Risk of Neuropsychiatric Adverse Effects of Lipid-Lowering Drugs: A Mendelian Randomization Study.

Background: Recent studies have highlighted the possible risk of neuropsychiatric adverse effects during treatment with lipid-lowering medications. However, there are still controversies that require a novel genetic-based approach to verify whether the impact of lipid-lowering drug treatment results in neuropsychiatric troubles including insomnia, depression, and neuroticism. Thus, we applied Mendelian randomization to assess any potential neuropsychiatric adverse effects of conventional lipid-lowering drugs such as statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and ezetimibe. Methods: A 2-sample Mendelian randomization study was conducted based on summary statistics from genome-wide association studies for lipids, insomnia, depression, and neuroticism. Single-nucleotide polymorphisms located in or near drug target genes of HMGCR, PCSK9, and NPC1L1 were used as proxies for statins, PCSK9 inhibitors, and ezetimibe therapy, respectively. To assess the validity of the genetic risk score, their associations with coronary artery disease were used as a positive control. Results: The Mendelian randomization analysis showed a statistically significant (P <.004) increased risk of depression after correcting for multiple testing with both statins (odds ratio=1.15, 95% CI: 1.04-1.19) and PCSK9 inhibitor treatment (odds ratio =1.19, 95%CI: 1.1-1.29). The risk of neuroticism was slightly reduced with statin therapy (odds ratio=0.9, 95%CI: 0.83-0.97). No significant adverse effects were associated with ezetimibe treatment. As expected, the 3 medications significantly reduced the risk of coronary artery disease. Conclusion: Using a genetic-based approach, this study showed an increased risk of depression during statin and PCSK9 inhibitor therapy while their association with insomnia risk was not significant.

Personality traits and behavioural and psychological symptoms in patients with mild cognitive impairment.

BACKGROUND AND AIMS: Both personality changes and behavioural and psychological symptoms (BPS) may be associated with mild cognitive impairment (MCI) in later life and help identify incipient dementia. We wished to investigate the links between personality and BPS in MCI. METHOD: We studied premorbid personality traits as estimated 5 years back and their changes in 83 control subjects and 52 MCI patients using the revised NEO Personality Inventory for the Five-Factor Model completed by a proxy. Information on BPS was obtained using the Neuropsychiatric Inventory (NPI). Analyses were controlled for current depression and anxiety. RESULTS: Premorbid neuroticism and openness to experience were associated with the total NPI score. The changes in neuroticism, extraversion, openness to experiences, and conscientiousness were associated with apathy and affective symptoms. CONCLUSIONS: Personality changes and BPS occur in MCI. The occurrence of affective BPS and apathy is associated with both premorbid personality traits and their changes.

Do antidepressants change personality?--a five-year observational study.

BACKGROUND: Whether antidepressants influence personality is a major clinical and societal issue due to their widespread use. In an observational study, we investigated whether depressive patients' neuroticism and extraversion scores covary with antidepressant pharmacotherapy, and if so, whether this remains significant after accounting for depressive or anxiety symptoms. METHODS: Major depressive disorder patients (N=237) were interviewed at up to four time-points in a five-year prospective longitudinal study. Changes in neuroticism plus extraversion scores were compared with changes in antidepressant pharmacotherapies and depressive plus anxiety symptoms to uncover any covariation between them. Autoregressive path models were used to examine this covariation at the sample level. Within-subject change was estimated using a random-effects latent change model. RESULTS: Significant covariation is present in the change trajectories between personality scores and depressive symptoms; declining depression scores were associated with rising extraversion and declining neuroticism. Although the personality scores of many patients changed significantly over the five-year study, none of these changes were associated with changes in antidepressant pharmacotherapy. LIMITATIONS: The study covered only two dimensions of personality. Single drug-specific analysis could not be done. Antidepressant blood levels were not measured. CONCLUSION: No evidence emerged for significant covariation of antidepressant pharmacotherapy with neuroticism or extraversion scores. By contrast, changes in both personality dimensions were associated with changes in depressive symptoms, those in neuroticism also in anxiety symptoms. If antidepressants influence these personality dimensions, the effect size is likely markedly smaller than that of the disorders for which they are prescribed.

Polypharmacy and decreased cognitive abilities in elderly patients.

GOAL: To estimate the prevalence of poly pharmacy and poly pharmacy effect on decline in cognitive abilities of randomly selected group of people over 65. METHODOLOGY: A preliminary pilot study was based on the results of other researchers. 54 patients over 65 were randomly interviewed. Poly pharmacy was defined as using 23 drugs. "A short portable mental status questionnaire" was used in estimating decline of cognitive abilities. RESULTS: According to the study results it was concluded that prevalence of poly pharmacy by the elderly is significant--48.1%. Most present drugs are the ones treating cardiovascular disease, anti diabetic, anti-inflammatory drugs, long acting benzodiazepines, antihistamines. Of the total respondents 33.3% of them live alone and do not have adequate supervision. We have found that poly pharmacy resulted in decline of cognitive abilities in 23 of 54 patients tested in rapid mental status check. CONCLUSION: It is necessary to conduct future research on this issue.

[Psychoneurological disorders in acute intoxications by psychotropic drugs and their correction using hyperbaric oxygenation].

The paper presents the results of a study of the clinical features of psychoneurological disorders in 178 patients with acute intoxications by various psychotropic drugs. Hyperbaric oxygenation showed positive changes in psychopathological syndromic kinesis. A sanogenetic rationale is provided for the method of choice in treating this category of patients.

Psychoneurological symptoms during interferon therapy in patients with chronic hepatitis: prospective study on predictive use of Cornell Medical Index and electroencephalogram.

BACKGROUND/AIMS: We assessed the usefulness of the Cornell Medical Index (CMI) and electroencephalogram (EEG) in the prediction and early detection of psychoneurological symptoms associated with interferon (IFN) therapy for chronic viral hepatitis. METHODS: Forty-eight consecutive patients received IFN for chronic viral hepatitis for 8-24 weeks. CMI was measured before IFN therapy. Serial EEGs were recorded before IFN therapy, 2, 4 weeks, and thereafter every 4 weeks in the therapy. RESULTS: Psychoneurological symptoms including insomnia, depression, and restlessness were seen in 11 (23%) of 48 patients. Five (13%) of 40 patients with CMI I and II and six (75%) of eight with CMI III developed psychoneurological symptoms (P<0.001). Sensitivity, specificity, and predictive accuracy of CMI III were 55%, 95%, and 75%, respectively. Abnormal EEG such as slow basic rhythm, appeared in 13 patients (27%) during IFN therapy. Psychoneurological symptoms were seen in six (46%) of the 13 patients with abnormal EEG, and in five (14%) of 35 in whom EEG remained normal (P<0.05). CONCLUSIONS: CMI is useful for the prediction of IFN-induced psychoneurological symptoms in patients with chronic viral hepatitis. Serial EEGs contribute to the screening and auxiliarily assessing the adverse effects of IFN on the central nervous system.

Toxic effect of chloromycetin on the ultrastructures of the motor neurons of the Chinese tree shrew (Tupaia belangeri).

This paper describes the toxic effects of chloromycetin on the motor neurons of the Chinese tree shrew (Tupaia belangeri chinensis) with horse radish peroxidase (HRP) as the labeling enzyme. When chloromycetin was administered orally at 2.5 mg/kg (body weight)/day for 3 days, Chinese tree shrews showed evidence of neurotoxicity. This included damage in cortical motor neuron synapses ending on neurons of the red nucleus and the ultrastructural changes in the mitochondria such as swelling of these organelles and blurring of their cristae. There was an increase of the mitochondrial matrix density and of the thickness of the synaptic membranes. These observations indicate that chloromycetin can lead to ultrastructural change of terminals of the cortical motor axons, and that Chinese tree shrews are sensitive animal model for chloromycetin neurotoxicity.

Role of the central nervous system in hemopoiesis regulation during experimental neuroses.

Pharmacological blockade of dopamine- and serotoninergic structures with haloperidol and cyproheptadine, respectively, attenuated hyperplasia of bone marrow granulocytopoiesis and erythropoiesis (cyproheptadine) caused by conflict situation. At the same time, haloperidol and, especially, cyproheptadine normalized suppressed erythropoiesis and modulated activated granulocytopoiesis under conditions of paradoxical sleep deprivation. These results indicate that central regulation of hemopoietic stems is mediated by different neurotransmitter mechanisms. Erythropoiesis depends on the state of serotoninergic structures, while granulocytopoiesis is regulated both by the dopamine- and serotoninergic systems.

Exposure to organic solvents and personality.

OBJECTIVES: Although cognitive and neuropsychological changes have been found after high cumulative exposures to solvents, it is not clear whether such exposures are associated with personality characteristics. To study this two groups of British and Chinese dockyard painters who had been heavily exposed to paint solvents have been investigated. METHODS: 260 Male dockyard painters in the United Kingdom, 539 local community controls, 109 Chinese dockyard painters, and 255 dockyard controls completed the Eysenck personality questionnaire, neuroticism (N) and social conformity or dissimulation (L) scales. The non-parametric Kruskal-Wallis test was used to evaluate differences in scores of personality traits between painters and controls. Adjusted relative risks for painters having high N and L scores were calculated in a Breslow-Cox regression analysis, and exposure-response relations were examined in multivariate logistic regression analysis. Non-parametric Spearman's correlation was used to examine relations between previously determined neuropsychological symptoms and personality. RESULTS: Both British and Chinese data showed that mean neuroticism scores of painters were significantly higher than controls, whereas scores of social conformity did not differ. Relative risk of being a painter increased significantly with increasing N scores, but L scores showed no such trend. In a case-control analysis, there were significant exposure-response relations for the N score. In the United Kingdom the odds ratios (ORs) (95% confidence interval (95% CI), were 2.03 (0.79 to 5.22) for 1-4 years of exposure, 2.38 (0.82 to 6.91) for 5-9 years, 7.05 (1.27 to 39.25) for 10-14 years, and 1.76 (0.63 to 4.89) for 15-41 years. In the Chinese painters, ORs were 4.66 (1.38 to 15.75) for 2-14 years, 10.03 (2.96 to 34.04) for 15-18 years, and 13.56 (3.78 to 48.59) for 19-43 years. Neuroticism was significantly positively related to neuropsychological symptoms in all subjects. Social conformity showed no association with neuropsychological symptoms in British painters and a negative relation among the Chinese painters. CONCLUSION: Increasing symptoms suggesting neuroticism seemed to relate to the duration of painting whereas scores for social conformity and dissimulation did not. The relation between exposure time and response suggests that increased neuroticism may be caused by long term occupational exposure to organic solvents.

[Mental disorders in workers exposed to chemicals at work]. / Psikhicheskie narusheniia u rabotaiushchikh s khimicheskimi veshchestvami.

The article considers data on boundary psychic disorders in subjects exposed to chemicals of I-II jeopardy classes. Chemical factor appears to increase risk of psychiatric diseases. The authors suggest periodic psychiatric examination of workers engaged into hazardous chemical production for better occupational selection, early diagnosis and treatment of boundary psychic disorders.

[Clinical and functional aspects of adverse effects of toxic substance complexes in firefighters]. / Kliniko-funktsional'naia kharakteristika neblagopriiatnogo deistviia kompleksa toksicheskikh veshchestv na organizm likvidatorov pozhara.

The study covered influence of combined toxic chemicals on fire extinguishers. Acute exposure of respiratory and peripheral nervous systems was demonstrated. Consequences of the exposure were proved to include polyneuropathies, neuroses and other health disorders.

[The neurobehavioral effects of solvents]. / Nevropovedencheski efekti na raztvoritelite.

The paper correlates basic literature on the neuropsychological consequences and a wide range of organic solvents, which are known to induce disorders that range from a "neurasthenic-like" psychological disorders to dementia. By highlighting the type of impairments that are most likely to be associated with organic solvents and their mixtures human neurotoxic solvent syndromes are identified and assessed. The paper provides with a briefly description of classes of solvents, their common characteristics, routes of solvent exposure and general toxic effects. General assessment strategies as well as specific neuropsychological procedures and diagnostic criteria are discussed. The confounding of neuropsychological evaluation with individual characteristics, attitudes and life style, psychosocial and medical disturbances and group dynamic processes that hamper the correct causal attribution of exposure effects is considered.

[A study of relationships among solvent inhalation, personality and expectancy; especially on affinity to hallucination, sensation seeking and neurotic tendency].

94 delinquents in two homes for resocialization were surveyed to elucidate the relationship among the status of volatile solvent inhalation, expectancy and personality. The subjects were classified into solvent-inhalation group and non-solvent-inhalation group, and the former was divided into solvent dependence group and abuse group according to DSM-III-R. Each group was given personality tests; general health questionnaire (GHQ), sensation seeking scale (SSS), the vividness of visual imagery (VVIQ), test of visual imagery control (TVIC) and Yatabe-Guilford test (YG). In addition we investigated expectancy and mental symptoms caused by inhalation in it. The results are summarized as follows; 1. Inhalation group scored higher on SSS than non-inhalation group. 2. Compared with abuse group, dependence group presented with 1) higher GHQ score meaning neurotic tendency; 2) higher TVIC score meaning imagery-control-ability; 3) a higher incidence of day-dream and hallucination, especially egosyntonic type; 4) higher expectancy of "enhancement of positive affection", "reduction of negative affection" and "hallucination seeking"; 5) lower expectancy of "association with friends". 3. Higher scored inhalers on TVIC showed visual hallucinations, especially egosyntonic type more frequently than lower ones. 4. Significant correlations were recognized between GHQ score and expectancy of "reduction of negative affection", and between lack of objectiveness score of YG subscale and "hallucination seeking" expectancy. These results suggested that 1) beginning of inhalation is associated with sensation seeking trait, 2) progression to solvent dependence is correlated with three expectancies, i.e., seeking egosyntonic hallucinations paralleling high imagery-control-ability and subjectivity, reducing negative affection paralleling neurotic tendency, and enhancing positive affection. According to the findings, indulgence to drug induced positive imagery led delinquents into splitting of personality. In their treatment we need to help them to integrate high imagery ability and sensation seeking for recovery.