Psychiatric Disease (psychiatric + disease)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Hyperostosis cranii in the elderly with various clinical symptoms

GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1 2004
Makoto Sohmiya
We report three elderly patients with hyperostosis cranii. Patient 1 had two episodes of unconsciousness; Patient 2, headache; and Patient 3, dementia. On the basis of Moore's classification using skull films, Patients 1 and 2 showed hyperostosis frontoparietalis and Patient 3 had hyperostosis frontalis interna. Electroencephalography showed transient generalized spike and slow wave complexes over the frontal lobes in Patient 1. Magnetic resonance images showed frontal lobes compressed by the thickness of the frontal bones in all patients and the thickness of the parietal bones in Patients 1 and 2. Since the findings in the present cases and those in the literature suggest that hyperostosis cranii could show unexpected neuropsychiatric symptoms, hyperostosis cranii should be checked in elderly patients whose presenting symptoms include epilepsy, dementia, psychiatric disease, headache and so on. Magnetic resonance images should be helpful in examining the relationship between clinical symptoms and the deformation of the brain by the skull. [source]


Neural connectivity as an intermediate phenotype: Brain networks under genetic control

HUMAN BRAIN MAPPING, Issue 7 2009
Andreas Meyer-Lindenberg
Abstract Recent evidence suggests that default mode connectivity characterizes neural states that account for a sizable proportion of brain activity and energy expenditure, and therefore represent a plausible neural intermediate phenotype. This implies the possibility of genetic control over systems-level connectivity features. Imaging genetics is an approach to combine genetic assessment with multimodal neuroimaging to discover neural systems linked to genetic abnormalities or variation. In the present contribution, we report results obtained from applying this strategy to both structural connectivity and functional connectivity data. Using data for serotonergic (5-HTTLPR, MAO-A) and dopaminergic (DARPP-32) genes as examples, we show that systems-level connectivity networks under genetic control can be identified. Remarkable similarities are observed across modalities and scales of description. Features of connectivity often better account for behavioral effects of genetic variation than regional parameters of activation or structure. These data provide convergent evidence for genetic control in humans over connectivity systems, whose characterization has promise for identifying neural systems mediating genetic risk for complex human behavior and psychiatric disease. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source]


Service provision for elderly depressed persons and political and professional awareness for this subject: a comparison of six European countries

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2003
Anke Bramesfeld
Abstract Objective Under-treatment of depression in late-life is a subject of rising public health concern throughout Europe. This study investigates and compares the availability of services for depressed elderly persons in Denmark, France, Germany, Sweden, Switzerland and the UK. Additionally, it explores factors that might contribute to an adequate services supply for depressed elderly people. Method Review of the literature and guide supported expert interviews. Analysis of the practice of care provision for depressed elderly persons and of indicators for political and professional awareness, such as university chairs, certification processes and political programmes in gerontopsychiatry. Results Only Switzerland and the UK offer countrywide community-oriented services for depressed elderly persons. Clinical experience in treating depression in late-life is not regularly acquired in the vocational training of the concerned professionals. Indicators suggest that the ,medical society' and health politics in Switzerland and the UK regard psychiatric disease in the elderly more importantly than it is the case in the other investigated countries. Conclusions Service provision for depressed elderly persons seems to be more elaborated and better available in countries where gerontopsychiatry is institutionalised to a greater extend in the ,medical society' and health politics. Copyright © 2003 John Wiley & Sons, Ltd. [source]


RNA from Borna disease virus in patients with schizophrenia, schizoaffective patients, and in their biological relatives

JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 4 2008
Sandra Odebrechet Vargas Nunes
Abstract Numerous interactions of the immune system with the central nervous system have been described recently. Mood and psychotic disorders, such as severe depression and schizophrenia, are both heterogeneous disorders regarding clinical symptomatology, the acuity of symptoms, the clinical course, the treatment response, and probably also the etiology. Detection of p24 RNA from Borna disease virus (BDV) by the reverse transcriptase polymerase chain reaction in patients with schizophrenia, schizoaffective disorder, and in their biological relatives was evaluated. The subjects were 27 schizophrenic and schizoaffective patients, 27 healthy controls, 20 relatives without psychiatric disease, and 24 relatives with mood disorder, who attended the Psychiatric Ambulatory of Londrina State University, Paraná, Brazil. The subjects were interviewed by structured diagnostic criteria categorized according to the Diagnostic and Statistical Manual of Mental Disorders-IV, axis I, (SCID-IV). The mean duration of illness in schizophrenic and schizoaffective patients was 15.341±1.494 years and the median age at onset was 22.4±7.371 years. There were no significant differences in gender (P=0.297), age (P=0.99), albumin (P=0.26), and body mass index (kg/m2) (p=0.28), among patients, controls, and relatives. Patients and biological relatives had significantly higher positive p24 RNA BDV detection than controls (P=0.04); however, the clinical significance of BDV remains to be clarified. J. Clin. Lab. Anal. 22:314,320, 2008. © 2008 Wiley-Liss, Inc. [source]


Patients' experience of involuntary psychiatric care: good opportunities and great losses

JOURNAL OF PSYCHIATRIC & MENTAL HEALTH NURSING, Issue 6 2002
I. M. JOHANSSON RN
Patients who are involuntary admitted to psychiatric care are extremely vulnerable as a consequence of the control from others, and of the personal limitations due to a psychiatric disease that can influence their own control of their lives. This group of patients are seldom asked about their experiences of being cared for. In this study five involuntary hospitalized psychiatric patients narrated their experience of being subjected to involuntary psychiatric care. The aim of the study was to obtain a deeper understanding of this experience. The interview text was analysed by means of a phenomenological hermeneutic method. The result of the analysis gave a complex picture of both support and violation. On the one hand experiences of not being seen or heard, of loss of liberty and of violation of integrity were found. On the other hand, there were experiences of respect and caring and opportunities to take responsibility for oneself were offered. Being treated involuntarily in psychiatric care was interpreted as a balancing act between good opportunities and great losses. [source]


Antipsychotic drugs and short-term mortality after peptic ulcer perforation: a population-based cohort study

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2008
C. CHRISTIANSEN
Summary Background, Peptic ulcer perforation is a serious surgical emergency with a substantial short-term mortality, but the influence of antipsychotic drug use on the prognosis remains unknown. Aim, To examine the association between antipsychotic drug use and 30-day mortality following peptic ulcer perforation. Methods, This cohort study comprised 2033 patients with a first-time hospitalization with peptic ulcer perforation, in Northern Denmark, between 1991 and 2004. Data on preadmission use of antipsychotics and other medications, psychiatric disease, other comorbidities and mortality were obtained through population-based medical databases. We used Cox regression analyses to compute adjusted mortality rate ratios (MRRs). Results, One hundred and sixteen (5.7%) patients with peptic ulcer perforation were current users of antipsychotic drugs at the time of hospital admission and 205 (10.1%) were former users. The overall 30-day mortality was 27%. Among current users of antipsychotics 30-day mortality was 39%. The adjusted 30-day MRR for current users of antipsychotic drugs compared with non-users was 1.7 (95% CI: 1.2,2.3). Former use was not a predictor of mortality. The increase in mortality was equal in users of conventional and atypical antipsychotics. Conclusion, Use of antipsychotic drugs is associated with substantially increased mortality following peptic ulcer perforation. [source]


Reflux symptoms are associated with psychiatric disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2001
B. Avidan
Methods: To evaluate the frequency of reflux symptoms in patients with a diagnosed psychiatric disorder and to assess potential risk factors for symptom occurrence. Methods: The presence of reflux symptoms was compared between a case population of 94 psychiatric patients and a control population of 198 non-psychiatric patients. Results: Heartburn, exercise-induced heartburn, cough and dysphagia were all reported significantly more frequently by subjects with psychiatric disorders than by control subjects. The presence of any psychiatric diagnosis exerted an increased risk for both heartburn (odds ratio, 2.71; 95% confidence interval, 1.01,7.30) and exercise-induced heartburn (3.34; 1.12,9.96). The type of psychiatric disorder, the type of psychotropic medication and the lifestyle did not influence the presence of reflux symptoms. Conclusions: Reflux symptoms occur more frequently in patients with than without a diagnosed psychiatric disorder. The reflux symptoms are not associated with any specific type of medication and may reflect a generally reduced threshold for or distorted perception of symptoms. [source]


Late onset Wilson's disease: Therapeutic implications

MOVEMENT DISORDERS, Issue 6 2008
Anna Cz, onkowska MD
Abstract The clinical symptoms of Wilson's disease (WD) usually develop between 3 and 40 years of age and include signs of liver and/or neurologic and psychiatric disease. We report on an 84-year-old woman with WD. Despite the absence of treatment, the only symptom she presented with, until the age of 74 years, was Kayser-Fleisher rings. At the age of 74, she developed slightly abnormal liver function. This case raises the following issues: (a) Should WD be considered in all patients of all ages who manifest signs related to the disease? (b) Are ATP7B mutations fully penetrant? (c) Should all patients diagnosed presymptomatically receive anticopper therapy? © 2008 Movement Disorder Society [source]


PERSONAL IDENTITY, ENHANCEMENT AND NEUROSURGERY: A QUALITATIVE STUDY IN APPLIED NEUROETHICS

BIOETHICS, Issue 6 2009
NIR LIPSMAN
ABSTRACT Recent developments in the field of neurosurgery, specifically those dealing with the modification of mood and affect as part of psychiatric disease, have led some researchers to discuss the ethical implications of surgery to alter personality and personal identity. As knowledge and technology advance, discussions of surgery to alter undesirable traits, or possibly the enhancement of normal traits, will play an increasingly larger role in the ethical literature. So far, identity and enhancement have yet to be explored in a neurosurgical context, despite the fact that 1) neurological disease and treatment both potentially alter identity, and 2) that neurosurgeons will likely be the purveyors of future enhancement implantable technology. Here, we use interviews with neurosurgical patients to shed light on the ethical issues and challenges that surround identity and enhancement in neurosurgery. The results provide insight into how patients approach their identity prior to potentially identity-altering procedures and what future ethical challenges lay ahead for clinicians and researchers in the field of neurotherapeutics. [source]


Role of valproate across the ages.

ACTA NEUROLOGICA SCANDINAVICA, Issue 2006
Treatment of epilepsy in adults
A workshop was held in Göteborg in June 2005 to discuss the place of valproate in treating adult epilepsies. Consensus positions were developed on the epilepsy types for which the drug is most suitable and the use of valproate in women of child-bearing age, in men and in patients with psychiatric comorbidity. Valproate was considered to be effective across a broad variety of epilepsy syndromes and seizure types and should be considered a suitable choice for first-line monotherapy of juvenile myoclonic epilepsy and other idiopathic generalized epilepsies. The use of valproate by women of child-bearing age is associated with potential harm to the foetus. A conservative approach to treatment is recommended in these patients whereby alternative antiepileptic drugs should be proposed to women planning pregnancies wherever satisfactory seizure control can be thereby maintained. In cases where valproate is used during pregnancy, either because the pregnancy was unplanned or because alternative treatment options of equivalent efficacy are unavailable, appropriate counselling, precautionary measures and monitoring should be provided. The evidence for an impact of valproate on male reproductive health is equivocal and considerations of male fertility should not be taken into account in deciding whether to prescribe valproate to men. Valproate can be proposed safely to patients with comorbid psychiatric disease or underlying psychiatric vulnerability. [source]


Predictors of headache 22 years after hospitalization for head injury

ACTA NEUROLOGICA SCANDINAVICA, Issue 1 2005
K. Nestvold
Objectives,,, To assess predictors of headache in patients who had sustained a head injury 22 years earlier. Materials and methods,,, A questionnaire about headache was sent to 361 subjects hospitalized for head injury in 1974,1975. Results,,, A total of 249 patients (69%) responded to the questionnaire. The prevalence of headache >14 days a month last year was 11%. In multivariate logistic regression analysis female sex (OR = 3.4, 95% CI 1.2,9.6), severe headache 3 months after the head injury (OR = 10.6, 95% CI 2.6,43.5) and psychiatric disease (OR = 2.9, 95% CI 1.1,7.7) predicted chronic headache. There was no significant association between chronic headache and post-traumatic amnesia or other trauma-related variables. Conclusion,,, Female sex and headache 3 months after the head injury were the strongest predictors of long-term headache, while there was little association between long-term headache and trauma variables. [source]


Complete rectal prolapse in young patients: psychiatric disease a risk factor of poor outcome

COLORECTAL DISEASE, Issue 4 2005
C. Marceau
Abstract Objective, Complete rectal prolapse is rare before the age of 50. The aim of our study was to identify the risk factors of total rectal prolapse before this age and to determine the surgical outcome in this specific group of patients. Patients and methods, The charts of all patients, younger than 50 years old, treated for total rectal prolapse between June 1995 and December 2001 were reviewed. Associated conditions were noted and pre and postoperative functions were compared in regards of constipation and evacuations problems, anal continence (Wexner score), recurrent prolapse and overall satisfaction. All patients underwent an abdominal rectopexy according to the Orr-Loygue procedure. Results, During the study period, 28 patients (21 females) with a mean age of 34 ± 9 years were treated for a total rectal prolapse in our institution. Five patient (17.8%) had minor complications. After a mean follow up of 25 months, the global continence improved significantly (Wexner score: 4.9 vs 2; P = 0.014): 8 patients suffering from liquid stools incontinence before surgery were continent after rectopexy, while 2 continent patients became incontinent to liquid stools after surgery. Fourteen patients had chronic psychiatric disease requiring permanent treatment. These patients suffered more frequently from constipation (12/14 vs 5/14; P =0.006) and required more often a digital evacuation before surgery (6/14 vs 1/14; P = 0.07) than non psychiatric patients. They also suffered from more severe constipation and required more enemas after surgery (1/14 vs 6/12; P = 0.03) compared to patients without psychiatric disease. The only two patients, who had recurrence also had psychiatric disease. Conclusion, Chronic psychiatric disease requiring long-term medication is observed in 50% of patients with total rectal prolapse under the age of 50 years. Moreover, the medically induced constipation in these patients could represent a cause of poorer functional outcome. Therefore, we recommand the identification of this preoperative risk factor to assess the results of total rectal prolapse treatment in patients younger than 50 years of age. [source]


Association of tryptophan hydroxylase gene polymorphism with depression, anxiety and comorbid depression and anxiety in a population-based sample of postpartum Taiwanese women

GENES, BRAIN AND BEHAVIOR, Issue 6 2004
H. S. Sun
Depression and anxiety disorders often coexist clinically and both are known to have a genetic basis, but the mode of inheritance is too complicated to be determined so far. Serotonin is the biogenic amine neurotransmitter most commonly associated with depression and anxiety. Since tryptophan hydroxylase (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, its role in the pathophysiology of these psychiatric diseases has been intensively studied. In this study, we examined whether polymorphism of the TPH1 gene is related to the etiology of major depression, anxiety and comorbid depression and anxiety. Five single nucleoside polymorphisms of the TPH1 gene were studied in a population-based sample of postpartum Taiwanese women consisting of 120 subjects with depression or/and anxiety and 86 matched normal controls. A significant difference (P = 0.0107) in genotype frequency for the T27224C polymorphism was found between the comorbid and normal groups, and risk analysis showed that the C allele conferred a strong protective effect (odds ratio = 0.27; 95% confident interval = 0.11,0.7). Three-allele haplotypes involving T27224C polymorphism were constructed and haplotype associations between particular haplotype combinations and various diseases identified. However, the associations were weak and the overall haplotype frequency profiles in all groups were similar. The results suggest that depression, anxiety, and comorbid depression and anxiety disorders may have related etiologies. In addition, this study suggests that the TPH1 gene might play a role in the pathogenesis of these closely related disorders. [source]


Transgenic expression of Cre recombinase from the tyrosine hydroxylase locus

GENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 2 2004
Jonas Lindeberg
Abstract Catecholaminergic neurons are affected in several neurological and psychiatric diseases. Tyrosine hydroxylase (TH) is the first, rate-limiting enzyme in catecholamine synthesis. We report a knockin mouse expressing Cre-recombinase from the 3,-untranslated region of the endogenous Th gene by means of an internal ribosomal entry sequence (IRES). The resulting Cre expression matches the normal pattern of TH expression, while the pattern and level of TH are not altered in the knockin mouse. Crossings with two different LacZ reporter mice demonstrated Cre-mediated genomic recombination in TH expressing tissues. In addition, LacZ was found in some unexpected cell populations (including oocytes), indicating recombination due to transient developmental TH expression. Our novel knockin mouse can be used for generation of tissue-specific or general knockouts (depending on scheme of crossing) in mice carrying genes flanked by loxP sites. This knockin mouse can also be used for tracing cell lineages expressing TH during development. genesis 40:67,73, 2004. © 2004 Wiley-Liss, Inc. [source]


Hepatitis C treatment in "difficult-to-treat" psychiatric patients with pegylated interferon-alpha and ribavirin: Response and psychiatric side effects,

HEPATOLOGY, Issue 4 2007
Martin Schaefer
We investigated and compared the results of treating the chronic hepatitis C (HCV) infection of different groups of psychiatric-risk patients and controls with pegylated interferon alpha (pegIFN-,) plus ribavirin. Seventy patients were prospectively screened for psychiatric disorders. Seventeen patients without psychiatric diseases or drug addiction (controls), 22 patients with psychiatric disorders, 18 patients who had received methadone substitution treatment and 13 patients who were former drug users were treated with pegIFN-, plus ribavirin. Sustained virological response (SVR), adherence, and psychiatric side effects (using the Montgomery-Asberg Depression Rating Scale and the Brief Psychiatric Rating Scale) in the groups were compared. An SVR was found in 58.6% of all patients: 58.8% of the controls, 50% of psychiatric patients, 72.2% of methadone patients, and 53.8% of former drug users. Methadone-substituted patients and former drug users had significantly higher dropout rates. Scores for neither depressive nor psychotic symptoms differed significantly between groups during treatment. However, the controls had lower pretreatment scores, followed by a significant higher increase to maximum scores. A stepwise logistic regression model showed that only genotype, not group (control, psychiatric, methadone, or former drug abuse), type of psychiatric diagnosis (affective disorder, personality disorder, or schizophrenic disorder), depression scores before and during treatment, change in depression score, antidepressive treatment, sex, or liver enzymes before treatment, was associated with SVR. Conclusion: In an interdisciplinary treatment setting psychiatric diseases and/or drug addiction did not negatively influence psychiatric tolerability of and antiviral response rate to HCV treatment with pegIFN-, and ribavirin. (HEPATOLOGY 2007.) [source]


An introduction to enantiomers in psychopharmacology

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S2 2001
Brian E. Leonard
Abstract There is growing scientific, clinical, commercial and regulatory recognition that enantiomers offer benefits over racemates in the management of psychiatric diseases as well as in clinical medicine generally. However, relatively few studies consider enantiomers' individual characteristics. This review considers some of the clinical benefits associated with using stereochemically pure drugs in psychiatric conditions other than depression. A review of the evidence shows that enantiomers offer four main benefits. Firstly, using a single enantiomer may allow a reduction in total dose, while maintaining or improving outcomes. For example, (+)-nefopam's antinociceptive activity is greater than that produced by both the racemate and (,)-nefopam, but with the same level of acute toxicity. Thus, a single enantiomer may offer greater efficacy, dose for dose, than the racemate. Secondly, assessing dose,response relationships is simpler. There is no reason to suppose that a racemate will necessarily contain the isomers' optimum therapeutic ratio, that one of the isomers will be inactive or that the enantiomers' dose,response curves will coincide. For example, the dose,response relationship for the induction of catalepsy in the rat by thioridazine suggested that the racemate was around 12 times more potent than (+)-thioridazine and three times more potent than (,)-thioridazine, when considering the actual concentrations in the striatum. Thirdly, using a single enantiomer may reduce pharmacokinetic and pharmacodynamic variability between patients. For example, the coefficients of variation for some of methadone's pharmacokinetic parameters may reach 70%, which might have clinical consequences. Finally, using a single enantiomer may reduce toxicity arising from the therapeutically inactive stereoisomer. For example, the single enantiomers of bupivacaine and ropivacaine are significantly less cardiotoxic than their respective racemates. This review illustrates why stereochemistry should be considered when assessing the toxicology, pharmacokinetics, metabolism and efficacy of a racemate. Indeed, the differences may be so marked that achiral analyses may be misleading, and clinicians should consider prescribing an enantiomer whenever possible. In many cases, prescribing a single enantiomer improves the benefit:risk ratio. Finally, there is no reason to suppose that a racemate's characteristics will apply to the constituent enantiomers. Copyright © 2001 John Wiley & Sons, Ltd. [source]


Glutamate and the glutamate receptor system: a target for drug action

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue S1 2003
Stefan Bleich
Abstract Glutamate is the most important excitatory neurotransmitter in the central nervous system. In the process, glutamate fulfills numerous physiological functions, but also plays an important role in the pathophysiology of different neurological and psychiatric diseases, especially when an imbalance in glutamatergic neurotransmission occurs. Under certain conditions, glutamate has a toxic action resulting from an activation of specific glutamate receptors, which leads to acute or chronic death of nerve cells. Such mechanisms are currently under discussion in acute neuronal death within the context of hypoxia, ischaemia and traumas, as well as in chronic neurodegenerative or neurometabolic diseases, idiopathic parkinsonian syndrome, Alzheimer's dementia and Huntington's disease. It is hoped that glutamate antagonists will lead to novel therapies for these diseases, whereby the further development of glutamate antagonists for blocking disease-specific subtypes of glutamate receptors may be of major importance in the future. Copyright © 2003 John Wiley & Sons, Ltd. [source]


Radiosynthesis of novel 18F-labelled derivatives of indiplon as potential GABAA receptor imaging tracers for PET

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 3 2008
Steffen Fischer
Abstract The involvement of gamma amino butyric acid (GABA) receptors in a variety of neurological and psychiatric diseases has promoted the development and use of radiolabelled benzodiazepines (BZ) for brain imaging by PET. However, these radioligands are unable to distinguish between the various subtypes of GABAA receptors. Novel non-BZ such as the pyrazolo-pyrimidine indiplon proved to be selective for the ,1 -subunit of the GABAA receptor. Here, we describe the syntheses of four novel 18F-labelled indiplon derivatives. Radiosyntheses were performed via n.c.a. 18F-nucleophilic substitution starting from the tosyl, bromo, and 4-nitrobenzoyl precursors to obtain fluorine substituted N -alkylamide side chain derivatives of indiplon, followed by multistep purification using semi-preparative high-performance liquid chromatography and solid phase extraction. Tosyl and bromo precursors were converted into 18F-labelled indiplon derivatives with good and reproducible radiochemical yield (RCY) (35,70%, decay corrected), high radiochemical purity (,98.5%), and high specific activity (,>,150,GBq/µmol). By contrast, a low RCY (5,10%) and specific activity (10,15,GBq/µmol) were achieved for the 4-nitrobenzoyl precursor. Copyright © 2008 John Wiley & Sons, Ltd. [source]


Intranasal delivery to the central nervous system: Mechanisms and experimental considerations

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2010
Shyeilla V. Dhuria
Abstract The blood,brain barrier (BBB) limits the distribution of systemically administered therapeutics to the central nervous system (CNS), posing a significant challenge to drug development efforts to treat neurological and psychiatric diseases and disorders. Intranasal delivery is a noninvasive and convenient method that rapidly targets therapeutics to the CNS, bypassing the BBB and minimizing systemic exposure. This review focuses on the current understanding of the mechanisms underlying intranasal delivery to the CNS, with a discussion of pathways from the nasal cavity to the CNS involving the olfactory and trigeminal nerves, the vasculature, the cerebrospinal fluid, and the lymphatic system. In addition to the properties of the therapeutic, deposition of the drug formulation within the nasal passages and composition of the formulation can influence the pathway a therapeutic follows into the CNS after intranasal administration. Experimental factors, such as head position, volume, and method of administration, and formulation parameters, such as pH, osmolarity, or inclusion of permeation enhancers or mucoadhesives, can influence formulation deposition within the nasal passages and pathways followed into the CNS. Significant research will be required to develop and improve current intranasal treatments and careful consideration should be given to the factors discussed in this review. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1654,1673, 2010 [source]


Antiepileptic drugs and risk of suicide: a nationwide study

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 5 2010
Jonas Bjerring Olesen MB
Abstract Purpose Patients with epilepsy or psychiatric diseases have increased risk of suicide, but whether the risk is influenced by antiepileptic drug (AED) treatment is unclear. Studies have suggested that AEDs in general increase the risk of suicidal behaviour shortly after initiation. This study investigated possible differences in suicide risk associated with different AEDs. Methods The use of AEDs in the Danish population from 1997 to 2006 was determined by prescription claims. The risk of suicide associated with use of AEDs was estimated by case-crossover analyses, where each case serves at its own control during different periods. For sensitivity, the risk of suicide was estimated by a time-dependent Cox proportional-hazard analysis in AED treatment-naďve patients. Results There were 6780 cases committing suicide in the 10-year study period, of which 422 received AED treatment at the time of suicide. The case-crossover analysis estimated AED treatment initiation to increase the risk of suicide (odds ratio (OR): 1.84, 95% confidence interval (CI): 1.36,2.49). Clonazepam (OR: 2.01, CI: 1.25,3.25), valproate (OR: 2.08, CI: 1.04,4.16), lamotrigine (OR: 3.15, CI: 1.35,7.34) and phenobarbital (OR: 1.96, CI: 1.02,3.75) were associated with a significant increased risk, while the remaining examined AEDs did not significantly influence the risk. In the cohort comprising of 169,725 AED treatment-naďve patients, the Cox proportional-hazard analysis yielded similar results. Conclusions This study suggests that clonazepam, valproate, lamotrigine and phenobarbital relatively shortly after treatment initiation may increase the risk of suicide. The increased risk of suicide associated with these AEDs appears to be a consistent finding. Copyright © 2010 John Wiley & Sons, Ltd. [source]


Effects of intraperitoneally injected lithium, imipramine and diazepam on nitrate levels in rat amygdala

PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2005
SHUJI MARUTA md
Abstract, Nitric oxide (NO) has been studied in relation to the etiologies of various neurologic and psychiatric diseases. However, little is known about whether clinically available psychotropic drugs affect the NO system in the brain. Using an in vivo brain microdialysis method, the effects of intraperitoneally administered lithium, imipramine and diazepam on levels of , a marker of in vivo NO production, were investigated in the rat amygdala. Lithium significantly reduced, while imipramine raised, levels as compared with controls. These observations suggest that lithium and imipramine induce opposite effects on NO-related systems in the brain. [source]


Specific GABAA agonists and partial agonists

THE CHEMICAL RECORD, Issue 6 2002
Povl Krogsgaard-Larsen
Abstract The GABAA receptor system is implicated in a number of neurological and psychiatric diseases, making GABAA receptor ligands interesting as potential therapeutic agents. Only a few different classes of structures are currently known as ligands for the GABA recognition site on the hetero-pentameric GABAA receptor complex, reflecting the very strict structural requirements for GABAA receptor recognition and activation. Within the series of compounds showing agonist activity at the GABAA receptor site that have been developed, most of the ligands are structurally derived from the GABAA agonists muscimol, THIP, or isoguvacine, which we developed in the initial stages of the project. Using recombinant GABAA receptors, functional selectivity was demonstrated for a number of compounds, including THIP, showing highly subunit-dependent potency and maximal response. In light of the interest in partial GABAA receptor agonists as potential therapeutics, structure,activity studies of a number of analogs of 4-PIOL, a low-efficacy partial GABAA agonist derived from THIP, have been performed. In this connection, a series of GABAA ligands has been developed that exhibit pharmacological profiles from moderately potent low-efficacy partial GABAA agonist activity to potent and selective antagonist effects. Very little information is available on direct-acting GABAA receptor agonists in clinical studies. However, the results of clinical studies on the effect of the partial GABAA agonist THIP on human sleep patterns show that the functional consequences of a direct-acting agonist are different from those seen after the administration of GABAA receptor modulators, such as benzodiazepines and barbiturates. © 2002 The Japan Chemical Journal Forum and Wiley Periodicals, Inc., Chem Rec 2: 419,430; 2002: Published online in Wiley Interscience (www.interscience.wiley.com) DOI 10.1002/tcr.10040 [source]


Eyeblink conditioning anomalies in bipolar disorder suggest cerebellar dysfunction

BIPOLAR DISORDERS, Issue 1 2009
Amanda R Bolbecker
Objectives:, Accumulating research implicates the cerebellum in non-motor psychological processes and psychiatric diseases, including bipolar disorder (BD). Despite recent evidence that cerebellar lesions have been documented to trigger bipolar-like symptoms, few studies have directly examined the functional integrity of the cerebellum in those afflicted with BD. Methods:, Using a single-cue delay eyeblink conditioning procedure, the functional integrity of the cerebellum was examined in 28 individuals with BD (9 manic, 8 mixed, and 11 euthymic) and 28 age-matched healthy controls. Results:, Analysis of the bipolar group as a whole indicated a conditioned response acquisition and timing deficit compared to controls. However, when the bipolar group was categorized according to mood state (mixed, manic, euthymic), individuals tested during mixed episodes were strikingly impaired, performing significantly worse than all other groups on both the acquisition and timing of conditioned responses. Conclusions:, These findings extend prior research implicating cerebellar functional abnormalities in BD and suggest that cerebellar dysfunction may be associated with mood state and course of illness. [source]


High suicidal ideation in persons testing for Huntington's disease

ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2000
T-B. Robins Wahlin
This study examined the first participants who registered for the Huntington's disease predictive testing program 1990,1995 in Stockholm, Sweden. A psychosocial investigation was performed to evaluate potential effects of the presymptomatic testing. The results showed no significant differences between 13 genecarriers and 21 noncarriers in pretest attitudes, expectations, general well-being, life satisfaction and lifestyle, the need for support, estimated sense of well-being or degree of health. However, both groups showed high suicidal ideation and self-injurious behavior. Noncarriers had a very high frequency of attempted suicide, and both groups had similarly pronounced psychiatric dysfunction. Their relatives also had high frequencies of psychiatric diseases, suicide or suicidal attempts. Most of the participants had a desire to meet a psychologist or a social worker. The need for counseling, using a well designed protocol, and the importance of focusing on suicide risk of participants in predictive testing programs is emphasized. [source]


Hospitalization in adolescence affects the likelihood of giving birth: a Swedish population-based register study

ACTA PAEDIATRICA, Issue 3 2009
K Ekholm Selling
ABSTRACT Aim: To examine the effect of hospitalization during adolescence on the likelihood of giving birth. Methods: 142 998 women born in 1973,75 were followed with the help of the Swedish Medical Birth Register (MBR) and the Swedish Total Population Register (TPR) up until the end of 2000 with respect to their likelihood of giving birth. All analyses were adjusted for parental socio-economic characteristics and factors related to the studied women's own birth. Results: The likelihood of giving birth between 20 and 27 years of age was positively affected by hospitalization at least once during adolescence according to the Swedish Hospital Discharge Register (HDR); adjusted hazard ratio (HR) = 1.32, 95% confidence interval: 1.29,1.35. Women hospitalized due to genitourinary diseases, respiratory diseases, abdominal problems and abuse of alcohol and drugs were more likely to have given birth during the study period, while hospitalizations according to cerebral palsy and congenital malformations tended to decrease childbearing. Women hospitalized due to psychiatric diseases had an increase likelihood of given birth at 20,24 years but a reduced thereafter. Conclusion: A majority of the causes of hospitalization during adolescence increased the likelihood of giving birth between ages 20 to 27. [source]