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Objectives: Ketamine can induce persisting psychosis in a subset of individuals who use it chronically and heavily. Previously, we found that the psychopathology and cognitive impairments in patients with ketamine dependence (KD) exhibiting persistent psychosis (KPP) bear resemblances with schizophrenia, albeit with less severity in those with no persistent psychosis (KNP). Furthermore, we also showed that patients with KD had higher blood levels of neurofilament light chain (NFL), a biomarker for neuroaxonal injury, compared to healthy controls. In this study, we aimed to investigate the differences in NFL levels between patients with KPP and KNP while comparing the levels of individuals with schizophrenia and healthy controls., Methods: We enrolled 64 treatment-seeking ketamine-dependent patients (53 with KNP and 11 with KPP), 37 medication-free patients with schizophrenia, and 80 healthy controls. Blood NFL levels were measured by single molecule array immunoassay., Results: NFL levels were highest in the KPP subgroup, followed by the KNP subgroup, and then the schizophrenia and control groups (mean ± SD: 24.5 ± 24.7, 12.9 ± 10.9, 9.2 ± 12.2, and 6.2 ± 2.2 pg/mL, respectively), with no significant difference observed between the schizophrenia and control groups., Conclusions: We found that KD is associated with higher NFL levels compared to schizophrenia, with the KPP subgroup showing the most consistent alterations. The observation of accentuated neuroaxonal pathology in individuals with KPP implies that this clinical manifestation is associated with a specific neurobiological phenotype, despite prior evidence suggesting syndromal similarity between schizophrenia and KPP., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Folate deficiency is shown to be associated with schizophrenia. Folate profile in patients with psychosis due to stimulant use has not been investigated. We aim to determine whether there is an association between serum folate level and the presence of psychosis in patients with methamphetamine (METH) use disorder., Methods: Forty patients diagnosed with METH-use disorder were included in this cross-sectional study. Serum folate levels were measured using enzyme immunoassay technique and compared between psychotic and non-psychotic subgroups (N = 25 and 15, respectively). We designed a logistic regression model to measure the extent of any association and also to adjust for potential confounders., Results: We detected lower serum folate level in the psychotics [3.4 (IQR = 5.3)] compared to non-psychotic METH users [8.9 (IQR = 2.5)], p = 0.01. The model demonstrated that every 1-unit increase in serum folate decreases the odds of presence of psychosis by 27% (R 2  = 53.5%, CI 12-64%, p = 0.006). The observed difference was not associated with the duration of METH use, patient's age at first METH use, or concurrent use of other substances., Conclusions: Our findings suggest that low folate level in psychotic METH users does not correlate with previously established risk factors for meth-induced psychosis such as duration of use, age of onset of using, and poly-drug use. We assume that low folate levels may play a crucial role in the pathophysiology of psychosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Lead was one of the most dangerous environmental toxic substances for a long time in western countries, and this is still the case for many places on earth today. Its neurotoxic potential is highly significant but its secure blood level concentration remains unknown. The aim of this study was to approach the above issue from the perspective of social psychiatry. A systematic search was made of Dialog and Datastar interfaces for data regarding the neuropsychiatric complications of direct or chronic exposure to lead, and a review of the relevant literature was conducted using the databases Medline, Embase, CAB Global Health and Cochrane. Lead affects the cholinergic, dopaminergic and gloutamergic systems, thus intervening in the normal function of neurotransmion. The consequence of neurotoxicity in the central nervous system includes apoptosis and excitotoxicity. Direct as well as chronic exposure causes serious neurological symptoms and possibly constant cognitive impairment. Acute encephalopathy, the most serious expression of lead poisoning, occurs in blood level concentrations over 100 μg/dL in adults and 80-100 μg/dL in children. Early symptoms of lead neurotoxicity include irritability, headaches and difficulties in concentration in both children and adults. Continuous exposure in children produces neurobehavioral symptoms, such as decreased concentration, inability to follow instructions, difficulty to play games and low IQ, which are associated with concentrations of 10-35 μg/dL. However, some studies claim that cognitive decline and low IQ can occur in concentrations <10 μg/dL. The commonest symptom in adults is peripheral neuropathy with foot drop. Prenatal exposure to lead has been correlated with antisocial behavior and schizophrenia. Long-term lead exposure causing low and medium lead concentration in blood has been linked to depression as well as generalized anxiety disorder and other behavioral disorders. High blood level concentrations correlate with psychotic symptoms like delusions and hallucinations but more rarely with psychotic syndromes. Despite the fact that lead has been banned from gasoline, paint and water pipes, quite significant quantities of lead still exist, particularly in deprived areas of modern cities, in transition zones and city centers, and there are also great concentrations around lead mines and in developing countries, but even for the remaining areas there is no safe threshold., Conclusions: Lead was and still is an environmental factor that increases neurologic and psychiatric morbidity. It also causes developmental disorders, especially in deprived areas. Prevention should be the single most important way of dealing with lead poisoning.

The clinical presentation, course and treatment of methamphetamine (METH)-associated psychosis (MAP) are similar to that observed in schizophrenia (SCZ) and subsequently MAP has been hypothesized as a pharmacological and environmental model of SCZ. However, several challenges currently exist in diagnosing MAP accurately at the molecular and neurocognitive level before the MAP model can contribute to the discovery of SCZ biomarkers. We directly assessed subcortical brain structural volumes and clinical parameters of MAP within the framework of an integrative genome-wide RNA-Seq blood transcriptome analysis of subjects diagnosed with MAP (N=10), METH dependency without psychosis (MA; N=10) and healthy controls (N=10). First, we identified discrete groups of co-expressed genes (that is, modules) and tested them for functional annotation and phenotypic relationships to brain structure volumes, life events and psychometric measurements. We discovered one MAP-associated module involved in ubiquitin-mediated proteolysis downregulation, enriched with 61 genes previously found implicated in psychosis and SCZ across independent blood and post-mortem brain studies using convergent functional genomic (CFG) evidence. This module demonstrated significant relationships with brain structure volumes including the anterior corpus callosum (CC) and the nucleus accumbens. Furthermore, a second MAP and psychoticism-associated module involved in circadian clock upregulation was also enriched with 39 CFG genes, further associated with the CC. Subsequently, a machine-learning analysis of differentially expressed genes identified single blood-based biomarkers able to differentiate controls from methamphetamine dependents with 87% accuracy and MAP from MA subjects with 95% accuracy. CFG evidence validated a significant proportion of these putative MAP biomarkers in independent studies including CLN3, FBP1, TBC1D2 and ZNF821 (RNA degradation), ELK3 and SINA3 (circadian clock) and PIGF and UHMK1 (ubiquitin-mediated proteolysis). Finally, focusing analysis on brain structure volumes revealed significantly lower bilateral hippocampal volumes in MAP subjects. Overall, these results suggest similar molecular and neurocognitive mechanisms underlying the pathophysiology of psychosis and SCZ regardless of substance abuse and provide preliminary evidence supporting the MAP paradigm as an exemplar for SCZ biomarker discovery.

Ketamine produces effects in healthy humans that resemble the positive, negative and cognitive symptoms of schizophrenia. We investigated the effect of ketamine administration on brain activity as indexed by blood-oxygen-level-dependent (BOLD) signal change response, and its relationship to ketamine-induced subjective changes, including perceptual distortion. Thirteen healthy participants volunteered for the study. All underwent a 15-min functional MRI acquisition with a ketamine infusion commencing after 5 min (approx 0.26 mg/kg over 20s followed by an infusion of approx. 0.42 mg/kg/h). Following the scan, participants self-rated ketamine-induced effects using the Psychotomimetic States Inventory. Ketamine led to widespread cortical and subcortical increases in BOLD response (FWE-corrected p < 0.01). Self-rated perceptual distortions and delusional thoughts correlated with increased BOLD response in the paracentral lobule (FWE-corrected p < 0.01). The findings suggest that BOLD increases in parietal cortices reflect ketamine effects on circuits that contribute to its capacity to produce perceptual alterations and delusional interpretations., (© The Author(s) 2015.)

Background: The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal., Methods: Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 11:00hours on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60mg/kg/i.g.) or a placebo and withdrawal was monitored., Results: Peak BELs of 225.52mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g., aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects., Conclusions: The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Context: Donepezil is a centrally-acting, reversible acetylcholinesterase inhibitor that is used in the treatment of Alzheimer disease. Altered mental status, nausea, vomiting, and bradycardia have been reported in therapeutic and supratherapeutic ingestions of donepezil, though pediatric exposures have not been well-described. We report a case of prolonged altered mental status and recurrent bradycardia in a child with a single-pill ingestion of donepezil., Case Details: A 14-month-old boy was brought to the Emergency Department 3 hours after ingesting one of his grandfather's donepezil tablets (10 mg). Upon arrival, he was somnolent and drooling, with multiple episodes of vomiting and diarrhea. Pupils were normal. Initial vitals: temperature, 36.8°C; blood pressure, 103/56 mmHg; heart rate, 140/min; respiratory rate, 36/min; oxygen saturation, 97%. His drooling, vomiting, and diarrhea resolved, but he remained intermittently agitated. Over the course of the following four days, he had intermittent, episodes of asymptomatic bradycardia to a low of 55/min, primarily when sleeping. A transient episode of junctional rhythm was observed. Serum donepezil level 97 hours post-ingestion was 10 ng/ml. He did not require atropine treatment, and was discharged in stable condition on hospital day 5., Discussion: Donepezil has a prolonged elimination of half-life in adults of approximately 70 hours. Despite its relative specificity for central AChEs, peripheral cholinergic symptoms have been described. We report a case of a symptomatic ingestion of donepezil in a child., Conclusions: Even after a single-tablet ingestion, donepezil may cause prolonged altered mental status and bradycardia in young children.

Background: Cocaine-induced psychosis (CIP) is among the most serious adverse effects of cocaine. Reduced serum brain-derived neurotrophic factor (BDNF) levels have been reported in schizophrenia and psychosis; however, studies assessing the involvement of BDNF in CIP are lacking., Methods: A total of 22 cocaine-dependent patients (aged 33.65 ± 6.85) who had never experienced psychotic symptoms under the influence of cocaine (non-CIP) and 18 patients (aged 34.18 ± 8.54) with a history of CIP completed a 2-week detoxification program in an inpatient facility. Two serum samples were collected from each patient at baseline and at the end of the protocol. Demographic, consumption and clinical data were recorded for all patients. A paired group of healthy controls was also included., Results: At the beginning of the detoxification treatment, serum BDNF levels were similar in both the non-CIP and the CIP groups. During early abstinence, the non-CIP group exhibited a significant increase in serum BDNF levels (p = 0.030), whereas the CIP group exhibited a decrease. Improvements in depression (Beck Depression Inventory, BDI, p = 0.003) and withdrawal symptoms (Cocaine Selective Severity Assessment, CSSA, p = 0.013) show a significant positive correlation with serum BDNF levels in the non-CIP group, whereas no correlation between the same variables was found in the CIP group., Conclusions: This study suggests that BDNF plays a role in the transient psychotic symptoms associated with cocaine consumption. In the non-CIP group, the increase in serum BDNF appears to be driven by the effects of chronic cocaine consumption and withdrawal. In contrast, patients with CIP share some of the neurotrophic deficiencies that characterize schizophrenia and psychosis., (Copyright © 2013 S. Karger AG, Basel.)

Background: Salvia divinorum (Salvia) is an increasingly popular recreational drug amongst adolescents and young adults. Its primary active ingredient, Salvinorin A (SA)-a highly selective agonist at the κ opiate receptor-is believed to be one of the most potent naturally occurring hallucinogens. However, there is little experimental data on the effects of SA in humans., Methods: In a 3-day, double-blind, randomized, crossover, counterbalanced study, the behavioral, subjective, cognitive, psychophysiological, and endocrine effects of 0 mg, 8 mg, and 12 mg of inhaled SA were characterized in 10 healthy individuals who had previously used Salvia., Results: SA produced psychotomimetic effects and perceptual alterations, including dissociative and somaesthetic effects, increased plasma cortisol and prolactin, and reduced resting electroencephalogram spectral power. The SA administration was associated with a rapid increase of its levels in the blood. SA did not produce euphoria, cognitive deficits, or changes in vital signs. The effects were transient and not dose-related. SA administration was very well-tolerated without acute or delayed adverse effects., Conclusions: SA produced a wide range of transient effects in healthy subjects. The perceptual altering effects and lack of euphoric effects would explain its intermittent use pattern. Such a profile would also suggest a low addictive potential similar to other hallucinogens and consistent with κ opiate receptor agonism. Further work is warranted to carefully characterize a full spectrum of its effects in humans, to elucidate the underlying mechanisms involved, and to explore the basis for individual variability in its effects., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

There is epidemiological evidence that frequent cannabis use in general and during puberty in particular increases the risk to suffer psychosis and psychotic symptoms. Based on these observations, there is growing interest in the role of the endogenous cannabinoid system (eCB system) - the point of action for psychoactive cannabinoids - in psychiatric disorders and schizophrenia in particular. It has been hypothesized nearly two decades ago that the eCB system may play a pathophysiological role in schizophrenia either in terms of an endogenous malfunction of the system itself and/or of a secondary malfunction as a result of the use of exogenous cannabinoids like Δ(9)-tetrahydrocannabinol, the major psychoactive phytocannabinoid in Cannabis sativa. To test this hypothesis, several studies have been performed investigating endogenous ligands to cannabinoid CB1-receptors such as anandamide both in cerebrospinal fluid and plasma of patients and controls. Here a mini-review of the role of anandamide in schizophrenia is provided.

Three case vignettes are presented documenting the rise in serum clozapine that occurred at a time of acute infection in these patients. The literature on this phenomenon is scant. The physiological processes that occur in the acute phase of the inflammatory response are summarized and provide an explanation of how clozapine levels may rise in response to infection. The risk of clozapine toxicity occurring in association with infections is highlighted.

The main ingredient in cannabis, Δ(9)-tetrahydrocannabinol (THC), can elicit acute psychotic reactions in healthy individuals and precipitate relapse in schizophrenic patients. However, the neural mechanism of this is unknown. We tested the hypothesis that THC psychopathology is related to changes in electroencephalography (EEG) power or inter-regional coherence. In a within-subjects design, participants (n=16) were given intravenous THC (1.25 mg) or placebo under double-blind conditions, during EEG recordings. Using fast-Fourier transform, EEG data were analyzed for power and coherence in the delta (1-3.5 Hz), theta (3.5-7 Hz), alpha (8-13 Hz), beta (14-25 Hz), low-gamma (30-40 Hz), and high-gamma (60-70 Hz) bands during engagement in the n-back test of working memory (WM). Compared with placebo, THC evoked positive and negative psychotic symptoms, as measured by the positive and negative syndrome scale (p<0.001) and slowed WM performance (p<0.05). Under THC, theta power was specifically reduced, (p<0.001) regardless of WM load; however, the reduction showed no relationship with psychotic symptoms or WM impairment. Coherence between bi-frontal electrodes in the theta band was also reduced by THC (p<0.05) and these reductions correlated with the change-in positive psychotic symptoms (rho=0.79, p<0.001). Bi-frontal specificity was suggested by the absence of a relationship between psychotic symptoms and fronto-parietal coherence. The results reveal that the pro-psychotic effects of THC might be related to impaired network dynamics with impaired communication between the right and left frontal lobes.

Objectives: Abuse of toluene-containing volatile solvents by adolescents is a significant public health problem. The present study characterized the long-term behavioural and neurochemical consequences of toluene exposure during adolescence., Methods: Male NMRI mice received one injection per day of either toluene (600 mg/kg) or corn oil during postnatal days (PN) 35-37 and (750 mg/kg) during PN38-39 and PN42-46. A variety of psychiatric disorder-relevant behavioural tests were examined at PN56-P84., Results: The toluene-exposed mice were significantly deficient in the social interaction test, nesting behaviour, social dominance tube test, and novel objective recognition test. However, toluene exposure did not affect locomotor activity and behavioural profiles in the forced swimming test, tail suspension test, emergence test and elevated plus maze. Neurochemically, the turnover rates of dopamine in the prefrontal cortex, striatum and nucleus accumbens were reduced in toluene-treated mice., Conclusions: Adolescent toluene exposure leads to social deficits and cognitive impairment at adulthood as well as neurochemical dysfunction in mice, which correlate with the symptoms observed in patients suffering from solvent-induced psychosis. These findings highlight the need for understanding the effects of solvent abuse on the developing nervous system and reveal an animal model suitable for research into pathophysiology of neurological and psychiatric consequences of solvent abuse.

The recreational drug 'ecstasy'[3,4-methylenedioxymethamphetamine (MDMA)] exerts a potent action on central serotonergic and dopaminergic neurons. These neurons utilize neurotrophins for their survival and function. In order to explore MDMA effects on neurotrophins, we measured by enzyme-linked immunosorbent assay the serum levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in 'ecstasy-addicted', 'ecstasy-addicted with signs of psychosis' and 'healthy' subjects. We found that BDNF serum levels were significantly increased in both groups of 'ecstasy-addicted' as compared with 'healthy subjects', supporting the hypothesis that BDNF is involved in MDMA action.

The case report describes the sudden emerge of psychotic symptoms of a 13-year old boy, suffering from attention deficit hyperactivity disorder (ADHD), while he was treated with a modified--release formulation of methylphenidate. The question of the attending physician, whether the symptoms indicate an early beginning of schizophrenia or whether the symptoms can be considered as an overdose phenomenon of methylphenidate should be discussed. The knowledge of the pharmacokinetics of methylphenidate as modified--release formulation and the serum concentration values of methylphenidate and its metabolite provide information for interpretation of the case reported, with regard to the purpose of therapeutic drug monitoring (TDM) for methylphenidate. Finally we conclude that the ingestion of an unintended overdose of methylphenidate may have caused the boy's psychotic symptoms and that routine therapeutic serum concentrations of methylphenidate have to be correlated to the point of time when the blood was drawn in relation to the intake of methylphenidate.

Objective: To evaluate clinical outcomes and the tolerability of 2 weeks' quetiapine (QTP) treatment for hospitalised patients in a naturalistic setting., Methods: Patients with schizophrenia (n = 18), drug-induced psychosis (n = 10; 3 cocaine, 4 hashish and marijuana, and 3 all three substances) or borderline personality disorder (n = 13), were diagnosed by two expert clinicians on the basis of an unstructured clinical interview, and were treated with QTP (250-1000 mg/day). The subjects were then clinically assessed at baseline, and after 7 and 15 days, using the Brief Psychiatric Rating Scale, the Positive and Negative Symptoms Scale (PANSS) and the Hamilton Rating Scale for Depression. At the end of the study, plasma QTP levels were determined and examined in relation to clinical outcome and tolerability., Results: The mean scores of each rating scale were significantly lower at the end of the study in the population as a whole, and within each diagnostic group. The percentage improvement was significantly greater in the patients with drug-induced psychosis than in those with schizophrenia (42.4 +/- 9.1% versus 23.6 +/- 13.5%). QTP was well tolerated, and the incidence of extrapyramidal side effects was low. There was a linear correlation between plasma levels and dose/kg of QTP (r = 0.31; p < 0.05). The improvement in PANSS significantly correlated with plasma levels and dose/kg in each diagnostic category (Spearman's coefficient was 0.75 [p < 0.01] for schizophrenia and borderline personality disorder, and was 0.68 [p < 0.05] for drug-induced psychosis)., Conclusion: The results suggest that 2 weeks' QTP treatment may improve the clinical outcome of psychotic re-exacerbation phases in different diagnostic categories and indicate that QTP improves clinical outcome in drug-induced psychosis, as QTP levels correlated with the clinical improvement measured by PANSS.

More and more young people consume cannabis in sometimes high dosage at an age when their brain is not yet fully developed and reacts particularly sensitive to toxic influences. Cannabis can induce and exacerbate psychotic symptoms and it can deteriorate the disease process in schizophrenic patients. First-episode schizophrenic patients with long-term cannabis consumption were significantly younger at disease-onset, mostly male and suffered more often from paranoid schizophrenia (with a better prognosis) than those without cannabis consumption in our investigation. The significance of higher serum neurotrophin levels in cannabis consuming schizophrenics as compared to those without cannabis consumption remains equivocal so far. The cognitive functions of this patient group are at least not worse than in those with schizophrenia alone. Taken together, the effect of cannabis on the brain vulnerable to schizophrenia is not yet completely understood; besides the undoubtedly deleterious effects, there may also be some neuroprotective effects.

Background: Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users., Case Presentations: We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation) following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented., Conclusion: While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.

The role of dopaminergic activity in susceptibility of methamphetamine (MAP) psychosis (flashbacks) to subsequent spontaneous recurrences was studied. Plasma monoamine metabolite levels were assayed in 23 flashbackers, of whom 10 experienced a single flashback, 8 exhibited subsequent flashbacks and 5 with the last episode; 18 nonflashbackers with a history of MAP psychosis; 9 subjects with persistent MAP psychosis; and 19 MAP user and 10 nonuser controls. All flashbackers had undergone frightening stressful experiences during previous MAP use. Their flashbacks were triggered by mild psychosocial stressors. Plasma norepinephrine (NE) levels increased with the increase in plasma levels of 3-methoxytyramine (3-MT), an index of dopamine release, during flashbacks in the 23 flashbackers. Of these, the 8 with subsequent episodes had markedly increased NE levels and increased 3-methoxytyramine levels during flashbacks. However, the 5 flashbackers with the last episode had moderately increased NE levels, and the 10 with a single episode displayed small increases in NE levels during flashbacks. Their 3-MT levels did not significantly differ from the levels in the control groups. Thus, increased DA release in addition to robust noradrenergic hyperactivity in response to mild psychosocial stressors may be important in susceptibility to subsequent flashbacks.

Corticosteroid-induced psychosis occurred in 5% of a prospective cohort of 92 patients with systemic lupus erythematosus (SLE). Psychosis was unpredictable by the routes and dosage of corticosteroid used. Factors predictive of psychosis were low serum levels of albumin, complement, and creatinine; history of anxiety disorders; and a family history of psychiatric illnesses. After multivariate adjustment, only hypoalbuminemia remained significant.

We measured plasma free HVA and MHPG in 39 cases of psychosis or mania judged to be caused by antidepressant exacerbation of symptoms. A total of 24 of patients had been receiving selective serotonin reuptake inhibitors (SSRI's). The SSRI group showed a pattern of increased plasma HVA similar to a comparison group of patients with a psychotic/manic relapse secondary to medication non-compliance.

We examine susceptibility to subsequent spontaneous recurrences of methamphetamine psychosis (i.e. flashbacks) in 11 flashbackers with a single episode and in nine flashbackers with subsequent episodes. All had undergone frightening stressful experiences during previous MAP use. Mild psychosocial stressors then triggered flashbacks. During flashbacks, the nine flashbackers with subsequent episodes had more markedly increased norepinephrine levels, with slightly increased 3-methoxytyramine levels. The duration of imprisonment in this subgroup approached significantly long levels than in the 11 flashbackers with a single episode. Robust noradrenergic hyperactivity with slightly increased dopamine release may therefore predict subsequent flashbacks. Longer exposure to distressing situations may also contribute to robust noradrenergic hyperactivity.

The relation is examined between increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes, and susceptibility to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (i.e., flashbacks). Plasma monoamine metabolite levels were assayed in 23 flashbackers, 19 nonflashbackers with a history of MAP psychosis, 10 subjects with persistent MAP psychosis, and 21 MAP user and 9 nonuser controls. All 23 flashbackers had undergone frightening stressful experiences during previous MAP use. Mild psychosocial stressors then triggered flashbacks. The 12 flashbackers with further episodes had markedly increased norepinephrine levels and slightly increased plasma levels of 3-methoxytyramine, an index of dopamine release. While the 11 flashbackers with a single episode displayed small increases in norepinephrine and 3-methoxytyramine levels. Thus, robust noradrenergic hyperreactivity, involving increased dopamine release in response to mild stress may predispose to further episodes of flashbacks.

Objective: To report a series of newly diagnosed thyrotoxic patients with concurrent acute psychosis, and to assess the association between the two disorders., Design: Retrospective study of thyrotoxic patients with associated psychosis ('thyrotoxic psychosis'; TP) requiring inpatient psychiatric care. New Zealand thyrotoxicosis annual incidence figures and first psychiatric admission rates for affective psychosis were utilised to statistically assess the co-occurrence of thyrotoxicosis and affective psychosis., Patients and Methods: During the 20-year study period, 18 inpatients (16 women and 2 men), mean age 54 years, with TP were identified. No patient had a past history of thyrotoxicosis, but four had required psychiatric inpatient care many years earlier. Thyrotoxicosis was documented by radioimmunoassay of thyroid hormone levels, and thyroid scintiscan. Psychiatric manifestations were classified using ICD9 criteria., Results: Thyroid hormone levels were markedly elevated in more than half of our TP patients. All younger patients had Graves' disease, and most older patients toxic nodular goitre. All patients were treated with antithyroid drugs, and all but one subsequently received (131)I therapy. Two patients were not mentally ill when thyrotoxicosis was diagnosed, but suffered major mood swings when thyroid hormone levels were falling. There was no specific psychiatric clinical picture but affective psychoses were commonest - seven depression, seven mania. The other diagnoses were two schizophreniform, one paranoid, and one delirium. Initially, neuroleptic medication was used in all but one patient, and during long-term follow-up (median 11 years) more than half our series had remained well with no further psychiatric problems. Statistical analysis was restricted to thyrotoxic patients with first psychiatric hospital admission for affective psychosis. During the 20-year period, there were nine thyrotoxic patients (95% confidence interval 4.5-17.1) with concurrent affective psychosis requiring first admission, and the calculated expected number was only 0.36. These findings indicate a clear association well above chance co-occurrence., Conclusion: TP is not a specific clinical picture, but affective psychoses are commonest. Statistical analysis of thyrotoxic patients with concurrent affective psychoses showed an incidence well above chance co-occurrence. It appears that thyrotoxicosis may be a precipitant of acute affective psychosis.

We examined increased sensitivity to stress in relation to spontaneous recurrences of methamphetamine (MAP) psychosis (i.e., flashbacks). Plasma monoamine metabolite levels were assayed in: 26 flashbackers, of whom 11 were on neuroleptics before and during the study, and the other 15 received neuroleptics in the course of the study; 18 non-flashbackers with a history of MAP psychosis; eight subjects with persistent MAP psychosis; and 23 MAP user and 11 non-user controls. The 26 flashbackers had experienced stressful events and/or MAP-induced fear-related psychotic symptoms during previous MAP use. Mild psychosocial stressors then triggered flashbacks. During flashbacks plasma norepinephrine levels increased markedly; among the flashbackers, those with a history of stressful events, whether or not they had experienced fear-related symptoms, showed a further increase in 3-methoxytyramine levels. Stressful experiences, together with MAP use, may therefore induce sensitization to stress associated with noradrenergic hyperactivity, involving increased dopamine release, and so triggering flashbacks.

Increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes may precipitate stress-related psychiatric disorders. The present study examines the relation between this increased sensitivity and vulnerability to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (i.e. flashbacks). Plasma monoamine metabolite levels were assayed in 18 subjects with flashbacks, of whom ten experienced a single flashback and eight experienced further subsequent flashbacks; in 21 subjects with a history of MAP psychosis who did not experience flashbacks; and 33 controls. A square-root transformation was applied to monoaminergic values, rendering the distribution normal. The subjects with flashbacks had undergone frightening stressful experiences during previous MAP use. The dominant factor triggering flashbacks was a mild fear of other people. During flashbacks, plasma noradrenaline levels markedly increased and 3-methoxytyramine levels, an indicator of dopamine release, were elevated. Among the 18 subjects with flashbacks, the ten with subsequent flashbacks had markedly increased noradrenaline levels during flashbacks, whereas the eight with a single flashback displayed small increases in noradrenaline levels as well as 3-methoxytyramine levels. Thus, a mild fear of other people may have elicited memories of MAP psychosis, related to frightening stressful experiences through increased sensitivity to stress associated with noradrenergic hyperactivity, involving increased dopamine release. Robust noradrenergic hyperreactivity to mild stress may predispose subjects to subsequent flashbacks.

In patients with Parkinson' disease and dopaminergic psychosis, clozapine treatment is recommended as the drug is free from extrapyramidal side effects and does not worsen motor symptoms of the underlying disease. The use of clozapine, however, is limited due to its hematotoxic side effects. For treatment of clozapine-induced agranulocytosis, granulocyte colony-stimulating factors (G-CSF) are recommended. We report the case of a 72-years-old male patient with clozapine-induced agranulocytosis and thrombopenia. Neutropenia was successfully treated with G-CSF, but thrombopenia persisted and resolved spontaneously after 14 days. Bone marrow toxicity of clozapine is not restricted to white cell maturation, but may also impair thrombocytopoesis.

Muscle dysfunction related to clozapine treatment is largely unrecognized. We evaluated weekly creatine kinase (CK) levels in 37 consecutive clozapine-treated outpatients with chronic psychotic disorders. Those with CK elevations underwent clinical neurologic evaluation, electromyography (EMG), and nerve conduction studies. Patients with probable myopathy had a quadriceps muscle biopsy. Twenty control patients had a single CK level determination. Twenty-nine of 37 clozapine-treated patients had CK elevations. Three patients had extreme CK elevations (> 20,000 IU/L), without myoglobinuria. Mean CK levels were significantly greater in clozapine patients (194 IU/L) than in control patients (142.3, p = 0.033). Of 18 clozapine-treated patients evaluated clinically, 6 had mild proximal weakness. EMG in 13 patients was myopathic in 5, normal in 5, and neurogenic in 3. Muscle biopsy in 5 patients showed rare regenerating myofibers and mild acute denervation (1), mild type II fiber atrophy (1), minimal acute denervation (1), and normal muscle (2). In conclusion, clozapine therapy may be associated with CK elevations and, rarely, mild myopathy.

Severe hyponatraemia may be cause unconsciousness, vomiting, seizures or exogenous psychosis and is associated with a high mortality. We report on a 44-year-old woman who presented with somnolence and psychomotor unrest. After rousing stimuli she showed no verbal response and did not follow any instructions. For three days she suffered from nausea and vomiting. Laboratory values included a natrium serum level of 97 mmol/l. CT scan demonstrated no abnormal findings. Because of severe arterial hypertonia she received for 12 days intensive diuretic therapy with 50 mg hydrochlorothiazide and 100 mg triamterene. Retrospectively, we proved that as a result of saluretic therapy, chronic hyponatremia had already existed before admission. Serum sodium was corrected slowly (< 12 mmol/l) with fluid restriction and normal saline solution. This is considered to be the first case report of a complete restitution after hyponatremia less than 100 mmol/l. We suggest that the preexisting chronic hyponatremia and the slow correction of serum sodium level are responsible for the favorable outcome of this case of severe hyponatremia.

3,4-Methylenedioxymethamphetamine (MDMA), also known as "ecstasy" is a popular recreational drug with potential for abuse. Although its neurotoxic effects have been established in animal studies, the acute and long-term effects of this serotonergic agent in humans are still unknown. We describe a 19-year-old woman with overlapping symptoms of neuroleptic malignant syndrome and serotonin syndrome after a single exposure to MDMA. We also review 15 other cases reported in the literature to draw attention to the serious neurotoxicity, including fatal outcomes, caused by the use of this increasingly popular, illicit drug.

Haloperidol levels in blood were measured monthly in 43 refractory chronic schizophrenic patients referred to a locked skilled nursing facility for long-term treatment. Gross toxic side effects (seizures, catatonia, confusion) and Neuroleptic Induced Deficit Syndrome in conjunction with blood levels over 30 ng/ml were identified in 13 of our 43 patients. Blood level reductions contributed to a reduction of side effects and clinical improvement and led to the expedited discharge of 6 of these 13 patients of the toxic subgroup. Considerable blood level variation was evident in single samples, and four levels appeared necessary to develop confidence for accuracy. Significant dose to blood level interindividual variability was identified, thereby bringing into question fixed-dose approaches to patients. The results strongly suggest the utility of haloperidol blood levels in the clinical setting.

Intoxication by medication containing bromid has become so rare in recent years, that the clinical syndrome is nearly forgotten. The revival of brom in neurology at present points to an increased rate of bromintoxications. With this background and a corresponding case-history the symptoms and therapy of bromintoxication is represented.

A sensitive and precise gas chromatography-mass spectrometry method with selected ion monitoring has been developed for identification and quantification of the phencyclidine derivative ketamine in human plasma. The assay is based on an alkaline extraction from aqueous to organic solvent from plasma and an efficient gas chromatographic separation on a DB-5 capillary column. The analytical procedure has a coefficient of variation of 0.7-6.2% and from 1.3 to 8.7% within-day and from day-to-day analysis, respectively. The low level of sensitivity was 10 ng/ml. It was used to measure low plasma concentrations in volunteers during ketamine-induced experimental psychosis. The method is not enantio selective.

An increased spiperone binding capacity in lymphocytes has been proposed as a possible biological marker for schizophrenia while in previous studies patients with alcohol dependence were shown to have a normal binding capacity. In a pilot study the spiperone binding capacity was studied in 8 patients with alcohol hallucinosis, 11 patients with acute drug-induced psychosis and 12 patients with other organic psychosis. An increased binding capacity, defined as > 4 fmol/l E6 cells, was found in only 1 patient with alcohol hallucinosis, 3 patients with drug-induced psychosis and 2 patients with other organic psychosis. Possible implications of these findings for future research are discussed.

Objective: Patients with lithium toxicity can pose difficulties in diagnosis and management in the general hospital setting. The authors examined patients who were referred to the Psychiatric Consultation-Liaison Service with suspicion of lithium overdose to delineate and characterize medical and psychiatric risk factors for toxicity and to follow the course and resolution of their toxicity., Method: The authors reviewed the charts of patients with lithium levels > 1.5 mEq/L who were admitted consecutively to a general hospital over an 18-month period., Results: Of twelve patients, eight were found to have developed lithium toxicity due to incidental and iatrogenic factors. These patients presented with a variety of confusing signs and symptoms. Hypothyroidism and coexisting organic illness contributed to the lack of clarity in their clinical picture., Conclusion: The widening scope of indication for lithium therapy leads to increased risk of toxic reactions which challenge the diagnostic skills of the consulting psychiatrist in a general hospital setting.

The question of toxic interactions resulting from combinations of lithium and neuroleptic drugs is largely based on anecdotal reports. We replicated the methods of Miller and Menninger (1987) who reported that 27% of manic patients on treatment with lithium and neuroleptics developed toxicity. We found no cases of neurotoxicity as defined in the earlier report. Pharmacologic mechanisms and differences in the clinical findings of the two studies are discussed.

To study the laboratory and mechanism of chronic alcoholic nervous disease (CAND), we have examined pyruvate and erythrocyte transketolase activity (E-TKA) in the blood of 20 patients with CAND with normal subjects as controls Then, they were treated with vitamin B. The results were: 1. the level of pyruvate in the blood of the patients with CANE was higher than that of the controls. The E-TKA in the blood of the patients with CAND was lower than that of the controls. There was significant difference in both the two indexes between the two groups, 2. After treatment, the syndromes of the patients were obviously relieved. The pyruvate and E-TKA in the blood of the patients returned to normal. It proves that: 1. the vitamin B in the body of the patients with CAND was lower than that of normal people. 2. the pyruvate and E-TKA in the patients' blood may be taken as laboratory indexes of the CAND. 3. The examination of E-TKA may be preclinical diagnosis to CAND. 4. CAND is mainly caused by vitamin B deficiency.

Recovery from lithium-induced neurotoxicity can take much longer than the 2 to 3 weeks previously reported. Contributing factors could include advanced age and underlying clinical or subclinical brain disease. However, the occurrence of lithium-induced neurotoxicity does not preclude reinstitution of lithium treatment. We report three case histories that illustrate these points.

Amantadine is an antiviral agent that is also used in the treatment of parkinsonism and neuroleptic-induced extrapyramidal symptoms. Toxic effects of amantadine relate primarily to the central nervous system and range from mild symptoms to disorientation and hallucinations. Anti-cholinergic agents may exacerbate these effects. We report a case of unsuspected amantadine overdose in a previously healthy 35-year-old woman who presented with acute psychosis manifested by delirium and visual hallucinations. Concomitant use of diphenhydramine contributed to the clinical presentation. Amantadine toxicity should be considered in the differential diagnosis of altered mental status in patients known to be taking the drug or with conditions commonly treated with amantadine.

A previously healthy 30-year-old black woman with no history of substance abuse was hospitalized after she attempted to drown her 4-year-old son. She had become progressively confused and delusional after a flu-like illness 2 weeks before. Serum and lumbar CSF samples assayed for phencyclidine (PCP) by gas chromatography-mass spectrometry with d5 PCP as an internal standard were positive. The patient recovered rapidly after treatment with haloperidol and acidification of her urine. Suspicion of PCP abuse should remain high among patients with psychosis, even for those with no history of substance abuse.

The authors describe the clinical symptoms of a disulfiram overdose in a male patient and present the plasma concentrations of disulfiram and its metabolites 4 and 7 days after the overdose.