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Background: The last few decades have seen a renaissance in the development of neuropsychiatric services on a global scale.
Methods: This paper reviews the existing literature on the changing role of the clinical neuropsychiatrist and discusses the evolving theory and practice of neuropsychiatry in the United Kingdom.
Results: The rapidly evolving specialty of neuropsychiatry is currently facing a number of challenges. These include, but are not limited to, uncertainties about the curricular requirements for clinical neuropsychiatrists and the changing roles within the wider scenario of health-care service provision.
Discussion: An informed historical perspective on this multifaceted discipline allows key insights into its future development.
Objective: Causative relations between infections and psychosis, especially schizophrenia, have been speculated for more than a century, suggesting a hypothesis of association between schizophrenia and hereditary immune defects. Mannan-binding lectin (MBL) is a pattern-recognition molecule of the innate immune defence. MBL deficiency is the most common hereditary defect in the immune system and may predispose to infection and autoimmunity. Mannan-binding lectin serine protease-2 (MASP-2) is an MBL-associated serine protease mediating complement activation upon binding of MBL/MASP to microorganisms. The objective was to investigate if schizophrenia is associated with serum concentrations of MBL and MASP-2 or with genetic variants of the genes MBL2 and MASP2 encoding these proteins.
Methods: The sample consisted of 100 patients with schizophrenia and 350 controls. Concentrations of MBL and MASP-2 in serum were measured and seven single nucleotide polymorphisms known to influence these concentrations were genotyped.
Results: Significant association of disease with genetic markers was found in MBL2 but not in MASP2. Significant difference in MBL serum concentration was found between patients and controls when adjusting for MBL2 haplotypes. For concentrations of MASP-2, a significant interaction effect between a MASP2 variant and disease was found. Interestingly, MASP-2 levels also depended significantly on variants in MBL2 exon 1.
Conclusion: This study supports previous studies showing increased complement activity in patients with schizophrenia, indicates aetiological heterogeneity among patients and underlines that multilocus genotypes have to be considered when investigating effects on MBL level. It appears that inclusion of additional components from the system of complement activation is warranted.
Objective: The trait of experiencing positive affect could make a unique contribution to the pathogenesis of affective disorders. Animal models of positive emotionality are scarce but 50-kHz ultrasonic vocalizations (USVs) in rats have been associated with rewarding experience. We have previously reported that persistent inter-individual differences in expression of 50-kHz USVs (chirps) exist, and that male rats producing fewer 50-kHz USVs are more sensitive to chronic variable stress (CVS). In this study we examined the effect of CVS on extracellular serotonin (5-HT) levels in hippocampus, comparing high-chirping (HC) and low-chirping (LC) rats.
Methods: Male rats were classified as HC- and LC-rats on the basis of stable levels of USV response using sessions of tickling-like stimulation. CVS procedure lasted 4 weeks. The administration of citalopram (1 μM) and measurements of levels of 5-HT were done by microdialysis. Corticosterone levels were also measured from trunk blood.
Results: Male LC-rats were more sensitive to CVS: the effect of stress on body weight gain was larger and corticosterone levels from full blood were higher in the stressed LC animals as compared to both the unstressed groups and the stressed HC animals. While no baseline differences in extracellular 5-HT levels in hippocampus were found between groups, the increase in extracellular 5-HT levels induced by citalopram was much higher in LC-rats.
Conclusion: Chronic stress appears to modify hippocampal 5-HT overflow in rats with low positive affectivity. This finding supports the notion of greater vulnerability to CVS in male rats with low positive affectivity.
Objective: Depression is suggested to involve disturbances in cholinergic as well as glutamatergic pathways, particularly the N-methyl-d-aspartate receptor-mediated release of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). The aim of this study was to determine whether the Flinders Sensitive Line (FSL) rat, a genetic model of depression, presents with corticolimbic changes in basal acetylcholine (ACh) levels and NO/cGMP signalling.
Methods: Basal levels of nitrogen oxides (NOx) and both basal and l-arginine-stimulated nitric oxide synthase (NOS) formation of l-citrulline were analysed in hippocampus and frontal cortex in FSL and control Flinders resistant line (FRL) rats by fluorometric and electrochemical high-performance liquid chromatography, respectively. In addition, ACh and cGMP levels were analysed by liquid chromatography tandem mass spectrometry and radioimmunoassay, respectively.
Results: Significantly elevated frontal cortical but reduced hippocampal ACh levels were observed in FSL versus FRL rats. Basal cGMP levels were significantly reduced in the frontal cortex, but not hippocampus, of FSL rats without changes in NOx and l-citrulline, suggesting that the reduction of cGMP follows through an NOS-independent mechanism.
Conclusions: These data confirm a bidirectional change in ACh in the frontal cortex and hippocampus of the FSL rat, as well as provide evidence for a frontal cortical ACh-cGMP interaction in the depressive-like behaviour of the FSL rat.
Introduction: Depressive syndromes are common following cerebrovascular accident (CVA) and many patients do not respond to pharmacotherapy. Electroconvulsive therapy (ECT) is a safe and effective treatment for mood disorders arising with many comorbid medical conditions. In this paper, we describe the successful treatment of post-CVA depression with ECT.
Methods: Retrospective chart review of 24 patients hospitalised for depression on an in-patient Medical Psychiatry unit between 2000 and 2010. Medical, neurologic and psychiatric histories, physical examination findings, results of laboratory, imaging and neurophysiologic investigations and treatment response with medications and ECT were recorded.
Results: Twenty patients (83%) showed a positive response to treatment with ECT. None had worsening of depression after the ECT or experienced exacerbation of post-stroke neurological deficits. Three patients suffered from minor complications of ECT (prolonged confusion or short-term memory problems).
Conclusions: This review supports the use of ECT after a stroke with appropriate clinical observation. The treatment was well tolerated and the majority obtained clinical benefit.
Objective: In this retrospective study, we tested the hypothesis that patients with epilepsy (PWE) with moderate to major depression have more severe memory deficits than PWE with mild depression or no depression.
Methods: Hundred and thirty-nine patients with chronic epilepsy were studied with the Self-Rating Depression Scale (SDS) and a neuropsychological-screening battery the day after admission on a specialised ward for PWE. For this study the data from the Memo-test for verbal memory and from the Benton-test for non-verbal memory were taken into account. For testing of the hypothesis of independence of memory deficits and grade of depression we performed a statistical analysis.
Results: Eighty-three patients (59.7%) had a pathological score in the SDS, but only 36 (25.9%) scored in the range of a moderate to major depression. When all 83 patients with a pathological score in the SDS were taken into account, these patients did not differ on any cognitive measure from those without pathological score in SDS. The only significant association in our study was found between pathological results in immediate verbal recall and a score in the SDS for moderate to major depression (p = 0.038).
Conclusion: Minor depressive symptoms may be a response to chronic illness without any impact on cognitive functioning. Nevertheless, a verbal memory deficit associated with major depression was observed in our study even in the presence of many confounding factors. This may be a hint for an association of severe depressive symptoms with left temporal dysfunction in PWE.
Objective: To date no studies have investigated the personality functioning underlying patients diagnosed with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) using the performance-based Rorschach test.
Methods: We scored and interpreted the Rorschach protocols of eight carefully diagnosed PLOSL patients according to Exner's Comprehensive System. The structural variables in the Rorschach are organised around the seven dimensions of personality functioning that they assess: coping style and resources, organising information, perceiving events, forming concepts and ideas, handling of emotions, self-perception and interpersonal perception.
Results: As a group PLOSL patients had many personality liabilities when contrasted with typical avoidant non-patient adults. A majority of patients showed an avoidant coping style (Lambda > 0.99), low productivity and poor verbal output in the low number of responses and few Blends. Also, they showed limited available resources to cope with problem-solving test. Problems in organising information efficiently, and perceiving events realistically as well as signs of disturbed thinking and concept formation were observed in many patients. Handling of emotions was characterised by avoidance of emotional stimuli but at the same time poor affect modulation. Capacities to view themselves and others were thoroughly limited.
Conclusions: PLOSL tends to have repercussions throughout the personality functioning. In line with clinical findings and later neuroradiological and neuropathological examinations the Rorschach revealed personality features typical for frontal type of dementia.
Background: We report a case of a false positive for clozapine, when analysing serum levels using a high-pressure liquid chromatography with ultraviolet (HPLC-UV) detection method.
Methods: A patient not taking clozapine tested positive for clozapine three times in two different samples. This false positive was discovered by chance, because of an administrative error made in the first analytic test request.
Results: The analysis of the first sample with a more specific method [HPLC-tandem mass spectrometry (LC-MS/MS)] showed that no clozapine was present.
Conclusions: It is important to acknowledge that depending on the method employed, a false positive should not be ruled out as a possibility. Moreover, and even more worryingly, it should also be taken into account that clozapine serum levels could be tested erroneously high if the unknown interference is present and the HPLC-UV method is used. Although the interfering compound could not be identified, the possibility of a cross-reaction when analysing serum clozapine levels with the HPLC-UV method warrants urgent attention.
Background: Although sinus node dysfunction is primarily related to degenerative fibrosis of nodal tissue in the elderly, it may occur at any age secondary to other cardiac abnormalities or extrinsic causes. Pharmacologic agents including psychotropic drug therapy may also play a role.
Method: We present the case of a 53-year-old woman with bipolar affective disorder in whom antipsychotic agents were suspected of inducing sinus node dysfunction.
Result: The combination of psychotropic agents including lithium, quetiapine and carbamazepine (first occasion) or escitalopram (second occasion) has been implicated as a cause for sinus node dysfunction.
Conclusion: Patients with severe mental illness usually require long-term psychotropic drug therapy, often in combination. This may enhance efficacy but also involves an increased risk of adverse effects including cardiotoxicity.