Continuity of cannabis use and violent offending over the life course.

BACKGROUND: Although the association between cannabis use and violence has been reported in the literature, the precise nature of this relationship, especially the directionality of the association, is unclear. METHOD: Young males from the Cambridge Study of Delinquent Development (n = 411) were followed up between the ages of 8 and 56 years to prospectively investigate the association between cannabis use and violence. A multi-wave (eight assessments, T1-T8) follow-up design was employed that allowed temporal sequencing of the variables of interest and the analysis of violent outcome measures obtained from two sources: (i) criminal records (violent conviction); and (ii) self-reports. A combination of analytic approaches allowing inferences as to the directionality of associations was employed, including multivariate logistic regression analysis, fixed-effects analysis and cross-lagged modelling. RESULTS: Multivariable logistic regression revealed that compared with never-users, continued exposure to cannabis (use at age 18, 32 and 48 years) was associated with a higher risk of subsequent violent behaviour, as indexed by convictions [odds ratio (OR) 7.1, 95% confidence interval (CI) 2.19-23.59] or self-reports (OR 8.9, 95% CI 2.37-46.21). This effect persisted after controlling for other putative risk factors for violence. In predicting violence, fixed-effects analysis and cross-lagged modelling further indicated that this effect could not be explained by other unobserved time-invariant factors. Furthermore, these analyses uncovered a bi-directional relationship between cannabis use and violence. CONCLUSIONS: Together, these results provide strong indication that cannabis use predicts subsequent violent offending, suggesting a possible causal effect, and provide empirical evidence that may have implications for public policy.

Contrasting effects of selective lesions of nucleus accumbens core or shell on inhibitory control and amphetamine-induced impulsive behaviour.

The core and shell subregions of the nucleus accumbens receive differential projections from areas of the medial prefrontal cortex that have dissociable effects on impulsive and perseverative responding. The contributions of these subregions to simple instrumental behaviour, inhibitory control and behavioural flexibility were investigated using a 'forced choice' task, various parameter manipulations and an omission schedule version of the task. Post-training, selective core lesions were achieved with microinjections of quinolinic acid and shell lesions with ibotenic acid. After a series of behavioural task manipulations, rats were re-stabilized on the standard version of the task and challenged with increasing doses of d-amphetamine (vehicle, 0.5 or 1.0 mg/kg i.p. 30 min prior to test). Neither core- nor shell-lesioned rats exhibited persistent deficits in simple instrumental behaviour or challenges to behavioural flexibility or inhibitory control. Significant differences between lesion groups were unmasked by d-amphetamine challenge in the standard version of the forced task. Core lesions potentiated and shell lesions attenuated the dose-dependent effect of d-amphetamine on increasing anticipatory responses seen in sham rats. These data imply that the accumbens core and shell subregions do not play major roles in highly-trained task performance or in challenges to behavioural control, but may have opposed effects following d-amphetamine treatment. Specifically, they suggest the shell subregion to be necessary for dopaminergic activation driving amphetamine-induced impulsive behaviour and the core subregion for the normal control of this behaviour via conditioned influences.

Oncologists' recognition of depression in their patients with cancer.

PURPOSE: This study was performed as part of a large depression screening project in cancer patients to determine the degree of physician recognition of levels of depressive symptoms in cancer patients and to describe patient characteristics that influence the accuracy of physician perception of depressive symptoms. METHODS: Twenty-five ambulatory oncology clinics affiliated with Community Cancer Care, Inc of Indiana enrolled and surveyed 1,109 subjects treated by 12 oncologists. Subjects completed the Zung Self-Rating Depression Scale (ZSDS) and physicians were asked to rate their patients' level of depressive symptoms, anxiety, and pain using numerical rating scales. Subjects' sex, age, primary tumor type, medications, primary caregiver, and disease stage at diagnosis were also recorded. RESULTS: Physician ratings of depression were significantly associated with their patients' levels of endorsement of depressive symptoms on the ZSDS. However, agreement between physicians and patients is most frequently clustered when patients report little or no depressive symptoms. While physician ratings are concordant with patient endorsement of no significant depressive symptomatology 79% of the time, they are only concordant 33% and 13% of the time in the mild-to-moderate/severe ranges, respectively. Physician ratings were most influenced by patient endorsement of frequent and obvious mood symptoms, ie, sadness, crying, and irritability. Physician ratings also appeared to be influenced by medical correlates of patients' level of depressive symptoms (functional status, stage of disease, and site of tumor). Additionally, patients whose depression was inaccurately classified reported significantly higher levels of pain and had higher levels of disability. Physicians' ratings of depression were most highly correlated with physicians' ratings of patients' anxiety and pain. CONCLUSION: Physicians' perceptions of depressive symptoms in their patients are correlated with patient's ratings, but there is a marked tendency to underestimate the level of depressive symptoms in patients who are more depressed. They are most influenced by symptoms such as crying and depressed mood, and medical factors that are useful, but not the most reliable, indicators of depression in this population. Physicians' ratings of their patients' distress symptoms seem to be global in nature--they are highly correlated with anxiety, pain, and global dysfunction. Physician assessment might be improved if they were instructed to assess and probe for the more reliable cognitive symptoms such as anhedonia, guilt, suicidal thinking, and hopelessness. Screening instruments and the use of brief follow-up interviews would help to identify patients who are depressed.

Temperature biofeedback in the treatment of migraine headaches: a controlled evaluation.

After an initial four-week baseline phase, during which daily records of headache frequency and intensity and daily medication records were kept, 30 patients with frequent (at least one per month) migraine headaches were randomly assigned to three conditions: (1) temperature biofeedback, autogenic training, and regular home practice; (2) progressive relaxation with regular home practice; and (3) a waiting-list control condition. Comparisons of headache data from the four weeks of baseline and last two weeks of treatment showed that both the relaxation and biofeedback groups improved significantly on total headache activity, duration of headaches, and peak headache intensity and reduced consumption of analgesic medication, while the waiting list control group did not. All three groups showed significant decreases in headache frequency. Although the relaxation training was more effective than biofeedback training at the last week of treatment, follow-up data at one, two, and three months showed no differences between the two treated groups on any dependent measure.

Comparing the effects of subchronic phencyclidine and medial prefrontal cortex dysfunction on cognitive tests relevant to schizophrenia.

RATIONALE: It is becoming increasingly clear that the development of treatments for cognitive symptoms of schizophrenia requires urgent attention, and that valid animal models of relevant impairments are required. With subchronic psychotomimetic agent phencyclidine (scPCP), a putative model of such impairment, the extent to which changes following scPCP do or do not resemble those following dysfunction of the prefrontal cortex is of importance. OBJECTIVES: The present study carried out a comparison of the most common scPCP dosing regimen with excitotoxin-induced medial prefrontal cortex (mPFC) dysfunction in rats, across several cognitive tests relevant to schizophrenia. METHODS: ScPCP subjects were dosed intraperitoneal with 5 mg/kg PCP or vehicle twice daily for 1 week followed by 1 week washout prior to behavioural testing. mPFC dysfunction was induced via fibre-sparing excitotoxin infused into the pre-limbic and infralimbic cortex. Subjects were tested on spontaneous novel object recognition, touchscreen object-location paired-associates learning and touchscreen reversal learning. RESULTS: A double-dissociation was observed between object-location paired-associates learning and object recognition: mPFC dysfunction impaired acquisition of the object-location task but not spontaneous novel object recognition, while scPCP impaired spontaneous novel object recognition but not object-location associative learning. Both scPCP and mPFC dysfunction resulted in a similar facilitation of reversal learning. CONCLUSIONS: The pattern of impairment following scPCP raises questions around its efficacy as a model of cognitive impairment in schizophrenia, particularly if importance is placed on faithfully replicating the effects of mPFC dysfunction.

Kinase dynamics. Using ancient protein kinases to unravel a modern cancer drug's mechanism.

Macromolecular function is rooted in energy landscapes, where sequence determines not a single structure but an ensemble of conformations. Hence, evolution modifies a protein's function by altering its energy landscape. Here, we recreate the evolutionary pathway between two modern human oncogenes, Src and Abl, by reconstructing their common ancestors. Our evolutionary reconstruction combined with x-ray structures of the common ancestor and pre-steady-state kinetics reveals a detailed atomistic mechanism for selectivity of the successful cancer drug Gleevec. Gleevec affinity is gained during the evolutionary trajectory toward Abl and lost toward Src, primarily by shifting an induced-fit equilibrium that is also disrupted in the clinical T315I resistance mutation. This work reveals the mechanism of Gleevec specificity while offering insights into how energy landscapes evolve.

Region specific changes in forebrain 5-hydroxytryptamine1A and 5-hydroxytryptamine2A receptors in isolation-reared rats: an in vitro autoradiography study.

The neurochemical correlates of the behavioural consequences of isolation rearing of rats are complex and involve many neurotransmitters, including the serotonergic system. Impaired functioning of the ascending serotonergic system has been implicated in many neuropsychiatric syndromes, including attention deficit hyperactivity disorder and schizophrenia. In the present investigation serotonergic function was assessed using in vitro receptor autoradiography. The 5-hydroxytryptamine(2A) (5-HT(2A)) receptor antagonist [(3)H]ketanserin and the 5-HT(1A) receptor antagonist, [(3)H]WAY100, 635 were used to compare 5-HT receptor subtype densities in the forebrains of socially and isolation-reared rats. Regions of highest receptor density were observed in the frontal cortex for 5-HT(2A) receptors and in the frontal cortex, dorsal hippocampus and lateral septum for 5-HT(1A) receptors. In isolation-reared rats, 5-HT(2A) receptor binding site densities were significantly increased by between 36 and 67% in the prelimbic, motor and cingulate cortices compared with socially reared controls. By contrast, 5-HT(1A) receptor binding site densities were significantly reduced by 22% in the prelimbic cortex, and significantly increased by between 10 and 50% in the motor cortex, somatosensory cortex, dentate gyrus and CA fields of the hippocampus. These data demonstrate that isolation-rearing produces significant effects on forebrain 5-HT(1A) and 5-HT(2A) receptor densities in the adult rat. It is hypothesised that altered serotonergic function, particularly in the hippocampus and prefrontal cortex, may underlie some of the behavioural abnormalities associated with isolation-rearing.

Specific abnormalities in serotonin release in the prefrontal cortex of isolation-reared rats measured during behavioural performance of a task assessing visuospatial attention and impulsivity.

RATIONALE: Rats reared in social isolation exhibit hyperactivity and specific attentional disturbances in later adult life. These behavioural abnormalities may be relevant to impulsivity and other neuropsychiatric syndromes such as attention-deficit hyperactivity disorder and schizophrenia where disturbances in circuitry involving the prefrontal cortex have been identified. OBJECTIVE: To establish whether isolation-reared rats show a differential susceptibility to cognitive processes that depend on the prefrontal cortex and its monoaminergic innervation. METHODS: Rats were reared in isolation from postnatal day 28 or in social groups of four and trained on the five-choice serial reaction time task, which assesses spatially divided visual attention. Following a range of manipulations designed to tax visual attention and response control, in vivo microdialysis was used in conjunction with behavioural testing to assess dopamine (DA) and serotonin (5-HT) release in the prefrontal cortex, either under baseline conditions prior to task initiation, or during task performance. Subjects were challenged with amphetamine (0.125 mg/kg intravenously) every 15 min, commencing 15 min after the start of the task. RESULTS: Apart from being consistently slower to collect food rewards and showing more perseverative responses to an auditory distractor, isolates were unimpaired on accuracy, impulsivity and correct latency measures on the five-choice task. Basal levels of DA and 5-HT in the prefrontal cortex were also unaffected by isolation rearing. Amphetamine increased the speed of responding in control and isolation-reared animals and increased premature (impulsive) responding, but only in socially-reared animals. Cortical DA release increased to a similar extent in both groups following amphetamine challenge. By contrast, 5-HT release was attenuated in isolates under these conditions. CONCLUSIONS: These findings highlight a rather specific deficit in 5-HT release in the prefrontal cortex of isolation-reared rats, although this appears not to affect visual attentional function. Rather, these data may be relevant to reduced impulsiveness of isolation-reared rats on the five-choice task. These findings are important in the context of animal models of attentional disturbances in schizophrenia.

Managing addiction in advanced cancer patients: why bother?

The management of addiction in patients with advanced cancer can be time-consuming, labor-intensive, and difficult. Some clinicians believe that it is not worth the effort, due in part to a failure to appreciate the deleterious impact of addiction on palliative care efforts and a view of addiction as intractable in any case. Indeed, it is possible that some clinicians perceive addiction not only fatalistically but, because of common misconceptions, believe that managing or attempting to decrease the patient's use of alcohol or illicit substances would be tantamount to depriving a dying patient of a source of pleasure. In this paper, we argue that managing addiction is an essential aspect of palliative care for chemically-dependent and alcoholic patients. The goal of such efforts is not complete abstinence, but exerting enough control over illicit drug and alcohol use to allow palliative care interventions to decrease suffering. To illustrate this view, we describe two patients with chemical-dependency. We highlight the impact of unchecked substance abuse on patients' perpetuation of their own suffering, the complication of symptom management, the diagnosis and treatment of mood/anxiety disorders, and the effect on the patients' family and caregivers.

I get tired for no reason: a single item screening for cancer-related fatigue.

This study examined the criterion validity and sensitivity and specificity of a single item to rapidly screen patients in ambulatory oncology clinics for cancer-related fatigue. In an effort to expand the utility of the Zung Self-Rating Depression Scale (ZSDS) as a screen for other symptoms, the utility of the single fatigue item was examined. The fatigue item reads "I get tired for no reason" and is rated on a four-point scale ranging from "none or a little of the time" to "most or all of the time." Fifty-two subjects were administered the Zung, the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale, and the Fatigue Symptom Inventory (FSI). The Zung item was highly correlated with the ZSDS (r= 0.63, p < 0.0001) and the FACT-An (r = -0.70, p < 0.0001), as well as to the individual items of the FSI, ranging from 0.41 (p < 0.003) to 0.71 (p < 0.0001). All 10 subjects considered to be depressed based on the ZSDS were also considered to fatigued on the FACT-An. Setting the ZSDS item cutoff point at level 3--"A good part of the time"--yielded a sensitivity of 78.95% and a specificity of 87.88%. It is concluded that a single item can be a fast and accurate way of screening cancer patients for fatigue to trigger additional follow-up, thus expanding the utility of a depression screening tool for problems other than the purely psychiatric.

The changeable nature of patients' fears regarding chemotherapy: implications for palliative care.

The side effects of chemotherapy are feared by cancer patients as they begin their treatment. In this study, we investigated patients' anticipatory fears about chemotherapy. We then re-assessed these fears three to six months after the initial interview for patients who received chemotherapy during that time. We also examined symptom distress at these intervals. Hair loss, vomiting, infection, nausea, and weight loss were ranked as the most feared side effects of cancer treatment for the group as they began treatment. Patients beginning chemotherapy endorsed frequent or intense levels of fatigue, worrying about the future, pain, and sleep problems. No differences were found in the reporting of symptoms based on gender, age, or educational level. While changes in symptom distress over the study period were unremarkable, changes in fears about chemotherapy were of interest. The most feared symptoms were re-ordered following the treatment experience. The endorsement of nausea and vomiting, alopecia, and loss of appetite decreased significantly. Thirty-five percent fewer chemotherapy patients reported vomiting as one of their most feared side effects; 45% fewer patients who received anti-emetics reported vomiting as one of their most feared side effects. Effective treatments, such as those that have been developed to treat acute chemotherapy-related emesis, can relieve the fears of patients on treatment. We conclude that patients' fears about treatment are fluid and malleable. Patients' fears of suffering related to chemotherapy treatment change in response to the provision of adequate management. We discuss the implications of these findings for palliative care education.

Oncology staff recognition of depressive symptoms on videotaped interviews of depressed cancer patients: implications for designing a training program.

We examined oncologists' and nurses' ability to recognize depressive symptoms in two cancer patients who were interviewed on videotape. The study was conducted in a rural community, hospital-based outreach network. Staff were given a one-hour in-service on the use of the Mini International Neuropsychiatric Interview (MINI)-a brief diagnostic interview-to provide a differential diagnosis (no psychiatric diagnosis, major depressive disorder, or adjustment disorder with depressed mood). Next, the staff viewed a videotape of an investigator (S.P.) utilizing the MINI to interview two depressed breast cancer patients. Staff subsequently rated depressive symptoms on the MINI and made a diagnosis. Findings indicated a high concordance among staff regarding symptom ratings on a straightforward example of major depressive disorder. Concordance on diagnosis, severity level, and specific symptoms declined slightly on a more difficult case involving primarily cognitive symptoms and a diagnosis of adjustment disorder. Following brief didactic training on depressive disorders, oncologists and nurses were able to identify depressive symptoms in cancer patients on videotape. Learning to use a semistructured interview can increase oncologists' awareness of depressive symptoms and may be a good training model.

An attempt to employ the Zung Self-Rating Depression Scale as a "lab test" to trigger follow-up in ambulatory oncology clinics: criterion validity and detection.

We examined issues of criterion validity and detection of depression employing the Zung Self-Rating Depression Scale (ZSDS) as a "lab test" to trigger follow-up interviews of ambulatory oncology patients by oncology staff and the possibility of subsequent algorithm-based antidepressant treatment. Sixty oncology patients were screened with the ZSDS and then interviewed using the Mini-International Neuropsychiatric Interview (MINI). We examined the sensitivity and specificity of various cutoffs on the ZSDS and a briefer version, the Brief Zung Self-Rating Depression Scale (BZSDS) as they predicted results of the MINI, which was used as the criterion. Mean age of patients was 58.3 years (SD = 11.9). Thirty-two were female (53.3%) and 28 were male (46.7%). The correlation of the ZSDS (r = -0.66, P <.0001) and BZSDS (r = -0.57, P <.0001) with the MINI overall suggested acceptable levels of criterion validity. Additionally, we examined various cutoff scores on the ZSDS and BZSDS to explore the false negative and false positive rates that are associated with each. For example, using the mild cutoff on the Zung (score > 48) to determine depression or adjustment disorder, 14 false negatives and 2 false positives were found. When the more stringent moderate cutoff (score > 56) was used, 25 false negatives and 0 false positives were found. Oncology staff can utilize such data to make decisions about where to set cut-offs that trigger follow-up based on the amount of error that is allowable in their attempts to identify depressive symptoms in their patients. We discuss that such decisions might be based on many factors including the resources available in a particular site for follow-up or the comfort of particular oncologists and nurses managing and prescribing psychotropic medications, or in providing supportive counseling.

Pattern reversal evoked potentials in psychiatric patients.

Elicitation of pattern reversal evoked potentials (PREPs) was added to routine clinical EEG examinations in 100 consecutive adult psychiatric admissions. Latencies and correlations between the peaks and troughs of the triphasic complex were examined with particular reference to current hypotheses about neurophysiologic dysfunctions in schizophrenia and other psychiatric illnesses. PREP data also were examined in relation to age, sex, handedness, concurrent medications, and the clinical EEG findings. The results obtained indicated that age, sex, handedness, neuroleptic and anticholinergic medications and underlying EEG characteristics exert minimal influences upon the PREP. Schizophrenics showed lower hemispheric correlations and greater response stability than did patients with other diagnoses. No lateralized differences in relation to diagnosis were identified.

Nurses' recognition of depression in their patients with cancer.

PURPOSE/OBJECTIVES: To determine the degree to which nurses recognize levels of depressive symptoms in their patients with cancer and to describe patient characteristics that influence the accuracy of nurses' perceptions of depressive symptoms. DESIGN: Descriptive, prospective correlational design. SETTING: 25 community-based ambulatory oncology clinics affiliated with Community Cancer Care of Indiana. SAMPLE: 40 clinic nurses rated the depression levels of 1,109 patients. METHODS: Patients completed the Zung Self-Rating Depression Scale (ZSDS) prior to their medical oncology clinic appointment. Nurses rated their patients' level of depressive symptoms, anxiety, and pain on a 0-10 numerical scale along with determining a performance status score. MAIN RESEARCH VARIABLES: Patient-rated depression and the nurse depression rating. FINDINGS: The most frequent agreement between nurses and patients was observed when patients reported little or no depressive symptoms. They were only concordant 29% and 14% of the time in the mild and moderate/severe ranges, respectively. Nurses' ratings were influenced most by patients' endorsement of frequent and obvious mood symptoms and nurse ratings of patients' anxiety and pain. CONCLUSIONS: A marked tendency existed to underestimate the level of depressive symptoms in patients who were more severely depressed. Nurses' ratings were most influenced by symptoms such as crying, depressed mood, and medical factors that are useful but perhaps not the most reliable indicators of depression in this population. IMPLICATIONS FOR NURSING PRACTICE: Nurse assessment of depression might be improved if greater emphasis were placed on the more diagnostically reliable symptoms of depression and if screening tools for depression were incorporated into nursing practice.

Flexible endoscopic tracheo-oesophageal puncture under local anaesthetic.

Blom-Singer valve prosthesis is an increasingly popular technique for voice rehabilitation in alaryngeal patients. Although primary voice puncture is being practised, the creation of the tracheo-oesophageal fistula is performed in the majority of patients as a secondary procedure. We describe a technique of secondary tracheo-oesophageal puncture using the flexible endoscope which can be performed under local anaesthetic and sedation. The technique overcomes the difficulty of passing a rigid oesophagoscope or forceps to the level of the tracheostome in a scarred and irradiated neck. The new technique also obviates the need for general anaesthesia. We have successfully used the technique in three patients.

Acute intestinal pseudo-obstruction due to malignant thymoma.

Acute intestinal pseudo-obstruction has been associated with various diverse aetiologies, including several types of malignancies. Malignant thymoma has never been reported before as a cause of acute intestinal pseudo-obstruction. We report here a case of malignant thymoma presenting as acute intestinal pseudo-obstruction. Existing literature on malignant causes of intestinal pseudo-obstruction is also reviewed and discussed.

Intraluminal brachytherapy in the treatment of oesophageal cancers--some preliminary results.

Cancer of the oesophagus is the sixth commonest cancer in males in Singapore. The majority occur in the elderly and patients are often debilitated at presentation. Treatment is often aimed at palliation only. In this article, the preliminary results of 15 patients treated solely on a high dose rate remote afterloading Gammamed brachytherapy machine with an Iridium 192 (Ir192) source are reported. The patients were given 15 Gray (Gy) in a single or two 7.5 Gray fractions. All the patients treated had some improvement of their dysphagia, and seven out of 11 (63%) evaluable patients had symptom improvement lasting at least 11 weeks.

Divergent effects of D2/3 receptor activation in the nucleus accumbens core and shell on impulsivity and locomotor activity in high and low impulsive rats.

RATIONALE: Previously we demonstrated reduced D2/3 receptor availability in the ventral striatum of hyper-impulsive rats on the five-choice serial reaction time task (5-CSRTT). However, the anatomical locus of D2/3 receptor dysfunction in high impulsive (HI) rats is unknown. OBJECTIVE: In the present study, we investigated whether D2/3 receptor dysfunction in HI rats is localised to the core or shell sub-regions of the nucleus accumbens (NAcb). METHODS: Rats were selected for low (low impulsive, LI) and high impulsivity on the 5-CSRTT and implanted with guide cannulae targeting the NAcb core and shell. The D2/3 receptor agonist quinpirole was locally injected in the NAcb (0.1, 0.3 and 1 µg per infusion) and its effects investigated on the performance of LI and HI rats on the 5-CSRTT as well as spontaneous locomotor activity in an open field. RESULTS: Intra-NAcb core quinpirole increased premature responding in HI rats but not in LI rats. In contrast, intra-NAcb shell quinpirole strongly increased locomotor activity in HI rats, unlike LI rats. This effect was blocked by intra-NAcb shell infusions of the D2/3 receptor antagonist nafadotride (0.03 µg). However, nafadotride was ineffective in blocking the effects of intra-NAcb core quinpirole on premature responding in HI rats. CONCLUSIONS: These findings indicate that impulsivity and hyperactivity are separately regulated by core and shell sub-regions of the NAcb and that HI rats show an enhanced response to D2/3 receptor activation in these regions. These results suggest that the symptom clusters of hyperactivity and impulsivity in attention-deficit hyperactivity disorder may be neurally dissociable at the level of the NAcb.

Enzyme-based choline and L-glutamate biosensor electrodes on silicon microprobe arrays.

Brain-implantable microprobe arrays, 6.5 mm shaft-length, incorporating several recessed Pt microelectrodes (50 µm×150 µm) and an integrated Ag/AgCl reference electrode fabricated by silicon micromachining dry etching techniques (DRIE) are described. The microelectrodes are coated by an enzyme membrane and a semi-permeable m-phenylenediamine layer for the selective detection of the neurotransmitters choline and L-glutamate at physiologically relevant concentrations. The functionalisation is based on electrochemically aided adsorption (EAA) combined with chemical co-cross-linking using glutaraldehyde and electrochemical polymerisation, respectively. These deposition methods are fully compatible with the fabricated microprobe arrays for the simultaneous detection of several analytes in different brain target areas. They are spatially controlled and allow fabricating biosensors on several microelectrodes in parallel or providing a cross-talk-free coating of closely spaced microelectrodes with different enzyme membranes. A sensitivity of 132±20 µA mM(-1) cm(-2) for choline and 95±20 µA mM(-1) cm(-2) for L-glutamate with limits of detections below 0.5 µM was obtained. The results of in vitro and in vivo experiments confirm the functional viability of the choline and l-glutamate biosensors.