Neuroleptic Treatment In Schizophrenia Research Articles

Altered functional connectivity links in neuroleptic-naïve and neuroleptic-treated patients with schizophrenia, and their relation to symptoms including volition.

In order to analyze functional connectivity in untreated and treated patients with schizophrenia, resting-state fMRI data were obtained for whole-brain functional connectivity analysis from 22 first-episode neuroleptic-naïve schizophrenia (NNS), 61 first-episode neuroleptic-treated schizophrenia (NTS) patients, and 60 healthy controls (HC). Reductions were found in untreated and treated patients in the functional connectivity between the posterior cingulate gyrus and precuneus, and this was correlated with the reduction in volition from the Positive and Negative Symptoms Scale (PANSS), that is in the willful initiation, sustenance, and control of thoughts, behavior, movements, and speech, and with the general and negative symptoms. In addition in both patient groups interhemispheric functional connectivity was weaker between the orbitofrontal cortex, amygdala and temporal pole. These functional connectivity changes and the related symptoms were not treated by the neuroleptics. Differences between the patient groups were that there were more strong functional connectivity links in the NNS patients (including in hippocampal, frontal, and striatal circuits) than in the NTS patients. These findings with a whole brain analysis in untreated and treated patients with schizophrenia provide evidence on some of the brain regions implicated in the volitional, other general, and negative symptoms, of schizophrenia that are not treated by neuroleptics so have implications for the development of other treatments; and provide evidence on some brain systems in which neuroleptics do alter the functional connectivity.

Influences on Therapist’s Decisions for Neuroleptic Treatment in Schizophrenia: The Role of Characteristics of the Patient and the Physician

We investigated factors influencing physicians' treatment decisions regarding 4 antipsychotic treatment strategies for schizophrenia (conventional oral/conventional depot/atypical oral/atypical depot). We analysed the influence of the patient's compliance with medication, socio-economic status (occupational prestige/educational attainment), as well as the influence of gender, age and practice setting (psychiatric/general hospital/private practice) of the prescribing physician.We examined the influence of these factors by means of case vignettes. 4 vignettes were constructed with varying levels for compliance and socio-economic status. For each vignette, physicians had to choose one treatment strategy from the 4 alternatives. Data were collected using a survey (n=1 342) of physicians in Germany and analysed using a weighted least-squares regression model and a random-effect logit model.Compliance and status had interactive effects on treatment selection. Low compliance was associated with an increase in selections of depot medication. For high-status, noncompliant patients, physicians selected mainly atypical oral and atypical depot antipsychotics. Low-status, noncompliant patients were mostly given conventional and atypical depot antipsychotics. Noncompliant, low-status patients received conventional depot antipsychotics 4 times as often as noncompliant, high-status patients. The physician's age and practice setting were also related to the treatment selection.Therapeutic decisions are influenced by patients' and the physicians' characteristics. There might be barriers for patients with low compliance and low socio-economic status that prevent them from being prescribed newer medications. Not all physicians seem to have the same choices of treatment options available to them.

Depressive psychosis associated with a cyclo oxygenase 2 inhibitor (meloxicam).

We describe a 60 year old man who developed a fluctuating depressive psychosis associated with meloxicam, a non-steroidal anti-inflammatory drug (NSAID). The psychological symptoms observed were temporally related to the administration of meloxicam and occurred in the presence of signs of meloxicam intolerance, such as skin rash and raised blood pressure. The depressive reaction resolved quickly following cessation of meloxicam, recurring on re-exposure. The psychiatric manifestations of NSAID intolerance are rare, however 40% of cases have a history of mental illness. Data from adverse event reporting systems suggest that the newer NSAIDs (COX-2 inhibitors) may have a higher propensity to cause psychiatric adverse effects and should be used with caution in individuals with a history of mental illness. This data may be provocative given current research in to the use of COX-2 inhibitors in augmenting neuroleptic treatment in schizophrenia.

In vivo occipital–frontal temperature-gradient in schizophrenia patients and its possible association with psychopathology: A magnetic resonance spectroscopy study

Background: Accumulating data suggest that schizophrenia patients' mental status might be modulated by their core/brain temperature. Hence, we intended to assess in vivo brain temperature ( T b) of schizophrenia patients vs. healthy subjects and to evaluate its potential association with patients' mental status. Methods: Absolute values of T b were measured in 9 neuroleptic-treated schizophrenia patients and 10 healthy comparison subjects using 1H magnetic resonance spectroscopy (MRS). Values were extracted by measuring the chemical shift between the peaks of water and N-acetyl-aspartate in the 1H MRS spectra. Results: A substantial (about 1.1 °C) and significantly higher occipital–frontal temperature-gradient was found in the schizophrenia patients compared to the healthy controls (1.27 °C vs. 0.18 °C; p = 0.032). Furthermore, a trend was found between the above mentioned occipital–frontal temperature-gradient in the schizophrenia patients and the severity of their psychopathology, as assessed by the total Positive and Negative Syndrome Scale (PANSS) scores ( r = 0.61; p = 0.08). Conclusions: Our findings corroborate previous results indicating putative correlation between core/brain temperature and the mental status of schizophrenia patients, emphasizing the possible role of within patients decreased frontal temperature and a significant occipital–frontal temperature-gradient as modulators of psychopathology. In addition, the MRS technique used for brain temperature assessment seems to be a potential non-invasive method to assess in vivo absolute T b in schizophrenia.

FMRT-Studien zur funktionellen Neuroanatomie motorischer Hirnareale: Einfluss von Krankheit und Antipsychotika auf die motorische Hirnaktivierbarkeit schizophrener Patienten

Functional Magnetic Resonance Tomography (FMRT) is a safe and noninvasive method to study human brain function by measuring task induced changes of the regional cerebral blood flow. Recent fMRT studies showed that stimulation method, psychiatric disorders and neuroleptic agents influence motor induced brain activation patterns specifically. Since these factors have been insufficiently controlled in most of the recent fMRT studies in particular on psychiatric disorders, results are often controversial. Using an intrapersonal study design and a standardized stimulation apparatus, we explored differential effects of typical and atypical neuroleptic treatment in schizophrenia. In addition to fMRT, 3D ultrasonic assisted motor analysis was used to investigate gait and hand movements. FMRT method, fMRT studies on human motor system, fMRT data on schizophrenia as well as on the influence of neuroleptic treatment are given. In particular, the own study design is presented and preliminary data are given.

Prevalence of Hyperprolactinemia in Schizophrenia

To evaluate the prevalence and severity of hyperprolactinemia among a large sample of patients with schizophrenia and related psychotic disorders treated with typical and atypical antipsychotic medications. Three electronic databases (general medical, psychiatric, and pharmacologic) containing the census data from November 2002 through March 2003 for a state-funded, inpatient hospital serving the chronically mentally ill were merged (N = 470). This database was purged of patient names, while the unique hospital identification number and demographic variables in each record were retained. These records were then screened to exclude patients with medications (except neuroleptics) or medical conditions known to elevate or suppress prolactin, leaving an overall sample (N = 422) in which to evaluate the prevalence of hyperprolactinemia. The sample was composed of patients with DSM-IV schizophrenia (N = 213), other related psychotic disorders (N = 131), mood disorders (N = 44), and other disorders (N = 34). For the overall sample (N = 422), which combined men and women, the mean serum prolactin level was 41.5 ng/mL; 290 of 422 patients were above the normal range. For women (N = 133), the mean serum prolactin level was 57.9 ng/mL, and 67% had levels above normal. For men (N = 289), the mean level was 33.9 ng/mL, with a 70% prevalence of hyperprolactinemia. While age did not influence the prevalence of elevated prolactin among men, age (reflecting reproductive status) was a significant variable in women; older age was associated with lower prolactin levels. For the study sample, a highly significant correlation was observed between neuroleptic dose (chlorpromazine equivalent) and serum prolactin level; however, this relationship was not determined on a medication-by-medication basis. Medications known to elevate prolactin were associated with higher prevalence rates of hyperprolactinemia, and "prolactin-sparing" medications had lower prevalence rates. However, when they were used in combination, the prolactin-elevating medication overwhelmed the effects of prolactin-sparing medication. This study suggested that neuroleptic treatment of schizophrenia is strongly associated with hyperprolactinemia and showed important differences between prolactin-sparing and prolactin-elevating medications.

Lower Corneal Temperature in Neuroleptic-Treated vs. Drug-Free Schizophrenia Patients

Antipsychotic drugs (APDs) can decrease core body temperature in schizophrenia patients. Core temperature may correlate with corneal temperature and thus, we hypothesized that neuroleptic-treated schizophrenia patients would display lower corneal temperature compared with drug-free patients. Corneal temperature of 12 typical APD-treated and 9 drug-free male schizophrenia patients was assessed using a FLIR thermal imaging camera. The APD-treated patients exhibited substantially and significantly lower corneal temperature compared with the drug-free patients (31.57 ± 0.98°C vs. 34.55 ± 1.65°C; p < 0.0001). Our results suggest that APDs may decrease corneal/core temperature in schizophrenia patients. The relevance of this finding to the pathophysiology of schizophrenia or to the antipsychotic effect of neuroleptics merit further investigation.

Precautionary measures reduce risk of definite neuroleptic malignant syndrome in newly typical neuroleptic-treated schizophrenia inpatients

Neuroleptic malignant syndrome (NMS) is a potentially lethal antipsychotic drug (APD)-induced thermoregulatory disturbance. We hypothesized that several precautionary measures taken after administeration of APDs might prevent progression to definite NMS. The study group included 657 consecutively admitted drug-free schizophrenia inpatients who received various typical APDs for 28 days. Specific predefined precautionary measures were employed for this group. The comparison group (n= 192) consisted of typical APD-treated schizophrenia inpatients in whom such precautionary measures were not imposed. The study group exhibited a significantly lower incidence of definite NMS (1/657=0.2% versus 4/192= 2.1%;P=0.01, odds ratio = 13.96; 95% confidence interval 1.55-125.63). Antipsychotics were discontinued in 28 patients (28/657= 4.3%) from the study group due to NMS (n=1) or early detection of potential NMS-related signs (probable abortive NMS) (n=27). Our findings suggest that specific precautionary measures can effectively reduce the incidence of definite NMS by approximately one order in newly medicated schizophrenia inpatients.

Interaction between angiotensin-converting enzyme and catechol-O-methyltransferase genotypes in schizophrenics with poor response to conventional neuroleptics

Angiotensin-converting enzyme (ACE) modulates dopamine turnover in the brain and catechol-O-methyltransferase (COMT) enzyme is an important agent in the metabolic inactivation of dopamine and norepinephrine. Functional polymorphism in the COMT and ACE genes causes variation in enzyme activities. We investigated the relationship of COMT and ACE gene polymorphism with response to conventional neuroleptic treatment in schizophrenia. In this study population we had earlier detected that COMT genotype is associated with unsatisfactory drug response. A total of 94 schizophrenic patients were evaluated either as responders (n=43) or non-responders (n=51). The responders had experienced a fair and steady response to conventional neuroleptics. The non-responders had failed to achieve an acceptable response to conventional neuroleptics. We also used a control population of 94 age- and gender-matched blood donors. Genotyping of the COMT and ACE genes was performed by polymerase chain reaction. The risk of having both low activity COMT and high activity ACE genotypes was over 10 times higher (odds ratio=10.89, 95%CI 1.14–103.98, P=0.04) in the non-responders compared to responders. ACE genotype alone did not differ between any groups. This finding may suggest a possible interaction with low activity COMT and high activity ACE genotype in association with poor response to conventional neuroleptics.

Less Driving Impairment on Buprenorphine than Methadone in Drug-Dependent Patients?

Less Driving Impairment on Buprenorphine than Methadone in Drug-Dependent Patients?

Asymmetrical hand force persistence and neuroleptic treatment in schizophrenia

The recent development of an isometric instrument for the precise quantification of hand force persistence has created a novel opportunity for the evaluation of potential motor asymmetries in schizophrenia and their response to treatment. A study of asymmetries in the unmedicated state may provide insight into the pathogenesis of schizophrenia, whereas alterations of asymmetries in response to antipsychotic medication could assist the delineation of a cerebral mechanism for the effects of pharmacotherapy. The hand force persistence of 21 unmedicated patients with schizophrenia was compared to 21 age, gender, and handedness matched normal controls. The effect of neuroleptic treatment on hand force persistence was then evaluated on a subset of 10 patients after at least 30 days of treatment. The anticipated asymmetry was evident in the unmedicated sample that showed impaired right hand force persistence compared to the normal control sample. The prospective comparison showed an alleviation of the asymmetry resulting from an improvement of right hand force persistence with treatment. In addition to providing further support to a primary left hemisphere cerebral involvement in schizophrenia, the present results suggest that prior investigations of motor asymmetry may have been compromised by the study of medicated patients. The apparently paradoxical improvement of motor skill may relate to the substantial number of patients treated with 2nd generation neuroleptic medications which may implicate an improvement in left hemisphere physiology in the cognitive advantages of the novel treatments.

Asymmetrical olfactory acuity and neuroleptic treatment in schizophrenia

Uni-rhinal olfactory acuity in schizophrenia was investigated in two experiments. The first assessed the presence of a predicted atypical asymmetry of nostril laterality and the second assessed the effect of antipsychotic treatment on the asymmetry. Although olfactory identification impairment has been well documented in schizophrenia, olfactory acuity has been neglected. This may be an oversight as cerebral structures of the mesial temporal lobe important to olfactory perception have often been implicated in the pathophysiology of schizophrenia and it is thus reasonable to postulate a primary impairment of olfactory acuity in schizophrenia. In addition, unmedicated patients with schizophrenia have exhibited asymmetrical laterality favouring the right over the left hemisphere in studies of visual, haptic, and auditory perception, and the few published prospective treatment studies have suggested a reversal of this asymmetry with first generation neuroleptic treatments. In experiment 1 a generalization of the perceptual asymmetry to olfactory acuity was examined by measurement of n-butanol olfactory thresholds with the Connecticut Chemosensory Perception Exam (CCPE) in an unmedicated sample of 17 patients with schizophrenia and 17 age, gender, and handedness matched normal controls. The patient sample showed an asymmetrical impairment of the left nostril that was not apparent in the normal control sample. In experiment 2, the CCPE was administered to a new sample of 10 patients with schizophrenia before and after neuroleptic treatment. The asymmetry observed in experiment 1 was replicated, and the relative advantage of the right nostril shifted to a relative advantage of the left nostril over the course of 8 weeks of treatment. Results are discussed in relation to cerebral aspects of schizophrenia and potential implications to cognitive change from treatment.

Asymmetrical hand force persistence and neuroleptic treatment in schizophrenia

Asymmetrical hand force persistence and neuroleptic treatment in schizophrenia

Asymmetrical olfactory acuity and neuroleptic treatment in schizophrenia

This study aimed to identify latent factors of the most widely used scale to measure neurological soft signs, the Neurological Evaluation Scale (NES), in a sample of schizophrenia patients, their relatives, and non-psychiatric controls.The NES was administered following the format and instructions of the original scale [Buchanan, R.W., Heinrichs, D.W., 1989. The Neurological Evaluation Scale (NES): a structured instrument for the assessment of neurological signs in schizophrenia. Psychiatry Res. 27, 335–350]. Three factor analyses were conducted using: (1) 23 items of the scale, (2) these 23 items in a sample restricted to African American participants, and (3) 12 items previously recommended based on adequate inter-rater reliability [Sanders, R.D., Forman, S.D., Pierri, J.N., Baker, R.W., Kelley, M.E., van Kammen, D.P., Keshavan, M.S., 1998. Inter-rater reliability of the neurological examination in schizophrenia. Schizophr. Res. 29, 287–292].Exploratory factor analysis in the overall sample (n = 110) revealed three factors of interest: a “coordination/Romberg” factor (which included the fist-edge-palm test, finger-thumb opposition, rapid alternating movements, and the Romberg test), a “sensory integration” factor (which included synkinesis, extinction, stereognosis, and audio-visual integration), and an “eye movements/tandem walk/overflow movements” factor (which included convergence, gaze impersistence, tandem walk, and adventitious overflow). Minimal differences were apparent when comparing these results with those obtained from an analysis including only African American participants (n = 99). Restricting the analysis to only 12 items resulted in two factors (with poor discriminant validity and internal consistency), which showed few similarities with previously reported exploratory factor analysis results.This study shows that results of empirically-derived factors of the NES vary substantially across study samples and research groups, though there appear to be at least two consistent latent variables, one related to the repetition of motor tasks and another tapping the processing of sensory stimuli. The factors demonstrated in the present study are more consistent with the original conceptually-derived subscales than prior factor analyses. Thus, until further research replicates consistent subscales of subtle neurological impairment in a variety of settings and samples, the total NES score may be more useful when comparing results across studies. Further research on latent neurological factors is needed.

Letters to the Editor

Letters to the Editor

Cerebrospinal fluid inositol monophosphatase: elevated activity in depression and neuroleptic-treated schizophrenia

Cerebrospinal fluid inositol monophosphatase: elevated activity in depression and neuroleptic-treated schizophrenia

Cerebrospinal fluid inositol monophosphatase: elevated activity in depression and neuroleptic-treated schizophrenia

Background: Inositol monophosphatase (IMPase) is a key enzyme in the regulation of the activity of the phosphatidyl inositol (PI) signaling pathway. This enzyme is also found in the cerebrospinal fluid (CSF), where it may prove useful as a marker of dysfunctional PI signal transduction. Methods: IMPase activity was measured in lumbar CSF of depressed and neuroleptic-treated schizophrenic patients. In addition, and to gain an insight into the factors that influence the levels of CSF IMPase, enzyme activity was measured in subgroups of schizophrenic patients treated for 3–7 days with lithium or 7 days with inositol. Results: CSF IMPase activity was significantly increased by 88% in depressed and by 172% in schizophrenic patients relative to control subjects. Lithium produced a marked increase in CSF IMPase activity in the group as a whole, and this group effect could be more specifically attributed to 3 of the 8 individuals in whom enzyme activity increased by over 300%. On the other hand, inositol had no effect on CSF IMPase activity. Conclusions: In the absence of a clear relationship between CSF IMPase activity and neuronal PI signaling pathways it is not possible to correlate these changes with altered neuronal function. Nevertheless, increased CSF IMPase activity in depression and schizophrenia may be a marker of the pathophysiological processes underlying these disorders. Moreover, the large lithium-induced increase in IMPase activity seen in a subgroup of schizophrenic subjects suggests a differential regulation of CSF enzyme activity in these patients.

Treatment compliance in schizophrenia

There is a myth that people with mental disorders comply poorly with treatment. In fact, psychiatric patients are no more likely than patients in other medical specialities to go against the advice of their doctor. However, it is easy to find instances where psychotropic medication is refused by the supposed beneficiary. The value of neuroleptic treatment in schizophrenia is now widely accepted, and failure to take such treatment is associated with relapse. Relapse may endanger the patient and other people. Despite this, people with schizophrenia frequently fail to take their treatment. One-third of patients leaving a general adult psychiatry ward can be expected to be non-compliant within two years (Buchanan, 1992).

In Response to "The neuroleptic treatment of schizophrenia: dosing strategies, depot preparations and novel medications" by Alexander S. Young, M.D. (volume 13, 18-26)

In Response to "The neuroleptic treatment of schizophrenia: dosing strategies, depot preparations and novel medications" by Alexander S. Young, M.D. (volume 13, 18-26)

S.14.01 Predictors of response to neuroleptic treatment in schizophrenia

S.14.01 Predictors of response to neuroleptic treatment in schizophrenia