Acta Neuropsychiatrica最新文献

Objectives: The transient receptor potential vanilloid type-1 channel (TRPV1) is expressed in the midbrain periaqueductal grey (PAG), a region of the brain related to aversive responses. TRPV1 antagonism in the dorsolateral PAG (dlPAG) induces anxiolytic-like effects in models based on conflict situations. No study, however, has investigated whether these receptors could contribute to fear responses to proximal threat. Thus, we tested the hypothesis that TRPV1 in the PAG could mediate fear response in rats exposed to a predator.

Methods: We verified whether exposure to a live cat (a natural predator) would activate TRPV1-expressing neurons in the PAG. Double-staining immunohistochemistry was used as a technique to detect c-Fos, a marker of neuronal activation, and TRPV1 expression. We also investigated whether intra-dlPAG injections of the TRPV1 antagonist, capsazepine (CPZ), would attenuate the behavioural consequences of predator exposure.

Results: Exposure to a cat increased c-Fos expression in TRPV1-positive neurons, mainly in the dorsal columns of the PAG, suggesting that TRPV1-expressing neurons are activated by threatening stimuli. Accordingly, local injection of CPZ inhibited the fear responses.

Conclusion: These data support the hypothesis that TRPV1 channels mediate fear reactions in the dlPAG. This may have an implication for the development of TRPV1-antagonists as potential drugs for the treatment of certain psychiatric disorders.

Objectives: Previous studies have demonstrated inconsistent findings regarding the efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) in treating motor symptoms of Parkinson's disease (PD). Therefore, this meta-analysis was conducted to assess the efficacy of low-frequency rTMS.

Methods: A comprehensive literature search (including PubMed, CCTR, Embase, Web of Science, CNKI, CBM-disc, NTIS,EAGLE, Clinical Trials, Current Controlled Trials, International Clinical Trials Registry) was conducted dating until June 2014. The key search terms ('Parkinson', 'PD', 'transcranial magnetic stimulation', 'TMS', 'RTMS' and 'noninvasive brain stimulation') produced eight high-quality randomised controlled trials (RCT) of low-frequency rTMS versus sham stimulation.

Results: These eight studies, composed of 319 patients, were meta-analysed through assessment of the decreased Unified Parkinson's Disease Rating Scale (UPDRS part III) score. Pooling of the results from these RCTs yielded an effect size of -0.40 (95%CI=-0.73 to -0.06, p<0.05) in UPDRS part III, which indicated that low-frequency rTMS could have 5.05 (95%CI=-1.73 to -8.37) point decrease in UPDRS part III score than sham stimulation.

Discussion: Low-frequency rTMS had a significant effect on motor signs in PD. As the number of RCTs and PD patients included here was limited, further large-scale multi-center RCTs were required to validate our conclusions.

Objective: We have made a 2-year follow-up study to evaluate the effect of repeated transcranial pulsating electromagnetic fields (T-PEMF) augmentation in patients who had achieved remission but later on relapsed, as well as to identify factors contributing to treatment-resistant depression in patients who did not respond to T-PEMF.

Methods: Using the Longitudinal Expert Assessment of All Data approach the patients were classified in four groups: A: patients who achieved remission; B: patients with doubtful effect; C: patients with no effect; and D: patients who were hard-to-assess.

Results: In group A, comprising 27 patients, 13 had relapsed; they obtained a clear remission after a repeated course of T-PEMF augmentation. In group D, comprising 16 patients, we identified misdiagnostic factors both concerning the event of remission after the previous T-PEMF augmentation and concerning the aetiology (psychosocial stressors and co-morbid conditions). Compared with the other groups, the group D patients had a smaller number of previous episodes (p=0.09) and a longer duration of the current episode (p=0.01).

Conclusion: T-PEMF has an effect among patients who relapsed after remission with the first series of T-PEMF. Treatment-resistant depression is a condition that has a high degree of multivariate problems. Misuse of alcohol or drugs, severe somatic disorders and other psychosocial problems may need other kinds of treatment before T-PEMF augmentation.

Objective: Severe depression may be a risk factor for diagnostic conversion into bipolar disorder (BD), and psychotic depression (PD) has been consistently associated with BD. The aims of the present study were to investigate the stability of the diagnosis of severe depression and the differences between PD and non-psychotic severe depression (non-PD), as well as to assess the effectiveness of electroconvulsive therapy (ECT).

Methods: Patients who were hospitalised for severe depression (diagnosed according to ICD-10) both with and without psychotic symptoms (n=89; mean age=55.6 years, SD=13.9) from 2001 to 2010 were retrospectively assessed.

Results: By the 75th month of follow-up assessments, 11(12.4%) patients had developed BD. Among these 11 converters, nine had developed BD within 1 year after admission. Only sub-threshold hypomanic symptoms were significantly related to developing BD. The number of depressive episodes and history of physical diseases were significantly increased in non-PD compared with PD patients, whereas ECT was significantly increased in PD compared with non-PD patients. There was a significant association between length of stay at the hospital and the number of days between admission and ECT.

Conclusion: Sub-threshold hypomanic symptoms may represent a prodrome of BD or an indicator of an already manifest phenotype, especially in older patients, which suggests cautious use of antidepressants. In severe depression, non-PD may often occur secondary to physical diseases and patients may experience increased recurrences compared with PD patients, which may be a more 'primary' disorder and often requires ECT treatments. ECT is effective for severe depression regardless of the presence of any psychotic feature; the earlier ECT is introduced, the better the expected treatment outcome.

Objective: Schizophrenia is associated with a reduction of the lifespan by 20 years, with type II diabetes and cardiovascular disease contributing the most to the increased mortality. Unrecognised or silent myocardial infarction (MI) occurs in ~30% of the population, but the rates of unrecognised MI in patients with schizophrenia have only been sparsely investigated.

Method: Electrocardiograms (ECG) from three psychiatric hospitals in Denmark were manually interpreted for signs of previous MI. Subsequently, ECGs were linked to the National Patient Registry in order to determine whether patients had a diagnosis consistent with previous MI.

Results: A total of 937 ECGs were interpreted, 538 men (57.4%) and 399 women (42.6%). Mean age at the time of ECG acquisition was 40.6 years (95% CI: 39.7-41.5, range: 15.9-94.6). We identified 32 patients with positive ECG signs of MIs. Only two of these patients had a diagnosis of MI in the National Patient Registry. An additional number of eight patients had a diagnosis of MI in the Danish National Patient Registry, but with no ECG signs of previous MI. This means that 30 out of 40 (75%) MIs were unrecognised. Only increasing age was associated with unrecognised MI in a stepwise multiple logistic regression model compared with patients with no history of MI, OR: 1.03 per year of age, 95% CI: 1.00-1.06, p=0.021.

Conclusion: Unrecognised MI is common among patients with schizophrenia and may contribute to the increased mortality found in this patient group.

Objective: We investigated whether the nitric oxide (NO) precursor, L-arginine, can prevent the antidepressant-like action of the fast-acting antidepressant, ketamine, in a genetic rat model of depression, and/or induce changes in the glutamate (Glu)/N-methyl-D-aspartate receptor (NMDAR)/NO/cyclic guanosine monophosphate (cGMP) signalling pathway. Hereby it was evaluated whether the NO signalling system is involved in the antidepressant mechanism of ketamine.

Methods: Flinders sensitive line (FSL) rats received single i.p. injections of ketamine (15 mg/kg) with/without pre-treatment (30 min prior) with L-arginine (500 mg/kg). Depression-like behaviour was assessed in the forced swim test (FST) in terms of immobility, and the activation state of the Glu/NMDAR/NO/cGMP pathway was evaluated ex vivo in the frontal cortex and hippocampus regions in terms of total constitutive NOS (cNOS) activity and cGMP concentration.

Results: L-Arginine pre-treatment prevented the antidepressant-like effect of ketamine in the FST, as well as a ketamine-induced increase in cGMP levels in the frontal cortex and hippocampus of FSL rats. Ketamine reduced cNOS activity only in the hippocampus, and this effect was not reversed by L-arginine.

Conclusion: Both the behavioural and molecular results from this study indicate an involvement for the NO signalling pathway in the antidepressant action of ketamine. Although not easily interpretable, these findings broaden our knowledge of effects of ketamine on the NO system.

Background: Dipyrone is one of the most commonly used non-opioid analgesic and antipyretic drug. Its anti-nociceptive and hypothermic effects have long been suspected to be centrally mediated. The involvement of the most recently discovered opioid peptide, nociceptin/orphanin FQ (N/OFQ), and its receptor (NOP) in pain transmission is controversial. It appears to be pro-nociceptive when administered supra-spinally, but exerts anti-nociceptive effects when injected spinally or systemically.

Objective: Investigation of the role of the N/OFQ system in paracetamol-induced anti-nociception and hypothermia led us to determine its role in the anti-nociceptive and hypothermic effects of dipyrone. Material and Methods Hot-plate and tail-flick tests were used to assess nociception, and a rectal thermometer was used to measure rectal temperature in mice.

Results: Mice injected with dipyrone (150, 300, 600 mg/kg, i.p.) displayed dose-related anti-nociception and hypothermia. The NOP receptor antagonist JTC-801 (3 mg/kg, i.p.), at a dose that exerted no effect when used alone, alleviated dipyrone-induced anti-nociception but did not reverse dipyrone-induced hypothermia.

Conclusion: We conclude that NOP receptors participate in the anti-nociceptive, but not in the hypothermic, effects of dipyrone.

Background: Although severe hoarding symptoms have been considered rare among obsessive-compulsive disorder (OCD) samples, the prevalence of animal hoarding in OCD is unknown. To help clarifying this issue, we searched for cases of animal hoarding among patients attending a university OCD clinic (n=420).

Methods: Chart review.

Results: Only two patients from our sample exhibited animal hoarding (<0.5%) and only one of them presented additional obsessive-compulsive symptoms. Both cases also collected inanimate objects, presented low insight, exhibited poor response to serotonin reuptake inhibitors and did not adhere to therapy.

Conclusions: There seems to be a lack of relationship between animal hoarding and OCD. However, further studies with larger numbers of patients are needed to better define their psychopathological profile and more appropriate nosological insertion.

In 1765 Giovanni Morgagni described a syndrome consisting of hyperostosis frontalis interna (HFI), obesity and hirsutism. In 1928 Stewart and in 1930 Morel added neuropsychiatric symptoms, e.g. depression and dementia, which led to the definition of the Morgagni-Stewart-Morel Syndrome (MSM). Although mostly women were characterized in literature no gender specifity is demanded. This case report presents the rare case of a 66 year old male psychiatric patient with Morgagni-Stewart-Morel Syndrome. The patient complained of loss of concentration and difficulties with activities of daily living. Admission diagnosis was an opioid misuse on the basis of a chronic pain syndrome. In this case report we are describing clinical features, the patient history and technical (MRI) and neuropsychological tests. Although severe psychiatric symptoms and neuropsychological deficits are commonly seen in these patients, our patient showed only mild symptoms. This case reports shows the possibility of a male patient with MSM. If MSM is a separate entity or just an epiphenomena of hormone dysregulation should be investigated in further studies.

Objective: Glucagon-like peptide 1 (GLP-1) receptor agonists are a new group of antidiabetic medications quickly gaining popularity. We aimed to examine behavioural and neuroendocrine changes following chronic treatment with GLP-1 receptor agonists in animal models.

Methods: The effects of chronic treatment with GLP-1 receptor agonists were determined on behavioural parameters [anxiety level in the light-dark compartment test, the motor activity in automated activity cages, immobility in the forced swimming test (FST)] and on corticosterone release in mice. The possible antidepressant effect of chronic liraglutide treatment was also studied in Flinders Sensitive Line (FSL) rats, a genetic model of depression.

Results: Two weeks of treatment with exenatide (10 µg/kg twice daily) or liraglutide (1200 µg/kg once daily) did not affect the anxiety level in a light-dark compartment test nor induce an antidepressant-like effect in the FST in mice. Moreover, chronic treatment with liraglutide had no effect on depression-related behaviour in FSL rats. Interestingly, hypolocomotion induced by the drugs in mice disappeared after chronic dosing. Both of the GLP-1 receptor agonists induced robust increases in corticosterone levels in mice under basal conditions as well as in the case of combination with swimming stress. Remarkably, exenatide was as potent a stimulator of corticosterone release after 2 weeks as after acute administration.

Conclusions: The increases in corticosterone release seen after acute exenatide or liraglutide treatment do not abate after 2 weeks of treatment demonstrating that tolerance does not develop towards this particular effect of GLP-1 agonists.