Treatment with Soteria-elements in acute psychiatry-Effectiveness for acutely ill and voluntarily treated patients.

Objective: This article aims at evaluating the treatment outcomes of acute psychiatric patients before and after the implementation of Soteria-elements in an acute psychiatric ward. The implementation process resulted in an interconnected small locked and much larger open area, enabling continuous milieu therapeutic treatment by the same staff in both areas. This approach enabled the comparison of structural and conceptual reconstruction regarding treatment outcomes of all voluntarily treated acutely ill patients before (2016) and after (2019). A subgroup analysis focused on patients suffering from schizophrenia. Methods: Using a pre-post design, the following parameters were examined: total treatment time, time in locked ward, time in open ward, antipsychotic discharge medication, re-admissions, discharge circumstances, and treatment continuation in day care clinic. Results: Compared to 2016, there was no significant difference in the total time of stay in the hospital. However, data show a significant decrease of days spent in locked ward, a significant increase of days in open ward, a significant increase of treatment discontinuation but without an increase of re-admissions, and a significant interaction of diagnosis and year regarding the medication dosage, resulting altogether in a reduction of antipsychotic medication for patients suffering from schizophrenia spectrum disorder. Conclusion: The implementation of Soteria-elements in an acute ward facilitates less potentially harmful treatments of psychotic patients, likewise enabling lower dosages of medication.

Treating Agitation in Patients with Dementia with a Therapy Dog in a Milieu Therapy Setting on a Geropsychiatric Ward.

BACKGROUND: Animal-assisted intervention has become a common therapeutic practice used for patients with dementia in home-dwelling and institutions. The most established procedure is a visiting service by specially trained dogs and their owners to improve social interactions and reduce symptoms of agitation. OBJECTIVES: The study aims to investigate the effects of a therapy dog on agitation of inpatients with dementia in a gerontopsychiatric ward. MATERIALS AND METHODS: The severity of agitation was assessed by a rater blinded for the presence of the dog via the Overt Agitation Severity Scale (OASS). The scale was conducted on 1 day with the dog and his handler present (resident doctor on the ward) and on another day with only the handler present. Each patient was his/her own control. Heart rate variability (HRV) and serum level of brain-derived neurotrophic factor (BDNF) of the patients were measured on both days. 26 patients with the Mini-Mental Status Examination (MMSE) score <21 and the diagnosis of dementia were included in the study. RESULTS: A significant reduction of agitation in the OASS could be shown when the dog was present (p = 0.006). The data neither demonstrated a difference in the HRV for the parameters mean heart rate (p = 0.65), root mean square of successive differences (p = 0.63), and high frequencies (p = 0.27) nor in serum BDNF concentrations (p = 0.42). DISCUSSION: Therapy dogs can be implemented as a therapeutic tool in a gerontopsychiatric ward to reduce symptoms of agitation in patients with dementia. The study was registered in the German Clinical Trials Register (DRKS00024093).

Myxedema Madness - Systematic literature review of published case reports.

Myxedema Madness is a rare but easily treatable cause of psychosis. Since Myxedema Madness was first described the question of a specific psychopathological symptom complex caused by severe hypothyroidism was raised in the literature. The present review of 52 published cases indicates that there are no specific somatic and psychopathological findings to diagnose a myxedema psychosis. It is diagnosed through the measurement of thyroid stimulating hormone and treated by application of L-thyroxine. Due to its excellent prognosis, myxedema madness should always be considered a differential diagnosis in new onset psychosis.

From Wish to Reality: Soteria in Regular Care-Proof of Effectiveness of the Implementation of Soteria Elements in Acute Psychiatry.

Objective: This article examines the influence of the implementation of Soteria elements on coercive measures in an acute psychiatric ward after reconstruction in 2017, thereby comparing the year 2016 to the year 2019. The special feature is that this is the only acute psychiatric ward in Hennigsdorf Hospital, connected now both spatially and therapeutically to an open ward and focusing on the treatment of patients suffering from schizophrenia and schizophrenia spectrum disorders. Methods: The following parameters were examined: aggressive assaults, use of coercion (mechanical restraints), duration of treatment in open or locked ward, type of discharge, coercive medication, and dosage of applied antipsychotics. For this purpose, the data of all legally accommodated patients in the year 2016 (before the reconstruction) and 2019 (after the reconstruction) were statistically analyzed in a pre-post mirror quasi-experimental design. Results: In 2019, the criteria of the Soteria Fidelity Scale for a ward with Soteria elements were reached. In comparison to 2016 with a comparable care situation and a comparable patient clientele, there was now a significant decrease in aggressive behavior toward staff and fellow patients, a significantly reduced number of fixations, a significantly reduced overall duration of inpatient stay, and a significant increase in treatment time in the open area of our acute ward. Conclusion: The establishment of Soteria elements in the acute psychiatric ward leads to a verifiable less violent environment of care for severely ill patients and to a drastic reduction in coercive measures.

Auditory mismatch negativity and repetition suppression deficits in schizophrenia explained by irregular computation of prediction error.

BACKGROUND: The predictive coding model is rapidly gaining attention in schizophrenia research. It posits the neuronal computation of residual variance ('prediction error') between sensory information and top-down expectation through multiple hierarchical levels. Event-related potentials (ERP) reflect cortical processing stages that are increasingly interpreted in the light of the predictive coding hypothesis. Both mismatch negativity (MMN) and repetition suppression (RS) measures are considered a prediction error correlates based on error detection and error minimization, respectively. METHODS: Twenty-five schizophrenia patients and 25 healthy controls completed auditory tasks designed to elicit MMN and RS responses that were investigated using repeated measures models and strong spatio-temporal a priori hypothesis based on previous research. Separate correlations were performed for controls and schizophrenia patients, using age and clinical variables as covariates. RESULTS: MMN and RS deficits were largely replicated in our sample of schizophrenia patients. Moreover, MMN and RS measures were strongly correlated in healthy controls, while no correlation was found in schizophrenia patients. Single-trial analyses indicated significantly lower signal-to-noise ratio during prediction error computation in schizophrenia. CONCLUSIONS: This study provides evidence that auditory ERP components relevant for schizophrenia research can be reconciled in the light of the predictive coding framework. The lack of any correlation between the investigated measures in schizophrenia patients suggests a disruption of predictive coding mechanisms in general. More specifically, these results suggest that schizophrenia is associated with an irregular computation of residual variance between sensory input and top-down models, i.e. prediction error.

Differential effects of chronic cannabis use on preattentional cognitive functioning in abstinent schizophrenic patients and healthy subjects.

INTRODUCTION: A number of studies indicate a higher risk for psychosis as well as for neurocognitive deficits in healthy cannabis users. However, little is known about the impact of cannabis use on outcome in schizophrenia. In fact, there is growing evidence that cannabis-using schizophrenic patients may show preserved or even better neurocognitive performance compared to schizophrenic non-users. METHODS: We measured mismatch negativity (MMN) to investigate preattentional neurocognitive functioning in long-term abstinent chronic cannabis users with (SZCA n=27) and without schizophrenia (COCA n=32) compared to schizophrenic patients (SZ n=26) and healthy controls (CO n=34) without any chronic drug use. RESULTS: Healthy cannabis users showed reduced frontal MMN compared to controls (p=0.036). In contrast, cannabis-using schizophrenic patients showed increased frontal MMN compared to schizophrenic patients without cannabis use (p=0.038). Comparing non-cannabis users, schizophrenic patients showed reduced frontal MMN (p=0.001). No significant differences were found between CO and SZCA (p=0.27), and COCA and SZCA (p=0.50). CONCLUSION: Results suggest that chronic cannabis use may have different effects on preattentional neurocognitive functioning in schizophrenic patients when compared to healthy subjects. This may be related to preexisting differences in the endocannabinoid system between schizophrenic patients and healthy subjects. However, due to the naturalistic design of the study, the results must be interpreted with caution.

Comparison of midlatency auditory sensory gating at short and long interstimulus intervals.

RATIONALE: Suppression of P50, N100 and P200 auditory evoked responses in a dual-click procedure is considered an index for the multistage sensory gating process. Whereas most studies use a protocol with long interstimulus intervals of 8-12 s between the stimuli pairs, there is also evidence that sensory gating occurs at much lower intervals. The aim of the study was to investigate whether a simple modified dual-click protocol with short interstimulus intervals elicts similar sensory gating ratios compared to the classic protocol. METHODS: P50, N100 and P200 amplitudes and sensory gating ratios were measured in 23 healthy subjects with 2 different dual-click protocols in 1 session: (1) a simple oddball modified with short interstimulus intervals of about 2.8 s (ISI2), and (2), the classic used with long intervals of about 8 s (ISI8). RESULTS: The amplitudes of the P50, N100 and P200 responses were mostly comparable and correlated between both protocols. Mean sensory gating ratios (ISI8/ISI2) were as follows: P50, 35.4/36.4%; N40P50, 36.1/39.9%; N100, 44.4/48.4%; P200, 46.8/43.3%; N100P200, 45.3/41.8%; all differences between protocols, p > 0.1. P50 ratio scores did not show a sufficient correlation between protocols [intraclass correlation coefficient (ICC) P50, 0.13; N40P50, 0.0] compared to N100 (ICC, 0.79), P200 (ICC, 0.6) and N100P200 (ICC, 0.61). CONCLUSION: Our results contradict the assumption that long interstimulus intervals of about 8 s are absolutely necessary to elicit a marked sensory gating phenomenon for P50, N100 and P200 auditory responses (at least when using a protocol with a simple attention task). However, because only healthy subjects were investigated, no prediction can be made for psychiatric patients, in whom neuronal processing may be different.

Neurotrophins: from pathophysiology to treatment in Alzheimer's disease.

Alzheimer's disease (AD) is the most common diagnosis among dementia. As increasing longevity results in larger numbers of AD patients and thus rising economic costs, there has been intense research about the pathophysiology and treatment strategies during the last years. Since neurotrophic factors are not only responsible for neuronal development but also critical for the maintenance of neurons, they represent mediators of high interest within the research of neurodegeneration. Thereby, NGF has been identified as a dynamic pattern during the time course of neurodegeneration in AD. Post mortem studies point to a lack of NGF action in early stages of AD. In contrast NGF is found in enhanced concentrations in brains with severe AD partly due to a pathologically altered axonal transport of NGF in the neurons. Therefore, pharmacological interventions strategies focus on an neurotrophin substitution in mild to moderate cases of AD. Intensive research mostly in rodents has recently led to first promising clinical trials of intracerebral neurotrophin application pointing to a growing role of neurotrophins in the establishment of new pharmacological strategies concerning AD.

Test-retest reliability of P50, N100 and P200 auditory sensory gating in healthy subjects.

RATIONALE: Suppression of middle latency auditory evoked responses is considered an index for the multistage sensory gating process. This has been observed in sequentially occurring P50, N100 and P200 components in a dual-click procedure. Since P50 sensory gating deficits have been observed in schizophrenic patients and first degree relatives, this parameter was suggested as an intermediate phenotype of the disease. However, most studies only show a low reliability for P50 sensory gating and neither N100 nor P200 sensory gating have been sufficiently tested. METHODS: Reliability of P50, N100 and P200 sensory gating was measured in 41 healthy subjects in two sessions, four weeks apart, using intra-class correlation. Sensory gating was calculated as ratio-gating (second response magnitude/first response magnitude x100) as well as difference-gating (first response magnitude minus second response magnitude). RESULTS: The difference-gating showed good to excellent reliabilities independently of the amplitude-measurement method applied (P50 peak-to-peak 0.75 and baseline-to-peak 0.74, N100 peak-to-peak 0.63 and baseline-to-peak 0.70, P200 peak-to-peak 0.82 and baseline-to-peak 0.79). Regarding ratio-gating, best temporal stability was observed for the P200 (peak-to-peak 0.58 and baseline-to-peak 0.62). Reliability of P50 ratio-gating strongly depends on the amplitude-measurement method (peak-to-peak 0.0 and baseline-to-peak 0.46). CONCLUSION: Regarding long-term reliability in healthy subjects the difference-gating of all three evoked responses and the ratio-gating of the P200 component may be useful tools for clinical or intermediate phenotype studies measuring different stages of the auditory sensory gating process. In contrast, the reliability of the P50 and N100 ratio-gating component seems to be insufficient for this purpose. However, long-term reliability remains to be confirmed in clinical samples.

Maintenance treatment with risperidone or low-dose haloperidol in first-episode schizophrenia: 1-year results of a randomized controlled trial within the German Research Network on Schizophrenia.

OBJECTIVE: Second-generation antipsychotics (SGAs) have proven superior to first-generation antipsychotics regarding relapse prevention, mainly in multiple-episode patients. Practice guidelines recommend SGAs as first-line treatment particularly in first-episode patients, although evidence for this group is still limited. Accordingly, the hypothesis of whether 1-year relapse rate in first-episode schizophrenia under maintenance treatment with risperidone is lower compared to haloperidol in low dose was tested. METHOD: Between November 2000 and May 2004, 1372 patients had been screened for eligibility in the inpatient facilities of 13 German psychiatric university hospitals. 159 remitted patients were enrolled after treatment of an acute first episode of schizophrenia according to ICD-10 F20 criteria. In the randomized controlled trial, double-blind antipsychotic treatment with risperidone or haloperidol was maintained in a targeted dose of 2 to 4 mg/day for 1 year. 151 patients were eligible for analysis. For 127 patients, this was a continuation trial after 8 weeks of randomized, double-blind, acute treatment with the same drugs; 24 patients were additionally randomly assigned after open acute treatment. RESULTS: With both antipsychotics (risperidone, N = 77; haloperidol, N = 74), no relapse evolved. Additionally, according to 2 post hoc defined measures of "marked clinical deterioration," significant differences occurred neither in the 2 respective deterioration rates (risperidone = 9%/23%; haloperidol = 8%/22%) nor in time until deterioration. Both antipsychotics were equally effective regarding significant symptom reduction and improvement in quality of life. Extrapyramidal symptoms were slightly higher with haloperidol. The overall dropout rate of 68%, however, was not significantly different between the 2 drug groups. CONCLUSION: Against the background of an overall favorable outcome, the hypothesized difference between risperidone and low-dose haloperidol regarding relapse prevention could not be supported for this sample of patients with first-episode schizophrenia. Possible design-related reasons for this finding are discussed. With regard to the high dropout rate, special programs are needed to keep schizophrenia patients who are in their early acute and postacute illness course in effective and safe treatment. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT00159081.

Cannabis induces different cognitive changes in schizophrenic patients and in healthy controls.

It is known that 60 to 80% of schizophrenic patients show deficits in cognition. There may be an increase in these deficits as a result of additional regular use of cannabis. The aim of the study was to evaluate the effect of chronic cannabis consumption on the cognitive functions of schizophrenic patients and healthy control subjects after a minimum abstinence time of 28 days. The study sample consisted of 39 schizophrenics (19 cannabis-abusers and 20 non-abusers) and 39 healthy controls (18 cannabis-abusers, 21 non-abusers). In a 2x2-factorial design (Diagnostic Groups [healthy controls, schizophrenic patients]xCannabis abuse [without, with]) with diagnostic group and cannabis consumption considered between-subject factors) we tested the hypothesis that dually diagnosed patients (i.e. suffering both from schizophrenia and cannabis abuse) perform worse in neuropsychological tests than schizophrenic patients without cannabis abuse. On the whole, schizophrenic patients performed worse than healthy control subjects. Surprisingly, rather than deteriorating neuropsychological performance, regular cannabis abuse prior to the first psychotic episode improved cognition in some tests. This was even more pronounced when regular consumption started before the age of 17. On the other hand, cannabis use deteriorated test performance in healthy controls, especially in cases when regular consumption started before the age of 17. To sum up, regular cannabis abuse has a different effect on cognitive function in schizophrenic patients and healthy controls.

Nerve growth factor in serum is a marker of the stage of alcohol disease.

Long-term alcohol abuse has deleterious effects on the peripheral and central nervous system. Nerve growth factor (NGF) is a pleiotropic neurotrophic protein involved in development, maintenance of function and regeneration of nerve cells. We examined patients in different stages of alcohol disease and measured their NGF serum concentrations based on the hypothesis that these reflect the state of disease. We examined 57 patients suffering from alcohol-dependence for more than 2 years (DSM IV) on day 8 of a qualified withdrawal, 18 patients with Korsakoff's syndrome and 40 healthy controls. In addition to clinical examination, careful history taking and a standard neuropsychological test battery, serum NGF concentrations were measured by a highly sensitive enzyme-immunoassay. Of the 57 patients 9 had suffered from severe withdrawal delirium in the past, other clinical parameters were alike. Cognitive test performance did not differ from the control group. Mean NGF levels of controls amounted to 42.1pg/ml (S.D. 68.0); mean levels of patients with alcohol dependence were raised significantly to 401.5pg/ml (S.D. 932.6) without delirium in the past and even further to 3292.5pg/ml (S.D. 4879.6) with former withdrawal delirium. By contrast, patients with persistent amnestic disorder (Korsakoff's syndrome) showed values identical to the controls. NGF serum levels were significantly elevated in alcohol-dependent patients, more so in those with prior delirium. Their cognitive tests being normal, this possibly reflects the activity of NGF as an endogenous repair mechanism for damaged neurons. In accordance with this hypothesis, NGF values are "normal" in patients with persistent alcohol-related cognitive decline.

Differential impact of heavy cannabis use on sensory gating in schizophrenic patients and otherwise healthy controls.

Cannabis abuse may precipitate the onset of schizophrenia and a dysfunction of the endocannabinoid system may be involved in the pathology of schizophrenia. Nevertheless, only few studies have addressed the neurobiological consequences of cannabis abuse for the development and course of schizophrenia. We measured the long-term effect of chronic cannabis abuse on the inhibitory function of the brain by the auditory P50 sensory gating in schizophrenic (n=15) and otherwise healthy chronic cannabis abusers (i.e. cannabis controls; n=11) and compared it to that of schizophrenic patients (n=12) and healthy controls (n=18) without cannabis or other drug abuse. All study subjects had to be abstinent from cannabis for at least 28 days. The main finding of our study was a P50 sensory gating deficit in cannabis controls that was correlated with the number of years with daily consumption (r=0.81; p=0.003). In contrast, we found no differences in P50 sensory gating between schizophrenic cannabis-abusers and non-abusers or healthy controls and no correlation with the number of years with daily consumption in those groups. To our knowledge this is the first study comparing the influence of chronic cannabis abuse in schizophrenic and otherwise healthy abusers on the inhibitory function of the brain. Our data provide some evidence that chronic cannabis abuse may affect sensory cortical circuits even after prolonged abstinence and they point to a possible differential effect in schizophrenic and otherwise healthy users.

Nerve growth factor serum concentrations rise after successful cognitive-behavioural therapy of generalized anxiety disorder.

Generalized anxiety disorder (GAD) is a chronic stress disease with permanent physical tension and cognitive strain. Raised nerve growth factor (NGF) serum levels were reported as an acute stress reaction in soldiers before their first parachute jump even before the rise in cortisol. Taking GAD as a clinical model of chronic stress, we measured NGF in the serum of 22 patients with GAD before and after cognitive-behavioural therapy (CBT) and compared them to those of healthy normal controls. Treatment response was tested by the values of the State and Trait of Anxiety Inventory (STAI) and the Hamilton Anxiety Scale (HAM-A) as treatment outcome variables. The NGF values of patients and controls were similar at baseline (p=0.8941); however, with successful treatment, corresponding to a mean reduction in the HAM-A by more than 50% and a reduction in the clinical global impression scale (CGI) median from 4 to 1, the patients' NGF serum concentrations rose significantly (p=0.0006) which might correspond to an altered stress reaction, possibly contributing to good therapeutic response with CBT. There were 3 patients with a HAM-A decrease of less than 15%. In those patients NGF rose only marginally. Hence, the increase in serum NGF seems to indicate good treatment response.

[Schizophrenia and cannabis consumption: epidemiology and clinical symptoms]. / Schizophrenie und Cannabiskonsum: Epidemiologie und Klinik.

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.

Adequate antipsychotic treatment normalizes serum nerve growth factor concentrations in schizophrenia with and without cannabis or additional substance abuse.

Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are important for the development and maintenance of neuron function. Neurodevelopment is thought to be impaired in schizophrenia, and vulnerable schizophrenic brains may be more sensitive to toxic influences. Thus, cannabis as a neurotoxin (and other substances) may be more harmful to schizophrenic brains than to non-schizophrenic brains, when used chronically. In a previous study we demonstrated an earlier disease onset and significantly higher serum NGF concentrations in drug-naïve schizophrenic patients with previous long-term cannabis abuse than in schizophrenics without cannabis abuse or cannabis abusers without schizophrenia. We therefore investigated whether this difference is still observed after treatment. Serum NGF measured in 114 treated schizophrenic patients (schizophrenia alone, n=66; schizophrenia plus cannabis abuse, n=42; schizophrenia plus multiple substance abuse, n=6) no longer differed significantly among those groups and from the control groups (healthy controls, n=51; cannabis controls, n=24; multiple substance controls, n=6). These results were confirmed by an additional prospective study in 28 patients suffering from schizophrenia (S) or schizophrenia with cannabis abuse (SC). Previously elevated serum NGF levels in the drug-naïve state, also differing between the groups (S: 83.44+/-265.25 pg/ml; SC: 246.89+/-310.24 pg/ml, S versus SC: p=0.03) dropped to 10.72+/-14.13 pg/ml (S) and 34.19+/-38.96 pg/ml (SC) (S versus SC, p>0.05), respectively, after adequate antipsychotic treatment. We thus conclude that antipsychotic treatment leads to recovery of neural integrity, as indicated by renormalized NGF values.

Brain-derived neurotrophic factor serum concentrations are increased in drug-naive schizophrenic patients with chronic cannabis abuse and multiple substance abuse.

Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are critically implicated in development and maintenance of function of neurons. Neurodevelopment is reported to be impaired in schizophrenia and vulnerable schizophrenic brains may be more sensitive to toxic influences. Thus, cannabis as a neurotoxin, may be more harmful to schizophrenic brains than to non-schizophrenic brains when used chronically. And neurotoxic events may promote disease-onset and lead to exaggerated release of neurotrophins. We investigated 157 drug-naive first-episode schizophrenic patients and found significantly elevated BDNF serum concentrations (by up to 34%) in patients with chronic cannabis abuse (n = 35, p < 0.001) or multiple substance abuse (n = 20, p < 0.001) prior to disease onset. Drug-naive schizophrenic patients without cannabis consumption showed similar results to normal controls and cannabis controls without schizophrenia. Thus, raised BDNF serum levels are not related to schizophrenia and/or substance abuse itself but may reflect a cannabis-related idiosyncratic damage of the schizophrenic brain. In line with this hypothesis, disease onset was 5.2 years earlier in the cannabis-consuming group (p = 0.0111).

Chronic cannabis abuse raises nerve growth factor serum concentrations in drug-naive schizophrenic patients.

Long-term cannabis abuse may increase the risk of schizophrenia. Nerve growth factor (NGF) is a pleiotropic neurotrophic protein that is implicated in development, protection and regeneration of NFG-sensitive neurones. We tested the hypothesis that damage to neuronal cells in schizophrenia is precipitated by the consumption of cannabis and other neurotoxic substances, resulting in raised NGF serum concentrations and a younger age for disease onset. The NGF serum levels of 109 consecutive drug-naive schizophrenic patients were measured and compared with those of healthy controls. The results were correlated with the long-term intake of cannabis and other illegal drugs. Mean (+/- SD) NGF serum levels of 61 control persons (33.1 +/- 31.0 pg/ml) and 76 schizophrenics who did not consume illegal drugs (26.3 +/- 19.5 pg/ml) did not differ significantly. Schizophrenic patients with regular cannabis intake (> 0.5 g on average per day for at least 2 years) had significantly raised NGF serum levels of 412.9 +/- 288.4 pg/ml (n = 21) compared to controls and schizophrenic patients not consuming cannabis (p < 0.001). In schizophrenic patients who abused not only cannabis, but also additional substances, NGF concentrations were as high as 2336.2 +/- 1711.4 pg/ml (n = 12). On average, heavy cannabis consumers suffered their first episode of schizophrenia 3.5 years (n = 21) earlier than schizophrenic patients who abstained from cannabis. These results indicate that cannabis is a possible risk factor for the development of schizophrenia. This might be reflected in the raised NGF-serum concentrations when both schizophrenia and long-term cannabis abuse prevail.

Meta-iodobenzylguanidine induces growth inhibition and apoptosis of neuroendocrine gastrointestinal tumor cells.

Neuroendocrine gastrointestinal tumors take up, decarboxylate and store large amounts of monoamines. Radioactive-labeled monoamines like the norepinephrine analogue meta-iodobenzylguanidine (MIBG) have been used for the imaging of neuroendocrine tumors for many years. MIBG is selectively taken up via norepinephrine transporters (NETs) localized in the plasma membrane of neuroendocrine gastrointestinal tumor cells and thereby offers the possibility for specific and innovative therapeutic approaches. We investigated the antiproliferative, cytotoxic, cell cycle-arresting and apoptosis-inducing effects of MIBG in the neuroendocrine gastrointestinal tumor cell line STC-1 and for control in the nonneuroendocrine colorectal cancer cell line HT-29. RT-PCR revealed the expression of NET in STC-1 but not in HT-29 cells. MIBG dose-dependently induced cytotoxicity and growth inhibition of STC-1 cells. It potently induced apoptosis in STC-1 cells as assessed by changes in the mitochondrial membrane potential, activation of caspase-3 and DNA fragmentation. Moreover, MIBG altered the expression of several genes involved in proliferation, apoptosis and stress responses as shown by cDNA arrays. In contrast, neither cytotoxicity, nor growth inhibition nor induction of apoptosis were detected in response to MIBG in the NET-deficient colorectal cancer cell line HT-29. Our data show that MIBG induces growth inhibition and apoptosis in neuroendocrine gastrointestinal tumor cells. MIBG did not arrest the cell cycle in either cell line. Thus, monoamine transporters in the plasma membrane of neuroendocrine gastrointestinal tumor cells are promising targets for innovative and specific treatment strategies of these tumors.