Investigating the Vapor-Phase Adsorption of Aroma Molecules on the Water-Vapor Interface using Molecular Dynamics Simulations.

Surfactants are amphiphilic additives primarily used to reduce the surface tension of water and manipulate its wettability on various surfaces. Recent reports suggest that volatile surfactants, such as aroma molecules, diffuse more quickly to the interface from the vapor-phase than conventional surfactants typically used in the aqueous phase. The ability to adsorb from the vapor phase, in addition to their use as cosurfactants, expands the potential applications of volatile surfactants, particularly in situations where adding surfactants from the liquid phase is difficult. Here, we present a molecular level understanding of the adsorption kinetics of linalool, a common aroma molecule, on the water interface using molecular dynamics simulations. We note that the value of surface tension while adsorption from vapor and liquid phases is dependent only on the surface coverage. A minimum surface tension of 32 ± 1.8 mN/m is obtained in both cases at a maximum surface coverage of 4.88 µmol/m2 at 300 K. We observe the extent of decrease of the H-bonds between linalool-water and linalool-linalool molecules at various surface coverages to explain the mechanism of surface tension reduction. We solve Gibb's adsorption equation to establish a correlation between the surface coverage of linalool and the corresponding bulk concentration in experiments. We investigate the free energy profile of linalool's adsorption behavior at different surface coverages and temperatures. Our report suggests that linalool adsorption onto the water interface is an enthalpy-driven process primarily dependent on the strength of the interaction between the hydroxyl group of linalool and water molecules. These insights are crucial for selecting a suitable aroma molecule for various applications that target the vapor-phase adsorption mechanism.

Estudio a gran escala (n = 400) de las diferenciasde la sustancia gris en la esquizofrenia mediantemorfometría optimizada basada en vóxels / A large scale (N = 400) investigation of gray matter differences in schizophrenia using optimized voxel-based morphometry

Fundamento: En muchos estudios se ha utilizado morfometría basada en vóxels (MBV) de imágenes de resonancia magnética (RM) como un método automatizado para estudiar las diferencias en la sustancia gris cortical en la esquizofrenia. No obstante, los resultados de estos estudios varían ampliamente, lo que probablemente se deba a las diferencias metodológicas o del análisis estadístico. Objetivo: Usar la MBV para estudiar las diferencias en la sustancia gris en la esquizofrenia en una muestra significativamente más amplia que cualquiera de las publicadas hasta la fecha y aumentar la potencia estadística lo suficiente para revelar las diferencias omitidas en los análisis a menor escala. Métodos: A partir de cuatro lugares geográficos, se adquirieron imágenes de resonancia magnética del cerebro en conjunto usando el mismo modelo de equipo de 1,5 T y la misma versión del programa informático, y se combinaron para formar una muestra de 200 pacientes tanto con un primer episodio como con esquizofrenia crónica y 200 individuos de control sanos apareados por edad, sexo y localización del escáner. Se evaluó la concentración de sustancia gris y se la comparó utilizando MBV optimizada. Resultados: Comparados con los individuos de control, en pacientes con esquizofrenia se detectó una concentración significativamente menor de sustancia gris en múltiples regiones corticales y subcorticales, algunas no descritas previamente. En conjunto, encontramos concentraciones menores de sustancia gris en regiones identificadas en estudios previos, que en su mayoría sólo documentaron subgrupos de las áreas afectadas. Conclusiones: En la esquizofrenia las diferencias en la sustancia gris se dilucidan más exhaustivamente usando una muestra a gran escala, diversa y representativA (AU)

Background: Many studies have employed voxelbased morphometry (VBM) of MRI images as an automated method of investigating cortical gray matter differences in schizophrenia. However, results from these studies vary widely, likely due to different methodological or statistical approaches. Objective: To use VBM to investigate gray matter differences in schizophrenia in a sample significantly larger than any published to date, and to increase statistical power sufficiently to reveal differences missed in smaller analyses. Methods: Magnetic resonance whole brain images were acquired from 4 geographic sites, all using the same model 1.5Tscanner and software version, and combined to form a sample of 200 patients with both first episode and chronic schizophrenia and 200 healthy controls, matched for age, gender and scanner location. Gray matter concentration was assessed and compared using optimized VBM. Results: Compared to healthy controls, schizophrenia patients showed significantly less gray matter concentration in multiple cortical and subcortical regions, some previously unreported. Overall, we found lower concentrations of gray matter in regions identified in prior studies, most of which reported only subsets of the affected areas. Conclusions: Gray matter differences in schizophrenia are most comprehensively elucidated using a large, diverse and representative sample (AU)

A large scale (N=400) investigation of gray matter differences in schizophrenia using optimized voxel-based morphometry.

BACKGROUND: Many studies have employed voxel-based morphometry (VBM) of MRI images as an automated method of investigating cortical gray matter differences in schizophrenia. However, results from these studies vary widely, likely due to different methodological or statistical approaches. OBJECTIVE: To use VBM to investigate gray matter differences in schizophrenia in a sample significantly larger than any published to date, and to increase statistical power sufficiently to reveal differences missed in smaller analyses. METHODS: Magnetic resonance whole brain images were acquired from four geographic sites, all using the same model 1.5T scanner and software version, and combined to form a sample of 200 patients with both first episode and chronic schizophrenia and 200 healthy controls, matched for age, gender and scanner location. Gray matter concentration was assessed and compared using optimized VBM. RESULTS: Compared to healthy controls, schizophrenia patients showed significantly less gray matter concentration in multiple cortical and subcortical regions, some previously unreported. Overall, we found lower concentrations of gray matter in regions identified in prior studies, most of which reported only subsets of the affected areas. CONCLUSIONS: Gray matter differences in schizophrenia are most comprehensively elucidated using a large, diverse and representative sample.

Neural correlates of deficient response inhibition in mentally disordered violent individuals.

In this study, response inhibition and associated neural activation during a motor inhibition paradigm were investigated in (i) men with antisocial personality disorder (APD) with a history of violence (n = 14), (ii) men with schizophrenia with a history of violence (n = 12), (iii) men with schizophrenia without a history of violence (n = 12), and (iv) healthy control subjects (n = 14) using functional magnetic resonance imaging (fMRI). At the behavioural level, individuals with schizophrenia showed impaired performance across all conditions, whereas an increased error rate was seen in the APD group only during the conditions requiring inhibition. At the neural level, both violent groups showed reduced thalamic activity, compared with controls, in association with modulation of inhibition by task demands. In addition, the violent schizophrenia group, compared with controls, showed reduced activity in the caudate nucleus during the condition requiring inhibition. It is concluded that violence may not be specifically associated with impaired voluntary inhibition in schizophrenia but this is likely in APD. Reduced thalamic function, perhaps due to its known association with sensorimotor disturbances, is implicated in violent behaviour across both disorders. In addition, caudate dysfunction may contribute, given its role in timing and temporal processing as well as suppression of motor actions, to deficient inhibition and violent behaviour in schizophrenia.

Neuropsychological function-brain structure relationships and stage of illness: an investigation into chronic and first-episode schizophrenia.

Neuropsychological function-brain structure relationships may differ as a function of illness stage because of progressive brain matter loss through the course of schizophrenia. In this study, we tested whether neuropsychological function-brain structure relationships differed as a function of illness stage. In addition, we tested whether these relationships differed between older and young healthy controls. Function-structure relationships were examined in 35 first-episode patients (31 with schizophrenia, 4 with schizoaffective disorder), 54 chronic schizophrenia patients, 21 older healthy controls and 20 young healthy controls. MRI volumes of frontal and temporal lobe structures, as well as the whole brain, were estimated using a region-of-interest approach. Hierarchical multiple regression analyses were performed between the MRI and neuropsychological measures. Stronger relationships of immediate memory-total prefrontal cortex (PFC) volume in chronic than first-episode patients, and in older than young controls were observed. The abstract reasoning (WCST perseverative errors)-total temporal lobe volume relationship was stronger in older than young controls. These function-structure relationships appeared unexplained by whole brain volume or age in chronic patients. A similar dissociation between young and older subjects of both healthy and patient groups suggests that a 'bigger-is-better' relationship style is present in older individuals regardless of a diagnosis of schizophrenia.

An fMRI study of face encoding and recognition in first-episode schizophrenia.

BACKGROUND: Schizophrenia has been associated with limited abilities to interact effectively in social situations. Face perception and ability to recognise familiar faces are critical for social interaction. Patients with chronic schizophrenia are known to show impaired face recognition. Studying first-episode (FE) patients allows the exclusion of confounding effects of chronicity, medication and institutionalisation in this deficit. OBJECTIVE: To determine brain (dys)functions during a face encoding and recognition paradigm in FE schizophrenia. METHODS: Thirteen antipsychotic-naïve FE schizophrenia patients and 13 age- and sex-matched healthy controls underwent functional magnetic resonance imaging during a face encoding and recognition paradigm. Behavioural responses were recorded on line. RESULTS: Patients recognised significantly fewer of previously presented faces than the controls (p = 0.008). At the neural level, both groups activated a network of regions including the fusiform area, occipital, temporal and frontal regions. In brain activity, the two groups did not differ in any region during encoding or recognition conditions (p > 0.05, corrected or uncorrected). CONCLUSIONS: Our findings show impaired face recognition without a significant alteration of related brain activity in FE schizophrenia patients. It is possible that neural changes become more strongly evident with progression of the illness, and manifest themselves as behavioural impairments during the early course.

N100 and P300 amplitude to Go and No-Go variants of the auditory oddball in siblings discordant for schizophrenia.

BACKGROUND: P300 amplitude reduction is reliably seen in schizophrenia. Inconsistent reports of isolated frontal and/or parietal deficits in unaffected family members may be clarified using a task that places greater load on frontal function. METHOD: Go and No-Go versions of the auditory oddball task were performed by eighteen schizophrenia patients, age-matched unaffected siblings and healthy controls matched closely to unaffected siblings on age, sex, education, socioeconomic-status, handedness and ethnicity. Groups were compared on P300 and N100 amplitude and latency. Spearman correlations were used to test the relationship between ERP amplitudes and neuropsychological measures of executive function and memory. The relationship between schizotypy--as measured using the structured interview--and ERPs was explored in a combined group of siblings and controls. RESULTS: Independent of task, patients had lower P300 than controls and reduced parietal amplitude compared to siblings. Siblings had enhanced frontocentral N100 compared to controls. No-Go P300 amplitude and N100 latency was associated with executive function measures. There were significant intraclass correlations between patients and siblings for No-Go P300 amplitude, particularly at the central midline electrode. Frontocentral N100 and P300 amplitude were positively correlated with anxiety-related aspects of schizotypy. CONCLUSION: Enhanced N100 is present in unaffected siblings. Parietal P300 is intact in unaffected siblings, but reduced in patients. The No-Go-oddball is more sensitive than the Go-oddball to executive function deficits in patients and as an index of heritability.

Neuroticism and brain responses to anticipatory fear.

Personality is known to influence cognitive and affective functioning as well as the risk of psychiatric disorders. Exploration of the neurobiological correlates of personality traits has the potential to enhance understanding of their significance in development of related psychopathological states. The authors examined the association between individual differences in neuroticism and brain activity in response to threat of electric shocks. Fourteen right-handed healthy men underwent functional MRI during a 5-min experiment that involved repeated presentations of two 30-s alternating conditions. In 1 of these conditions, subjects were told to expect mild but painful electric shocks; there was no possibility of receiving shocks in the other condition. The results revealed that neuroticism correlated positively with the ratings of fear of shock and negatively (indicating suppression) with brain activity from safe to shock conditions in the anterior and posterior cingulate, superior/middle temporal gyrus extending to the hippocampus, precuneus, putamen, thalamus, and middle occipital gyrus. The observations support recent psychophysiological research that has demonstrated reduced processing of pain in subjects with higher levels of neuroticism, especially the anxiety component of this trait.

Regional cortical thinning in subjects with violent antisocial personality disorder or schizophrenia.

Violent behavior is associated with antisocial personality disorder and to a lesser extent with schizophrenia. Neuroimaging studies have suggested that several biological systems are disturbed in schizophrenia, and structural changes in frontal and temporal lobe regions are reported in both antisocial personality disorder and schizophrenia. The neural substrates that underlie violent behavior specifically and their structural analogs, however, remain poorly understood. Nor is it known whether a common biological basis exists for aggressive, impulsive, and violent behavior across these clinical populations. To explore the correlates of violence with brain structure in antisocial personality disorder and schizophrenia, the authors used magnetic resonance imaging data to investigate for the first time, to the authors' knowledge, regional differences in cortical thickness in violent and nonviolent individuals with schizophrenia and/or antisocial personality disorder and in healthy comparison subjects. Subject groups included right-handed men closely matched for demographic variables (total number of subjects=56). Violence was associated with cortical thinning in the medial inferior frontal and lateral sensory motor cortex, particularly in the right hemisphere, and surrounding association areas (Brodmann's areas 10, 11, 12, and 32). Only violent subjects with antisocial personality disorder exhibited cortical thinning in inferior mesial frontal cortices. The biological underpinnings of violent behavior may therefore vary between these two violent subject groups in which the medial frontal cortex is compromised in antisocial personality disorder exclusively, but laminar abnormalities in sensorimotor cortices may relate to violent behavior in both antisocial personality disorder and schizophrenia.

Effect of ispronicline, a neuronal nicotinic acetylcholine receptor partial agonist, in subjects with age associated memory impairment (AAMI).

Cognitive decline seen in the normal elderly is associated with selective loss of neuronal nicotinic acetylcholine receptors (nAChRs). Nicotine given either by inhalation or transdermally helps cognition, but unacceptable side effects limit its utility. The present study assessed the safety, tolerability and effect on cognition of ispronicline, a highly selective partial agonist at the 4beta2 nAChR, in elderly subjects (n =76) with age associated memory impairment (AAMI). This double-blind, placebo-controlled cross-over study explored ascending oral doses of ispronicline in the range 50-150 mg given as a single morning dose for a period of 3 weeks. Pharmacokinetics (PK) were assessed, as well as cognitive function measured by means of the Cognitive Drug Research (CDR) computerized test battery. Ispronicline had a favourable safety profile and was well tolerated at doses below 150 mg. No effect of clinical importance was seen on biochemistry, haematology, urine analysis, vital signs, electrocardiogram (ECG) or Holter monitoring. The most frequent drug induced adverse event was light-headedness (dizziness). A beneficial effect was seen on cognition across the dose range. This was most marked at 50 mg on factors measuring attention and episodic memory. PK analysis indicated a plasma Cmax range of 5-25/35 ng/ml ispronicline was associated with the most beneficial effect. These early results demonstrate ispronicline was well tolerated and did not display the side effects typical of nicotine. Ispronicline also had a beneficial effect on cognition in subjects with AAMI. This was seen most strongly in a Cmax range that had been predicted from pre-clinical animal studies.

Startle gating in antipsychotic-naïve first episode schizophrenia patients: one ear is better than two.

Prepulse inhibition (PPI) of the startle reflex to binaural prepulse stimuli is reliably reported to be reduced in patients with schizophrenia. Monaural acoustic prestimuli produce more inhibition of the eye blink reflex than binaural prestimuli in healthy people. The effect of monaural prestimulation on reflex inhibition in patients with schizophrenia is not known. In this study, inhibition of the acoustic startle response by monaural and binaural acoustic prestimuli was assessed in 20 antipsychotic-naïve first episode schizophrenia patients and compared with 20 age and sex-matched healthy subjects. The results revealed less PPI, especially with binaural prestimuli, in patients than healthy subjects but both groups showed more PPI with monaural than binaural prestimuli. It is concluded that first episode schizophrenia patients show deficient sensorimotor gating but they are not impaired in the mechanism underlying stronger PPI with monaural than binaural prepulses.

A fMRI investigation of startle gating deficits in schizophrenia patients treated with typical or atypical antipsychotics.

A key feature of schizophrenia is the inability to screen out irrelevant sensory input. Prepulse inhibition (PPI) of the startle response, a cross-species measure of sensorimotor gating, provides a valuable opportunity to study this feature. PPI is reliably impaired in schizophrenia. Animal models of disrupted PPI have proved valuable for the evaluation of antipsychotic substances. The cortico-striato-pallido-thalamic circuitry is primarily responsible for modulation of PPI in animals. We examined PPI and its brain correlates, using functional magnetic resonance imaging (fMRI), in men with schizophrenia treated with typical or atypical antipsychotics. Thirty men with schizophrenia on stable doses of typical antipsychotics (n=10), risperidone (n=10) or olanzapine (n=10; 9 with usable fMRI data) and 12 healthy men underwent psychophysiological testing and fMRI during a tactile PPI paradigm. The results showed reduced PPI of the eye-blink startle response in patients compared with healthy controls. Within the patient group, those on typical antipsychotics showed significantly impaired PPI but risperidone- or olanzapine-treated patients showed a milder (non-significant) deficit. Increased activity in the striatum, thalamus, insula, hippocampal, temporal, inferior frontal and inferior parietal regions occurred in association with PPI in controls. Patients treated with risperidone or olanzapine, but not with typical antipsychotics, showed significant activation in PPI-relevant regions. Our findings provide preliminary evidence that atypical antipsychotics positively influence PPI and partially restore associated brain functions in schizophrenia. Imaging data buttress the validity of PPI as a useful animal model of schizophrenia.

Frontal lobe volumes in schizophrenia: effects of stage and duration of illness.

While the changes in the volume of the temporal lobe and its sub-regions over the course of illness have been studied in patients with schizophrenia, few studies have examined changes in the frontal lobe between the first episode and the chronic stage. In this study, we focussed on the effect of illness stage and duration of illness on the volume of frontal lobe regions, though we also examined several other regions to establish the specificity of any effects, if observed, in this region. We compared the volumes of brain regions among 34 first-episode schizophrenia patients, 49 chronic schizophrenia patients, 18 healthy controls matched, on average, to the first-episode patients and 21 healthy controls matched, on average, to the chronic patients. Logarithmic regression analyses examined the relationships between the duration of illness and the brain regional volumes in the patient group. The results showed that chronic patients had smaller prefrontal cortical grey matter volumes, but larger premotor cortical and putamen volumes compared to first-episode patients and matched healthy controls. Although there were significant patient-by-control group interactions in the cerebellum and sensori-motor cortical grey matter volumes, these did not survive correction for multiple comparisons. There was a significant exponential relation between the duration of illness and the volumes of prefrontal cortex, parieto-occipital cortex grey matter, thalamus and putamen, suggesting that these regions are susceptible to change as the disorder persists. The enlargement of the premotor cortex and putamen are likely to be a result of antipsychotic medication.

Does self-perceived mood predict more variance in cognitive performance than clinician-rated symptoms in schizophrenia?

Symptoms are known to account for a small variance in some cognitive functions in schizophrenia, but the influence of self-perceived mood remains largely unknown. The authors examined the influence of subjective mood states, psychopathology, and depressive symptoms in cognitive performance in a single investigation in schizophrenia. A group of 40 stable medicated patients with schizophrenia (20 men, 20 women) and 30 healthy comparison subjects (15 men, 15 women) were assessed on neurocognitive measures of verbal abilities, attention, executive functioning, language, memory, motor functioning, and information processing. All subjects provided self-ratings of mood prior to cognitive testing. Patients were also rated on psychopathology and depressive symptoms. Patients performed worse than comparison subjects on most cognitive domains. Within the patient group, subjective feelings of depression-dejection, fatigue-inertia, confusion, and tension-anxiety predicted (controlling for symptoms) poor performance on measures of attention, executive function, and verbal memory. In the same group of patients, clinician-rated symptoms of psychopathology and depression predicted significantly poor performance only on tests of motor function. In comparison subjects, vigor related to better, and fatigue and inertia to worse, spatial motor performance. Self-perceived negative mood state may be a better predictor of cognitive deficits than clinician-rated symptoms in chronic schizophrenia patients.

Insight in first-episode psychosis.

BACKGROUND: We report here a study examining the relationships between insight and psychopathology, cognitive performance, brain volume and co-morbid depression in 251 patients experiencing a first episode of psychosis, who were then randomly assigned to 2 years of double-blind treatment with either olanzapine or haloperidol. METHOD: Repeated measures of insight were obtained at baseline and 12, 24, 52 and 104 weeks by the Insight and Treatment Attitudes Questionnaire (ITAQ). RESULTS: Older age, female gender and white ethnicity were associated with more insight. Higher total, positive, negative and general psychopathology scores on the Positive and Negative Syndromes Scale (PANSS) were associated with less insight. Higher depression scores were associated with more insight. Better neurocognitive function and large brain volumes were associated with more insight. More insight throughout the study was associated with longer time to medication non-adherence. However, baseline insight was not significantly related to the probability of discontinuing the study before 2 years. Insight improved significantly over the course of the study, but the improvement in insight was not significantly different between the two antipsychotic treatment groups. CONCLUSIONS: Multiple factors contribute to insight. Patients experiencing a first episode of psychosis who have little insight are at increased risk of discontinuing their medication.

Cognitive effects of adjunctive 24-weeks Rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind investigation.

Cognitive impairment has the greatest impact on illness outcome in schizophrenia. The most significant challenge in schizophrenia therapeutics, thus, is to develop an efficacious treatment for cognitive impairments. Acetylcholinesterase inhibitors, such as Physostigmine and Rivastigmine, are considered effective treatments for cognitive decline in Alzheimer's Disease, where the loss of cholinergic neurons is thought to be responsible for various cognitive deficits. The current study investigated the cognitive effects of Rivastigmine given as an add-on therapy to antipsychotic-treated schizophrenia patients in a placebo-controlled double-blind design. The study initially involved 40 patients, of which 21 patients (11 assigned to Rivastigmine and 10 assigned to placebo) agreed to continued participation, remained on the study drug, and underwent assessment of executive functioning, verbal skills, verbal and spatial working memory, attention and psychomotor speed on three occasions: (i) at baseline, and then (ii) after 12 weeks and (iii) 24 weeks of treatment with placebo or Rivastigmine. The results failed to reveal significant improvement on any cognitive measure with Rivastigmine treatment, compared with the placebo treatment. Some cognitive variables showed significant practice effects in both the placebo and Rivastigmine groups. No effects were noted in symptoms or side effects ratings. The beneficial cognitive effects of Rivastigmine seen in an open-label preliminary study are not substantiated by this study. Future studies should investigate the effects of other procholinergic drugs, such as Galantamine, which also act on the nicotine receptors and may produce stronger cognitive effects in schizophrenia.

Neural dysfunction and violence in schizophrenia: an fMRI investigation.

Contemporary theories and evidence implicate frontal lobe dysfunction in violent behaviour as well as in schizophrenia. We applied functional magnetic resonance imaging (fMRI) to investigate and compare brain activation during an 'n-back' working memory task in groups of men with (i) schizophrenia and a history of serious physical violence (VS; n=13), (ii) schizophrenia without a history of violence (NVS: n=12), (iii) antisocial personality disorder (APD) and a history of serious physical violence (n=10), and (iv) no history of violence or a mental disorder (n=13). We observed comparable performance in all four groups during the control (0-back) condition. Subtle working memory deficits were seen in the NVS and APD groups but severe deficits emerged in the VS group relative to the healthy group. The VS group showed activation deficit bilaterally in the frontal lobe and precuneus when compared to the healthy group, and in the right inferior parietal region when compared to the NVS group during the working memory load condition. Frontal (bilateral) as well as right inferior parietal activity was negatively associated with the ratings of violence across all schizophrenia patients, with the right parietal region showing this association most strongly. APD patients, relative to healthy subjects, showed activation deficit in the left frontal gyrus, anterior cingulate and precuneus. It is concluded that reduced functional response in the frontal and inferior parietal regions leads to serious violence in schizophrenia perhaps via impaired executive functioning.

Predictors of antipsychotic medication adherence in patients recovering from a first psychotic episode.

BACKGROUND: Many patients recovering from a first psychotic episode will discontinue medication against medical advice, even before a 1-year treatment course is completed. Factors associated with treatment adherence in patients with chronic schizophrenia include beliefs about severity of illness and need for treatment, treatment with typical versus atypical antipsychotic and medication side effects. METHOD: In this 2-year prospective study of 254 patients recovering from a first episode of schizophrenia, schizophreniform, or schizoaffective disorder we examined the relationship between antipsychotic medication non-adherence and patient beliefs about: need for treatment, antipsychotic medication benefits, and negative aspects of antipsychotic medication treatment. We also examined the relationship between medication non-adherence and treatment with either haloperidol or olanzapine, and objective measures of symptom response and side effects. RESULTS: The likelihood of becoming medication non-adherent for 1 week or longer was greater in subjects whose belief in need for treatment was less (HR=1.75, 95% CI 1.16, 2.65, p=0.0077) or who believed medications were of low benefit (HR=2.88, 95 CI 1.79-4.65, p<0.0001). Subjects randomized to haloperidol were more likely to become medication non-adherent for >or=1 week than subjects randomized to olanzapine (HR-1.51, 95% CI 1.01, 2.27, p=0.045). CONCLUSION: Beliefs about need for treatment and the benefits of antipsychotic medication may be intervention targets to improve likelihood of long-term medication adherence in patients recovering from a first episode of schizophrenia, schizoaffective, or schizophreniform disorder.

Volumetric structural brain abnormalities in men with schizophrenia or antisocial personality disorder.

Brain abnormalities are found in association with antisocial personality disorder and schizophrenia, the two mental disorders most implicated in violent behaviour. Structural magnetic resonance imaging was used to investigate the whole brain, cerebellum, temporal lobe, lateral ventricles, caudate nucleus, putamen, thalamus, hippocampus, amygdala and the prefrontal, pre-motor, sensorimotor, occipito-parietal regions in 13 men with antisocial personality disorder, 13 men with schizophrenia and a history of violence, 15 men with schizophrenia without violent history and 15 healthy non-violent men. Compared to controls, the antisocial personality disorder group displayed reductions in whole brain volume and temporal lobe as well as increases in putamen volume. Both schizophrenia groups regardless of violence history exhibited increased lateral ventricle volume, while the schizophrenia group with violent history showed further abnormalities including reduced whole brain and hippocampal volumes and increased putamen size. The findings suggest that individuals with antisocial personality disorder as well as those with schizophrenia and a history of violence have common neural abnormalities, but also show neuro-anatomical differences. The processes by which they came to apparently common ground may, however, differ. The finding of temporal lobe reductions prevalent among those with antisocial personality disorder and hippocampal reduction in the violent men with schizophrenia contributes support for the importance of this region in mediating violent behaviour.

A behavioural and functional neuroimaging investigation into the effects of nicotine on sensorimotor gating in healthy subjects and persons with schizophrenia.

RATIONALE: Schizophrenia patients display an excessive rate of smoking compared to the general population. Nicotine increases acoustic prepulse inhibition (PPI) in animals as well as healthy humans, suggesting that smoking may provide a way of restoring deficient sensorimotor gating in schizophrenia. No previous study has examined the neural mechanisms of the effect of nicotine on PPI in humans. OBJECTIVES: To investigate whether nicotine enhances tactile PPI in healthy subjects and patients with schizophrenia employing a double-blind, placebo-controlled, cross-over design and, if so, what are the neural correlates of nicotine-induced modulation of PPI. MATERIALS AND METHODS: In experiment 1, 12 healthy smokers, 12 healthy non-smokers and nine smoking schizophrenia patients underwent testing for tactile PPI on two occasions, 14 days apart, once after receiving (subcutaneously) 12 microg/kg body weight of nicotine and once after receiving saline (placebo). In experiment 2, six healthy subjects and five schizophrenia patients of the original sample (all male smokers) underwent functional magnetic resonance imaging (fMRI) under the same drug conditions and the same tactile PPI paradigm as in experiment 1. RESULTS: Nicotine enhanced PPI in both groups. A comparison of patterns of brain activation on nicotine vs placebo conditions showed increased activation of limbic regions and striatum in both groups after nicotine administration. Subsequent correlational analyses demonstrated that the PPI-enhancing effect of nicotine was related to increased hippocampal activity in both groups. CONCLUSIONS: Nicotine enhances tactile PPI in both healthy and schizophrenia groups. Our preliminary fMRI findings reveal that this effect is modulated by increased limbic activity.