Association between thyroid function and comorbid anxiety in first-episode and drug naïve patients with major depressive disorder

European Archives of Psychiatry and Clinical Neuroscience - Existing studies have shown that thyroid dysfunction is associated with depression. However, its role in major depressive disorder (MDD)...     

Prolactin serum levels correlate with inflammatory status in drug-naïve first-episode schizophrenia

Objectives. The present study was to examine the relationship between serum levels of prolactin and the inflammatory status in drug-naïve, first-episode schizophrenia patients with normal weight. Methods. Patients with normal weight, drug-naïve, first-episode schizophrenia and healthy controls were enrolled in the study. Serum levels of prolactin (PRL) were measured using electrical chemiluminescence immunoassay. Serum levels of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). Results. Sixty patients with normal weight, drug-naïve, first-episode schizophrenia and 60 healthy controls were enrolled. The schizophrenia group had higher serum levels of PRL, IL-1β, IL-6 and TNF-α compared with the control group. There was a gender difference of hyperprolactinemia in schizophrenia group. There were positive relationships between serum levels of PRL and serum levels of IL-1β, IL-6 and TNF-α within the schizophrenia group. Within the schizophrenia group, TNF-α was the strongest predictor among the three cytokines for serum levels of prolactin after controlling for gender, age, education, smoking status and disease duration. Conclusions. Patients with normal weight, drug-naïve, first-episode schizophrenia present elevated serum levels of PRL, which might be related to the up-regulated inflammatory status in this patient population.     

Altered peripheral blood compounds in drug-naïve first-episode patients with either schizophrenia or major depressive disorder: a meta-analysis

ImportanceSchizophrenia and major depressive disorder (MDD) are associated with increased risks of immunologic disease and metabolic syndrome. It is unclear to what extent growth, immune or glucose dysregulations are similarly present in these disorders without the influence of treatment or chronicity.ObjectiveTo conduct a meta-analysis investigating whether there are altered peripheral growth, immune or glucose metabolism compounds in drug-naïve first-episode patients with schizophrenia or MDD compared with controls.Data sources and study selectionCase-control studies reporting compound measures in drug-naïve first-episode patients with schizophrenia or MDD compared with controls in the Embase, PubMed and PsycINFO databases.Data extraction and synthesisTwo independent authors extracted data for a random-effects meta-analysis.Main outcomes and measuresPeripheral growth, immune or glucose metabolism compounds in schizophrenia or MDD compared with controls. Standardized mean differences were quantified with Hedges’ g (g).Results74 studies were retrieved comprising 3453 drug-naïve first-episode schizophrenia patients and 4152 controls, and 29 studies were retrieved comprising 1095 drug-naïve first-episode MDD patients and 1399 controls. Growth factors: brain-derived neurotrophic factor (BDNF) (g = -0.77, P < .001) and nerve growth factor (NGF) (g = -2.51, P = .03) were decreased in schizophrenia. For MDD, we observed a trend toward decreased BDNF (g = −0.47, P = .19) and NGF (g = −0.33, P = .08) levels, and elevated vascular endothelial growth factor levels (g = 0.40, P = .03). Immune factors: interleukin (IL)-6 (g = 0.95, P < .001), IL-8 (g = 0.59, P = .001) and tumor necrosis factor alpha (TNFα) (g = 0.48, P = .002) were elevated in schizophrenia. For C-reactive protein (CRP) (g = 0.57, P = .09), IL-4 (g = 0.44, P = .10) and interferon gamma (g = 0.33, P = .11) we observed a trend toward elevated levels in schizophrenia. In MDD, IL-6 (g = 0.62, P = .007), TNFα (g = 1.21, P < .001), CRP (g = 0.53, P < .001), IL-1β (g = 1.52, P = .009) and IL-2 (g = 4.41, P = .04) were elevated, whereas IL-8 (g = −0.84, P = .01) was decreased. The fasting glucose metabolism factors glucose (g = 0.24, P = .003) and insulin (g = 0.38, P = .003) were elevated in schizophrenia.Conclusions and relevanceBoth schizophrenia and MDD show alterations in growth and immune factors from disease onset. An altered glucose metabolism seems to be present from onset in schizophrenia. These findings support efforts for further research into transdiagnostic preventive strategies and augmentation therapy for those with immune or metabolic dysfunctions.     

Inflammatory cytokines,complement factor H and anhedonia in drug-naïve major depressive disorder

ObjectiveAnhedonia is a core symptom of major depressive disorder (MDD) and often associated with poor prognosis. The main objective of the present study was to explore the relationship between complement factor H (CFH), inflammatory cytokines and anhedonia in drug-naïve MDD patients.MethodsA total of 215 participants (61 MDD patients with anhedonia, 78 MDD patients without anhedonia, and 76 control subjects) were included. Severity of depression and levels of anhedonia were evaluated by Hamilton Rating Scale for Depression-17 (HAMD-17) and SHAPS (Snaith-Hamilton Pleasure Scale). Plasma levels of CFH, interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) were measured.ResultsThe plasma levels of CFH, IL-10 and TNF-α were higher in drug-naïve MDD patients than control subjects. Compared to MDD patients without anhedonia, patients with anhedonia showed higher levels of CFH and IL-6. The stepwise regression analysis revealed that IL-10, TNF-α, as well as IL-10 × TNF-α were associated with depressive symptoms measured by HAMD-17 in drug-naïve MDD patients, while only CFH levels were identified as a mediator factor for the severity of anhedonia in the patients.ConclusionMDD patients with anhedonia showed different inflammatory characteristics compared to patients without anhedonia. Our results provide novel evidence suggesting that increased plasma CFH levels may be a potential biomarker of anhedonia of subtyping MDD.     

Duloxetine's modest short-term influences in subcortical structures of first episode drug-naïve patients with major depressive disorder and panic disorder

We developed this study to follow up the hanges in subcortical structures after 6 weeks' treatment with therapy of duloxetine in first episode drug-na?ve patients with major depressive disorder and panic disorder. Fifteen patients received duloxetine 60mg/d therapy for 6 weeks and achieved remission. They all underwent structural magnetic resonance imaging (MRI) of the brain at baseline and week 6. Fifteen healthy controls were also scanned twice at baseline and week 6 to exclude possible biases. Structural MRI data were preprocessed with FMRIB's Integrated Registration and Segmentation Tool function (FIRST version 1.2) of FSL (FMRIB Software Library; version 4.1.1) to perform subcortical segmentations of the brain using a shape and appearance model. Nonparametric corrections of these structural volumes in an F-test between pre- and post-treatment were used to identify the changes after duloxetine therapy. A false discovery correction of the F-test by FIRST was also performed. A paired t-test using SPSS was applied to confirm the changes in these structures. The patients had consistent changes of volumes in bilateral nucleus accumbens, left putamen, left hippocampus and brainstem after 6 weeks of treatment with duloxetine. There were no consistent changes in other subcortical structures. There were modest increases of the volumes of the above areas, which were not significant after false discovery correction by FIRST F-test comparisons. The volumetric increases were correlated with responses of clinical symptoms. The results suggested that duloxetine possibly contributed to modest increases in several subcortical areas of these patients with remission.     

Association of high BMI with subclinical hypothyroidism in young,first-episode and drug-naïve patients with major depressive disorder: a large-scale cross-sectional study

European Archives of Psychiatry and Clinical Neuroscience - Thyroid dysfunction is known to be associated with obesity, but the reliability of this relationship is easily affected by drug...     

Are metabolic indices different between drug-naïve first-episode psychosis patients and healthy controls?

OBJECTIVE: To compare glucose and lipid metabolism parameters between drug-na?ve first-episode psychosis (FEP) patients with a diagnosis of schizophrenia spectrum disorder and healthy controls matched for age, ethnicity, and gender. METHOD: Baseline evaluations of fasting glucose and lipid metabolism parameters and the oral glucose tolerance test were performed with FEP patients (n=38), having no more than 10 days of cumulative exposure to antipsychotic medication, and normal community controls (n=36). Analysis of variance (ANOVA) was conducted to examine between group differences. RESULTS: FEP patients did not show a higher prevalence of the precursors to diabetes (impaired fasting glucose, impaired glucose tolerance, insulin resistance), and no significant difference in beta-cell function or lipid profile measures, compared to healthy controls. FEP patients showed a higher waist to hip ratio compared to controls. CONCLUSIONS: FEP patients having a schizophrenia spectrum disorder do not differ from healthy controls, in their baseline measures of glucose and lipid metabolites, nor in the prevalence of diabetes or its precursors, before (or close to) the onset of antipsychotic treatment.     

Striatal volume abnormalities in treatment-naïve patients diagnosed with pediatric major depressive disorder

OBJECTIVE: The striatum, including the putamen and caudate, plays an important role in executive and emotional processing and may be involved in the pathophysiology of mood disorders. Few studies have examined structural abnormalities of the striatum in pediatric major depressive disorder (MDD) patients. We report striatal volume abnormalities in medication-na?ve pediatric MDD compared to healthy comparison subjects. METHOD: Twenty seven medication-na?ve pediatric Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) MDD and 26 healthy comparison subjects underwent volumetric magnetic resonance imaging (MRI). The putamen and caudate volumes were traced manually by a blinded rater, and the patient and control groups were compared using analysis of covariance adjusting for age, sex, intelligence quotient, and total brain volumes. RESULTS: MDD patients had significantly smaller right striatum (6.0% smaller) and right caudate volumes (7.4% smaller) compared to the healthy subjects. Left caudate volumes were inversely correlated with severity of depression in MDD subjects. Age was inversely correlated with left and right putamen volumes in MDD patients but not in the healthy subjects. CONCLUSIONS: These findings provide fresh evidence for abnormalities in the striatum of medication-na?ve pediatric MDD patients and suggest the possible involvement of the striatum in the pathophysiology of MDD.     

Prolactin levels in drug-naïve patients with schizophrenia and other psychotic disorders

Objective: Hyperprolactinaemia as a side effect of dopamine receptor blockers is common in patients with schizophrenia and other psychotic disorders and may lead to amenorrhoea, galactorrhoea, hypogonadism, subfertility and osteoporosis. The aim of our study was to determine whether hyperprolactinaemia occurs also in patients with schizophrenia and other psychotic disorders prior to any antipsychotic treatment.

Methods: Serum prolactin, thyroid-stimulating hormone (TSH), triiodothyronine (T3), free tetraiodothyronine (FT4) and cortisol levels were measured in 40 newly diagnosed, drug naïve, patients with schizophrenia and other psychotic disorders and in 40 age and gender matched healthy subjects.

Results: The median prolactin value was 12.5?ng/ml (range: 2–38?ng/ml) for patients and 8.6?ng/ml (range: 4–17.6?ng/ml) for healthy subjects (p?=?0.011). Patients had lower levels of T3 compared to healthy controls (mean: 1.08?ng/ml, SD: 0.16 vs. 1.18?ng/ml, 0.18, respectively; p?=?0.008). Serum TSH, FT4 and cortisol levels were similar between the two groups. Multiple regression analysis revealed that the difference in serum prolactin values was independent of thyroid function (TSH, FT4, T3) and serum cortisol levels.

Conclusions: A higher serum prolactin level was found in drug naïve, newly diagnosed patients with schizophrenia and other psychotic disorders compared to healthy controls, prior to starting any antipsychotic treatment.     

Platelet serotonin uptake in drug-naïve depressive patients before and after treatment with citalopram

We investigated the kinetic parameters of serotonin (5-HT) uptake into platelets in a group of 26 drug-na?ve patients suffering from major depression before and after 3-7 weeks of treatment with citalopram. The degree of depression was rated using the Hamilton Depression Rating Scale (HDRS). The 5-HT uptake characteristics in untreated depressive patients were not significantly different from those of normal subjects. The apparent Michaelis constant (K(M)) was significantly increased, the apparent maximal velocity (V(max)) was not different from baseline, and the uptake efficiency (V(max)/K(M)) was significantly decreased after citalopram treatment. A significantly positive correlation between K(M) and V(max) was found in all groups. There was a significantly lower V(max) and V(max)/K(M) in the female compared with the male depressed patients before citalopram treatment; a hypothesis was supported that lowered 5-HT uptake may reflect a gender-linked vulnerability to a serotonin-related depression. A significant negative correlation between 5-HT uptake efficiency and the initial HDRS score suggests that platelet 5-HT uptake can be used as a marker of effective depressive disorder pharmacotherapy. The initial severity of depression was significantly negatively correlated with V(max), which supported a hypothesis that the initial severity of depressive disorder could be related to the lower V(max).     

Frequency-specific altered global signal topography in drug-naïve first-episode patients with adolescent-onset schizophrenia

Adolescent-onset schizophrenia (AOS) is a severe neuropsychiatric disease associated with frequency-specific abnormalities across distributed neural systems in a slow rhythm. Recently, functional magnetic resonance imaging (fMRI) studies have determined that the global signal. (GS) is an important source of the local neuronal activity in 0.01–0.1 Hz frequency band. However, it remains unknown whether the effects follow a specific spatially preferential pattern in different frequency bands in schizophrenia. To address this issue, resting-state fMRI data from 39 drug-naïve AOS patients and 31 healthy controls (HCs) were used to assess the changes in GS topography patterns in the slow-4 (0.027–0.073 Hz) and slow-5 bands (0.01–0.027 Hz). Results revealed that GS mainly affects the default mode network (DMN) in slow-4 and sensory regions in the slow-5 band respectively, and GS has a stronger driving effect in the slow-5 band. Moreover, significant frequency-by-group interaction was observed in the frontoparietal network. Compared with HCs, patients with AOS exhibited altered GS topography mainly located in the DMN. Our findings demonstrated that the influence of the GS on brain networks altered in a frequency-specific way in schizophrenia.

     

Alterations in functional network centrality in first-episode drug-naïve adolescent-onset schizophrenia

Brain Imaging and Behavior - Schizophrenia is a disorder resulting from aberrant brain networks and circuits. In the current study, we aimed to investigate specific network alterations in...     

Lowered zinc and copper levels in drug-naïve patients with major depression: Effects of antidepressants,ketoprofen and immune activation

Abstract

Objectives: The aim of the present work is to examine the effects of treatment with sertraline with and without ketoprofen on serum levels of zinc and copper in association with immune-inflammatory biomarkers in drug-naïve major depressed patients.

Methods: We measured serum zinc and copper, interleukin (IL)-1β, IL-4, IL-6, IL-18, interferon-γ, and transforming growth factor-β1 in 40 controls and 133 depressed patients. The clinical efficacy of the treatment was measured using the Beck Depression Inventory-II (BDI-II) at baseline and 8?weeks later.

Results: We found significantly reduced serum zinc and copper in association with upregulation of all cytokines, indicating activation of the immune-inflammatory responses system (IRS) and the compensatory immune regulatory system (CIRS). Treatment with sertraline significantly increased zinc and decreased copper. During treatment, there was a significant inverse association between serum zinc and immune activation. The improvement in the BDI-II during treatment was significantly associated with increments in serum zinc coupled with attenuation of the IRS/CIRS.

Conclusions: Lower zinc is a hallmark of depression, while increments in serum zinc and attenuation of the immune-inflammatory response during treatment appear to play a role in the clinical efficacy of sertraline.     

Apathy in drug-naïve patients with Parkinson's disease

ObjectiveThe aim of this study is to explore the prevalence and clinical correlates of apathy in early-stage Parkinson's disease (PD) from a cohort of Chinese patients.MethodsA cross-sectional analysis of 133 treatment-naive PD patients was conducted. Each subject was categorized as PD with or without apathy using the Lille Apathy Rating Scale (LARS).ResultsOf 133 patients, 30 PD patients (22.56%) reported apathy, of whom 23 (17.29%) did not have concomitant depression. The stepwise binary logistic regression model indicated that the lower Frontal assessment battery (FAB) score (OR = 0.623, 95% CI = 0.466–0.834, P = 0.001), the higher sleep/fatigue score from the Non-Motor Symptoms Scale (NMSS) (OR = 1.171, 95% CI = 1.071–1.279, P = 0.001), the higher Hamilton Depression Rating Scale including 24 items (HAMD-24) score (OR = 1.112, 95% CI = 1.005–1.230, P = 0.039) and the higher Unified Parkinson's Disease Rating Scale (UPDRS) part III score (OR = 1.119, 95% CI = 1.045–1.198, P = 0.001) were associated with apathy. No significant associations were found between apathy and other parameters such as age, sex distribution, disease duration, anxiety, Fatigue Severity Scale (FSS) score, Montreal Cognitive Assessment (MOCA) score and remaining domain scores for NMSS.ConclusionsApathy is not rare (22.56%) in Chinese treatment-naïve PD patients. Apathy in PD is not only related to the severity of motor symptoms of the disease but also to some non-motor symptoms, such as executive dysfunction, depression and sleep disturbances.     

Altered amygdala resting-state functional connectivity following acupuncture stimulation at BaiHui (GV20) in first-episode drug-Naïve major depressive disorder

Amygdala is an important locus of dysfunction implicated in major depressive disorder(MDD). Aberrant amygdala networks(AN) had been reported in resting-state functional magnetic resonance imaging (rs-fMRI) study. The safety and efficacy of acupuncture treatment for MDD have been verified in previous clinical studies. This study is aimed to investigate whether acupuncture at GV20 could modulate the abnormal AN of patients with the first-episode, drug-naïve MDD by using rs-fMRI combined with functional connectivity (FC) method. Thirty MDD patient underwent 6-min rs-fMRI scans respectively before and after 20-min electro-acupuncture stimulate(EAS) at GV20. Twenty-nine healthy subjects underwent only a 6-min rs-fMRI scan. Based on the amygdala as the seed region, FC method was adopted to examine abnormal AN in patients by comparing with healthy subjects and to evaluate the influence of EAS on intrinsic connectivity within the AN in patients with MDD. Compared to healthy subjects, MDD patients had aberrant intrinsic AN which mainly showed increased FC between amygdala and hippocampus, precuneus, precentral gyrus and angular gyrus, as well as decreased FC between amygdala and orbital frontal cortex(OFC). Moreover, our results indicated that EAS at GV20 induced increased/decreased FC between amygdala and certain regions in MDD patients. In addition, the intrinsic amygdala FC within other certain brain regions in MDD patients were regulated by EAS at GV20. The abnormal AN of MDD patients could be modulated by EAS at GV20. Our findings may further provide the potential imaging evidence to support the modulatory mechanisms of acupuncture on MDD.

     

Serum brain-derived neurotrophic factors in Taiwanese patients with drug-naïve first-episode schizophrenia: Effects of antipsychotics

Objectives: Brain-derived neurotrophic factors (BDNF) are known to be related to the psychopathology of schizophrenia. However, studies focussing on drug-naïve first-episode schizophrenia are still rare.

Methods: Over a 5-year period, we investigated the serum BDNF levels in patients with first-episode drug-naïve schizophrenia and compared them to age- and sex-matched healthy controls. We also explored the association between antipsychotic doses, positive and negative syndrome scale (PANSS) scores, and serum BDNF levels before and after a 4-week antipsychotic treatment.

Results: The baseline serum BDNF levels of 34 patients were significantly lower than those of the controls (df?=?66, P?=?.001). Although the PANSS scores of 20 followed-up patients improved significantly after antipsychotic treatment, the elevation of the serum BDNF levels was not statistically significant (P?=?.386). In addition, Pearson’s correlation test showed significant correlations between pre-treatment negative scale scores and percentage changes in BDNF (P?=?.002).

Conclusions: The peripheral BDNF levels in Taiwanese patients with drug-naïve first-episode schizophrenia, compared with healthy controls, did not elevate after antipsychotic treatment, and pre-treatment negative symptoms played a pivotal role in trajectories of serum BDNF levels. Large samples will be needed in future studies to verify these results.