psychosis; however, the relationship between these disturbances during the first-episode of psychosis (FEP) and later vocational functioning is unclear. Demonstrating this relationship is critical if we expect speech and communication deficits to emerge as targets for early intervention. Method: We analyzed three 1-min speech samples using automated speech analysis and Bayes networks in an antipsychotic-naive sample of 39 FEP patients and followed them longitudinally to determine their vocational status (engaged or not engaged in employment education or training-EET vs. NEET) after 6-12 months of treatment. Five baseline linguistic variables with prior evidence of clinical relevance (total and acausal connectives use, pronoun use, analytic thinking, and total words uttered in a limited period) were included in a Bayes network along with follow-up NEET status and Social and Occupational Functioning Assessment Scale (SOFAS) scores to determine dependencies among these variables. We also included clinical (Positive and Negative Syndrome Scale 8-item version (PANSS-8)), social (parental socioeconomic status), and cognitive features (processing speed) at the time of presentation as covariates. Results: The Bayes network revealed that only total words spoken at the baseline assessment were directly associated with later NEET status and had an indirect association with SOFAS, with a second set of dependencies emerging among the remaining linguistic variables. The primary (speech-only) model outperformed models including parental socioeconomic status, processing speed or both as latent variables. Conclusion: Impoverished speech, even at subclinical levels, may hold prognostic value for functional outcomes and warrant consideration when providing measurement based care for first-episode psychosis.

The effect of bevacizumab, 5-fluorouracil, and triamcinolone on the healing modulation of surgical wounds in rats.

In this study, we aimed to analyze the effect of 5-fluorouracil, triamcinolone, and bevacizumab on scar modulation in an experimental rat model of surgical lesions. Rats (Rattus norvegicus albinus) were divided into four groups: bevacizumab, 5-fluorouracil + triamcinolone, bevacizumab + 5-fluorouracil + triamcinolone, and control (received no medication) groups. A linear, dorsal incision was created and sutured for the first intention wound healing, mimicking the surgical incision of upper blepharoplasty. Treatments were initiated on day 7, and the rats were euthanized on day 14. Only in the 5-fluorouracil + triamcinolone group was there a difference in the number of infiltrated monocytes. There was 56%, 86%, and 85% decrease in the number of neovessels in the bevacizumab, 5-fluorouracil + triamcinolone, and bevacizumab + 5-fluorouracil + triamcinolone groups, respectively, compared with the control. Picrosirius red staining showed higher collagen density and more organized collagen in the treatment groups than in the control group. Scar modulation was observed in all groups, but the 5-fluorouracil + triamcinolone group presented the best results. To our knowledge, this is the first study to evaluate the influence of three medications in combination on healing. When used together, these medications can prevent the development of unsightly scars, and are therefore promising alternatives to corticosteroids.

Progressive changes in descriptive discourse in First Episode Schizophrenia: a longitudinal computational semantics study.

Computational semantics, a branch of computational linguistics, involves automated meaning analysis that relies on how words occur together in natural language. This offers a promising tool to study schizophrenia. At present, we do not know if these word-level choices in speech are sensitive to the illness stage (i.e., acute untreated vs. stable established state), track cognitive deficits in major domains (e.g., cognitive control, processing speed) or relate to established dimensions of formal thought disorder. In this study, we collected samples of descriptive discourse in patients experiencing an untreated first episode of schizophrenia and healthy control subjects (246 samples of 1-minute speech; n = 82, FES = 46, HC = 36) and used a co-occurrence based vector embedding of words to quantify semantic similarity in speech. We obtained six-month follow-up data in a subsample (99 speech samples, n = 33, FES = 20, HC = 13). At baseline, semantic similarity was evidently higher in patients compared to healthy individuals, especially when social functioning was impaired; but this was not related to the severity of clinically ascertained thought disorder in patients. Across the study sample, higher semantic similarity at baseline was related to poorer Stroop performance and processing speed. Over time, while semantic similarity was stable in healthy subjects, it increased in patients, especially when they had an increasing burden of negative symptoms. Disruptions in word-level choices made by patients with schizophrenia during short 1-min descriptions are sensitive to interindividual differences in cognitive and social functioning at first presentation and persist over the early course of the illness.

Counteracting Effects of Glutathione on the Glutamate-Driven Excitation/Inhibition Imbalance in First-Episode Schizophrenia: A 7T MRS and Dynamic Causal Modeling Study.

Oxidative stress plays a key role in the pathophysiology of schizophrenia. While free radicals produced by glutamatergic excess and oxidative metabolism have damaging effects on brain tissue, antioxidants such as glutathione (GSH) counteract these effects. The interaction between glutamate (GLU) and GSH is centered on N-Methyl-D-aspartate (NMDA) receptors. GSH levels increase during glutamate-mediated excitatory neuronal activity, which serves as a checkpoint to protect neurons from oxidative damage and reduce excitatory overdrive. We studied the possible influence of GSH on the glutamate-mediated dysconnectivity in 19 first-episode schizophrenia (FES) patients and 20 healthy control (HC) subjects. Using ultra-high field (7 Tesla) magnetic resonance spectroscopy (MRS) and resting state functional magnetic resonance imaging (fMRI), we measured GSH and GLU levels in the dorsal anterior cingulate cortex (dACC) and blood-oxygenation level-dependent activity in both the dACC and the anterior insula (AI). Using spectral dynamic causal modeling, we found that when compared to HCs, in FES patients inhibitory activity within the dACC decreased with GLU levels whereas inhibitory activity in both the dACC and AI increased with GSH levels. Our model explains how higher levels of GSH can reverse the downstream pathophysiological effects of a hyperglutamatergic state in FES. This provides an initial insight into the possible mechanistic effect of antioxidant system on the excitatory overdrive in the salience network (dACC-AI).

Small Words That Matter: Linguistic Style and Conceptual Disorganization in Untreated First-Episode Schizophrenia.

This study aimed to shed light on the linguistic style affecting the communication discourse in first-episode schizophrenia (FES) by investigating the analytic thinking index in relation to clinical scores of conceptual and thought disorganization (Positive and Negative Syndrome Scale, PANSS-P2 and Thought and Language Index, TLI). Using robust Bayesian modeling, we report three major findings: (1) FES subjects showed reduced analytic thinking, exhibiting a less categorical linguistic style than healthy control (HC) subjects (Bayes factor, BF10 > 1000), despite using the same proportion of function and content words as HCs; (2) the lower the analytic thinking score, the higher the symptoms scores of conceptual disorganization (PANSS-P2, BF = 22.66) and global disorganization of thinking (TLI, BF10 = 112.73); (3) the linguistic style is a better predictor of conceptual disorganization than the cognitive measure of processing speed in schizophrenia (SZ). These findings provide an objectively detectable linguistic style with a focus on Natural Language Processing Analytics of transcribed speech samples of patients with SZ that require no clinical judgment. These findings also offer a crucial insight into the primacy of linguistic structural disruption in clinically ascertained disorganized thinking in SZ. Our work contributes to an emerging body of literature on the psychopathology of SZ using a first-order lexeme-level analysis and a hypothesis-driven approach. At a utilitarian level, this has implications for improving educational and social outcomes in patients with SZ.

A Prospective Randomized Study of Lateral Brow-Eyelid Complex Volume after Internal Browpexy Using Three-Dimensional Stereophotogrammetry.

Background: A full lateral brow-eyelid complex may help rejuvenate and feminize the face. Objectives: To compare periorbital volume change of patients as measured by three-dimensional (3D) stereophotogrammetry before and after blepharoplasty with or without internal browpexy sutures. Methods: This is a prospective randomized controlled study of 124 eyelids of 62 adult female patients who underwent cosmetic upper eyelid blepharoplasty by a single surgeon. Subjects were randomized to blepharoplasty alone (control) or blepharoplasty with an adjunctive "brassiere suture" internal browpexy (intervention). An observer masked to the intervention measured the brow-eyelid volume using standardized images obtained with a 3D camera, before and after surgery. The minimum follow-up was 6 months postoperatively. Results: Sixty eyelids (30 patients) were treated with upper blepharoplasty alone and 64 eyelids (32 patients) had blepharoplasty plus internal browpexy. The mean volume gain was 0.85 mL in the internal browpexy intervention group and 0.19 mL in the control group. The volume increased in all patients receiving browpexy and this change was greater than after blepharoplasty alone (p < 0.05). The mean follow-up time was 16.8 months (range 6-24 months). Conclusions: Adjunctive internal browpexy during blepharoplasty was associated with increased volume of the lateral brow-eyelid complex.

Progressive Changes in Glutamate Concentration in Early Stages of Schizophrenia: A Longitudinal 7-Tesla MRS Study.

Progressive reduction in glutamatergic transmission has been proposed as an important component of the illness trajectory of schizophrenia. Despite its popularity, to date, this notion has not been convincingly tested in patients in early stages of schizophrenia. In a longitudinal 7T magnetic resonance spectroscopy (1H-MRS), we quantified glutamate at the dorsal anterior cingulate cortex in 21 participants with a median lifetime antipsychotic exposure of less than 3 days and followed them up after 6 months of treatment. Ten healthy controls were also scanned at 2 time points. While patients had significantly lower overall glutamate levels than healthy controls (F(1,27) = 5.23, P = .03), we did not observe a progressive change of glutamate concentration in patients (F(1,18) = 0.47, P = .50), and the group by time interaction was not significant (F(1,27) = 0.86, P = .36). On average, patients with early psychosis receiving treatment showed a 0.02 mM/y increase, while healthy controls showed a 0.06 mM/y reduction of MRS glutamate levels. Bayesian analysis of our observations does not support early, post-onset glutamate loss in schizophrenia. Interestingly, it provides evidence in favor of a lack of progressive glutamate change in our schizophrenia sample-indicating that the glutamate level at the onset of illness was the best predictor of the levels 6 months after treatment. A more nuanced view of glutamatergic physiology, linked to early cortical maturation, may be required to understand glutamate-mediated dynamics in schizophrenia.