Psychiatry - Research Publications
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ItemThe relationship between Hippocampal asymmetry and working memory processing in combat-related PTSD - a monozygotic twin study(BMC, 2012-12)BACKGROUND: PTSD is associated with reduction in hippocampal volume and abnormalities in hippocampal function. Hippocampal asymmetry has received less attention, but potentially could indicate lateralised differences in vulnerability to trauma. The P300 event-related potential component reflects the immediate processing of significant environmental stimuli and has generators in several brain regions including the hippocampus. P300 amplitude is generally reduced in people with PTSD. METHODS: Our study examined hippocampal volume asymmetry and the relationship between hippocampal asymmetry and P300 amplitude in male monozygotic twins discordant for Vietnam combat exposure. Lateralised hippocampal volume and P300 data were obtained from 70 male participants, of whom 12 had PTSD. We were able to compare (1) combat veterans with current PTSD; (2) their non-combat-exposed co-twins; (3) combat veterans without current PTSD and (4) their non-combat-exposed co-twins. RESULTS: There were no significant differences between groups in hippocampal asymmetry. There were no group differences in performance of an auditory oddball target detection task or in P300 amplitude. There was a significant positive correlation between P300 amplitude and the magnitude of hippocampal asymmetry in participants with PTSD. CONCLUSIONS: These findings suggest that greater hippocampal asymmetry in PTSD is associated with a need to allocate more attentional resources when processing significant environmental stimuli.
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ItemUse of video feedback intervention in an inpatient perinatal psychiatric setting to improve maternal parenting(SPRINGER WIEN, 2012-08)This study utilizes video feedback to improve maternal parenting behavior in clinically depressed mothers admitted to a perinatal inpatient psychiatric unit. Depressed mothers (n = 74) were randomized to "video" (n = 25), "verbal" (n = 26), or "standard care" (n = 23). "Video" mothers were taped playing with their infant; interaction was reviewed with a mental health specialist. "Verbal" mothers only discussed interaction with their infant. "Standard care" mothers received only routine inpatient care. Mothers were assessed for mental health status, perceptions of baby behavior, and parenting competence. There was significant improvement in mental health status of all participants, regardless of intervention. Neither intervention had an advantage, compared to standard care, in improving parenting confidence or perceptions of infant behavior. Video mothers were more likely to report no change in their parenting confidence the more feedback sessions completed. The number of intervention sessions for each participant was limited by the duration of their inpatient admission. Most participants were on simultaneous pharmacotherapy and psychotherapy, as well as receiving intensive mothercraft assistance; this may have influenced intervention effectiveness. Results suggest that this type of intervention may be beneficial, but in the current format does not add sufficiently to standard care to be detected by the measures used.
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ItemIndividual development of preschool children-prevalences and determinants of delays in Germany: a cross-sectional study in Southern Bavaria(BMC, 2012-12-05)BACKGROUND: Even minor abnormalities of early child development may have dramatic long term consequences. Accurate prevalence rates for a range of developmental impairments have been difficult to establish. Since related studies have used different methodological approaches, direct comparisons of the prevalence of developmental delays are difficult. The understanding of the key factors affecting child development, especially in preschool aged children remains limited. We used data from school entry examinations in Bavaria to measure the prevalence of developmental impairments in pre-school children beginning primary school in 1997-2009. METHODS: The developmental impairments of all school beginners in the district of Dingolfing-Landau, Bavaria were assessed using modified "Bavarian School Entry Model" examination from 1997 to 2009 (N=13,182). The children were assessed for motor, cognitive, language and psychosocial impairments using a standardised medical protocol. Prevalence rates of impairments in twelve domains of development were estimated. Using uni- and multivariable logistic regression models, association between selected factors and development delays were assessed. RESULTS: The highest prevalence existed for impairments of pronunciation (13.8%) followed by fine motor impairments (12.2%), and impairments of memory and concentration (11.3%) and the lowest for impairments of rhythm of speech (3.1%). Younger children displayed more developmental delays. Male gender was strongly associated with all developmental impairments (highest risk for fine motor impairments = OR 3.22, 95% confidence interval 2.86-3.63). Preschool children with siblings (vs. children without any siblings) were at higher risk of having impairments in pronunciation (OR 1.31, 1.14-1.50). The influence of the non-German nationality was strong, with a maximum risk increase for the subareas of grammar and psychosocial development. Although children with non-German nationality had a reduced risk of disorders for the rhythm of speech and pronunciation, in all other 10 subareas their risk was increased. CONCLUSIONS: In preschool children, most common were delays of pronunciation, memory and concentration. Age effects suggest that delays can spontaneously resolve, but providing support at school entry might be helpful. Boys and migrant children appear at high risk of developmental problems, which may warrant tailored intervention strategies.
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ItemInterleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain(BMC, 2012-06-13)BACKGROUND: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. METHODOLOGY: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs.Principal findings/resultsIn a whole-brain analysis, the polymorphism rs1800795 (-174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = -10, z = -15; F(2,286) = 8.54, p(uncorrected) = 0.0002; p(AlphaSim-corrected) = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. CONCLUSIONS/SIGNIFICANCE: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.
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ItemAn Unusual Presentation of Herpes Simplex Virus Encephalitis(HINDAWI LTD, 2012)We present a case of a 65-year-old man with an acute alteration in mental state that was initially diagnosed as a functional psychiatric condition. After extensive workup, herpes simplex virus type 1 (HSV-1) was detected in the patient's cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), and he responded rapidly to treatment with acyclovir. The case illustrates the importance of actively excluding organic causes in such patients, the need to have a low threshold of suspicion for HSV encephalitis, and the central role of CSF PCR testing for the diagnosis of HSV encephalitis, even in the absence of CSF biochemical abnormalities.
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ItemNo Preview AvailableCaspase-1-mediated regulation of fibrogenesis in diet-induced steatohepatitis(NATURE PUBLISHING GROUP, 2012-05)Non-alcoholic steatohepatitis (NASH) is typically associated with pro-apoptotic caspase activation. A potential role for pro-inflammatory caspases remains incompletely understood. Our aims were to examine a potential role of caspase-1 in the development of liver damage and fibrosis in NASH. C57BL/6 wild type (WT) developed marked steatohepatitis, activation, fibrosis and increased hepatic caspase-1 and interleukin-1β expression when placed on the methionine- and choline-deficient (MCD) diet. Marked caspase-1 activation was detected in the liver of MCD-fed mice. Hepatocyte and non-parenchymal fractionation of the livers further demonstrated that caspase-1 activation after MCD feeding was mainly localized to non-parenchymal cells. Caspase-1-knockout (Casp1(-/-)) mice on the MCD diet showed marked reduction in mRNA expression of genes involved in inflammation and fibrogenesis (tumor necrosis factor-α was 7.6-fold greater in WT vs Casp1(-/-) MCD-fed mice; F4/80 was 1.5-fold greater in WT vs Casp1(-/-) MCD-fed mice; α-smooth muscle actin was 3.2-fold greater in WT vs Casp1(-/-) MCD-fed mice; collagen 1-α was 7.6-fold greater in WT vs Casp1(-/-) MCD-fed mice; transforming growth factor-β was 2.4-fold greater in WT vs Casp1(-/-) MCD-fed mice; cysteine- and glycine-rich protein 2 was 3.2-fold greater in WT vs Casp1(-/-) MCD-fed mice). Furthermore, Sirius red staining for hepatic collagen deposition was significantly reduced in Casp1(-/-) MCD-fed mice compared with WT MCD-fed animals. However, serum alanine aminotransferase levels, caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells were similar in Casp1(-/-) and WT mice on the MCD diet. Selective Kupffer cell depletion by clodronate injection markedly suppressed MCD-induced caspase-1 activation and protected mice from fibrogenesis and fibrosis associated with this diet. The conclusion of this study is that it uncovers a novel role for caspase-1 in inflammation and fibrosis during NASH development.
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ItemNo Preview AvailableKPNA3 variation is associated with schizophrenia, major depression, opiate dependence and alcohol dependence(HINDAWI LTD, 2012)KPNA3 is a gene that has been linked to schizophrenia susceptibility. In this study we investigated the possible association between KPNA3 variation and schizophrenia. To investigate a wider role of KPNA3 across psychiatric disorders we also analysed major depression, PTSD, nicotine dependent, alcohol dependent and opiate dependent cohorts. Using a haplotype block-based gene-tagging approach we genotyped six KPNA3 single nucleotide polymorphisms (SNPs) in 157 schizophrenia patients, 121 post-traumatic stress disorder patients, 120 opiate dependent patients, 231 alcohol dependent patients, 147 nicotine dependent patients and 266 major depression patients. One SNP rs2273816 was found to be significantly associated with schizophrenia, opiate dependence and alcohol dependence at the genotype and allele level. Major depression was also associated with rs2273816 but only at the allele level. Our study suggests that KPNA3 may contribute to the genetic susceptibility to schizophrenia as well as other psychiatric disorders.
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ItemLong acting risperidone in Australian patients with chronic schizophrenia: 24-month data from the e-STAR database(BIOMED CENTRAL LTD, 2012-03-26)BACKGROUND: This observational study was designed to collect treatment outcomes data in patients using the electronic Schizophrenia Treatment Adherence Registry (e-STAR). METHODS: Patients with schizophrenia or schizoaffective disorder in Australia who were prescribed risperidone long-acting injection (RLAI) between 2003 and 2007 were assessed 12-months retrospectively, at baseline and 24-months prospectively at 3-monthly intervals. The intent-to-treat population, defined as all patients who received at least one dose of RLAI at baseline, was used for the efficacy and safety analyses. RESULTS: At total of 784 patients (74% with schizophrenia, 69.8% male) with a mean age of 37.1 ± 12.5 years and 10.6 ± 9.5 years since diagnosis were included in this Australian cohort. A significant improvement in mean Clinical Global Impression - severity score was observed at 24-months (4.52 ± 1.04 at baseline, 3.56 ± 1.10 at 24-months). Most of this improvement was seen by 3-months and was also reflected in mean Global Assessment of Functioning score, which improved significantly at 24-months (42.9 ± 14.5 at baseline, 59 ± 15.4 at 24-months). For patients still receiving RLAI at 24-months there was an increase from a mean baseline RLAI dose of 26.4 ± 5 mg to 43.4 ± 15.7 mg. Sixty-six percent of patients discontinued RLAI before the 24-month period--this decreased to 46% once patients lost to follow-up were excluded. CONCLUSION: Over the 24-month period, initiation of RLAI was associated with improved patient functioning and illness severity in patients with schizophrenia or schizoaffective disorder. Improved outcomes were observed early and sustained throughout the study. TRIAL REGISTRATION: Clinical Trials Registration Number, NCT00283517.
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ItemCo-prescription of medication for bipolar disorder and diabetes mellitus: a nationwide population-based study with focus on gender differences(BMC, 2012-11-27)BACKGROUND: Studies have shown a correlation between bipolar disorder and diabetes mellitus. It is unclear if this correlation is a part of common pathophysiological pathways, or if medication for bipolar disorder has negative effects on blood sugar regulation. METHODS: The Norwegian prescription database was analyzed. Prescriptions for lithium, lamotrigine, carbamazepine and valproate were used as proxies for bipolar disorder. Prescriptions for insulin and oral anti-diabetic agents were used as proxies for diabetes mellitus. We explored the association between medication for bipolar disorder and diabetes medication by logistic regression RESULTS: We found a strong association between concomitant use of medication to treat diabetes mellitus and mood stabilizers for the treatment of bipolar disorder. Females had a 30% higher risk compared to men of being treated for both disorders. Persons using oral anti-diabetic agents had higher odds of receiving valproate than either lithium or lamotrigine. Use of insulin as monotherapy seemed to have lower odds than oral anti-diabetic agents of co-prescription of mood stabilizers, compared to the general population. CONCLUSIONS: This study showed a strong association between the use of mood stabilizers and anti-diabetic agents. The association was stronger among women than men.
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ItemThe function of 'functional': a mixed methods investigation(B M J PUBLISHING GROUP, 2012-03)OBJECTIVE: The term 'functional' has a distinguished history, embodying a number of physiological concepts, but has increasingly come to mean 'hysterical'. The DSM-V working group proposes to use 'functional' as the official diagnostic term for medically unexplained neurological symptoms (currently known as 'conversion disorder'). This study aimed to explore the current neurological meanings of the term and to understand its resilience. DESIGN: Mixed methods were used, first interviewing the neurologists in a large UK region and then surveying all neurologists in the UK on their use of the term. RESULTS: The interviews revealed four dominant uses--'not organic', a physical disability, a brain disorder and a psychiatric problem--as well as considerable ambiguity. Although there was much dissatisfaction with the term, the ambiguity was also seen as useful when engaging with patients. The survey confirmed these findings, with a majority adhering to a strict interpretation of 'functional' to mean only 'not organic', but a minority employing it to mean different things in different contexts - and endorsing the view that 'functional' would one day be a neurological construct again. CONCLUSIONS: 'Functional' embodies real divisions in neurologists' conceptualisation of unexplained symptoms and, perhaps, between those of patients and neurologists: its diversity of meanings allows it to be a common term while meaning different things to different people, or at different times, and thus conceal some of the conflict in a particularly contentious area. This flexibility may help explain the term's longevity.