Ventricular Netrin-1 deficiency leads to defective pyramidal decussation and mirror movement in mice.

The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.

Clinical application of repetitive transcranial magnetic stimulation for post-traumatic stress disorder: A literature review.

The efficacy of traditional treatment for post-traumatic stress disorder (PTSD) is still unsatisfactory. Repetitive transcranial magnetic stimulation (rTMS) has been widely used in the treatment of various types of mental disorders, including PTSD. Although rTMS has been demonstrated to be effective in many cases, there are still arguments regarding its mechanism and protocol. This review aims to summarize the origin, development, principle, and future direction of rTMS and introduce this neuro-stimulation therapy to relevant clinicians.

A shared effect of paroxetine treatment on gray matter volume in depressive patients with and without childhood maltreatment: A voxel-based morphometry study.

AIMS: This study assessed whether antidepressant drug treatment has a common effect on gray matter (GM) volume in MDD patients with and without childhood maltreatment (CM). METHODS: T1-weighted structural magnetic resonance imaging data were collected from 168 participants, including 51 MDD patients with CM, 31 MDD patients without CM, 48 normal controls with CM, and 38 normal controls without CM. MDD patients received 6 months of treatment with paroxetine, and 24 patients with CM, and 16 patients without CM received a second MRI scan. A whole-brain voxel-based morphometry approach was used to estimate GM volume in each participant at two time points. Two-way analysis of variance (ANOVA) was used to determine the effects of MDD and CM on GM volume at baseline. Repeated measures two-way ANOVA was used to determine the treatment-by-CM interactive effect and main effect of treatment during paroxetine treatment. We further investigated the relationship between GM volume and clinical variables. RESULTS: At baseline, significant MDD-by-CM interactive effects on GM volume were mainly observed in the left parahippocampal gyrus, left entorhinal cortex, and left cuneus. GM volume was significantly lower mainly in the right middle temporal gyrus in patients with MDD than in normal controls. We did not find any significant treatment-by-CM interactive effects. However, a treatment-related increase in GM was found in the right middle temporal gyrus in both MDD groups. CONCLUSIONS: These results suggest that paroxetine treatment operates via a shared neurobiological mechanism in MDD patients with and without CM.

Abnormalities of cortical-limbic-cerebellar white matter networks may contribute to treatment-resistant depression: a diffusion tensor imaging study.

BACKGROUND: White matter abnormalities can cause network dysfunction that underlies major depressive disorder (MDD). Diffusion tensor imaging (DTI) is used to examine the neural connectivity and integrity of the white matter. Previous studies have implicated frontolimbic neural networks in the pathophysiology of MDD. Approximately 30% of MDD patients demonstrate treatment-resistant depression (TRD). However, the neurobiology of TRD remains unclear. METHODS: We used a voxel-based analysis method to analyze DTI data in young patients with TRD (n = 30; 19 males, 11 females) compared with right-handed, age- and sex-matched healthy volunteers (n = 25; 14 males, 11 females). RESULTS: We found a significant decrease in fractional anisotropy (FA) (corrected, cluster size >50) in the left middle frontal gyrus (peak coordinates [-18 46-14]), left limbic lobe uncus (peak coordinates [-18 2-22]), and right cerebellum posterior lobe (peak coordinates [26-34 -40]). There was no increase in FA in any brain region in patients. We also found a significant negative correlation between mean regional FA values in the three areas and Beck Depression Inventory symptom scores. CONCLUSIONS: We found significant differences in white matter FA in the frontal lobe, limbic lobe and cerebellum between TRD patients and controls. These data suggest that abnormalities of cortical-limbic-cerebellar white matter networks may contribute to TRD in young patients.

[Prevalence and risk factors for posttraumatic stress disorder among survivors from a coal mining accident after 2 and 10 months].

OBJECTIVE: To investigate the prevalence of posttraumatic stress disorder (PTSD) among survivors from a coal mining accident after 2 and 10 months and factors related to PTSD. METHODS: To estimate the prevalence of PTSD, 104 miners were surveyed through the PTSD Checklist-Civilian Version (PCL-C). Forty survivors including 24 severe PTSD patients and 24 non-PTSD subjects were evaluated thoroughly. RESULTS: The current prevalence rate among survivors from the coal mining accident at 2 months was 50%. There were significant differences in PTSD symptoms, anxiety and depression, personality, and memory performance between the PTSD patients and non-PTSD controls. State anxiety, time to renew the work, depression, neuroticism, and the place they were staying, and length of service were predictors of PTSD. After 10 months of the accident, 30.6% survivors still met the criterion of PTSD. Compared with 2 months after the accident, PTSD symptoms, anxiety, and memory performance improved clearly, while the depressive symptoms had no significant difference. The state anxiety, time to renew the work, positive coping, emotional balance, and length of service were the factors of PTSD symptom healing. CONCLUSION: The current prevalence of PTSD among survivors from coal mining accident is high. The mining accident has great influence on victims, and psychological or medication interventions are necessary. There are lots of risk factors for the prevalence of PTSD, such as state anxiety, depression, neuroticism, and shorter duration of service. Positive coping may be a beneficial factor for PTSD recovery.

[Effect of 5-HT and postsynaptic 5-HT1 A on the mood and recogniztion of the repeated restraint stress in rats].

OBJECTIVE: To explore the role of 5-HT and postsynaptic 5-HT1A receptors in the stress adaptation. METHODS: p-PCA was used to deplete the 5-HT in rats. The 5-HT1A agonist 8-OH-DPAT and antagonist WAY100635 were used to determine the effect of postsynaptic 5-HT1A receptors on the ratso behaviors in the Elevated Plus-Maze test, the Forced Swimming test, and the Morris Water Maze test. RESULTS: Compared with the intact rats, the 5-HT depleted rats showed more seriously anxious behaviors in the Elevated Plus-Maze test and more obvious learned helplessness in the Forced Swimming test. After having been stressed the 5-HT depleted rats showed significantly impaired learning and memory compared with the intact rats according to Morris Water Maze test. Activation of postsynaptic 5-HT1A receptors by 8-OH-DPAT in the 5-HT depleted rats or the 5-HT depleted stress rats significantly decreased the symptoms of anxiety and learned helplessness behaviors which were prevented by the treatment of WAY100635. The 8-OH-DPAT and WAY100635 had no obvious effect on the 5-HT depletion or 5-HT depleted stress rats in the Morris Water Maze test. CONCLUSION: Deficiency of 5-HT in rats may suppress its ability to stress adaptation. Activation of post-synaptic 5-HT1A receptors can attenuate the anxiety and depressive behavior symptoms, and facilitate rats to adapt stress.

Subsequently enhanced CPP to morphine following chronic but not acute footshock stress associated with corticosterone mechanism in rats.

The purpose of this study was to determine the morphine-induced place preference in rats pre-exposed to footshock stress and corticosterone (CORT). The authors also studied the involvement of dopamine mechanisms in the CORT-induced place preference. The results showed that chronic footshock or CORT exposure but not acute footshock or CORT exposure similarly potentiated the conditioned place preference to morphine. The CORT-induced conditioned place preference were established only with high and middle dose (5, 3 mg/kg) CORT. The dopamine levels in NAc of rats injected with CORT (5, 3, 1 mg/kg, i.p.) increased significantly. The findings suggest that the increase of dopamine levels in NAc induced by CORT might be the medium between stress and morphine.

Lower levels of whole blood serotonin in obsessive-compulsive disorder and in schizophrenia with obsessive-compulsive symptoms.

It has been reported that some schizophrenic patients suffer from obsessive-compulsive symptoms (OCS), and clozapine treatment is quite often associated with an occurrence/increase of OCS in schizophrenic patients. The aim of the study was to explore whether differences would exist in the clinical symptomatology and the whole blood serotonin (5-HT) concentrations in patients with obsessive-compulsive disorder (OCD), schizophrenic patients with and without OCS (S+OCS, S-OCS), and clozapine-treated schizophrenic patients with and without clozapine-induced OCS (CLZ+OCS, CLZ-OCS). We found that S+OCS patients (n=15) showed significantly lower scores on the Hamilton Anxiety Scale (HAMA), but similar levels of compulsions and obsessions using Yale-Brown Obsessive-Compulsive Scale (YBOCS) as compared to the patients (n=35) with OCD. S+OCS patients scored significantly lower on the Positive and Negative Syndrome Scale (PANSS) but higher on the Hamilton Depression Scale (HAMD) compared with S-OCS patients (n=19). However, CLZ+OCS patients (n=15) suffered from dominant compulsions but fewer obsessions compared with the OCD and S+OCS patients. OCD, S+OCS and CLZ+OCS groups had significantly lower levels of whole blood 5-HT than did the healthy volunteers (n=15), S-OCS and CLZ-OCS groups. It suggests that alterations in serotonin metabolism may be a common biological characteristic of OCS in OCD as well as in schizophrenia.