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Gabapentin, a third-generation antiepileptic drug, is a structural analogue of γ-aminobutyric acid, which is an important mediator of central nervous system. There is clinical data indicating its effectiveness in the treatment of psychiatric illnesses such as bipolar disorder and anxiety disorders.
Objectives
We aimed to investigate the antidepressant and anxiolytic-like effects and mechanisms of gabapentin in rats.
Material and Methods
Female Spraque–Dawley rats weighing 250±20 g were used. A total of 13 groups were formed, each containing 8 rats: gabapentin (5, 10, 20, 40 mg/kg), amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg), ketamine (10 mg/kg), gabapentin 20 mg/kg was also combined with amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg) and ketamine (10 mg/kg). All the drugs were used intraperitoneally as single dose. Saline was administered to the control group. Elevated plus maze and forced swimming tests were used as experimental models of anxiety and depression, respectively.
Results
It was observed that gabapentin showed an anxiolytic-like and antidepressant-like effect in all doses in rats. Its antidepressant effect was found to be the same as the antidepressant effects of amitriptyline and sertraline. There was no change in the antidepressant effect when gabapentin was combined with amitriptyline and ketamine, but there was an increase when combined with sertraline and diazepam. Gabapentin and amitriptyline showed similar anxiolytic effect, whereas ketamine and diazepam had more potent anxiolytic effect compared with them.
Conclusions
These data suggest that gabapentin may possess antidepressant- and anxiolytic-like effects.
Shared decision making (SDM) is an essential component of patient-centered care, but there is little information about its use in the psychiatric care.
Objective
To measure to what extent psychiatric patients feel they were involved in the process and steps of decision making about treatment choice and to analyse the influence of socio-demographic, clinical, and psychological processes on this perception.
Methods
Cross-sectional survey involving 1100 consecutive psychiatric outpatients invited to complete the nine-item Shared Decision-Making Questionnaire (SDM-Q-9), health locus of control and control preferences, self-efficacy and drug attitude scales, as well as a questionnaire including socio-demographic and clinical variables.
Results
A high response rate of 77% was registered, resulting in a sample of 846 psychiatric outpatients. SDM-Q-9 total score indicate a moderately low degree of perceived participation, with differing perceived implementation of the individual the SDM process steps. Patient diagnosis evidenced significant differences in SDM perception. Patients’ perception of SDM was explained by four main variables: the older the patient, the lower self-reported SDM; having a diagnosis of schizophrenia increases the likelihood of lower SDM; a positive attitude towards psychiatric drugs favors greater SDM, as well as a higher level of self-efficacy.
Conclusion
The result of this study suggests that SDM is currently not widely practiced in psychiatric care. Further research is needed to examine if the low level of participation self-reported is justified by psychiatric patients’ decisional capacity.
The World Health Organization estimates that major depression affects about 350 million people all over the world and reports this disorder as the major contributor to the global burden of diseases. Despite the well-defined symptomatology, major depression is a heterogeneous psychiatric disorder whose pathophysiology is not clearly established. Although several treatments are available, most depressed patients do not achieve the complete remission of symptoms. Factors linked to the persistence of the disorder have been investigated, particularly those related to the way of life. Moreover, it has been suggested that nutritional aspects may influence its development. Among them, a diet rich in ω-3 has been associated with a reduced risk of major depression, although its deficiency is associated with depressive disorders.
Methods
This review provides a general view about evidences of the use of ω-3 in major depression cases.
Results
Several studies have demonstrated beneficial effects of ω-3 in the prevention and treatment of major depression. However, not all the results have shown significant statistical benefits.
Conclusions
More studies are necessary to clarify detailed mechanisms of the antidepressant effects of ω-3 and may explain the source of contradictions in results published until the moment.
Schizoaffective disorder is a disease with both affective and psychotic symptoms. In this study, we aimed to compare oxidative metabolism markers of schizoaffective disorder, bipolar disorder and schizophrenic patients. Furthermore, we also aimed to investigate whether schizoaffective disorder could be differentiated from schizophrenia and bipolar disorder in terms of oxidative metabolism.
Methods
Total oxidant status (TOS) and total antioxidant status (TAS) were measured in the blood samples that were collected from schizoaffective patients (n = 30), bipolar disorder patients (n = 30) and schizophrenic patients (n = 30). Oxidative stress index (OSI) was calculated by dividing TOS by TAS.
Results
TOS and OSI were found to be higher in patients with schizoaffective disorder compared with those in schizophrenia and bipolar disorder patients. TAS was not significantly different between the groups.
Conclusion
Schizoaffective disorder was found to be different from bipolar disorder and schizophrenia in terms of oxidative parameters. This result may indicate that schizoaffective disorder could differ from bipolar disorder and schizophrenia in terms of biochemical parameters. Increased TOS levels observed in schizoaffective disorder may suggest poor clinical course and may be an indicator of poor prognosis.
Cognitive deficits in schizophrenia play a crucial role in its clinical manifestation and seem to be related to changes in the cholinergic system, specifically the action of acetylcholinesterase (AChE). Considering this context, the aim of this study was to evaluate the chronic effects of ketamine in the activity of AChE, as well as in behavioural parameters involving learning and memory.
Methods
The ketamine was administered for 7 days. A duration of 24 h after the last injection, the animals were submitted to behavioural tests. The activity of AChE in prefrontal cortex, hippocampus and striatum was measured at different times after the last injection (1, 3, 6 and 24 h).
Results
The results indicate that ketamine did not affect locomotor activity and stereotypical movements. However, a cognitive deficit was observed in these animals by examining their behaviour in inhibitory avoidance. In addition, an increase in AChE activity was observed in all structures analysed 1, 3 and 6 h after the last injection. Differently, serum activity of AChE was similar between groups.
Conclusion
Chronic administration of ketamine in an animal model of schizophrenia generates increased AChE levels in different brain tissues of rats that lead to cognitive deficits. Therefore, further studies are needed to elucidate the complex mechanisms associated with schizophrenia.
Schizophrenia (SZ) is a common severe psychiatric disorder and a complex polygenic inherited disease that has not yet been fully interpreted. Heredity was proven to play an important role in the development of SZ. The association between the NOTCH4 gene rs3131296 polymorphism and SZ was reported to reach significance at the genome-wide level; therefore, it is necessary to replicate this association in other different populations.
Methods
To evaluate the association of the NOTCH4 gene rs3131296 polymorphism with the risk for SZ, and to explore whether a significant association could be replicated in different ethnic groups of China, we conducted this case–control study on 282 SZ cases (188 Han and 94 Zhuang) and 282 controls (188 Han and 94 Zhuang) among the Chinese Zhuang and Han populations.
Results
The results showed no statistically significant difference in the genotype or allele frequencies of the NOTCH4 gene variant rs3131296 between SZ patients and healthy controls in either the Zhuang or Han samples (p > 0.05). In addition, no significant difference was found in genotype or allele frequencies of the NOTCH4 gene variant rs3131296 between cases and controls in the combined samples including Zhuang and Han samples.
Conclusions
Our study failed to replicate the significant association between the NOTCH4 gene rs3131296 polymorphism and the risk for SZ.
Stress can stimulate increased production of oxygen radicals. We investigated the correlations between serum levels of lipid peroxidation markers and those in brain samples in different stress models.
Methods
Animals (n = 96) were divided equally into eight groups: a control group and groups treated with vitamin E (Vit E); exposed to immobilisation stress; exposed to immobilisation stress and treated with Vit E; exposed to cold stress; exposed to cold stress and treated with Vit E; exposed to both immobilisation and cold stress; and a final group exposed to both immobilisation and cold stress and treated with Vit E. Thiobarbituric acid-reactive substance (TBARS) in brain samples and levels of TBARS, corticosterone, conjugated dienes (CD), lipids, and paraoxonase-1 (PON1) activity in serum were analysed.
Results
Serum corticosterone (p < 0.001), CD (p < 0.05), lipid (p < 0.05) levels, and brain TBARS (p < 0.05) levels were significantly higher in all stress groups than in controls, and the elevated levels were reversed in the Vit E-treated stress groups (p < 0.05). Serum PON1 activity was not different among the groups (p > 0.05). Serum TBARS levels increased significantly in all stress groups (p < 0.05), but this elevation was only reversed in the group exposed to both immobilisation and cold stress and treated with Vit E (p < 0.001).
Conclusion
These results suggest that serum levels of lipid peroxidation markers can be determined readily and may be useful as indicators to evaluate the effects of oxidative stress in the brain.
Deep brain stimulation is currently an experimental treatment for major depressive disorder. Information is lacking, however, on how sham responding may affect efficacy. This article applies exploratory meta-analysis to address that topic.
Methods
Data on benefits of deep brain electrical stimulation come from a recent review. Stimulated brain regions included subgenual cingulate, capsular interna, nucleus accumbens, and medial forebrain bundle. Expert opinion plus random number software was used to generate hypothetical values for sham responding.
Results
An effect size of 1.71 (95% CI: 1.47–1.96) was obtained for deep brain stimulation versus sham treatment in patients suffering from long-term treatment-resistant depression.
Conclusion
Preliminary findings on deep brain electrical stimulation suggest that the procedure may be 71% more effective than sham treatment. Expressing these findings as patients-needed-to-treat, deep brain electrical stimulation is required by 2.9 patients with long-term treatment-resistant depression in order for one of them to benefit.
Neurosyphilis is caused by dissemination into the central nervous system of Treponema pallidum. Although the incidence of syphilis in the Netherlands has declined since the mid-1980s, syphilis has re-emerged, mainly in the urban centres. It is not known whether this also holds true for neurosyphilis.
Methods
The epidemiology of neurosyphilis in Dutch general hospitals in the period 1999–2010 was studied in a retrospective cohort study. Data from the Dutch sexually transmitted infection (STI) clinics were used to analyse the number of patients diagnosed with syphilis in this period.
Results
An incidence of neurosyphilis of 0.47 per 100 000 adults was calculated, corresponding with about 60 new cases per year. This incidence was higher in the western (urbanised) part of the Netherlands, as compared with the more rural areas (0.6 and 0.4, respectively). The number of patients diagnosed with syphilis in STI clinics increased from 150 to 700 cases in 2004 and decreased to 500 new cases in 2010. The sex ratio was in favour of men, yielding a percentage of 90% of the syphilis cases and of 75% of the neurosyphilitic cases. The incidence of neurosyphilis was highest in men aged 35–65 years, and in women aged 75 years and above. The most frequently reported clinical manifestation of neurosyphilis was tabes dorsalis. In this study, 15% of the patients were HIV seropositive.
Conclusion
The incidence of neurosyphilis in a mixed urban–rural community such as the Netherlands is comparable to that in other European countries. Most patients are young, urban and men, and given the frequent atypical manifestations of the disease reintroduction of screening for neurosyphilis has to be considered.
Evidence for a possible association between a low level of cholesterol and increased suicidal behaviour has accumulated in the recent 3 decades. The present study investigates whether lipid levels can make state-dependent markers of suicidal behaviour in Polish patients with mood disorder recently admitted to a psychiatric hospital owing to an acute depressive episode.
Materials and methods
The study was conducted on 223 patients (73 male and 150 female) with unipolar (n=171) and bipolar (n=52) depression. They were interviewed to assess any occurrence of suicidal thoughts, suicidal tendencies and/or suicidal attempts during the 3 months before admission. Laboratory measurements [total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides and total lipids] were obtained within 24–72 h after hospital admission.
Results
Suicidal thoughts, tendencies, and attempts were associated with low total cholesterol, LDL cholesterol, and total lipids in both male and female patients, in both diagnostic categories. Triglycerides were significantly lower in male and female patients with suicidal thoughts compared with their non-suicidal counterparts. No association with suicidality was found with HDL cholesterol.
Conclusions
The results of our study support a majority of research showing the association in depressed patients between suicidal behaviour and low levels of total and LDL cholesterol. In addition, the data suggest a similar association with low total lipids, and in some instances, with low triglycerides.
Adverse effects of antidepressant drug treatmenton sexual function are well documented but the effects of antidepressants on sperm production have not been researched extensively.
Methods
A narrative of an interventional case report of sperm parameters in a 30-year-old Caucasian man with a diagnosis of mixed depressive and anxiety disorder, who underwent citalopram treatment, followed by agomelatine treatment. Clinical observations prompted a review of the pre-clinical and clinical literature on the effects of antidepressant administration or treatment on sperm production and parameters. Findings from the review are discussed to suggest potential underlying mechanisms.
Results
Abnormal sperm parameters were associated with treatment with the SSRI citalopram. There was an improvement in sperm concentration, motility, progressive motility and sperm morphology following its withdrawal. There was no similar association during subsequent treatment with agomelatine. The clinical observations reflect findings from animal studies, which indicate that antidepressants can have untoward effects on spermatogenesis.
Conclusions
SSRI treatment can be associated with impaired semen quality. Potential underlying mechanisms include changes in sperm DNA integrity, activation of IDO and shifting tryptophan metabolism. Further studies of the effects of antidepressants on spermatogenesis might benefit from including investigation of changes in IDO activity during antidepressant administration.
Catatonic features are observed in several psychiatric illnesses but can also be found following substance misuse. Loperamide is an anti-diarrhoeal medication that acts on opioid receptors in the intestine, reducing peristalsis. It is normally unable to pass through the intestinal wall or the blood–brain barrier; however, high dosages can in fact induce the effects on the central nervous system.
Case report
We describe the case of a 20-year-old man who presented with severe catatonia following excessive intake of loperamide, fully remitted with lorazepam.
Conclusion
We speculate on a possible increase of loperamide's bioavailability after overdose owing to reduced expression and functioning of P-glycoprotein.
To present the pilot study on the European Portuguese validation of the Confusion Assessment Method (CAM).
Methods
The translation process was carried out according to International Society Pharmacoeconomics and Outcomes Research guidelines with trained researchers and inter-rater reliability assessment. The study included 50 elderly patients, admitted (≥24 h) to two intermediate care units. Exclusion criteria were: Glasgow Coma Scale (total score ≤11), blindness/deafness, inability to communicate and not able to speak Portuguese. The sensitivity and specificity of CAM were assessed, with DSM-IV-TR criteria of delirium used as a reference standard.
This study aims to document the nature and progression of the spontaneous writing impairment observed in patients with Alzheimer's disease (AD) over a 12-month period using both a cross-sectional and prospective longitudinal design.
Methods
Thirty-one minimal–moderate AD patients and 30 controls matched for age and socio-cultural background completed a simple and complex written description task at baseline. The AD patients then had follow-up assessments at 6 and 12 months.
Results
Cross-sectional comparisons indicated that minimal–moderate AD patients produced more semantic paraphasias, phonological paraphasias, and empty and indefinite phrases, whilst producing fewer pictorial themes, repairing fewer errors, and producing shorter and less complex sentences than controls. The two groups could not be distinguished on visual paraphasias. Longitudinal follow-up, however, suggested that visual processing deteriorates over time, where the prevalence of visual errors increased over 12 months.
Discussion
The findings suggest that the deterioration of writing skills observed in the spontaneous writings of AD patients shows a pattern of impairment dominated by semantic errors with a secondary impairment in phonological processing, which is later joined by a disruption of visuospatial and graphomotor processing.
The ability to accurately judge facial expressions is important in social interactions. Individuals with bipolar disorder have been found to be impaired in emotion recognition; however, the specifics of the impairment are unclear. This study investigated whether facial emotion recognition difficulties in bipolar disorder reflect general cognitive, or emotion-specific, impairments. Impairment in the recognition of particular emotions and the role of processing speed in facial emotion recognition were also investigated.
Methods
Clinically stable bipolar patients (n = 17) and healthy controls (n = 50) judged five facial expressions in two presentation types, time-limited and self-paced. An age recognition condition was used as an experimental control.
Results
Bipolar patients’ overall facial recognition ability was unimpaired. However, patients’ specific ability to judge happy expressions under time constraints was impaired.
Conclusions
Findings suggest a deficit in happy emotion recognition impacted by processing speed. Given the limited sample size, further investigation with a larger patient sample is warranted.
Aripiprazole has a low risk for causing extrapyramidal syndrome and can remit neuroleptic-induced tardive dyskinesia (TD). Here, we presented a case in which TD was suppressed, but not cured, by long-term aripiprazole treatment.
Case
This 74-year-old male patient had bipolar I disorder and had developed TD many times after several antipsychotic treatments. The lowest chlorpromazine dose equivalent among the previous antipsychotic treatments was 25 mg/day of quetiapine. His TD always improved immediately after the dosage was shifted to aripiprazole. However, his insomnia or other psychiatric symptoms worsened the first three times when the treatment was shifted to aripiprazole, making the transition a failure. Before the fourth attempt of aripiprazole transition, the patient was in a euthymic state but again developed TD under olanzapine 10 mg/day treatment. During the fourth attempt of aripiprazole transition, his TD had remained in complete remission for more than 1 year after the dosage shifted to 10 mg/day of aripiprazole. He developed TD again when we tapered the aripiprazole dose to 5 mg/day, but his TD remitted when we restored his aripiprazole dose to 10 mg/day.
Conclusion
Aripiprazole could be an effective drug in elderly bipolar patients with antipsychotic-induced TD while the patients are in a euthymic state. However, aripiprazole may only suppress TD rather than cure it.