Effect of treatment on serum brain–derived neurotrophic factor levels in depressed patients

Researchers have reported that serum brain–derived neurotrophic factor (sBDNF) of drug–free depressed patients are lower than those of healthy controls and proposed that low sBDNF levels might reflect failure of neuronal plasticity in depression. In this study, we compared sBDNF levels of depressed patients (n = 28) before and after 8 weeks of antidepressant treatment, with those of healthy controls (n = 18) to test the hypothesis that initially low sBDNF levels of drug–free depressed patients will increase parallel with their clinical response to antidepressant treatment. The severity of depression and response to treatment were assessed with Hamilton Rating Scale for Depression (HAM–D). sBDNF was assayed with the sandwich ELISA method. Baseline sBDNF levels of patients (mean, 20.8 ng/ml; [S.D., 6.7]) were significantly lower than those of controls (mean, 26.8 ng/ml; [S.D., 9.3]; p = 0.015), and were negatively correlated with HAM–D scores (r = –0.49, p = 0.007). After 8 weeks of treatment, sBDNF levels of patients had increased significantly (mean, 33.3 ng/ml; [S.D., 9.9]; p < 0.001) and no longer differed from those of controls. These results support the hypothesis that BDNF might play a critical role in the pathophysiology of major depressive disorder and successful antidepressant treatment increases the attenuated BDNF levels in depressed patients.     

Effect of antidepressant treatment on water load test and cortlsol changes in patients with functional dyspepsia

BACKGROUND: It has been demonstrated that patients with functional dyspepsia have experiences social life stress events, and accompanied by psychological disorders, mainly manifested as depression and anxiety. Mental factors can lead to excessive gastrointestinal consensual reaction, and result in different brain-gut axis disturbance, and then cause the gastrointestinal sensorimotor abnormality and endocrine changes. OBJECTIVE: To observe the effect of antidepressant treatment on the changes of water load and serum cortisol in patients with functional dyspepsia, and analyze the therapeutic mechanism. DESIGN: A comparative observation. SETTING: The First Affiliated Hospital o Zhengzhou University. PARTICIPANTS: Forty-five patients with functional dyspepsia accompanied by depression were selected from the Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University from July 2004 to July 2006, and they were 25–65 years of age, and their disease courses ranged 1–10 years. They were all accorded with the diagnostic standards for RomeⅡfunctional dyspepsia functional dyspepsia. As the patients' will, they were divided into treatment group (n =30, 12 males and 18 females) and control group (n =15, 6 males and 9 females), and there were no significant differences in the data between the two groups (P > 0.05). The programs were discussed and agreed by the committee of medical ethics of the First Affiliated Hospital of Zhengzhou University. Informed contents were obtained from all the patients. METHODS: In the treatment group, the patients were treated with venlafaxine sustained release capsule (75 mg per day), and those with sleep disorder were added by benzodiazepines (alprazolam). In the control group, the patients were given routine treatments of antacid, prokinetics, etc. Before and after 8-week treatment, the following examinations were performed: ① The gastrointestinal symptoms were assessed according to the symptoms; ② The severity of depression was evaluated with Hamilton depression scale (HAMD); ③The relaxation of proximal stomach was observed using water load test; ④ The serum level of cortisol was detected. MAIN OUTCOME MEASURES: ① Symptom score; ② HAMD score; ③ Water load amount; ④ Serum level of cortisol. RESULTS: All the 45 patients were involved in the analysis of results. ① Symptom score: The scores of gastrointestinal symptoms were decreased as compared with those before treatment in both the treatment group and control group (P < 0.05). ② HAMD scores: The scores of HAMD were decreased as compared with those before treatment in both the treatment group and control group (P < 0.05). ③ Water load amount: The total effective rate was significantly higher in the treatment group than the control group (P < 0.05). ④ The serum levels of cortisol after treatment were significantly lower than those before treatment in the patients with severe gastrointestinal symptoms in the treatment group and control group (P < 0.05). CONCLUSION: Antidepressants can normalize the cortisol level of patients with functional dyspepsia, and then decrease gastric sensitivity and ameliorates the receptive relaxation of proximal stomach, also increase the water load amount correspondingly, and finally control the gastrointestinal symptoms of functional dyspepsia.     

Femoxetine in the treatment of patients with depressive illness–a randomized comparison with amitriptyline

The significance of the antidepressants' serotonin-potentiating properties in relationship to the therapeutic effect has been one of the key research areas within depression during the last decades.

On this basis a number of drugs with more selective influence on the serotonin system has been developed and the following study is a controlled clinical evaluation of femoxetine, a phenylpiperidine derivative with potent serotonin-potentiating properties in patients suffering from a depressive illness.     

HPA axis activation determined by the CRH challenge test in patients with few versus multiple episodes of treatment–refractory depression

Objective In clinical guidelines, risk factors for a malignant illness course include 3 or more lifetime episodes of depression. Our aim was to investigate the activation of the hypothalamic–pituitary–adrenal hormonal axis in treatment–refractory affective disorder in pauciepisodic (one or two episodes) versus multiepisodic (three or more episodes) patients. Methods We evaluated the HPA axis in 37 patients with treatment–refractory affective disorder and in 27 healthy volunteers by measuring adrenocorticotropin hormone (ACTH) and cortisol responses following administration of corticotropin–releasing hormone (CRH). In retrospective life charts was recorded every previous illness episode for each patient. Results Seven of the patients were pauciepisodic and 30 were multiepisodic. The pauciepisodic patients had significantly larger peak and total ACTH responses to CRH compared to the multiepisodic patients as well as to the control group. Multiepisodic patients showed no difference compared to controls in ACTH secretion pre- and post–CRH. Cortisol secretion was the same in all three groups. Conclusions The pituitary adrenocortical responses were stronger in pauciepisodic patients than in multiepisodic patients and in volunteers. This cross–sectional study suggests that the HPA axis, in refractory multiepisodic affective disorders, might weaken its original activity as the illness recurs with more episodes.     

The neurosurgical treatment of patients in dystonic state – Overview of the literature

Treatment options for patients in dystonic state include sedation, artificial ventilation, intrathecal baclofen infusions and stereotactic procedures. The main aim of this overview is the presentation and assessment of stereotactic procedures applied for treating patients in severe dystonic state. We performed literature overview starting from 1998 to 2012 with case reports regarding all patients treated by stereotactic procedures for dystonic state. We were able to find 15 articles describing 22 patients. Ablative procedures were described in 5 articles (3 thalamotomies, 3 pallidotomies) and were done in 6 patients. In the remaining 10 articles, globus pallidus internus stimulation was utilized in another 16 patients. We can conclude that bilateral pallidal deep brain stimulation seems to be the best stereotactic target for patients in dystonic state.     

Glycogen synthase kinase-3β in the platelets of patients with mood disorders: Effect of treatment

Glycogen synthase kinase (GSK)-3β, an important component of the Wnt signaling pathway, is involved in numerous cellular functions. That GSK-3β may be involved in the pathophysiology of bipolar (BP) illness is based on the observation that lithium, a mood-stabilizing drug, inhibits GSK-3β both in vitro and in vivo.We determined the protein expression of GSK-3β in the cytosol and membrane fractions of the platelets obtained from patients with major depressive disorder (MDD) and BP illness, before treatment and after treatment with antidepressants or mood-stabilizing drugs, respectively. Protein expression was determined using the Western blot technique.We observed that the protein expression of GSK-3β was significantly reduced in the membrane and cytosol fractions of platelets from drug-free patients with BP illness, but not from the drug-free patients with MDD, compared with normal control subjects. Treatment with mood-stabilizing drugs significantly increased the protein expression of GSK-3β in the membrane and cytosol fractions of platelets from BP patients compared with pre-treatment levels, and the post-treatment levels were similar to those observed in normal control subjects. On the other hand, there was no significant effect of treatment with antidepressants on GSK-3β protein expression either in the membrane or in the cytosol fractions of platelets from MDD patients.These results suggest that GSK-3β may play an important role in the pathophysiology of BP illness but not MDD and that its abnormality may be corrected by treatment with mood-stabilizing drugs, suggesting that GSK-3β may be a state rather than a trait marker for BP illness.     

The relationship of neuropsychological test performance with the PANSS in antipsychotic naïve, first-episode psychosis patients

The NIMH-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative requires, among other things, the establishment of a reliable, valid, and consensus-derived method of assessing cognition. The derived battery will provide a standardized way to assess the effects of cognition-enhancing agents across clinical trials. To this end, the first of six consensus-oriented conferences was held April 2003. The goals were twofold: (a) To select which cognitive constructs to measure in a consensus battery, and (b) to select which criteria to use in evaluating tests for inclusion in the battery. Based on consultation with experts on the RAND Panel Method, 74 experts were invited to participate in a pre-meeting survey to provide information relevant to decisions on the cognitive battery. The survey included sections on reliability, validity, test administration, norms and interpretation of tests, cognitive domains and their integration, battery duration, and overall importance of test qualities. For selection of cognitive targets, the results showed that experts ranked executive functions, attention/vigilance, memory processes, and problem-solving ability highest. For test qualities, the experts ranked test-retest reliability, good coverage of key individual cognitive constructs, and comparable alternate forms highest. This article presents the results of the pre-conference survey that was the first step in the RAND process towards development of the NIMH-MATRICS consensus battery to assess cognition in schizophrenia.     

Efficacy of semantic–phonological treatment combined with tDCS for verb retrieval in a patient with aphasia

Recent studies reported enhanced performance on language tasks induced by transcranial direct current stimulation (tDCS) in patients with aphasia. One chronic patient with non-fluent aphasia received 20 sessions of a verb anomia training combined with off-line bihemispheric tDCS applied to the dorsolateral prefrontal cortex (DLPFC) – anodal tDCS over left DLPFC plus cathodal tDCS over right DLPFC. A significant improvement in verb naming was observed at all testing times (4, 12, 24, and 48 weeks from post-entry/baseline testing) for treated and untreated verbs. Our findings show beneficial effects of verb anomia training in combination with tDCS in chronic aphasic patient, suggesting a long-lasting effect of this treatment.     

The influence of visual and auditory information on the perception of speech and non‐speech oral movements in patients with left hemisphere lesions

Patients with lesions of the left hemisphere often suffer from oral‐facial apraxia, apraxia of speech, and aphasia. In these patients, visual features often play a critical role in speech and language therapy, when pictured lip shapes or the therapist's visible mouth movements are used to facilitate speech production and articulation. This demands audiovisual processing both in speech and language treatment and in the diagnosis of oral‐facial apraxia. The purpose of this study was to investigate differences in audiovisual perception of speech as compared to non‐speech oral gestures. Bimodal and unimodal speech and non‐speech items were used and additionally discordant stimuli constructed, which were presented for imitation. This study examined a group of healthy volunteers and a group of patients with lesions of the left hemisphere. Patients made substantially more errors than controls, but the factors influencing imitation accuracy were more or less the same in both groups. Error analyses in both groups suggested different types of representations for speech as compared to the non‐speech domain, with speech having a stronger weight on the auditory modality and non‐speech processing on the visual modality. Additionally, this study was able to show that the McGurk effect is not limited to speech.     

The influence of insulin infusion on the metabolism of amyloid β peptides in plasma

BackgroundAccumulating body of evidence suggests pathophysiologic links between Alzheimer’s disease and diabetes mellitus (DM). For example, the two crucial peptides playing a role in both degenerative disorders, amyloid β (Aβ) and insulin, are metabolized by the same enzyme, insulin degrading enzyme. Euglycemic hyperinsulinemic clamp is a method of estimating insulin sensitivity, based on the assumption that during steady-state hyperinsulinemic euglycemia, glucose infusion rate equals tissue glucose uptake, that is, the higher the glucose infusion rate, the higher the insulin sensitivity.ObjectiveThe aim of this study was to analyze the influence of insulin on the plasma concentrations of Aβ peptides.MethodsBlood samples were collected from 20 healthy young male volunteers before insulin infusion (clamp) and then at 120 and 360 minutes. In the second protocol, insulin was accompanied by Intralipid, which is mainly a mixture of triacylglycerols, and heparin, given as an activator of lipoprotein lipase, inducing insulin resistance. Analyses of plasma Aβ1-42, Aβx-42, Aβ1-40, and Aβx-40 were performed with multiplexing technology. Furthermore, concentrations of the Aβ peptides in healthy persons were compared with those in 16 type 1 DM patients receiving chronic insulin therapy.ResultsWhen applied alone (i.e., without Intralipid), insulin infusion increased concentrations of Aβ42 (full length and N-terminally shortened) but not of Aβ40. When combined with Intralipid, infusion of insulin resulted in increased concentrations of all peptides (nonsignificant tendency in case of Aβx-40). We did not observe differences between Aβ peptide concentrations in healthy subjects and those in type 1 DM patients.ConclusionInfusion of insulin in nonphysiologic high doses increases plasma concentrations of Aβ peptides; in case of Aβ40, only when applied together with Intralipid, which perhaps might be explained by hypothetical shift of insulin degrading enzyme activity from degradation of Aβ peptides to the degradation of insulin.     

The influence of impaired processing speed on cognition in first-episode antipsychotic-naïve schizophrenic patients

BackgroundImpaired cognition is a prominent feature of schizophrenia. To what extent the heterogeneous cognitive impairments can be accounted for by considering only a single underlying impairment or a small number of core impairments remains elusive. This study examined whether cognitive impairments in antipsychotic-naïve, first-episode schizophrenia patients may be determined by a relative slower speed of information processing.MethodForty-eight antipsychotic-naïve patients with first-episode schizophrenia and 48 matched healthy controls were administered a comprehensive battery of neuropsychological tests to assess domains of cognitive impairments in schizophrenia. Composite scores were calculated, grouping tests into cognitive domains.ResultsThere were significant differences between patients and healthy controls on global cognition and all cognitive domains, including verbal intelligence, processing speed, sustained attention, working memory, reasoning and problem solving, verbal learning and memory, visual learning and memory, and reaction time. All these significant differences, except for verbal intelligence and global cognition, disappeared when processing speed was included as a covariate.ConclusionAt the first stage of illness, antipsychotic-naïve patients with schizophrenia display moderate/severe impairments in all the cognitive domains assessed. The results support the contention of a global cognitive dysfunction in schizophrenia that to some extent may be determined by impaired processing speed.     

Predictors of treatment response to pharmacotherapy in patients with persistent postural–perceptual dizziness

Journal of Neurology - The study aimed to identify the predictors of response to selective serotonin reuptake inhibitors (SSRIs) for 12&nbsp;weeks in patients with persistent...     

The neuroprotective effect of the GSK-3β inhibitor and influence on the extrinsic apoptosis in the ALS transgenic mice

The age-related neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases are characterized by the abnormal accumulation or aggregation of proteins. Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. The formation of AGEs promotes the deposition of proteins due to the protease resistant crosslinking between the peptides and proteins. Several proteins implicated in neurodegenerative diseases such as amyloid β, tau, α-synuclein, and prions are glycated and the extent of glycation is correlated with the pathologies of the patients. These data suggest that AGEs contribute to the development of neurodegenerative diseases. In this review we summarize recent advances on the investigation of the roles of AGEs in neurodegenerative diseases, with special focus on Alzheimer's and Parkinson's diseases. It is clear that AGEs modification triggers the abnormal deposition and accumulation of the modified proteins, which in turn sustain the local oxidative stress and inflammatory response, eventually leading to the pathological and clinical aspects of neurodegenerative diseases. Further characterization of the molecular mechanisms responsible for AGEs mediated neurotoxicity will provide important clues on the development of novel strategies for the prevention and treatment of neurodegenerative diseases.     

The influence of intrapersonal sensorimotor experiences on the corticospinal responses during action–observation

The coupling of perception and action has been strongly indicated by evidence that the observation of an action primes a response in the observer. It has been proposed that these primed responses may be inhibited when the observer is able to more closely distinguish between self- and other-generated actions – the greater the distinction, then the greater the inhibition of the primed response. This self–other distinction is shown to be enhanced following a period of visual feedback of self-generated action. The present study was designed to examine how sensorimotor experiences pertaining to self-generated action affect primed responses from observed actions. Single-pulse transcranial magnetic stimulation was used to investigate corticospinal activity elicited during the observation of index- and little-finger actions before and after training (self-generated action). For sensorimotor training, participants executed finger movements with or without visual feedback of their own movement. Results showed that the increases in muscle-specific corticospinal activity elicited from action–observation persisted after training without visual feedback, but did not emerge following training with visual feedback. This inhibition in corticospinal activity during action–observation following training with vision could have resulted from the refining of internal models of self-generated action, which then led to a greater distinction between “self” and “other” actions.     

Error processing in patients with Parkinson’s disease: the influence of medication state

Summary. One of the hallmarks of Parkinson’s disease (PD) is a depletion of dopamine. Error processing, as reflected in a component of the event-related potential, the so-called error (related) negativity (Ne or ERN) is likely dependent on the midbrain dopaminergic system. In case of an unfavourable event such as an error, this system is assumed to send an error signal to the mediofrontal cortex, which elicits the Ne. Hence, the Ne should be altered in patients with PD. In fact, we earlier found a reduction of the Ne in medicated patients with PD in different tasks while another group found no such reduction in “off-medication” patients in a flanker task. In the present study, we reinvestigated this issue by measuring the Ne in a large group of treated PD patients in the “on”- and “off”-parkinsonian medication state and in matched control subjects in a flanker task. The Ne was found to be the same in the “on-medication” and “off-medication” state, while the motor score in the Unified Parkinson’s Disease Rating Scale was different. In both medication states the Ne was smaller in the patients than in the controls. The results show that the Ne reduction found earlier is unaffected by short-term differences in parkinsonian medication. The question remains open whether the long-term medication could have contributed to the Ne reduction. Correspondence: Rita Willemssen, Leibniz Research Centre of Working Environment and Human Factors (IfADo), Ardeystr. 67, 44139 Dortmund, Germany