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In this work a voice controlled wheelchair is made for physically challenged peoples or patients whose hind limbs are not in working condition. Hence, he or she can control the wheelchair by own voice commands or of the family members. To accomplish the task Arduino microcontroller board is used which receives the voice commands either from Bluetooth module via smartphone or from voice recognition module from microphone attached to it. Further matching it with preloaded voice commands and develop movement accordingly. In the subsequent sections of the paper give more concentration on further objectives to achieve reduction in motor speed smooth movement of vehicle by two motors and the wheels as per the command. The main objective of current work is to make it as simple as possible. Certain theoretical results are also obtained by formulation and design calculation.

Fundamento En muchos estudios se ha utilizado morfometria basada en voxels (MBV) de imagenes de resonancia magnetica (RM) como un metodo automatizado para estudiar las diferencias en la sustancia gris cortical en la esquizofrenia. No obstante, los resultados de estos estudios varian ampliamente, lo que probablemente se deba a las diferencias metodologicas o del analisis estadistico. Objetivo Usar la MBV para estudiar las diferencias en la sustancia gris en la esquizofrenia en una muestra significativamente mas amplia que cualquiera de las publicadas hasta la fecha y aumentar la potencia estadistica lo suficiente para revelar las diferencias omitidas en los analisis a menor escala. Metodos A partir de cuatro lugares geograficos, se adquirieron imagenes de resonancia magnetica del cerebro en conjunto usando el mismo modelo de equipo de 1,5 T y la misma version del programa informatico, y se combinaron para formar una muestra de 200 pacientes tanto con un primer episodio como con esquizofrenia cronica y 200 individuos de control sanos apareados por edad, sexo y localizacion del escaner. Se evaluo la concentracion de sustancia gris y se la comparo utilizando MBV optimizada. Resultados Comparados con los individuos de control, en pacientes con esquizofrenia se detecto una concentracion significativamente menor de sustancia gris en multiples 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 mayoria solo documentaron subgrupos de las areas afectadas. Conclusiones En la esquizofrenia las diferencias en la sustancia gris se dilucidan mas exhaustivamente usando una muestra a gran escala, diversa y representativa.

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.

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.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.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.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.Gray matter differences in schizophrenia are most comprehensively elucidated using a large, diverse and representative sample.

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.

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.

Sustained attention is affected by schizophrenia. The simplest form of Continuous Performance Test (CPT-X) is a purer test of vigilance than more demanding variants but widely thought too insensitive to detect abnormalities in those with genetic predisposition to schizophrenia. We used a 7-minute CPT to compare 61 patients diagnosed with schizophrenia, 45 of their never-psychotic relatives, and 47 control subjects. We found a significant impairment in stimulus discrimination in both patients (p=0.001) and their relatives (p=0.006). There was no difference in stimulus discrimination between relatives of patients with impaired and unimpaired stimulus discrimination. Relatives of patients with unimpaired stimulus discrimination were still inferior to controls (p=0.02). Reactions slowed in all groups equally as the test progressed. Patients showed increased mean reaction time (p

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.

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.

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.

Facilitation of central cholinergic activity may form a potential treatment strategy for cognitive impairment in schizophrenia. In a randomized, placebo-controlled, double-blind, parallel-group design, we investigated the neural correlates of cognitive effects of rivastigmine, an acetylcholinesterase inhibitor, given as an add-on therapy to antipsychotic-treated schizophrenia patients. Thirty-six chronic schizophrenia patients with mild cognitive impairment took part. After 1 week on placebo (baseline), all patients entered a double-blind protocol; 18 were allocated to receive rivastigmine and 18 placebo for the next 12 weeks (final sample with usable imaging data: 11 patients on rivastigmine, 10 on placebo). All patients underwent functional magnetic resonance imaging during a parametric ‘n-back’ task, involving monitoring of dots in particular locations on a screen at a given delay from the original occurrence, twice: at baseline and 12 weeks post-rivastigmine/placebo treatment. Compared to placebo, rivastigmine produced only a small and non-significant improvement in task accuracy across all conditions with no change in response latency, and increased activity in the extrastriate visual cortex in areas associated with visual and spatial attention but not in any region within the working memory network. Our observations suggest that cholinergic enhancement with rivastigmine at doses known to be effective in Alzheimer's disease does not produce strong and clinically meaningful cognitive and neural changes in schizophrenia patients treated with atypical antipsychotics although the neural effects in terms of enhanced neuronal activity in regions associated with visual and spatial attention are consistent with those reported previously with cholinergic enhancement in healthy subjects.

BackgroundSubstantial weight gain is common with many atypical antipsychotics.AimsTo evaluate the extent, time course and predictors of weight gain and its effect on study retention among people with first-episode psychosis treated with olanzapine or haloperidol.MethodSurvival analysis assessed time to potentially clinically significant weight gain (⩾7%) and the effect of weight gain on study retention. Weight gain during the 2-year study was summarised using last-observation-carried-forward (LOCF), observed cases and study completion approaches.ResultsAfter 2 years of treatment, LOCF mean weight gain was 10.2 kg (s.d.=10.1) for olanzapine (n=131) and 4.0 kg (s.d.=7.3) for haloperidol (n=132); observed cases mean weight gain was 15.4 kg (s.d.=10.0) for olanzapine and 7.5 kg (s.d.=9.2) for haloperidol. Change in body mass index was significantly predicted only by treatment group (P< 0.0001).ConclusionsOlanzapine was associated with significantly greater weight gain than haloperidol, with both leading to greater weight gain than previously described.

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.

This study assessed the neural correlates of the effects of rivastigmine, a CNS-selective cholinesterase inhibitor, given as an add-on therapy to antipsychotics-treated patients with schizophrenia who displayed moderate cognitive impairments, using functional magnetic resonance imaging (fMRI) during a sustained attention task. The study used a placebo-controlled, randomized, double-blind longitudinal design. Twenty patients stable on antipsychotics, 11 assigned to receive rivastigmine and 9 to receive placebo, underwent fMRI and clinical assessments at baseline and after 12 weeks. The fMRI task used a periodic block design and involved 3 conditions: rest, detecting a nonzero number ("nonzero" condition), and detecting a specific number ("specific number" condition) among a series of 6-digit numbers. Online data (via button presses) were acquired on both occasions. Behavioral results showed a trend (P = 0.075) for the rivastigmine-treated patients to have more correct responses and the placebo group to have fewer correct responses at 12 weeks compared with baseline in the "nonzero" condition. There was also an increase in regional brain activity in the cerebellum in the rivastigmine group at 12 weeks in both conditions, which was only partially explained by change in behavioral measures; no change was observed in the placebo group. Our results showed that rivastigmine treatment increased cerebellar activity and influenced attentional processes.

Background Schizophrenia may involve dysfunction to primary auditory, speech, and language processes governed by the superior temporal gyrus (STG). These processes are implicated in hallucinations, delusions, and thought disorder. The current study explored the relationship between unreality symptoms (hallucinations and delusions) and specific STG substructures, including Heschl’s gyrus (HG) and planum temporale (PT). Methods Twenty-five right-handed men within their first episode of psychosis were assessed using the Positive and Negative Syndrome Scale (PANSS) for the presence of hallucinations and delusional behavior (a composite score of delusions, grandiosity, suspiciousness, and unusual thought content). T1-weighted magnetic resonance imaging (MRI) scans were acquired using a 1.5 Tesla scanner. Stereological measurements of HG and PT volume were obtained. Linear regression methods explored the relationship between regional volumes and symptoms. Results Reductions in left HG were associated with hallucinations and delusions. Increases in left PT were associated with delusional behavior. Conclusions Current results implicate HG dysfunction in unreality symptoms in men with recent-onset schizophrenia.

Previous research has reported cognitive impairment in patients with schizophrenia and antisocial personality disorder (APD), the two psychiatric illnesses most implicated in violent behaviour. Previous studies have focused on either group exclusively, and have been criticized for procedural inadequacies and sample heterogeneity. The authors investigated and compared neuropsychological profiles of individuals with APD and violent and nonviolent individuals with schizophrenia in a single investigation. The study involved four groups of subjects: (i) individuals with a history of serious violence and a diagnosis of APD, (ii) individuals with a history of violence and schizophrenia, (iii) individuals with schizophrenia without a history of violent behaviour and (iv) healthy control subjects. All study groups were compared on a neuropsychological battery designed to assess general intellectual function, executive function, attention, and processing speed. Cognitive deficits were more widespread among individuals with schizophrenia regardless of history of violence, compared with those with APD. Significant impairment in patients with APD was limited to processing speed. Violent individuals with schizophrenia demonstrated poorer performance than their nonviolent schizophrenia peers on a measure of executive function. Different cognitive impairments are manifested by individuals with APD and schizophrenia with violent behaviours, suggesting differences in underlying pathology. Furthermore, cognitive impairment appears to be more a feature of schizophrenia than of violent behaviour, although there is evidence that a combination of schizophrenia and violent behaviour is associated with greater cognitive deficits.

The first episode of schizophrenia represents a transition from a premorbid to a morbid state. Studying the first episode of schizophrenia is useful since it is devoid of the confounds of chronicity and long-term medication. It is also likely to direct us to the core deficits of the illness. Studies on first-episode schizophrenia suggest a generalized neuropsychologic impairment, but that memory, attention and executive function are more severely impaired. Support for a neurodevelopmental model of neuropsychologic impairment in schizophrenia is derived from the findings that much of the neuropsychologic impairment is present by illness onset, that neuropsychologic impairment remains stable over time and that there is a weak relation between duration of untreated psychosis and neuropsychologic impairment. However, neuropsychologic impairment is moderated by neuroleptic treatment, with some evidence that atypical antipsychotics may have some beneficial effects over conventional antipsychotics. The causal mechanisms of brain abnormality in the temporal and frontal lobes appear to be different to that of neuropsychologic impairment in schizophrenia. The observation that there is a brain volume decrement over time and that the rate of change is higher during the first 5 years would be consistent with a neurodegenerative model of schizophrenia. At the same time, the basal ganglia are vulnerable to volumetric increase secondary to neuroleptic medication. Understanding the roles of the neurodevelopmental and neurodegenerative models of schizophrenia is important in deciding intervention strategies.

Learned irrelevance (LIrr) is closely related to latent inhibition (LI). In LI a to-be-conditioned stimulus (CS) is prexposed alone prior to the opportunity to learn an association between the CS and an unconditioned stimulus (UCS). In LIrr preexposure consists of intermixed presentations of both CS and UCS in a random relationship to each other. In both paradigms preexposure leads in normal subjects to reduced or retarded learning of the CS-UCS association. Acute schizophrenics fail to show LI. LI is usually demonstrated as a one-off, between-groups difference in trials to learning, so posing problems for neuroimaging. We have developed a novel, continuous, within-subject paradigm in which normal subjects show robust and repeated LIrr. We show that this paradigm is suitable for functional magnetic resonance imaging (fMRI) and gives rise, in normal subjects, to activation in the hippocampal formation, consistent with data from animal experiments on LI. We also report, consistent with previous studies of LI, loss (indeed, significant reversal) of LIrr in acute (first 2 weeks of current psychotic episode) schizophrenics. Chronic schizophrenics failed to demonstrate learning, precluding measurement in this group of LIrr. These findings establish the likely value of the new paradigm for neuroimaging studies of attentional dysfunction in acute schizophrenia.

Aims and MethodTo investigate the attitudes that psychiatrists hold towards people with mental illness. Each member of the Royal College of Psychiatrists in the UK was sent a questionnaire based on previous research in this area, supplemented with relevant questions on management.Results2813 of 6524 questionnaires were returned (43%). Psychiatrists' attitudes compared favourably with those of the general population. Among other findings, they believed that the risk of dangerousness was overemphasised, that misdiagnosis of schizophrenia in Black people is common, and that polypharmacy and the use of antipsychotic medication above British National Formulary levels occurs too often.Clinical ImplicationsPsychiatrists' attitudes are substantially more favourable towards people with mental illness than those of the general population with individual, but important, exceptions. Some aspects of psychiatric management, especially of antipsychotic medication, may undermine this, however. Comparison with other groups, e.g. general practitioners, nurses and social workers, would be useful in planning how to reduce the stigmatisation of people with mental illness.

The authors investigated the structural brain correlates of antisaccade performance.Magnetic resonance imaging was used to measure the volumes of the prefrontal, premotor, sensorimotor, and occipitoparietal cortices as well as the caudate, thalamus, cerebellar vermis, and cerebrum in 20 first-episode psychosis patients and 18 healthy comparison subjects. Antisaccades were recorded by using infrared oculography.Groups significantly differed in terms of antisaccade error rate and amplitude gain and tended to differ in terms of latency but not brain region volumes. Premotor cortex volume predicted antisaccade error rate among comparison subjects. In the patient group, caudate volume was related to latency and amplitude gain. Negative symptoms, independent of structural volumes, predicted error rate.These findings point to altered structure-function relationships in first-episode psychosis.

Gonadal as well as stress hormones have recently been implicated in pathophysiology and sex differences in onset, prognosis and treatment of schizophrenia. The present study investigated the effects of serum levels of oestrogen, progesterone, testosterone and cortisol on neuropsychological functioning and psychopathology in a group of 37 patients (17 women, 20 men) with schizophrenia. Neuropsychological measures included tests of attention, verbal abilities, language, memory, executive functioning, motor and speed of information processing. The results showed that oestrogen and age was associated with low positive symptom scores, and within gender, cortisol predicted poor performance on the information processing domain in men. These findingsdemonstrate that cortisol, in addition to the commonly reported effects of oestrogen, influences neuropsychological functioning in schizophrenia with differential effects on specific domains of cognitive functioning and underscore the need for further investigation of the modulating role of hormones on neuropsychological functioning in schizophrenia.

Research has shown that many of the long-term deficits that are observable in schizophrenia populations are present prior to the emergence of psychotic symptoms. Recent research suggests schizophrenia has a “prodromal” period, whereby significant changes from premorbid functioning can be observed. Accurate classification of this period could have far-reaching implications for schizophrenia prevention. This article aims to provide an indepth evaluation of the perceived benefits of vulnerability marker research in this unique phase. It is hoped that identification of such markers may improve the predictive potency of prodromal criteria, and perhaps pave the way for future screening and primary prevention strategies.

The study of social cognition in psychiatric disorders has become increasingly popular in recent years. This is due to the its proposed link to social functioning and the inability of general neurocognitive skills to explain the spectrum of impairments observed in patients. This article reviews research into two of the processes thought to underlie social cognition (emotion perception and theory of mind) in schizophrenia and autism. This is followed by a look at neuroimaging studies and their efforts to localize the neural correlates of emotion perception and theory of mind in the two disorders. We concluded that while a specific impairment in emotion perception and theory of mind skills cannot be generalized to all individuals with autism and schizophrenia, there are subpopulations that have lingering deficits of social cognition tasks. Neuroimaging work consistently points to the involvement of the fusiform gyrus and amygdala in emotion processing, while the medial prefrontal and frontal cortex are implicated in tasks invoking theory of mind. We propose that deficits of social cognition may benefit from cognitive remediation therapy and pharmacological cognitive enhancers.

Background: Dysfunctions in brain regions known to be involved in affect and mood states are thought to be implicated in depression and may have a role in determining the type and symptoms of this illness. Methods: Functional magnetic resonance imaging was used to elucidate neural correlates of cognitive generation of affect, using a previously published paradigm of evoking affect with picture-caption pairs, in patients with unipolar, treatment-resistant depression. Results: Compared with control participants, patients showed relatively decreased response in the anterior cingulate (rostral; right) with both negative and positive picture-caption pairs and in the medial frontal gyrus and hippocampus (all left) with positive picture-caption pairs. They demonstrated increased response in the inferior (right) and middle temporal gyri (left) with negative picture-caption pairs, and in the parahippocampal gyrus (right), inferior frontal gyrus (left), subgenual cingulate (right), striatum (right), and brain stem (left) with positive picture-caption pairs. Conclusions: Reduced medial/middle prefrontal and hippocampal activity may account for positive affect disturbances and temporal lobe hyperactivity for negative affect disturbances in treatment-resistant depression. The results also corroborate previous observations from resting positron emission tomography studies and further elucidate the association between hypoactive rostral cingulate and nonresponsiveness to treatment in depression.

Schizophrenia patients are known to manifest widespread, multifaceted cognitive deficits. There is now an increasing emphasis on the critical importance of cognitive deficits for the functional outcome in schizophrenia. Typical antipsychotics, although effective in reducing positive symptoms of the illness, have not shown much effect on cognitive functions. Atypical antipsychotics have shown promise of improving some cognitive functions. This naturalistic study aimed to determine whether olanzapine and clozapine improve cognitive functioning in a sample of 48 patients with chronic schizophrenia who had either failed to show sufficient clinical improvements or suffered from distressing side effects with conventional antipsychotics and were switched to either olanzapine or clozapine for clinical reasons and, if so, whether the two drugs produce similar or different cognitive effects. All patients completed a comprehensive battery of neuropsychological tests designed to index executive functioning, verbal learning, verbal and visual and memory, attention, working memory, and psychomotor speed at: (i) baseline, (ii) after 6 weeks and (iii) after 6 months of treatment with olanzapine or clozapine. From the initial 48 patients who remained on olanzapine (n=16) or clozapine (n=14) for the entire duration with continuous participation, 30 provided data for this study. There were improvements over time (i.e. from baseline through 6 weeks to 6 months) in both treatment groups on verbal fluency, verbal learning and verbal and visual memory measures. The findings indicate similar beneficial effects of olanzapine and clozapine on verbal learning and memory measures in patients showing a favourable clinical response to these drugs.

The startle response is inhibited when the startle-eliciting stimulus is preceded 30–500 ms by a prepulse. This effect, known as prepulse inhibition (PPI), is believed to represent a sensorimotor gating mechanism, which protects the brain from experiencing sensory overload. PPI is disturbed in many psychiatric disorders. Within healthy populations, women show less PPI than men. This study employed a new PPI paradigm with a single prepulse or two prepulses to measure PPI in 15 men and 15 women. Startle stimuli were preceded on some trials by a single discrete prepulse with a 120-ms prepulse-to-pulse interval. On other trials, a second discrete prepulse preceded the first with 30–480-ms prepulse-to-prepulse intervals. Women showed less PPI than men with a single prepulse. PPI, however, was quantitatively identically reduced (greatest reduction when the second prepulse preceded the first with a 120-ms interval) in the two sexes by two-prepulse trials, relative to that with a single prepulse. Women showed a smooth transition from reduced PPI to an observed prepulse facilitation (PPF) with two prepulse trials. We conclude that sex difference consists in a general shift of the inhibition/facilitation curve in the direction of facilitation in women relative to men.

Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial.Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase.Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%).As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.

Background. There is considerable variability between patients in their expression of the diverse range of symptoms encompassed by the syndrome of schizophrenia, which may modulate functional activation to cognitive processing.Method. Here we investigate associations between schizophrenic subsyndrome scores, identified by factor analysis, and experimentally controlled brain activation. Five factors were defined by rotated principal components analysis of PANSS rating scale measurements in 100 patients with schizophrenia. A subsample of 30 patients and a group of 27 comparison subjects were studied using functional magnetic resonance imaging (fMRI) during the performance of two periodically designed cognitive activation experiments: verbal working memory and psychomotor sequencing.Results. Factor analysis replicated the five dimensions consistently reported. Within the patient group, power of activation by working memory was negatively associated with global symptom severity in left lingual and temporo-parietal cortices; negatively associated with positive subsyndrome scores in left inferior frontal and superior temporal cortices and basal ganglia; and positively associated with negative subsyndrome scores in lateral and medial premotor cortex. No relationship was observed between subsyndrome scores and functional activation during the motor task. Between-group comparisons demonstrated reduced power of response to the working memory task by patients in bilateral dorsolateral prefrontal and left pre- and post-central cortices.Conclusions. In this study we observed task-specific modulation of functional response associated with symptom expression in schizophrenia. Our findings are compatible with previous empirical findings and theoretical conceptualization of human brain function, in terms of capacity constraints on activation in the face of competing demands from pathological and task-related cognitive activity.

The advent of functional imaging has led to a new wave of insights into the pathophysiology and treatment of psychiatric disorders. In this Perspective, schizophrenia is used as an example of such a psychiatric disorder to illustrate these advances. Schizophrenia is a chronic and debilitating disorder characterized by a heterogeneous group of symptoms, including positive symptoms (delusions, hallucinations, disorganized thought), negative symptoms (flattened affect, stereotyped thinking, difficulty in abstract thinking), and multifaceted cognitive deficits, most prominently in the areas of attention, memory, and executive functioning (1). Emil Kraepelin gave us the first clinical account of schizophrenia in 1896. He named it dementia praecox, literally, early or premature deterioration of one’s mental faculties. In using this term, Kraepelin was referring to the fact that the disorder often strikes in adolescence or early adulthood and runs a chronic, lifelong, disabling course. In his writing about the disorder, Kraepelin emphasized the evident cognitive impairment in individuals that he studied, which comprised deficits in attention, motivation, problem solving, learning, and memory. He was also the first to link these cognitive impairments with poor functional outcome in patients with schizophrenia, such as deficits in social functioning, independent living, and self-care abilities. The term “schizophrenia” (schizo, split; phreno, mind) was coined by the Swiss psychiatrist Eugen Bleuler in 1911. Although Bleuler disputed Kraepelin’s assumption that the disorder struck only in early adulthood and always entailed dementia-like cognitive degeneration, he agreed that cognitive impairment was a core feature of schizophrenia, or its fundamental symptom. Other “peculiar” features, such as hallucination and delusions, were considered by Blueler to be secondary or “accessory” symptoms. The discovery of antipsychotics in the 1950s revolutionized the treatment of schizophrenia and directed emphasis toward positive symptoms. At that time, treatment with antipsychotics, with their encouraging effect on psychotic symptoms, led to the closure of most hospitals for chronic patients with severe and enduring mental illness and offered much hope for these patients to be reintegrated into society. However, by the 1960s it became obvious that a reduction in positive symptoms did not lead to recovery from schizophrenia and did not significantly improve functional outcome (2). The understanding of the fundamental deficits in schizophrenia came full circle as it came to be accepted that cognitive dysfunction plays a central role in the illness, just as Kraepelin and Bleuler had suggested at the dawn of the 20th century. Cognitive deficits are a core feature of schizophrenia, which (a) may precipitate psychotic and negative symptoms (3); (b) are relatively stable over time, with progressive deterioration after the age of 65 in some patients (4); (c) persist upon the remission of psychotic symptoms (5); (d) are related to but separate from negative symptoms (6, 7); and (e) determine functional impairment characteristic of the patients with this disorder (8). Functional brain imaging in schizophrenia was originally intended to elucidate the underlying physiological disturbances that lead to manifest illness. This Perspective will deal mainly with attempts by researchers to understand the pathophysiology and the mechanism of drug action using functional magnetic resonance imaging (fMRI), a technique that has the obvious advantages of minimal invasiveness, no radioactivity, widespread availability, and virtually unlimited study repetitions. These attributes make it ideally suited to the study of in vivo brain function in psychiatric illness like schizophrenia, facilitating the characterization of developmental changes in brain function from childhood and throughout the clinical course of the illness, and in response to treatment. In this article, some current issues surrounding the interpretation of functional imaging data in schizophrenia will be considered. Various investigators have examined links between brain activation, cognitive functioning, and symptoms, in the hope of identifying those regions and circuits that may be abnormal in schizophrenia. Ultimately, fMRI may help delineate disease pathways based upon pathophysiological correlates that may complement nosology. If this is successful, neural network models might be built to emulate brain malfunctions for each disease. This, in turn, may lead to better therapeutic options.

This article has discussed the relationship between cognitive deficits and functional outcome in schizophrenia. This relationship was noted first by Kraepelin and Bleuler at the beginning of the twentieth century. With the introduction of conventional neuroleptics, the focus shifted toward the treatment of positive symptoms. In the past few decades, cognitive dysfunction has been recognized as a fundamental feature of schizophrenia and has been shown repeatedly to have a negative association with functional outcome [6]. Improvement in cognitive functioning became one of the most important clinical targets in the treatment of schizophrenia in the 1990s [82]. Main domains of cognition that are disrupted significantly in schizophrenia include attention, executive function, verbal and visuospatial working memory, and learning and memory. Although conventional antipsychotics are effective in treating positive symptoms, they lack the ability to improve cognitive impairment and produce poor functional outcome. Previous research has shown superior efficacy of atypical antipsychotics on cognitive impairments in schizophrenia compared with conventional antipsychotics. Because the heterogeneity of atypical antipsychotics in their pharmacologic properties, they have differential profiles of cognitive efficacy in patients with schizophrenia. Establishing the cognitive profile of each atypical antipsychotic is an important task. This knowledge can be used to address individual cognitive problems and needs. Because cognitive deficits have been shown to have associations with different aspects of clinical symptoms, limited learning in rehabilitation programs, and functional outcome in schizophrenia, targeting individual cognitive deficits would lead to greater treatment success in terms of clinical and functional outcome. Although atypical antipsychotics have some benefit on cognitive function, further efforts to improve cognitive function are required. Attempts at improving cognition in schizophrenia with specific cognitive enhancers pharmacologically and psychological therapies such as cognitive remediation might lead to better functional outcome in patients with schizophrenia.

Prepulse inhibition (PPI) of the startle reflex refers to the ability of a weak prestimulus, the prepulse, to inhibit the response to a closely following strong sensory stimulus, the pulse. PPI is found to be deficient in a number of psychiatric and neurological disorders associated with abnormalities at some level in the limbic and cortico-pallido-striato-thalamic circuitry. We applied whole-brain functional magnetic resonance imaging to elucidate the neural correlates of PPI using airpuff stimuli as both the prepulse and the pulse in groups of (i) healthy subjects and (ii) schizophrenic patients. Cerebral activation during prepulse-plus-pulse stimuli with stimulus-onset asynchronies of 120 ms was contrasted with activation during pulse-alone stimuli. In healthy subjects, PPI was associated with increased activation bilaterally in the striatum extending to hippocampus and thalamus, right inferior frontal gyrus and bilateral inferior parietal lobe/supramarginal gyrus, and with decreased activation in the right cerebellum and left medial occipital lobe. All activated regions showed significantly greater response in healthy subjects than schizophrenic patients, who also showed a trend for lower PPI. The findings demonstrate involvement of the striatum, hippocampus, thalamus, and frontal and parietal cortical regions in PPI. Dysfunctions in any of these regions may underlie observations of reduced PPI in schizophrenia.

The treatment of sexual dysfunction or deviancy requires an understanding of the underlying neural substrates. Neuroimaging techniques offer insight into brain regions involved in sexual arousal and inhibition. The development of robust paradigms has implications for the assessment and treatment of sexual disorder in men and women.

Procedural learning (PL) is a type of rule-based learning in which performance facilitation occurs with practice on task without the need for conscious awareness. Schizophrenic patients have often (though not invariably) been found to show impaired PL. We performed functional magnetic resonance imaging (fMRI) during a blocked, periodic sequence-learning task with groups of: (i) healthy subjects, and (ii) schizophrenic patients on conventional antipsychotics. Healthy subjects showed significant PL, but patients did not. In healthy subjects, PL was associated with increased activation in the striatum, thalamus, cerebellum, precuneus, medial frontal lobe, and cingulate gyrus. The power of activation in the thalamus, striatum, precuneus, cingulate gyrus and BA 6 was related to the magnitude of PL in these subjects. No regions, except the anterior inferior gyrus, were significantly activated in patients. The caudate nucleus, thalamus, precuneus, and sensorimotor regions were activated significantly differently between the two groups. The findings demonstrate the involvement of the striatum, cerebellum, thalamus, cingulate gyrus, precuneus, and sensorimotor regions in PL. Further fMRI studies of PL in normal subjects treated with conventional antipsychotics, drug naïve patients, and patients given atypical antipsychotics would help to clarify the roles of schizophrenic disease processes and antipsychotic medication in impaired PL and associated brain abnormalities in schizophrenia.

OBJECTIVE: The nature and time course of temporal lobe abnormalities in psychotic illness remain controversial. Confounds include disease chronicity, gender, and handedness. The present study investigated temporal substructures in right-handed male patients experiencing their first episode of psychotic illness. METHOD: Magnetic resonance imaging scans were obtained for 25 minimally treated patients experiencing their first psychotic episode and 16 healthy comparison subjects. Group differences in volumes of the hippocampus, amygdala, planum temporale, and Heschl’s gyrus were tested. RESULTS: The patients had smaller bilateral hippocampal and left planum temporale volumes than the comparison subjects. Paranoid and nonparanoid patients differed in left amygdala volume. CONCLUSIONS: The authors conclude that bilateral hippocampal and left planum temporale abnormalities are present near the onset of psychosis.

Alzheimer's disease is common in the elderly and causes tremendous distress to patients and their carers. With the advent of newer pharmacological treatments, significant improvement in the early diagnosis of Alzheimer's disease is required. This article examines the usefulness of neuroimaging techniques to predict Alzheimer's disease in prediagnosis individuals.

The critical flicker fusion threshold (CFFT) is thought to index alertness and cortical arousal. Sedative drugs reduce CFFT while psychostimulants increase it. Procyclidine is an anticholinergic that is used to control the extrapyramidal side-effects of antipsychotics in schizophrenia. This study examined the effects of clinically relevant doses of oral procyclidine administration on CFFT and heart rate in two separate experiments (Experiment 1, drug dose: 10 mg, n = 16; Experiment 2, drug dose: 15 mg, n = 12) involving healthy subjects using a double-blind, placebo-controlled, cross-over design. 10 mg procyclidine had no significant effect on CFFT, heart rate or self-ratings of mood, but the 15 mg dose significantly lowered CFFT at 1 h and 2 h after procyclidine administration, increased drowsiness ratings and produced a drop in heart rate. The effects observed in this study may have implications for treatment compliance of schizophrenic patients, choice of antipsychotics, prescribing to patients with heart disease and monitoring of cardiac function under treatment. Further investigations are required to quantify the effects of procyclidine on CFFT and cardiac function in patients with schizophrenia.

Working memory dysfunction is considered to be fundamental to the cognitive and clinical features evident in schizophrenia. Functional neuroimaging studies have begun to elucidate the neurobiological basis of such deficits, however, interpretation of these studies may be confounded by performance impairment, when the cognitive load exceeds the limited response capacity of patients with schizophrenia. In this study, patients were pre-selected on the basis of intact performance on a relatively low-load verbal working memory task, in order to mitigate against performance confounds. Subjects included 20 right-handed male subjects with chronic schizophrenia, and 20 right-handed, age-matched, male healthy controls, without personal or familial psychiatric history. All subjects underwent fMRI scanning whilst performing a verbal n-back task. There were no significant between-group differences in target identification; the patient group showed a significantly increased mean response latency. Both groups demonstrated robust fronto-parietal activation. In the control subjects, the power of functional response was positively correlated with reaction time in bilateral posterior parietal cortex, however, this coupling of behavioural performance and cerebral response was not evident in the patients. This deficit, apparent within the performance capacity of the patients, may represent a fundamental abnormality in schizophrenia, and may compromise performance at higher cognitive loads.

Conventional treatment paradigms for schizophrenia have typically focused on reducing positive symptomatology; however, it is increasingly apparent that negative and cognitive symptoms are also important treatment targets. Cognitive function, in particular, is known to affect multiple outcome domains, including performance of basic daily activities, and social and occupational functioning. While traditional antipsychotics have little, or even a detrimental, effect on neurocognitive impairment in patients with schizophrenia, available data suggest that cognitive function may be improved during treatment with atypical antipsychotics. Quetiapine is a novel atypical antipsychotic with proven efficacy in schizophrenia across all domains. Results of well-controlled, double-blind, randomised studies show quetiapine to significantly improve cognitive function compared with treatment with haloperidol. Quetiapine has also been shown to be effective and well tolerated in patients particularly vulnerable to the extrapyramidal side effects (EPS) associated with conventional antipsychotics, making it well suited for use as first-line therapy. © 2001 Elsevier Science B.V. All rights reserved.

The prevalence of tobacco smoking is known to be higher in patients with schizophrenia than other psychiatric disorders and general population. These patients also show reduced prepulse inhibition (PPI) of the startle response. PPI refers to a reduction in response to a strong startling stimulus if preceded shortly by a stimulus of sub-threshold intensity. PPI is thought of as an objective index of sensorimotor gating. Nicotine administered subcutaneously or via cigarette smoking enhances PPI in healthy human beings. It also enhances PPI at low, but not high, doses in the rat. We examined the influence of smoking on PPI of the acoustic startle response in 46 male patients with chronic schizophrenia. In a naturalistic design, patients (n = 9) who smoked a cigarette less than 10 min prior to being tested on PPI were compared with other smoking (n = 23) and non-smoking patients (n = 14). We found that the group of patients who smoked a cigarette prior to being tested had significantly greater PPI than other two groups. These observations suggest a PPI-enhancing effect of cigarette smoking on PPI in patents with schizophrenia. Higher prevalence of cigarette smoking in schizophrenic patients may reflect an attempt to improve sensorimotor gating deficits. Copyright © 2001 John Wiley & Sons, Ltd.

BackgroundThere has been relatively little research on caregivers of people experiencing their first episode of psychosis.AimsTo investigate dimensions of caregiving and morbidity in caregivers of people with first-episode psychosis.MethodCaregivers of 40 people with first-episode psychosis were interviewed at home about their experience of caregiving, coping strategies and distress.ResultsCaregivers used emotional and practical strategies to cope with participants' negative symptoms and difficult behaviours and experienced more worry about these problems. They increased supervision when the participants displayed difficult behaviours. Twelve per cent of caregivers were suffering from psychiatric morbidity as defined by the General Health Questionnaire. Those living with the participant had more frequent visits to their general practitioner.ConclusionsAt first-episode psychosis, caregivers are already having to cope with a wide range of problems and are developing coping strategies. Caregivers worried most about difficult behaviours and negative symptoms in participants.

The 10th Biennial Winter Workshop on Schizophrenia (5-11 February 2000), organized by Drs Tim Crow and Steven Hirsch, attracted a wide range of contributions, not only from European countries, but from all across the world, encompassing clinical, neuropsychological, cognitive, experimental, pharmacological and neuroimaging approaches to enhance the understanding of possible causes, features and the treatments of this illness. The Kongresszentrum, Davos, Switzerland was once again the venue. We present a flavour of the variety of presentations, the news and the views emerging from these presentations, and discuss their implications for further advancement in the field of schizophrenia research.

Objective: Structural magnetic resonance imaging (MRI) studies that focus on firstepisode psychosis avoid some common confounds, such as chronicity of illness, treatment effects, and long-term substance abuse. However, such studies may select subjects with poor short-term treatment response or outcome. In this study, the authors focus on structural brain abnormalities in never or minimally treated patients who underwent MRI scanning early in their first episode of psychosis. Method: The authors examined 37 patients (13 medication naive, 24 previously treated) who were experiencing their first episode of psychosis; the mean duration of symptoms was short (31 weeks). These patients were comparable in age, gender, handedness, ethnicity, and parental socioeconomic status to a group of 25 healthy comparison subjects. A three-dimensional, inversion recovery prepared, fast spoiled gradient/recall in the steady state scan of the whole brain that used 1.5-mm contiguous sections was performed to acquire a T1-weighted data set. Human ratings of volumetric measurement of brain structures were performed with stereological techniques on three-dimensional reconstructed MRIs. Results: The patient group had significant deficits in cortical gray matter, temporal lobe gray matter, and whole brain volume as well as significant enlargement of the lateral and third ventricles. Structural deviations were found in both treatment-naive and minimally treated subjects. No relationships were found between any brain matter volumes and positive or negative symptoms. Conclusions: Structural brain abnormalities were distributed throughout the cortex with particular decrement evident in gray matter. This feature is consistent with altered cell structure and disturbed neuronal connectivity, which accounts for the functional abnormality of psychosis.

We used multislice functional magnetic resonance imaging (fMRI) to investigate the association between behavioral and neurophysiological measures of working memory task performance in 20 right-handed male healthy volunteers. Images were acquired over a 5-min period at 1.5 Tesla. We used a periodic design, alternating 30-s blocks of the "n-back" working memory task with 30-s blocks of a sensorimotor control task to activate verbal working memory systems. The power of functional response to the task was estimated by sinusoidal regression at each voxel. The relationship between power of fMRI response and mean reaction time over all 11 working memory trials was explored by multiple regression, with age and mean reaction time to the control task as covariates, at voxel and regional levels of analysis. All subjects were able to perform the n-back task accurately. A spatially distributed network was activated, including dorsolateral prefrontal cortex, inferior frontal gyrus, lateral premotor cortex, and supplementary motor area (SMA) in the frontal lobes. More posteriorly, there were major foci of activation in parietal and occipitoparietal cortex, precuneus, lingual, and fusiform gyri of the ventral occipital lobe, inferior temporal gyrus, and cerebellum. The power of functional response was positively correlated with reaction time in bilateral posterior parietal cortex (Talairach coordinates in x, y, z (mm) 35, -44, 37 and -32, -56, 42), indicating that subjects who found the task difficult, and responded with a slower reaction time, tended to activate these regions more powerfully. One interpretation of this regionally specific relationship between prolonged reaction time and increased power of posterior parietal activation is consistent with prior studies identifying similar areas of parietal cortex as the site of the phonological storage function in verbal working memory.

BackgroundThird rather than lateral ventriculomegaly may be a more specific finding in psychosis. The relevance of ventricular abnormality remains unclear.AimsTo investigate the developmental correlates of ventricular enlargement.MethodInformation on childhood development and magnetic resonance images in 1.5-mm contiguous sections were collected on 21 patients experiencing a first episode of psychosis.ResultsPatients (n=21) had significantly less whole brain volume and enlarged third and lateral ventricles compared to controls (n=25). Third ventricle (r=0.48, P < 0.03) and lateral ventricle (r=0.65, P < 0.01) volumes correlated with developmental score. Patients with developmental delay had significantly larger third and lateral ventricles than those without.ConclusionsEnlargement of both third and lateral ventricles is found in first-episode psychosis and is related to developmental delay in childhood. Insult to periventricular areas is relevant to the neurobiology of the disease. These findings support the view that schizophrenia involves disturbance of neurodevelopmental processes in some patients.

Background Prepulse inhibition of the startle reflex response refers to the ability of a weak prestimulus to transiently inhibit the response to a closely following strong sensory stimulus. This effect represents an operational index of sensorimotor gating and is found to be deficient in schizophrenia. Prepulse inhibition deficits in schizophrenia seem to be partially normalized by typical antipsychotics and more fully by some atypical antipsychotics. Early onset of schizophrenia, particularly in men, has been associated with abnormal brain maturation, profound neuropsychological deficits, and less responsiveness to antipsychotic medication. We evaluated the effects of the age of onset of illness, current positive and negative symptoms, and the type of medication (typical vs atypical) on prepulse inhibition of the startle response in schizophrenia. Methods Thirty-eight male schizophrenic patients and 20 healthy male controls underwent testing for prepulse inhibition of the acoustic startle response. Results Earlier onset of illness was associated with reduced prepulse inhibition, while adult onset of illness was not. No significant relationships occurred between current symptoms and prepulse inhibition. Patients given typical, but not atypical, antipsychotics exhibited less prepulse inhibition compared with healthy controls. Conclusion Early onset of illness is associated with profound deficits in prepulse inhibition of the startle response in men with schizophrenia.

This paper is concerned with the problem of evaluating goodness-of-fit of a path analytic model to an interregional correlation matrix derived from functional magnetic resonance imaging (fMRI) data. We argue that model evaluation based on testing the null hypothesis that the correlation matrix predicted by the model equals the population correlation matrix is problematic because P values are conditional on asymptotic distributional results (which may not be valid for fMRI data acquired in less than 10 min), as well as arbitrary specification of residual variances and effective degrees of freedom in each regional fMRI time series. We introduce an alternative approach based on an algorithm for automatic identification of the best fitting model that can be found to account for the data. The algorithm starts from the null model, in which all path coefficients are zero, and iteratively unconstrains the coefficient which has the largest Lagrangian multiplier at each step until a model is identified which has maximum goodness by a parsimonious fit index. Repeating this process after bootstrapping the data generates a confidence interval for goodness-of-fit of the best model. If the goodness of the theoretically preferred model is within this confidence interval we can empirically say that the theoretical model could be the best model. This relativistic and data-based strategy for model evaluation is illustrated by analysis of functional MR images acquired from 20 normal volunteers during periodic performance (for 5 min) of a task demanding semantic decision and subvocal rehearsal. A model including unidirectional connections from frontal to parietal cortex, designed to represent sequential engagement of rehearsal and monitoring components of the articulatory loop, is found to be irrefutable by hypothesis-testing and within confidence limits for the best model that could be fitted to the data.