Psychosocial, psychiatric and work-related risk factors associated with suicide in Ireland: optimised methodological approach of a case-control psychological autopsy study.

BACKGROUND: Suicide has profound effects on families and communities, but is a statistically rare event. Psychological autopsies using a case-control design allow researchers to examine risk factors for suicide, using a variety of sources to detail the psychological and social characteristics of decedents and to compare them to controls. The Suicide Support and Information System Case Control study (SSIS-ACE) aimed to compare psychosocial, psychiatric and work-related risk factors across three groups of subjects: suicide decedents, patients presenting to hospital with a high-risk self-harm episode, and general practice controls. METHODS: The study design includes two inter-related studies; one main case-control study: comparing suicide cases to general practice (GP) controls, and one comparative study: comparing suicide cases to patients presenting with high-risk self-harm. Consecutive cases of suicide and probable suicide are identified through coroners' registration of deaths in the defined region (Cork City and County, Ireland) and are frequency-matched for age group and gender with GP patient controls recruited from the same GP practice as the deceased. Data sources for suicide cases include coroners' records, interviews with health care professionals and proxy informants; data sources for GP controls and for high-risk self-harm controls include interviews with control, with proxy informants and with health care professionals. Interviews are semi-structured and consist of quantitative and qualitative parts. The quantitative parts include a range of validated questionnaires addressing psychiatric, psychosocial and occupational factors. The study adopts several methodological innovations, including accessing multiple data sources for suicide cases and controls simultaneously, recruiting proxy informants to examine consistency across sources. CONCLUSIONS: The study allows for the investigation of consistency across different data sources and contributes to the methodological advancement of psychological autopsy research. The study will also inform clinical and public health practice. The comparison between suicide cases and controls will allow investigation of risk and protective factors for suicide more generally, while the comparison with high-risk self-harm patients will help to identify the factors associated specifically with a fatal outcome to a self-harm episode. A further enhancement is the particular focus on specific work-related risk factors for suicide.

Association between psychological distress and cancer type in patients referred to a psycho-oncology service.

Psychological distress is common in patients with cancer and psychological well-being is increasingly seen as an important component of cancer care. The aim of this study was to examine the relationship between cancer type and subjective distress. The following data were collected from a database of consecutive psycho-oncology referrals to the Liaison Psychiatry service in Cork University Hospital from 2006 to 2015: demographics, cancer diagnosis, Distress Thermometer (DT) score. 2102 out of 2384 referrals were assessed. Of those assessed, the most common cancer diagnoses were breast (23%, n=486) followed by haematological (21%, n=445). There were significant difference in DT score between the different cancer types, (?2(13)=33.685, p=0.001, Kruskal-Wallis test). When adjusted for age, gender and whether or not the cancer was recently diagnosed, there was no significant association between cancer type and psychological distress. In conclusion, cancer type is not associated with level of distress in cancer.

The incidence and clinical correlates of lithium toxicity: a retrospective review.

BACKGROUND: Lithium is a commonly prescribed pharmacological treatment for mood disorders. It is associated with a number of side effects and potentially serious toxicity. To date, there is little data from Irish samples on the subject of Lithium toxicity. AIM: To examine the incidence and clinical correlates of lithium toxicity in Cork, Ireland. RESULTS: Our study identified 130 cases of biochemical lithium toxicity over 5 years, with an incidence rate of approximately 5.4 cases per 100,000 per year. Mean toxic lithium level was 2.16 mmol/L ±SD 0.87 mmol/L. Of these, 36% cases were reviewed medically in the general hospital at the time of toxicity. A number of issues in relation to lithium toxicity were identified. Neurological symptoms were common, including tremor, confusion, ataxia, drowsiness. However, only 4.2% patients were reviewed by a neurologist while in hospital. Medications that interact with lithium were found in 50% cases, with significant polypharmacy in 15%. The psychiatric services were involved in patient care in 76% cases, and 85% patients presenting with toxicity were reviewed by a psychiatrist. Rates of admission to hospital and haemodialysis were 70 and 11%, respectively. CONCLUSION: Improvements in the standards of care in relation to lithium prescribing are required.

Neurology referrals to a liaison psychiatry service.

The objective of the present study was to assess the activity of the Liaison Psychiatry service of Cork University Hospital in relation to all in-patient neurology referrals over a 12-month period. Of 1685 neurology admissions, 106 (6%) were referred to liaison psychiatry for assessment. 91 referrals (86%) met criteria for a psychiatric disorder according to DSM-IV, the commonest being major depression (24%) and somatoform disorder (23%). Patients with multiple sclerosis or epilepsy comprised nearly half of all referrals (48 cases; 45%). Approximately 20% of M.S. in-patients (21 cases) were referred for psychiatric assessment, with the corresponding figure in epilepsy being 25% (18 cases). Although only 106 (6%) neurology in-patients were referred to liaison psychiatry, psychiatric diagnoses were documented in 327 (20%) discharge forms, presumably reflecting previous diagnosis. The above findings indicate that psychiatric illness is common among neurology inpatients screened by liaison psychiatry yet referral rates are relatively low in terms of the overall number of neurology in-patients. Psychiatric disorders were diagnosed in 86% of referrals indicating high concordance between neurologists and liaison psychiatry regarding the presence of a psychiatric disorder.

Alcohol misuse in the general hospital: some hard facts.

AIMS: To examine (1) the prevalence of alcohol use disorders in adult general hospital inpatients; (2) the accuracy of documentation in relation to alcohol use. METHODS: A total of 210 random patients were interviewed out of 1,448 consecutive new admissions to CUH over 7 days. Case notes were reviewed for 206 (98%). Alcohol consumption was assessed using the Fast Alcohol Screening Test (FAST) and weekly drinking diary. FAST-positive (and a random sample of FAST-negative) patients then had a standardized interview. RESULTS: A total of 82% admitted for drinking alcohol. Among them 22% were drinking in excess of guidelines, 9% had DSM-IV Alcohol Abuse and 7% dependence. The sensitivity and specificity of the FAST for detecting those drinking above guidelines were 89 and 94% and for detecting a DSM-IV diagnosis was 100 and 73%. The majority of case notes contained inadequate information about alcohol intake. CONCLUSION: Alcohol use disorders are common and often undetected in the general hospital setting.

The role of the standard EEG in clinical psychiatry.

BACKGROUND: The EEG is a commonly requested test on patients attending psychiatric services, predominantly to investigate for a possible organic brain syndrome causing behavioural changes. AIMS: To assess referrals for EEG from psychiatric services in comparison with those from other sources. We determine which clinical factors were associated with an abnormal EEG in patients referred from psychiatric sources. METHODS: A retrospective review of EEG requests in a 1-year period was performed. Analysis of referral reasons for psychiatric patients was undertaken, and outcome of patients referred from psychiatric services post-EEG was reviewed. RESULTS: One thousand four hundred and seventy EEGs were reviewed, of which 91 (6.2%) were referred from psychiatry. Neurology service referrals had detection rates of abnormal EEGs of 27%, with psychiatric referrals having the lowest abnormality detection rate of 17.6% (p < 0.1). In psychiatric-referred patients the only significant predictors found of an abnormal EEG were a known history of epilepsy (p < 0.001), being on clozapine (p < 0.05), and a possible convulsive seizure (RR = 6.51). Follow-up data of 53 patients did not reveal a significant clinical impact of EEG results on patient management. CONCLUSIONS: Many patients are referred for EEG from psychiatric sources despite a relatively low index of suspicion of an organic brain disorders, based on reasons for referral documented, with an unsurprising low clinical yield.

Central 5-HT receptor hypersensitivity in migraine without aura.

Serotonin has long been implicated as a key neurotransmitter in migraine. There is a dearth of research specifically examining 5-HT1A receptor sensitivity in migraine despite the importance of this receptor in regulating central serotonergic tone. In this study we examined the hypothesis that migraine without aura is associated with hypersensitivity of central 5-HT1A receptors, using a 5-HT1A neuroendocrine challenge drug and comparing serum prolactin responses between a test group with migraine and a matched group of healthy controls. Twelve female subjects fulfilling International Headache Society (IHS) criteria for migraine without aura were evaluated. Following an overnight fast, subjects presented for testing at 9am. An intravenous canula was inserted and serum prolactin was assessed at baseline and every 30 min for 3 h following a single dose of 30 mg oral buspirone, a 5-HT1A-receptor agonist. Subjects were assessed during the first 5 days of the menstrual cycle. No subjects were taking psychotropic medication or migraine prophylactic treatment. Patients with current or previous psychiatric disorder, daily headache or analgesic overuse were excluded. 16 healthy female volunteers matched for age and menstrual status were also evaluated and served as controls. There was no difference in baseline prolactin between groups. There was a significant rise in prolactin following buspirone in both groups. Subjects with migraine had a significantly increased prolactin response to buspirone (delta max) compared to controls (P < 0.001). This study supports the hypothesis that migraine without aura is associated with a relative hypersensitivity of central 5-HT1A receptors. This is of relevance given the role of the 5-HT1A receptor in controlling raphe 5-HT tone and in the possible association between migraine and anxiety and depression.

Lethal catatonia responding to high-dose olanzapine therapy.

We present the case of a 31-year-old woman with recent refractory bipolar disorder who developed a malignant syndrome preceded by catatonic motor features. This resistant case of lethal catatonia responded selectively to high-dose olanzapine treatment. The case illustrates the need to consider lethal catatonia in apparent cases of neuroleptic malignant syndrome that do not respond to conventional treatment with dantrolene and bromocriptine.

Group II and III metabotropic glutamate receptors modulate paired pulse depression in the rat dentate gyrus in vitro.

We have investigated the effect of a number of group I, II and III metabotropic glutamate (mGlu) receptor agonists and antagonists on paired pulse depression in the medial perforant path of the rat dentate gyrus in vitro. A triphasic pattern of a large depression at short intervals (10-50 ms), a reduction of this depression at intermediate intervals (50-200 ms) and again a large depression at late intervals (> 200 ms) was observed. The group I mGlu receptor agonist, (S)-3,5-dihydroxy phenylglycine ((S)-DHPG; 20 microM) had no significant effect on paired pulse depression at any interstimulus intervals. The mGlu receptor group II and III agonists, L-CCG-1 ((2S,3S,4S)-alpha-(carboxy-cyclopropyl)-glycine), DCG-IV ((2S,1'R,2'R,3'R)-2-2',3'-dicarboxy cyclopropylglycine), 1S,3R-ACPD (1S,3R-1-aminocyclopentate-1,3-dicarboxylic acid) and L-AP4 (L-2-amino-4-phosphono butyric acid) reduced paired pulse depression at interstimulus intervals of 200 ms or less. Application of the non specific mGlu receptor antagonist, MCPG (alpha-methyl carboxy-phenylglycine; 200 microM) completely inhibited the 1S,3R ACPD-induced reduction in paired pulse depression but was without effect on the L-AP4 response. The relatively specific group II antagonist MCCG ((2S,3S,4S)-2-methyl-2-carboxy cycloproprylglycine) at 200 microM and 500 microM, attenuated but did not completely inhibit the DCG-IV induced reduction of paired pulse depression. The putative group III pre-synaptic mGlu receptor antagonist alpha-methyl-L-AP4 and MSOP ((RS)-alpha-methylserine-O-phosphate) both at 200 microM inhibited the L-AP4-induced reduction in paired pulse depression at intermediate phase interstimulus intervals but not at early interstimulus intervals. These results specifically demonstrate the involvement of group III and III mGlu receptor ligands in the modulation of paired pulse depression in the medial perforant pathway.

Periocular FK-506 delays allograft rejection in rat penetrating keratoplasty.

FK-506 is a new immunosuppressant with the ability to inhibit activation of T-lymphocytes that would be cytolytic to an allograft. We studied periocular injection of FK-506 in a rat penetrating keratoplasty model. Corneas were transplanted from Brown Norway rats into Lewis rat recipients. The transplanted rats received periocular injection of either 0.5 mg/kg FK-506 or an equivalent volume of FK-506 vehicle only. Injections were given 1 day before, at keratoplasty, and every other day after keratoplasty until allograft rejection. The group receiving FK-506 had a significant delay in allograft rejection (p < 0.05). The FK-506 group rejected 12-20 days postkeratoplasty with a mean rejection time (MRT) of 14.3 days, compared with 8-14 days (MRT 11.1 days) for the control group. We conclude that periocular administration of FK-506 is effective in prolonging allograft survival in the rat penetrating keratoplasty model.

Asparaginyl deamidation-methylation of rat ventricular myosin light chains.

Spontaneous asparaginyl deamidation can produce damage to cytoskeletal proteins, and may lead to their targeting for subsequent rapid intracellular breakdown or repair. To test if myofibrillar proteins are subject to spontaneous deamidation damage in vitro, purified rat ventricular myosin light chain 1 (MLC1v) and phosphorylatable myosin light chain 2 (MPLC2v) were incubated (37 degrees C, 4 h, pH 2-11), and tested as substrates for human erythrocyte and rat cardiac protein carboxyl methyltransferase (PCMT). PCMT catalyzes the transfer of a methyl group from [3H-methyl] S-adenosyl methionine to deamidated asparaginyl residues and altered aspartyl residues on damaged proteins. MLC1v and MPLC2v underwent extensive incubation damage at neutral and alkaline pH. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography revealed 3H-incorporation into MLC1v, MPLC2v, and a Mr = 14,000 polypeptide. 3H-methylated, CNBr-cleavage fragments of PCMT-methylated light chains were then separated by reverse-phase high performance liquid chromatography, and sequenced by automated Edman degradation. The major 3H-labeled peptide of the Mr = 14,000 protein proved homologous to residues 84 to 104 of rat MPLC2v, with a proposed deamidation site at Asn99-Ala100. The major 3H-labeled peptide from MLC1v proved homologous to residues 73 to 111 of rat cardiac MLC1v, with a proposed deamidation site at Asn108-Ser109. These results indicate that both myofibrillar protein subunits undergo selective non-enzymatic degradation at neutral and alkaline pH, resulting in the formation of methyl acceptor sites for human erythrocyte and rat cardiac PCMT. PCMT-catalyzed methylation of ventricular myosin light chains may be important in the repair, or subsequent proteolysis of these long-lived structural proteins of the myofibril.