Thiol-disulphide Homeostasis in Patients with Schizophrenia: The Potential Biomarkers of Oxidative Stress in Acute Exacerbation of Schizophrenia.

Objective: : Recent evidence suggests that oxidative stress contributes to the pathophysiology of schizophrenia. This study aimed to compare thiol-disulphide homeostasis in acute and stable phases of schizophrenia for the first time. Methods: : Among the patients with schizophrenia, 61 in the acute-phase and 61 in the stable phase of their illness were enrolled in the study. Native thiol (NT), total thiol (TT), disulphide (SS), disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol for thiol-disulphide homeostasis were compared between the groups. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive/Negative Symptoms (SAPS/SANS), Clinical Global Impression-Severity Scale (CGI-S), Barnes Akathisia Rating Scale, and Simpson-Angus Scale were used to assess symptoms. Results: : After controlling for age, sex, body mass index, and smoking status there were significant differences in NT, TT, SS/NT, SS/TT, and NT/TT, but not SS. Thiol/disulphide homeostasis has shifted in favour of the oxidative side in patients with acute-phase compared to that in stable schizophrenia. BPRS, SAPS, and CGI-S scores were significantly correlated with all six thiol-disulphide parameters, but not SANS, when controlling for age and sex. Significant receiver operating characteristic (ROC) curves were obtained for all thiol-disulphide homeostasis parameters. Discriminant analysis was found to be statistically significant in discriminating between groups. Conclusion: : These results show that oxidative status increases thiol-disulphide homeostasis in patients with acute-phase schizophrenia compared to those with stable schizophrenia. These findings suggest that thiol-disulphide parameters can be used as biomarkers for the acute exacerbation of schizophrenia.

Examining the association between exposome score for schizophrenia and cognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

BACKGROUND: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected siblings, and healthy controls. METHODS: This cross-sectional sample consisted of 1200 patients, 1371 siblings, and 1564 healthy controls. Neurocognition, social cognition, and perception were assesed using a short version of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the Degraded Facial Affect Recognition Task (DFAR), and the Benton Facial Recognition Test (BFR), respectively. Regression models were used to analyze the association between ES-SCZ and cognitive domains in each group. RESULTS: There were no statistically significant associations between ES-SCZ and cognitive domains in SSD. ES-SCZ was negatively associated with T-score of cognition in siblings (B=-0.40, 95% CI -0.76 to -0.03) and healthy controls (B=-0.63, 95% CI -1.06 to -0.21). Additionally, ES-SCZ was positively associated with DFAR-total in siblings (B=0.83, 95% CI 0.26 to 1.40). Sensitivity analyses excluding cannabis use history from ES-SCZ largely confirmed the main findings. CONCLUSIONS: Longitudinal cohorts may elucidate how environmental exposures influence the onset and course of cognitive impairments in trans-syndromic psychosis spectrum.

The association between cannabis use and facial emotion recognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

Schizophrenia is frequently accompanied with social cognitive disturbances. Cannabis represents one established environmental factor associated with the onset and progression of schizophrenia. The present cross-sectional study aimed to investigate the association of facial emotion recognition (FER) performance with cannabis use in 2039 patients with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). FER performance was measured using the Degraded Facial Affect Recognition Task (DFAR). Better FER performance as indicated by higher DFAR-total scores was associated with lifetime regular cannabis use in schizophrenia (B = 1.36, 95% CI 0.02 to 2.69), siblings (B = 2.17, 95% CI 0.79 to 3.56), and HC (B = 3.10, 95% CI 1.14 to 5.06). No associations were found between DFAR-total and current cannabis use. Patients with schizophrenia who started to use cannabis after the age of 16 showed better FER performance than patients who started earlier (B = 2.50, 95% CI 0.15 to 4.84) and non-users (B = 3.72, 95 CI 1.96 to 5.49). Better FER performance was found also in siblings who started to use cannabis after 16 compared to non-users (B = 2.37, 95% CI 0.58 to 4.16), while HC using cannabis performed better than non-users at DFAR-total regardless of the age at onset. Our findings suggest that lifetime regular cannabis use may be associated with better FER regardless of the psychosis risk, but that FER might be moderated by age at first use in people with higher genetic risk. Longitudinal studies may clarify whether there is a cause-and-effect relationship between cannabis use and FER performance in psychotic and non-psychotic samples.

Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway.

BACKGROUND: There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation. METHODS: We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls. RESULTS: The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: -0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465). CONCLUSIONS: The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

Examining facial emotion recognition as an intermediate phenotype for psychosis: Findings from the EUGEI study.

BACKGROUND: Social cognition impairments, such as facial emotion recognition (FER), have been acknowledged since the earliest description of schizophrenia. Here, we tested FER as an intermediate phenotype for psychosis using two approaches that are indicators of genetic risk for schizophrenia: the proxy-genetic risk approach (family design) and the polygenic risk score for schizophrenia (PRS-SCZ). METHODS: The sample comprised 2039 individuals with schizophrenia, 2141 siblings, and 2049 healthy controls (HC). The Degraded Facial Affect Recognition Task (DFAR) was applied to measure the FER accuracy. Schizotypal traits in siblings and HC were assessed using the Structured Interview for Schizotypy-Revised (SIS-R). The PRS-SCZ was trained using the Psychiatric Genomics Consortium results. Regression models were applied to test the association of DFAR with psychosis risk, SIS-R, and PRS-SCZ. RESULTS: The DFAR-total scores were lower in individuals with schizophrenia than in siblings (RR = 0.97 [95% CI 0.97, 0.97]), who scored lower than HC (RR = 0.99 [95% CI 0.99-1.00]). The DFAR-total scores were negatively associated with SIS-R total scores in siblings (B = -2.04 [95% CI -3.72, -0.36]) and HC (B = -2.93 [95% CI -5.50, -0.36]). Different patterns of association were observed for individual emotions. No significant associations were found between DFAR scores and PRS-SCZ. CONCLUSIONS: Our findings based on a proxy genetic risk approach suggest that FER deficits may represent an intermediate phenotype for schizophrenia. However, a significant association between FER and PRS-SCZ was not found. In the future, genetic mechanisms underlying FER phenotypes should be investigated trans-diagnostically.

Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

BACKGROUND: A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls. METHODS: This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate. RESULTS: ES-SCZ was associated with the GAF dimensions in patients (symptom: B = -1.53, p-value = 0.001; disability: B = -1.44, p-value = 0.001), siblings (symptom: B = -3.07, p-value < 0.001; disability: B = -2.52, p-value < 0.001), and healthy controls (symptom: B = -1.50, p-value < 0.001; disability: B = -1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group. CONCLUSIONS: Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.

Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene-environment interaction. The EUGEI study.

BACKGROUND: First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes. METHODS: We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS. RESULTS: In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group. CONCLUSIONS: The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene-environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.

Estimating Exposome Score for Schizophrenia Using Predictive Modeling Approach in Two Independent Samples: The Results From the EUGEI Study.

Exposures constitute a dense network of the environment: exposome. Here, we argue for embracing the exposome paradigm to investigate the sum of nongenetic "risk" and show how predictive modeling approaches can be used to construct an exposome score (ES; an aggregated score of exposures) for schizophrenia. The training dataset consisted of patients with schizophrenia and controls, whereas the independent validation dataset consisted of patients, their unaffected siblings, and controls. Binary exposures were cannabis use, hearing impairment, winter birth, bullying, and emotional, physical, and sexual abuse along with physical and emotional neglect. We applied logistic regression (LR), Gaussian Naive Bayes (GNB), the least absolute shrinkage and selection operator (LASSO), and Ridge penalized classification models to the training dataset. ESs, the sum of weighted exposures based on coefficients from each model, were calculated in the validation dataset. In addition, we estimated ES based on meta-analyses and a simple sum score of exposures. Accuracy, sensitivity, specificity, area under the receiver operating characteristic, and Nagelkerke's R2 were compared. The ESMeta-analyses performed the worst, whereas the sum score and the ESGNB were worse than the ESLR that performed similar to the ESLASSO and ESRIDGE. The ESLR distinguished patients from controls (odds ratio [OR] = 1.94, P < .001), patients from siblings (OR = 1.58, P < .001), and siblings from controls (OR = 1.21, P = .001). An increase in ESLR was associated with a gradient increase of schizophrenia risk. In reference to the remaining fractions, the ESLR at top 30%, 20%, and 10% of the control distribution yielded ORs of 3.72, 3.74, and 4.77, respectively. Our findings demonstrate that predictive modeling approaches can be harnessed to evaluate the exposome.

Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study.

Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy-genetic liability measures suggest gene-environment interaction in the etiology of schizophrenia spectrum disorders, but the molecular evidence is scarce. Here, by analyzing the main and joint associations of polygenic risk score for schizophrenia (PRS-SCZ) and environmental exposures in 1,699 patients with a diagnosis of schizophrenia spectrum disorders and 1,542 unrelated controls with no lifetime history of a diagnosis of those disorders, we provide further evidence for gene-environment interaction in schizophrenia. Evidence was found for additive interaction of molecular genetic risk state for schizophrenia (binary mode of PRS-SCZ above 75% of the control distribution) with the presence of lifetime regular cannabis use and exposure to early-life adversities (sexual abuse, emotional abuse, emotional neglect, and bullying), but not with the presence of hearing impairment, season of birth (winter birth), and exposure to physical abuse or physical neglect in childhood. The sensitivity analyses replacing the a priori PRS-SCZ at 75% with alternative cut-points (50% and 25%) confirmed the additive interaction. Our results suggest that the etiopathogenesis of schizophrenia involves genetic underpinnings that act by making individuals more sensitive to the effects of some environmental exposures.

Reasons for clozapine discontinuation in patients with treatment-resistant schizophrenia.

Although clozapine is more effective than other antipsychotics in the treatment of schizophrenia, the rate of its discontinuation is also high. The aim of this retrospective chart-review study was to investigate the causes of clozapine discontinuation in patients with treatment-resistant schizophrenia. This study included a total of 396 patients with schizophrenia, 240 still on clozapine therapy and 156 who discontinued clozapine, and compared their clinical characteristics. Those who discontinued clozapine had a longer history of illness and more hospitalizations before clozapine and tended to be older. Inadequate response was more common among clozapine discontinuers compared to continuers. The most common reason for discontinuation was the side-effects associated with clozapine (49%). Discontinuation from patient decision or by the psychiatrist due to noncompliance was the second (29.7%) and discontinuation due to lack of efficacy was the third most frequent reason (21.3%). The patients who discontinued clozapine because of cardiac side effects were younger, had shorter duration of clozapine use, and had lower maximum clozapine dose compared to the other discontinuers. Our findings point out the importance of enhancing psychiatrists' ability to handle manageable side effects to minimize discontinuations and maximize the benefits of clozapine in patients with treatment-resistant schizophrenia.

Neurochemical differences between bipolar disorder type I and II in superior temporal cortices: A proton magnetic resonance spectroscopy study.

BACKGROUND: Despite the diagnostic challenges in categorizing bipolar disorder subtypes, bipolar I and II disorders (BD-I and BD-II respectively) are valid indices for researchers. Subtle neurobiological differences may underlie clinical differences between mood disorder subtypes. The aims of this study were to investigate neurochemical differences between bipolar disorder subtypes. METHODS: Euthymic BD-II patients (n = 21) are compared with BD-I (n = 28) and healthy comparison subjects (HCs, n = 30). Magnetic Resonance Imaging (MRI) and proton spectroscopy (1H MRS) were performed on a 3T Siemens Tim Trio system. MRS voxels were located in the left/right superior temporal cortices, and spectra acquired with the single voxel Point REsolved Spectroscopy Sequence (PRESS). The spectroscopic data were analyzed with LCModel (Version 6.3.0) software. RESULTS: There were significant differences between groups in terms of glutamate [F = 6.27, p = 0.003], glutamate + glutamine [F = 6.08, p = 0.004], inositol containing compounds (Ino) (F = 9.25, p < 0.001), NAA [F = 7.63, p = 0.001] and creatine + phosphocreatine [F = 11.06, p < 0.001] in the left hemisphere and Ino [F = 5.65, p = 0.005] in the right hemisphere. Post-hoc comparisons showed that the BD-I disorder group had significantly lower metabolite levels in comparison to the BD-II and the HC groups. LIMITATIONS: This was a cross-sectional study with a small sample size. In addition, patients were on various psychotropic medications, which may have impacted the results. CONCLUSIONS: Neurochemical levels, in the superior temporal cortices, measured with 1H-MRS discriminated between BD-II and BD-I. Although further studies are needed, one may speculate that the superior temporal cortices (particularly left hemispheric) play a critical role, whose pathology may be related to subtyping bipolar disorder.

Effects of Sono-feedback during aspiration of Baker's cysts: A controlled clinical trial.

OBJECTIVE: To determine whether (diagnostic and interventional) ultrasound imaging can be used to provide visual feedback affecting treatment outcome (pain and disability). DESIGN: Controlled clinical trial. SUBJECTS: A total of 52 patients with (ultrasonographically confirmed) symptomatic Baker's cysts were enrolled. METHODS: The cysts were drained under ultrasound guidance and, if necessary, corticosteroid injections were given on the follow-up visit. In group I (n = 26) the patients did not observe the procedures on the ultrasound (US) screen. In group II (n = 26) the US images/videos were shown and explained to the patients. The patients were included in one of the groups consecutively, unless they refused the protocol of that group. Treatment outcome was assessed via US measurements, aspirate volumes, visual analogue scale (VAS) (knee pain, procedure discomfort), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Rauschning-Lindgren Classification (RLC), Kellgren-Lawrence grading scale, Hospital Anxiety and Depression Scale, and paracetamol intake. RESULTS: The 2 groups were similar regarding US measurements, aspirate volume and paracetamol use (p-values > 0.05). In both groups all VAS (p < 0.001) and WOMAC (p < 0.05) scores decreased after treatment. Although initial VAS and WOMAC scores were similar between the groups, all VAS/WOMAC scores, except VAS-2, WOMAC-2 pain, and WOMAC-3 stiffness, were significantly lower in group II (all p < 0.05). Initial RLC scores were similar between the groups; however, group II had significantly lower scores at visits 2 and 3. CONCLUSION: In patients with Baker's cysts (diagnostic/interventional) US imaging can be used as a simple means of visual biofeedback, favourably affecting the treatment outcome (pain and disability).

The distinction between unipolar and bipolar depression: a cognitive theory perspective.

BACKGROUND: There is very limited data about the cognitive structure of bipolar depression when compared to unipolar depression. The aim of the study was to look into the differences between unipolar and bipolar depressed patients regarding their cognitive structure in view of Beck's cognitive theory. METHODS: In this study, 70 bipolar patients during a depressive episode, 189 unipolar depressed patients and 120 healthy subjects were recruited. The participants were interviewed by using a structured clinical diagnostic scale. To evaluate the cognitive structure differences, the Automatic Thoughts Questionnaire (ATQ) and the Dysfunctional Attitude Scale (DAS) were used. RESULTS: We found that on the mean ATQ total score, the unipolar depressed patients scored significantly higher (92.9±22.7) than both the bipolar depressed patients (73.2±24.7) and the healthy subjects (47.1±19.6), even after controlling for all confounding factors, e.g. gender, marital status, depressive symptom severity (F = 157.872, p<0.001). The bipolar depressed patients also scored significantly higher on the mean ATQ total score than the healthy controls. On the mean DAS total score, and on the mean score of its subscale of need for approval, the bipolar depressed patients scored (152.8±21.2 and 48.2±7.4, respectively) significantly higher than both the unipolar depressed patients (160.9±29.0 and 51.9±9.7, respectively) and the healthy subjects (127.9±32.8 and 40.2±12.2, respectively), even after controlling for any confounding factor (F=45.803 [p<0.001] and F=43.206 [p<0.001], respectively). On the mean score of the perfectionistic attitude subscale of the DAS, the depressed groups scored significantly higher than the healthy subjects, but they did not seem to separate from each other (F=41.599, p<0.001). CONCLUSIONS: These results may help enhance the understanding of the potentially unique psychotherapeutic targets and the underlying cognitive theory of bipolar depression.

The factors contributing to death anxiety in cancer patients.

Suffering comes in many ways for patients confronting cancer. One of these is an unspecifiable fear about death, which is an existential issue. The aim of this study was to investigate the relationship between death anxiety and its correlates in cancer patients. Seventy cancer patients were assessed using SCID-I, Templer's Death Anxiety Scale, the Hospital Anxiety (A) and Depression (D) Scale, the Distress Thermometer, the Visual Analogue Scale for pain (VAS), the Global Assessment of Functioning, and Glock and Stark's Dimensions of Religious Commitment scales, and these assessments were compared between cancer patients with and without death anxiety. Multiple regression analysis was conducted after correlation analysis between death anxiety and sociodemographic and clinical variables. Axis I psychiatric diagnosis, pain scores, and negative believes about what will happen after death were found to be higher in patients having death anxiety than patients not having death anxiety. Also life expectancy was perceived as shortened in patients with death anxiety. Death anxiety was associated with anxiety, depressive symptoms, and beliefs about what will happen after death. In conclusion, death anxiety could not be regarded as a natural consequence of having cancer; it is associated with the unresolved psychological and physical distress.

Hippocampus, glucocorticoids and neurocognitive functions in patients with first-episode major depressive disorders.

The aim of this study was to determine whether there was any relationship between hippocampal volume, and glucocorticoid regulation, and cognitive dysfunctions in drug-naïve major depressive disorder (MDD) patients during their first episode. Twenty drug-free female MDD patients in their first episode and 15 healthy females as control subjects were included in the study. All subjects underwent 3.0 Tesla (T) magnetic resonance imaging (MRI), comprehensive neuropsychological testing and dexamethasone suppression tests (DST). The volumes of the right and left hippocampus of the patients were found to be significantly smaller than those of the controls. Patients were found to have significantly lower scores on measures of attention, working memory, psychomotor speed, executive functions, and visual and verbal memory fields. The performance of the patients only in the recollection memory and memory of reward-associated rules were positively correlated with hippocampal volumes. The volumes of the left and right hippocampus did not correlate with basal or post-dexamethasone cortisol levels. Our findings indicate that depressed patients have smaller hippocampi even in the earlier phase of their illness. Further research efforts are needed to explain the mechanisms that are responsible for the small hippocampus in depressed patients.

Antidepressant effect detected on proton magnetic resonance spectroscopy in drug-naïve female patients with first-episode major depression.

AIM: Recent neuroimaging studies support functional and structural alterations in the dorsolateral prefrontal cortex (DLPFC), particularly on the left side in patients with major depressive disorders (MDD). The aim of the present study was to examine the biochemical characteristics of left DLPFC as measured on proton ((1)H) magnetic resonance spectroscopy (MRS) in patients with drug-naïve first-episode MDD and a healthy control group. A second aim was to assess the effect of antidepressant treatment on the metabolites of DLPFC. METHODS: Short-echo single-voxel (1)H-MRS was done for the left DLPFC in 17 female drug-free MDD patients (mean age +/- SD, 30.9 +/- 6.9 years) and 13 matched control subjects (mean age +/- SD, 29.1 +/- 6.2 years) and was repeated at 8 weeks following antidepressant treatment. RESULTS: Comparison of baseline values indicated that there were no significant differences in any of the metabolite ratios (N-acetyl aspartate/creatine [NAA/Cr], myoinositol [Ino]/Cr, and choline [Cho]/Cr) between patients and controls. Significant differences were detected between pre- and post-treatment Ino/Cr ratios (0.67 +/- 0.13, 0.58 +/- 0.22, P = 0.032, respectively), although there was no difference in NAA/Cr and Cho/Cr ratios. CONCLUSION: Although no significant metabolic alterations exist in female patients with drug-naïve first-episode MDD as evaluated on (1)H-MRS, an increase in Ino/Cr was observed following 8-week antidepressant treatment. These findings give rise to the possibility that non-neuronal cells, particularly glial cells that are probably damaged, play a role in the action of antidepressant treatment.

Selective serotonin reuptake inhibitors reduce the attack frequency in familial mediterranean Fever.

Familial Mediterranean Fever (FMF) is characterized by recurrent acute attacks of fever and serositis, and colchicine is the primary treatment. The pathogenesis of the disease has not been fully understood. Resistance to colchicine remains to be a problem in up to 30% of the patients and yet there seems to be no alternative treatment. In this study our objective was to investigate whether a selective serotonin re-uptake inhibitor (SSRI) could affect the attack frequency and acute phase response in FMF patients who were unresponsive to colchicine. We retrospectively evaluated the hospital files of 11 colchicine-unresponsive FMF patients who had been treated with SSRIs. According to the records and re-evaluation of the patients, the total number of the FMF attacks was calculated before and after the SSRI, adjunct to colchicine. The laboratory values including erythrocyte sedimentation rate, C-reactive protein, fibrinogen and white blood cell counts were also noted before and after the SSRI treatment from their hospital files. The mean attack frequency before adding SSRI to colchicine was 8.09 +/- 3.53 per 6 months, and at the end of this period there was a great decline in the number of mean attack frequency (0.36 +/- 0.50 attacks per 6 months) (p < 0.001). Acute phase reactants were significantly decreased after SSRI treatment (p < 0.001). All of the colchicine-unresponsive patients had depression and 3 of those patients also had fibromyalgia. SSRIs appear to be useful adjuncts in the management of FMF patients who continue to have attacks despite regular colchicine treatment.