Relationship between plasma TNF-α levels and agitation symptoms in first episode patients with schizophrenia.

BACKGROUND: Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to investigate their association with agitation in first episode patients with schizophrenia (FEPS). METHODS: The plasma TNF-α and sTNF-α R1 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) in the FEPS with (n = 36) and without agitation (n = 49) symptoms, and healthy controls (HCs, n = 54). The psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS), and the agitation symptoms were evaluated by the PANSS excitatory component (PANSS-EC). RESULTS: The plasma TNF-α levels in patients with and without agitation symptoms were significantly higher than those in HCs. The patients with agitation had significantly higher plasma TNF-α levels compared to the patients without agitation. There were no significant differences in the sTNF-α R1 levels among the three groups. Furthermore, the plasma TNF-α levels were positively correlated with the PANSS total score, Positive and General psychopathological subscores, and PANSS-EC score in the FEPS, but the relationships were not found for the plasma sTNF-α R1 levels. CONCLUSIONS: These results suggested that TNF-α might play an important role in the onset and development of agitation symptoms of schizophrenia.

Vitamin D and behavioral disorders in older adults: results from the CLIP study.

OBJECTIVES: Vitamin D is involved in brain health and function. Our objective was to determine whether vitamin D deficiency was associated with behavioral disorders in geriatric patients. DESIGN: The observational cross-sectional CLIP (Cognition and LIPophilic vitamins) study. The report followed the STROBE statement. SETTING: Geriatric acute care unit in a tertiary university hospital in France for 3 months at the end of winter and beginning of spring. PARTICIPANTS: 272 patients ≥65 years consecutively hospitalized or seen in consultation. MEASUREMENTS: Participants were separated into two groups according to vitamin D deficiency (i.e., serum 25-hydroxyvitamin D ≤25 nmol/L). Behavior was assessed using the reduced version of the Neuropsychiatric Inventory Scale (NPI-R) score and subscores. Age, sex, BMI, education level, comorbidities, MMSE and GDS scores, use psychoactive drugs and vitamin D supplements, and serum concentrations of calcium, parathyroid hormone, TSH and estimated glomerular filtration rate (eGFR) were used as potential confounders. RESULTS: Participants with vitamin D deficiency (n = 78) had similar NPI-R score (17.4 ± 20.3 versus 17.2 ± 16.1, p = 0.92) but higher (i.e., worse) subscore of agitation and aggressiveness (2.0 ± 3.3 versus 1.2 ± 2.4, p = 0.02) and higher (i.e., worse) subscore of disinhibition (0.99 ± 2.98 versus 0.38 ± 1.42, p = 0.02) than those without vitamin D deficiency (n = 194). In multiple linear regressions, vitamin D deficiency was inversely associated with the subscore of agitation and aggressiveness (ß = 1.37, p = 0.005) and with the subscore of disinhibition (ß = 0.96, p = 0.008). CONCLUSION: Vitamin D deficiency was associated with more severe subscores of agitation and aggressiveness and of disinhibition among older adults. This provides a scientific basis to test the efficacy of vitamin D supplementation on behavioral disorders in older patients with vitamin D deficiency.

Blood-based biomarkers of agitation in Alzheimer's disease: Advances and future prospects.

Agitation is a common neuropsychiatric symptom that becomes more prevalent as Alzheimer's disease (AD) increases in severity. The treatment of agitation is an urgent and unmet need due to the poor outcomes associated with it, its disruptive impact on patients and caregivers, and the lack of efficacious and safe treatments. Recent research on agitation in AD with blood-based biomarkers has advanced the search for its biomarkers beyond the brain and provides new insights to understand its mechanisms and improve treatments. Here, we reviewed studies of blood-based biomarkers of agitation in AD, which show that inflammatory biomarkers are increased in patients with agitation, may predict the development of agitation, and are associated with symptom severity. In addition, they may also track symptom severity and response to treatment. Other biomarkers associated with agitation include markers of oxidative stress, brain cholesterol metabolism, motor activity, and clusterin, a chaperone protein. These results are promising and need to be replicated. Preliminary evidence suggests a role for these biomarkers in interventional studies for agitation to predict and monitor treatment response, which may eventually help enrich study samples and deliver therapy likely to benefit individual patients. Advances in blood-based biomarkers of AD including those identified in "-omic" studies and high sensitivity assays provide opportunities to identify new biomarkers of agitation. Future studies of agitation and its treatment should investigate blood-based biomarkers to yield novel insights into the neurobiological mechanisms of agitation, monitoring symptoms and response to treatment, and to identify patients likely to respond to treatments.

Blood DNA Methylation Levels in the WNT5A Gene Promoter Region: A Potential Biomarker for Agitation in Subjects with Dementia.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) cause a heavy burden for both patient and caregivers. These symptoms are diverse, and their mechanism is still unclear. Agitation is the most common and difficult to treat among BPSD. In recent years, while changes in DNA methylation levels have been receiving attention as a biomarker of aging and dementia, associations with BPSD have not been examined. OBJECTIVE: Focusing on agitation, the objective of the present study was to identify a region where changes in DNA methylation levels are associated with agitation. METHODS: Using genome-wide DNA methylation analysis data for 7 dementia subjects with agitation, 5 dementia subjects without agitation, and 4 normal elderly controls, we determined a signaling pathway in the WNT5A gene promoter region to be associated with agitation. Based on this result, we measured DNA methylation levels in this region for 26 dementia subjects with agitation and 82 dementia subjects without agitation by means of methylation-sensitive high-resolution melting (MS-HRM) analysis. RESULTS: The WNT5A DNA methylation level in dementia subjects with agitation was significantly lower than in those without agitation (p = 0.001). Changes in WNT5A DNA methylation levels were not influenced by age, sex, body mass index, APOE ɛ4, medication, or inflammatory cytokines. CONCLUSION: Our results suggested an association of agitation with Wnt signaling, in particular with changes in WNT5A DNA methylation levels, which could be a potentially useful biomarker for predicting the appearance of agitation. It may contribute to the elucidation of the mechanism of BPSD.

[C-reactive protein and agitation in patients with schizophrenia: A cohort study with a control group]. / Protéine C-réactive et agitation chez des patients atteints de schizophrénie : suivi d'une cohorte avec groupe témoin.

BACKGROUND: Recent studies first reported the relevant role of the immune system in the pathophysiology of schizophrenia and then the association between inflammation and agitation. OBJECTIVES: In this study, we aim to explore the relationship between CRP (C-reactive protein) levels and agitation in patients with schizophrenia. METHODS: We conducted a cohort study with a comparison group of 60 patients with a DSM5 diagnosis of schizophrenia who were followed by the Department of Psychiatry of the University Hospital of Marrakech in Morocco. Patients were divided into two groups according to the state of agitation evaluated by the PANSS Excitement scale. These two groups have been matched according to age and gender. A comparison of CRP level, clinical and laboratory characteristics between the two groups and a monitoring of CRP level in the agitated group after 3 weeks of treatment were performed. RESULTS: Inpatients with agitation displayed a significantly high CRP (P<0.0001), a high score of PANSS total (P<0.0001), PANSS positive (P<0.0001) and general PANSS (P<0.0001). After treatment, there was a significant reduction in CRP (P<0.0001) and PANSS excitement (P<0.0001). CONCLUSION: These results confirm the role played by inflammation and immunity in agitation behavior in patients with schizophrenia and highlight the interest of the CRP assay at the time of admission of patients as a potential marker of agitation in hospitalized patients with schizophrenia.

Association between circulating zinc/ferritin levels and parent Conner's scores in children with attention deficit hyperactivity disorder.

ADHD is one of the most common neurobehavioral disorders among children and adolescents. In this prospective study, we aimed to measure circulating zinc and ferritin levels in children with ADHD, pick up the deficient ones to give zinc and iron supplements then compare before and after treatment according to their Conner's scores and Wecsler IQ test. Current study included fifty children diagnosed as having ADHD by DSMV criteria, their zinc and ferritin levels were measured by Colorimetric method and enzyme-linked immunosorbent assay (ELISA) respectively. They were divided into: group I (zinc only deficient),group II (zinc and ferritin deficient),group III (non-deficient), cases with mineral deficiency received zinc (55 mg/day) and/or iron (6 mg/kg/day) for 6 months then reassessed by parent Conner's rating scale. In group 1, there was no significant difference between the Wecsler verbal and non-verbal IQ scores and oppositional and cognitive problems in Conner's scores before and after zinc supplements, although there was significant improvement in attention, hyperactivity, emotional liability and impulsivity. In group II, there was significant improvement in verbal and total IQ but not in performance IQ, also there was significant improvement in hyperactivity, emotional liability and impulsivity with no significant difference in oppositional, cognitive problems and inattention before and after zinc/ iron supplements. In Conclusion, Zinc supplements in adjuvant to the main treatment significantly improved symptoms of ADHD children. However, a combined zinc and iron supplements was superior to zinc alone in alleviating ADHD symptoms as well as IQ improvement.

24S-Hydroxycholesterol Is Associated with Agitation Severity in Patients with Moderate-to-Severe Alzheimer's Disease: Analyses from a Clinical Trial with Nabilone.

BACKGROUND: Agitation is a prevalent and difficult-to-treat symptom of Alzheimer's disease (AD). The endocannabinoid system (ECS) has been a target of interest for the treatment of agitation. However, ECS signaling may interact with AD-related changes in brain cholesterol metabolism. Elevated brain cholesterol, reflected by reduced serum 24-S-hydroxycholesterol (24S-OHC), is associated with reduced membrane fluidity, preventing ligand binding to cannabinoid receptor 1. OBJECTIVE: To assess whether 24S-OHC was associated with agitation severity and response to nabilone. METHODS: 24S-OHC was collected from AD patients enrolled in a clinical trial on nabilone at the start and end of each phase. This allowed for the cross-sectional and longitudinal investigation between 24S-OHC and agitation (Cohen Mansfield Agitation Inventory, CMAI). Post-hoc analyses included adjustments for baseline standardized Mini-Mental Status Exam (sMMSE), and analyses with CMAI subtotals consistent with the International Psychogeriatric Association (IPA) definition for agitation (physical aggression and nonaggression, and verbal aggression). RESULTS: 24S-OHC was not associated with CMAI scores cross-sectionally or longitudinally, before and after adjusting for baseline sMMSE. However, 24S-OHC was associated with greater CMAI IPA scores at baseline (F(1,36) = 4.95, p = 0.03). In the placebo phase only, lower 24S-OHC at baseline was associated with increases in CMAI IPA scores (b = -35.2, 95% CI -65.6 to -5.0, p = 0.02), and decreases in 24S-OHC were associated with increases in CMAI IPA scores (b = -20.94, 95% CI -57.9 to -4.01, p = 0.03). CONCLUSION: 24S-OHC was associated with agitation severity cross-sectionally, and longitudinally in patients with AD. However, 24S-OHC did not predict treatment response, and does not change over time with nabilone.

Irisin and BDNF serum levels and behavioral disturbances in Alzheimer's disease.

Behavioral dysfunctions (BPSD) represent the most important problem in Alzheimer's dementia (AD) management. We assessed the serum levels of two myokines in AD patients, preliminary investigating, as secondary aim, their role as potential biomarkers for agitation/aggression (AA) and aberrant motor behavior (AMB): irisin, since it is able to modify the motor pattern, and BDNF, since it was transcribed following irisin stimulation. Forty AD patients were recruited and characterized according to the expressed neuropsychiatric syndrome. Myokines were measured by ELISA. Irisin serum levels were slightly elevated in AA+ patients (+ 10.0%; p < 0.05) and correlated with the duration of AA (r = 0.74, p < 0.03). BDNF failed to show such differences. We propose that these selected myokines are not useful as surrogate markers for agitation in AD, but might represent interesting secondary outcomes when testing drugs for those BPSD implying elevated motor activity.

A prospective three-year follow-up study on the clinical significance of anti-neuronal antibodies in acute psychiatric disorders.

The clinical significance of anti-neuronal antibodies for psychiatric disorders is controversial. We investigated if a positive anti-neuronal antibody status at admission to acute psychiatric inpatient care was associated with a more severe neuropsychiatric phenotype and more frequent abnormalities during clinical work-up three years later. Patients admitted to acute psychiatric inpatient care who tested positive for N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (CASPR2) and/or glutamic acid decarboxylase 65 (GAD65) antibodies (n = 24) were age - and sex matched with antibody-negative patients (1:2) from the same cohort (n = 48). All patients were invited to follow-up including psychometric testing (e.g. Symptom Checklist-90-Revised), serum and cerebrospinal fluid (CSF) sampling, EEG and 3 T brain MRI. Twelve antibody-positive (ab+) and 26 antibody-negative (ab-) patients consented to follow-up. Ab+ patients had more severe symptoms of depression (p = 0.03), psychoticism (p = 0.04) and agitation (p = 0.001) compared to ab- patients. There were no differences in CSF analysis (n = 6 ab+/12 ab-), EEG (n = 7 ab+/19 ab-) or brain MRI (n = 7 ab+/17 ab-) between the groups. In conclusion, anti-neuronal ab+ status during index admission was associated with more severe symptoms of depression, psychoticism and agitation at three-year follow-up. This supports the hypothesis that anti-neuronal antibodies may be of clinical significance in a subgroup of psychiatric patients.

Plasma biomarkers are associated with agitation and regional brain atrophy in Alzheimer's disease.

This study investigated the relationships among plasma biomarkers, regional brain atrophy, and clinical symptoms in patients with Alzheimer's disease (AD; n = 177), mild cognitive impairment (MCI; N = 60) and controls (n = 108). The Mini-Mental Status Examination (MMSE), Clinical Dementia Rating (CDR), and Neuropsychiatric Inventory (NPI) subscales were administered to subjects. Magnetic resonance imaging was performed and medial temporal atrophy (MTA) and posterior atrophy (PA) were assessed visually. We examined associations among cognition, NPI score, plasma ß-amyloid (Aß) and clusterin levels, and regional brain atrophy in patients with AD by regression analysis. The mean MTA score was associated with the plasma Aß1-42/Aß1-40 ratio (r = 0.38, p = 0.01) and with MMSE scores (r = 0.43, p < 0.01). The plasma clusterin level was correlated with CDR sum of box and right-side PA scores (r = 0.28, p = 0.01 and r = 0.30, p = 0.03, respectively). Right-side PA scores were correlated significantly with NPI agitation/aggression (r = 0.30, p = 0.03) subscale scores. In conclusion, the plasma ratio of Aß1-42/Aß1-40 and clusterin level may be associated with different patterns of regional brain atrophy, which in turn may account for the clinical symptoms in patients with AD.

Serum high-sensitivity C-reactive protein: A delicate sentinel elevated in drug-free acutely agitated patients with schizophrenia.

Increased levels of high-sensitivity C reactive protein (hsCRP) have been reported in schizophrenia, but to date, no study is designed to examine serum hsCRP in acutely agitated patients with schizophrenia, an extreme state that requires immediate diagnosis and medical treatment. Serum hsCRP levels were assessed in 32 clinically acutely agitated patients and 42 healthy control subjects matched for demographic properties. Further, serum hsCRP levels in acutely agitated patients were compared with control subjects and with the levels after the patients were treated with anti-psychiatric medications. Meanwhile, the influence of clinical subtypes, family history, and gender, as well as the levels of white blood cell (WBC) counts were also considered. In results, serum hsCRP levels were significantly higher in acutely agitated patients with schizophrenia than in healthy subjects. The elevation of serum hsCRP in patients was not affected by gender, family history (P>0.05), and clinical classification of schizophrenia (P>0.05). However, the elevation of hsCRP was suppressed by the medical treatment for schizophrenia with acute agitation (P<0.05). In addition, WBC counts, another inflammation-related indicator, were also increased significantly in acutely agitated patients compared with healthy subjects, consistent with the elevation of serum hsCRP. In conclusion, hsCRP is an important indicator of immune alterations in the pathogenesis of schizophrenia and has potential to be developed into a sensitive marker for the acute agitation in schizophrenia.

Population pharmacokinetics of intramuscular droperidol in acutely agitated patients.

BACKGROUND: Intramuscular droperidol is used increasingly for sedation of aggressive and violent patients. This study aimed to characterise the pharmacokinetics of intramuscular droperidol in these patients to determine how rapidly it is absorbed and the expected duration of measurable drug concentrations. METHODS: We undertook a population pharmacokinetic analysis of a subgroup of patients from a clinical trial comparing droperidol and midazolam: 17 receiving 5 mg and 24 receiving 10 mg droperidol. Droperidol was measured using high-performance liquid chromatography. Pharmacokinetic modelling was performed under a nonlinear mixed effects modelling framework (NONMEM v7.2). The model was used to simulate concentration time profiles of three typical doses, 5 mg, 10 mg and 10 mg + 10 mg repeated at 15 min. RESULTS: A two-compartment first-order input with first-order output model fitted the data best. The absorption rate constant was poorly characterised by the data and an estimate of the first order rate constant of absorption when fixed to 10 h-1 provided a stable model and lowest objective function. This represents extremely rapid absorption with a half-life of 5 min. The final model had a clearance of 41.9 l h-1 and volume of distribution of the central compartment of, 73.6 l. Median and interquartile range of initial (alpha) half-life was 0.32 h (0.26-0.37 h) and second (beta) half-life was 3.0 h (2.5-3.6 h). Simulations indicate that 10 mg alone provides an 80% probability of being above the lower limit of quantification (5 µg l-1 ) for 7 h, 2 h longer than for 5 mg. Giving two 10 mg doses increased this duration to 10 h. CONCLUSIONS: Intramuscular droperidol is rapidly absorbed with high therapeutic concentrations after 5 and 10 mg doses, and supports clinical data in which droperidol sedates rapidly for up to 6 h.

High prolactin levels are associated with more delirium in septic patients.

PURPOSES: We investigated whether high prolactin levels were associated with delirium in septic patients because neuropsychiatric disorders are frequently associated with hyperprolactinemia. MATERIALS AND METHODS: Prolactin levels were measured daily for 4 days in 101 patients with sepsis. Delirium was assessed using the Richmond Agitation Sedation Scale and the Confusion Assessment Method in the ICU. RESULTS: Delirium developed in 79 patients (78%) and was more common in patients older than 65 years. Prolactin levels were higher in patients with delirium than in those without over the 4 days of observation (P = .032). In patients with delirium, higher prolactin levels were associated with a lower incidence of nosocomial infection (P = .006). Multivariable logistic regression showed that the Sequential Organ Failure Assessment score at intensive care unit admission (odds ratio, 1.24; 95% confidence interval, 1.04-1.48; P = .002) and the combined effect of prolactin levels with age (odds ratio, 1.018; 95% confidence interval, 1.01-1.031; P = .006) were associated with the development of delirium. CONCLUSIONS: High prolactin levels may be a risk factor for delirium in septic patients.

Non-targeted screening for novel psychoactive substances among agitated emergency department patients.

CONTEXT: Novel psychoactive substances (NPS) are being created and introduced at an unprecedented rate, causing frequent, large-scale epidemics. Current identification of NPS in clinical settings in the USA is limited to the retrospective case or small cluster analysis. OBJECTIVE: The purpose of this study was to assess the utility of non-targeted comprehensive drug screening in the agitated patients in an emergency department (ED) setting. MATERIALS AND METHODS: This is a prospective, observational case series that was conducted in the ED of an urban Level I Trauma Center with an annual census of approximately 65,000 patients per year. Since it is common clinical practice at this facility for haloperidol to be used as a second-line chemical restraint when initial dose(s) of benzodiazepines are deemed insufficient, we surmised that the subset of ED patients with psychomotor agitation severe enough to receive both these pharmaceuticals would be likely users of NPS. For 1 month, biweekly pharmacy medication audits identified 49 of these patients. There were sufficient, remaining blood samples from 23 of these patients for analysis. Serum from stored blood samples was analyzed using liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS; LC 1260, TOF/MS 6230, Agilent). Retrospective chart review was done to identify patient clinical information. RESULTS: Six patient samples yielded seven different NPS: JWH-073, JWH-081, JWH-200, methylenedioxybenzylpiperazine, mephedrone, methoxetamine, and herkinorin. CONCLUSION: This study demonstrates that prospective, non-targeted NPS screening in a selected ED patient population is feasible and effective in identifying NPS.

[Anorexia nervosa and hyperactivity in adolescence: psychiatric and internal medicine features]. / Anoressia nervosa e iperattività in adolescenza: correlati psichiatrici e internistici.

AIM: The aim of the present study was to verify the influence of hyperactivity on internistic and psychiatric parameters in early onset anorexia nervosa restricting type (ANR). METHODS: Seventy-three adolescent females (mean age 13.5 years, SD: 2.27) with a diagnosis of ANR (DSM-IV-TR) were consecutively enrolled in the Child and Adolescent Eating Disorders Unit of the IRCCS-Stella Maris and assessed by an extensive clinical protocol. All patients completed: psychiatric evaluation for description of the DCA and comorbidities; pediatric assessment including complete auxological data, blood pressure, heart rate and other electro/echo cardiographic and biohumoral parameters. The hyperactivity was estimated by the application of the "Structured Interview for Anorexic and Bulimic Disorder-Expert Form" (Item 40) in the context of clinical observation. Subjects were identified according to their level of hyperactive (ANR+H) and non-hyperactive (ANR-H) activity. RESULTS: In the ANR+H group heart rate, leptin, sodium, potassium and gamma plasma proteins significantly differ compared to the group ANR-H. Patients with hyperactivity also have a complete form of ANR in 94% of cases compared with 66.7% of non-hyperactive; significant differences were found also in thought and attention CBCL and YSR subscales, combined with major internalizing problems. CONCLUSION: This study provides preliminary data which can orient research towards the development of specific treatments for the hyperactivity, in order to improve the prognosis and thus avoid the chronicity of the disorder and the development of complications in adult life.

Increased systemic inflammatory interleukin-1ß and interleukin-6 during agitation as predictors of Alzheimer's disease.

OBJECTS: Identification of biomarkers for Alzheimer's disease (AD) is important for its early diagnosis and prevention and a key in advancing our understanding of its pathophysiology. The aim of this study was to determine whether systemic inflammatory interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) as well as hypertension (HT), diabetes mellitus (DM), and body mass index (BMI) are predictors of AD. METHODS: We performed a 10-year follow-up study on 133 elderly who were institutionalized in a nursing home. The associations of IL-1ß and IL-6 at both rest and agitation, as well as HT, DM, and BMI at baseline, were analyzed with the incidences of vascular dementia (VD) and AD during a 10-year follow-up period. RESULTS: The Kaplan-Meier method with log-rank test and Cox regression analyses for the total of 133 subjects showed significantly higher incidences of both VD and AD in subjects with DM or HT at baseline. Resting IL-1ß or IL-6 value, or agitation score, was not significantly associated with the subsequent development of VD or AD. The analyses of 40 subjects who had shown agitation at least once in the previous 3 months demonstrated that IL-1ß and IL-6 values at the agitation stage were significantly associated with AD, but not with VD. CONCLUSION: Our results indicate that systemic inflammatory IL-1ß and IL-6 at the agitation stage are risk factors for the development of AD, but not VD. Inflammatory mechanisms for AD seem to be causal and specific to the development of AD.

Ferritin and hyperactivity ratings in attention deficit hyperactivity disorder.

BACKGROUND: Iron is a co-factor of tyrosine hydroxylase which is a critical enzyme in dopamine synthesis. Dopamine has been implicated in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Our objective was to investigate the association of ferritin level with parent and teacher ratings and cognitive measures after controlling for age, sex, ADHD subtype, comorbid conditions, hemoglobin, mean corpuscular volume and reticulocyte distribution width in a large sample. METHODS: The study included 713 children and adolescents with ADHD (613 boys; age 7-15 years). Conners' Parent Rating Scale (CPRS) and Conners' Teacher Rating Scale (CTRS) were obtained. In a subgroup of patients we conducted Digit Span, Digit Symbol, Trail-making Tests as measures of attention and executive functioning. RESULTS: Multiple regression analysis indicated that CPRS Hyperactivity score was significantly associated with ferritin level (B =-0.12; t =-3.1; P < 0.01). Other CPRS and CTRS scores as well as cognitive measures were not associated with ferritin level. CONCLUSIONS: Although it is not possible to make an inference on causality in cross-sectional studies, the results of this largest-scale cross-sectional field study to date suggest that lower ferritin level might be associated with parent-reported hyperactivity after controlling for important confounding factors.

Responses to alcohol and cigarette use during ecologically assessed drinking episodes.

RATIONALE: Tobacco and alcohol are frequently used together, and this may be partly explained by a distinct profile of subjective effects associated with co-administration. Ecological momentary assessment studies have examined effects of naturally occurring co-use, but, to date, have not assessed differing effects as alcohol levels rise and fall. OBJECTIVES: The objective of the study was to describe subjective states and appraisals of cigarette and alcohol effects reported during the entirety of real-world drinking episodes. METHODS: Currently-smoking frequent drinkers (N = 255) carried electronic diaries for 21 days. Analyses focused on reports made during 2,046 drinking episodes. Signaled prompts intensively oversampled moments in the hours following consumption of the first drink in an episode. Multilevel regression analyses were used to predict ratings of buzz, dizziness, excitement, and sluggishness as a function of person-level and contextual covariates, estimated blood alcohol concentration (eBAC) level, ascending vs. descending eBAC, smoking, and their interactions. Appraisals of cigarette and alcohol effects were also examined within this framework. RESULTS: Buzz, excitement, and pleasure from alcohol and cigarettes were prominent features of real-world drinking episodes. Smoking was associated with enhanced buzz and excitement when eBAC was high and descending. Smoking slightly accentuated the relation between eBAC and ratings of drinking pleasure among women, but this relation was somewhat weakened by smoking among men. CONCLUSIONS: Smoking during drinking episodes may be partly explained by a persistence of stimulant alcohol effects beyond the blood alcohol concentration peak. Acute effects of nicotine and tobacco use on the descending limb deserve further scrutiny in experimental alcohol challenge research.

[Pregabalin--a drug with abuse potential?]. / Pregabalin--ein Arzneistoff mit Missbrauchspotential?

A case of pregabalin misuse associated with delusional ideas in a drug addict is reported. Pregabalin has been approved as an adjunct therapy for epilepsy, but also for neuropathic pain and generalized anxiety disorders and is widely used today. It has also been used in clinical trials to study its potential utility as a treatment for tobacco, alcohol and benzodiazepine addiction. Web sites, case reports and an epidemiological study (Swedish National Register of Adverse Drug Reactions) suggest that the drug may be abused, especially by substance-dependent individuals. Pregabalin was analyzed by LC/MS/MS following precipitation of serum proteins. Vigabatrin was used as internal standard. The concentration of 25 pg pregabalin/mL serum determined in the present case is the second highest value published so far after misuse of the substance. Due to paradoxical agitation, anxiety attacks and abnormal thinking, the man was exculpated. Further studies are required to assess the actual abuse potential of pregabalin.