Differential brain activation during facial emotion discrimination in first-episode schizophrenia

Background

Aberrant brain activation during facial emotion discrimination has been described in chronic schizophrenia, while little is known about early stages of the illness. The aim of the current study was to investigate valence-specific brain activation of emotion discrimination in first-episode schizophrenia. These patients provide the advantage of lacking the effects of long-term medication and chronic illness course and can hence further enhance the understanding of underlying psychopathological mechanisms.

Methods

Using event-related fMRI, we investigated 18 first-episode schizophrenia patients and 18 matched healthy subjects during an explicit emotion discrimination task presenting happy, sad and neutral monochromatic facial expressions. A repeated measure analysis of variance (ANOVA) with the factors Group (patients, healthy subjects), Gender and Emotion (happy, sad, neutral) was performed on behavioural and functional data.

Results

Behavioural performance did not differ between groups. Valence-independent hypoactivations in patients were observed for the anterior cingulate and orbitofrontal cortex while hyperactivations emerged in the posterior cingulate and the precuneus. Emotion-specific group differences were revealed in inferior parietal and orbitofrontal brain areas and the hippocampus.

Conclusions

First-episode schizophrenia already affects areas involved in processing of both, emotions and primary facial information. Our study underlines the role of dysfunctional neural networks as the basis of disturbed social interactions in early schizophrenia.     

Individual differences in trait anhedonia: a structural and functional magnetic resonance imaging study in non-clinical subjects

Anhedonia, the reduced capacity to gain pleasure from pleasurable experiences, is a key symptom of major depression and schizophrenia. Reduced hedonic capacity can also be measured as an enduring trait in non-clinical subjects. Such altered hedonic capacity is likely the result of a basic neuropsychophysiological dysfunction and a vulnerability marker that potentially precedes and contributes to the liability of developing psychiatric disorders. The characterization of the structural and functional neural correlates of trait anhedonia in non-clinical individuals may provide new insights for the early detection of such psychiatric diseases. Twenty-nine non-clinical subjects were scanned at the Montreal Neurological Institute. Trait anhedonia was measured using the Chapman Revised Physical Anhedonia Scale. Semi-automated and automated structural MRI segmentation techniques were used to explore structural correlates of trait anhedonia. Seventeen of the 29 subjects also underwent a functional imaging task where responses to the viewing of affective stimuli were examined to identify the functional correlates of trait anhedonia. Trait anhedonia was inversely related to anterior caudate volume, but positively related to ventromedial prefrontal cortex activity during the processing of positive information. These findings may reflect a specific kind of vulnerability for the development of psychiatric affective disorders and suggest that trait anhedonia may be linked to a volumetric reduction in the basal ganglia and to a prefrontal functional abnormality during hedonic processing.     

Relation between emotional face memory and social anhedonia in schizophrenia

Background

There is an interest in investigating the relation between emotional memory impairments in schizophrenia and specific symptom dimensions. We explored potential links between emotional memory and social anhedonia severity in patients with schizophrenia and in healthy individuals.

Methods

Twenty-nine patients with schizophrenia and 27 matched healthy individuals completed the Chapman Revised Social Anhedonia Scale and then performed an emotional face recognition memory task involving happy, sad and neutral face expressions. We calculated emotional memory performance using 2 independent measures: the discrimination accuracy index Pr and the response bias Br. We also measured valence ratings of the face stimuli. We performed correlation analyses using the inter-individual variability in social anhedonia severity and the individual score obtained for each memory performance variable and for each face valence rating condition.

Results

Patients with schizophrenia reported higher levels of social anhedonia compared with healthy individuals. They also showed lower recognition accuracy for faces compared with healthy participants. We found no significant correlation between social anhedonia severity and any of the memory performance variables for both patients with schizophrenia and healthy individuals. Regarding potential links between social anhedonia severity and face valence ratings, we found that individuals with elevated social anhedonia had a tendency to rate the face stimuli as more negative.

Limitations

Our negative finding may be partly explained by a lack of statistical power owing to our small patient sample. In addition, our patient sample had unusually high estimated IQ scores, which highlights potential issues regarding the generalization of our findings. Finally, we used a yes–no recognition memory task with a very short retention interval delay.

Conclusion

Our results suggest that social anhedonia is not directly linked to emotional memory deficits and biases and does not interfere with the modulatory effect of positively valenced emotion on memory.     

Anhedonia as predictor of clinical events after acute coronary syndromes: a 3-year prospective study

Background

Depression after acute coronary syndromes (ACS) is an important risk factor for further coronary events; but the influence of anhedonia, the decreased capacity to experience pleasure, has received little attention. The aim of the study was to investigate the effects of anhedonia on prognosis at 3-year follow-up in patients hospitalized for ACS.

Method

Consecutively admitted ACS patients (n = 291) completed the Chapman Physical Anhedonia Scale (PAS) and the Hospital Anxiety and Depression Scale depression subscale (HAD-D) at baseline (1-4 days after their admission). Two definitions of anhedonia were taken into account: dimensional definition using PAS score as well as categorical definition using several cutoff scores (hedonics: PAS less than 23 or 29; anhedonics: PAS equal to or greater than 23 or 29). Patients were followed during 3 years for adverse clinical events divided into severe cardiac events (mortality or myocardial infarction [MI]) and clinical events (mortality, MI, recurrence of ACS, hospital readmission, and onset or deterioration of heart failure).

Results

At follow-up, there were 176 clinical events (36 deaths, 8 MIs, 58 ACS, 55 hospital readmissions, 19 heart failures). Dimensional anhedonia and depression were associated with poor prognosis, but anhedonia was the only predictor of severe cardiac events and clinical events after adjusting for demographic and clinical variables. Contrary to depression, categorical anhedonia (PAS >23) was an independent and significant predictor of severe cardiac events after adjusting for clinical variables. The incidence of death/MI in hedonics vs anhedonics was 11.1% vs 22.1% (hazard ratio = 2.18; 95% confidence interval, 1.11-4.26).

Conclusions

Dimensional and categorical anhedonias predicted independently severe cardiac events and clinical events after ACS.     

Reduced hedonic capacity in major depressive disorder: evidence from a probabilistic reward task

Objective

Anhedonia, the lack of reactivity to pleasurable stimuli, is a cardinal feature of depression that has received renewed interest as a potential endophenotype of this debilitating disease. The goal of the present study was to test the hypothesis that individuals with major depression are characterized by blunted reward responsiveness, particularly when anhedonic symptoms are prominent.

Methods

A probabilistic reward task rooted within signal-detection theory was utilized to objectively assess hedonic capacity in 23 unmedicated subjects meeting DSM-IV criteria for major depressive disorder (MDD) and 25 matched control subjects recruited from the community. Hedonic capacity was defined as reward responsiveness - i.e., the participants’ propensity to modulate behavior as a function of reward.

Results

Compared to controls, MDD subjects showed significantly reduced reward responsiveness. Trial-by-trial probability analyses revealed that MDD subjects, while responsive to delivery of single rewards, were impaired at integrating reinforcement history over time and expressing a response bias toward a more frequently rewarded cue in the absence of immediate reward. This selective impairment correlated with self-reported anhedonic symptoms, even after considering anxiety symptoms and general distress.

Conclusions

These findings indicate that MDD is characterized by an impaired tendency to modulate behavior as a function of prior reinforcements, and provides initial clues about which aspects of hedonic processing might be dysfunctional in depression.     

Cloninger's temperament traits and preclinical atherosclerosis: The Cardiovascular Risk in Young Finns Study

Objective

Cloninger's psychobiological model of temperament has recently raised interest as a risk factor for CHD. However, there are no studies that have examined the associations of Cloninger's temperament traits with atherosclerosis.

Methods

The subjects were 398 men and 657 women (mean age 31.7 years) participating in the Cardiovascular Risk in Young Finns Study. Linear regression analyses were used to examine the cross-sectional associations between temperament traits and preclinical atherosclerosis. Preclinical atherosclerosis was measured with carotid intima-media thickness ultrasound.

Results

Higher novelty seeking (NS) and reward dependence (RD) and lower harm avoidance (HA) were associated with preclinical atherosclerosis. In NS and RD, associations remained significant after adjustments for various risk factors. The effect sizes of these associations were comparable to those of traditional risk factors of coronary heart disease, which is a major finding. No association for persistence (P) was found.

Conclusions

The present findings imply that examining a wider range of temperament and personality factors may offer new information that can help in explaining the between-individual variation in atherosclerosis and CHD morbidity.     

Additive effects of elevated C-reactive protein and exposure to Herpes Simplex Virus type 1 on cognitive impairment in individuals with schizophrenia

Objectives

We investigated the effect of elevated levels of C-reactive protein (CRP) and exposure to Herpes simplex virus type 1 (HSV-1) on the severity of cognitive impairment in individuals with schizophrenia.

Methods

We measured the levels of CRP and of antibodies to HSV-1 in serum samples from 588 individuals with schizophrenia by enzyme immunoassay tests. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and psychiatric symptoms with the Positive and Negative Syndrome Scale (PANSS). The effects of HSV1 and CRP on cognitive functioning were analyzed with linear and logistic regression analyses adjusting for demographic and clinical variables.

Results

The individuals with elevated CRP levels and HSV-1 seropositivity had lower RBANS cognitive scores. The strongest effect was found in individuals who had both serological evidence of HSV-1 exposure and elevated levels of CRP. These individuals had odds of 2.35 to have an RBANS Total score <= 60 as compared to individuals who were HSV-1 seronegative and who did not have elevated levels of CRP (p = .002). The risks of decreased cognitive functioning associated with HSV-1 exposure and elevated levels of CRP were independent and additive. There was no effect of HSV-1 exposure and CRP levels on the severity of symptoms as measured by the PANSS (all p > .5).

Conclusions

Elevated levels of CRP and exposure to HSV-1 are associated with the severity of cognitive impairment in schizophrenia. These findings indicate that infection and inflammation may play a major role in the cognitive deficits associated with schizophrenia.     

Acetyl-l-Carnitine in the treatment of anhedonia, melancholic and negative symptoms in alcohol dependent subjects

Objective

Aim of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy of Acetyl-l-Carnitine (ALC), at different dosages, on specific anhedonic symptoms in detoxified alcohol dependent subjects. Secondary endpoints were the effect of ALC on melancholic and negative symptoms.

Method

Sixty-four anhedonic alcohol dependent patients with minor or absent withdrawal symptoms were randomized: 23 received ALC at a dosage of 3 g/day, 21 received ALC at a dosage of 1 g/day, and 20 were given placebo. ALC was given intravenously for 10 days, followed by 80 days of oral treatment plus a follow-up period of 45 days. The presence of anhedonic symptoms was determined by the SHAPS (Snaith-Hamilton Pleasure Scale) and the VASa (Visual Analogue Scale for Anhedonia); negative and melancholic symptoms were evaluated by the SANS (Scale for the Assessment of Negative Symptoms), and the BRMS (Bech-Rafaelsen Melancholia Scale).

Results

The natural course of anhedonia in the placebo group showed a decline until day 30 and remains stable for the rest of the study. Intravenously ALC accelerated the improvement of anhedonia reaching constant low levels early, on day 10. At this step levels of anhedonia (SHAPS, VASa) and melancholic symptoms (BRMES) resulted significantly reduced (p < 0.05) in both the ALC 3 g and ALC 1 g groups with respect to placebo; SANS scores significantly reduced only in the ALC 1 g respect to placebo (p = 0.014). During oral treatment with ALC, anhedonia scores did not differ from placebo.

Conclusion

Intravenously ALC was effective in accelerating the abstinence-associated improvement of anhedonia, melancholic and negative symptoms, whereas oral ALC treatment starting on day 10 showed no further improvements. Accordingly, in alcohol dependent subjects, ALC may be considered as a new potentially useful drug for the treatment of anhedonia.     

Depression and cognitive deficits in geriatric schizophrenia

Objective

Past reports have found patients with comorbid depression and schizophrenia spectrum disorders exhibit greater deficits in memory and attention compared to schizophrenia spectrum disorder patients without depressive symptoms. However, in contrast to younger schizophrenia patients, the few past studies using cognitive screens to examine the relationship between depression and cognition in inpatient geriatric schizophrenia have found that depressive symptomatology was associated with relatively enhanced cognitive performance. In the current study we examined the relationship between depressive symptoms and cognitive deficits in geriatric schizophrenia spectrum disorder patients (n = 71; mean age = 63.7) on an acute psychiatric inpatient service.

Method

Patients completed a battery of cognitive tests assessing memory, attention and global cognition. Symptom severity was assessed via the PANSS and Calgary Depression Scale for Schizophrenia.

Results

Results revealed that geriatric patients' depression severity predicted enhancement of their attentional and verbal memory performance. Patients' global cognitive functioning and adaptive functioning were not associated with their depression severity.

Conclusion

Contrary to patterns typically seen in younger patients and non-patient groups, increasing depression severity is associated with enhancement of memory and attention in geriatric schizophrenia spectrum disorder patients. Also, diverging from younger samples, depression severity was unassociated with patients adaptive and global cognitive functioning.     

Cerebellar hyperactivity during smooth pursuit eye movements in bipolar disorder

Introduction

Smooth pursuit eye movements (SPEM) are abnormal in individuals with schizophrenia and individuals with bipolar disorder. Functional imaging methods have revealed greater hippocampal activity and less frontotemporal, visual, and posterior cerebellar activity in individuals with schizophrenia when performing a SPEM task. The underlying neurobiology of SPEM deficits in bipolar disorder is unknown.

Methods

Functional magnetic resonance imaging at 3T was performed on fourteen subjects with bipolar disorder and 14 subjects without psychiatric illness during a block design SPEM task. Clinical measures were assessed on the day of testing and related to imaging measures.

Results

Subjects with bipolar disorder had greater hemodynamic response than control subjects in cerebellar vermis. Responses were associated with levels of depressive symptoms on the day of study.

Discussion

Increased cerebellar vermis activity during the smooth pursuit eye movement task in individuals with bipolar disorder further implicates cerebellar involvement in bipolar disorder. Increased hemodynamic response within the hippocampus was not seen in these individuals and may be a finding specific to schizophrenia.     

Disturbed functional connectivity within brain networks subserving domain-specific subcomponents of working memory in schizophrenia: Relation to performance and clinical symptoms

Introduction

Disturbed interregional functional connectivity has been hypothesized to be a promising marker of schizophrenia. The relationship between working memory (WM) impairment, disturbed functional connectivity, and the characteristic symptoms of schizophrenia, however, remains elusive.

Methods

We used functional MRI (fMRI) to investigate in patients with schizophrenia and matched controls the patterns of functional connectivity during the performance of different tasks selectively engaging subcomponent processes of working memory.

Results

Compared with controls, patients showed reduced connectivity of the prefrontal cortex with the intraparietal cortex and the hippocampus and abnormal negative interactions between the ventrolateral and dorsolateral prefrontal cortex during the non-articulatory maintenance of phonological information. During the maintenance of visuospatial information, patients presented reduced connectivity between regions in the superior parietal and occipital cortex, as well as enhanced positive connectivity of the frontal eye field with visual processing areas.

Discussion

Our findings suggest complex dysregulations within the networks supporting working memory functions in schizophrenia, which manifest as decreased positive and abnormal negative interactions. Correlations between the connection strength and WM performance suggest that these dysregulations may be neurofunctional correlates of the WM deficits seen in schizophrenia. Altered prefronto-hippocampal and parieto-occipital connectivity was further found to be associated with higher positive symptoms, providing a possible explanation for the development of delusions and disorganization symptoms.

Conclusion

The present findings can help to better understand the relationship between altered patterns of synchronized brain activity and the cognitive and clinical symptoms of schizophrenia.     

Traduction et étude de validation de la version française de l’échelle d’expérience temporelle du plaisir (EETP, Temporal Experience of Pleasure Scale [TEPS], Gard et al., 2006) : étude chez 125 étudiants et chez 162 sujets présentant un trouble psychiatrique

Objectives

Using complementary methods, Gard et al. (2007) [13] reported that schizophrenia patients reported as much pleasure in the moment as controls in their daily lives and on a measure of trait consummatory pleasure (consummatory subscale of the Temporal Experience of Pleasure Scale [TEPS-CONS]) but the schizophrenia patients reported experiencing less trait pleasure in anticipation of future events (anticipatory subscale of the TEPS [TEPS-ANT]) compared to healthy controls. The aim of the present study was to replicate the Gard et al. (2007) [13] study using the French version of the TEPS.

Patients and method

Hundred and twenty-five university students were recruited as well as 162 inpatients with either schizophrenia or mood, neurotic or personality disorders. All participants completed the French versions of the following rating scales: the 18-item TEPS, the 61-item revised Physical Scale (PAS) and the 41-item Social Anhedonia Scale (SAS), the 14-item Snaith Hamilton Pleasure Scale (SHAPS) and the 21-item Beck Depression Inventory-II (BDI-II). We also created PAS anticipatory (PAS-ANT) and PAS consummatory (PAS-CONS) scales from the university student sample. Firstly, we examined the construct, concurrent validities and reliability of the TEPS using respectively confirmatory factorial analyses (CFA) to test the two-factor structure of the TEPS, Pearson's correlations between the ten-item TEPS-ANT or eight-item TEPS-CONS and the other anhedonia scales and Cronbach's alpha coefficients. Secondly, we compared the three groups (university students, schizophrenia subjects, other psychiatric subjects) using analyses of variance (ANOVA) on the measures of anticipatory and consummatory anhedonias.

Results

For the results of the CFA, we used three parameters to test the adequacy of the data to the model: the normed chi-square, the root mean square residual and the root mean square error of approximation. The three parameters were respectively for the university and psychiatric samples: 1.66, 0.09, 0.074 and 2.19, 0.09, 0.087. Cronbach's alpha coefficients were satisfactory (>0.7) for the TEPS-ANT. Significant correlations were observed between either the TEPS-CONS or the TEPS-ANT and the anhedonia scales suggesting satisfactory concurrent validities. Analyses of Variance (ANOVA) reported significant difference between groups for the TEPS-ANT but not for the TEPS-CONS. Similar results were observed using the PAS-ANT and PAS-CONS.

Conclusion

The French version of the TEPS had satisfactory psychometric properties and replicated the Gard et al. (2007) [13] study reporting that schizophrenic subjects had low anticipatory pleasure than healthy controls but did not differ on consummatory pleasure. Moreover, the difference on anticipatory pleasure between healthy and schizophrenic subjects was independent of depression and there was no difference between schizophrenic subjects and non-schizophrenic psychiatric controls concerning anticipatory pleasure. Further studies are needed to explore the hypothesis that specific subgroups of schizophrenic subjects (for exemple, deficit schizophrenic subjects) could be more anhedonic in either form of anhedonia (anticipatory and/or consummatory anhedonia), additionally comparisons should be further made with psychiatric controls without a schizophrenia diagnosis.     

Anhedonia in Japanese patients with Parkinson's disease: analysis using the Snaith-Hamilton Pleasure Scale

Background

Anhedonia, a lowered ability to experience physical or social pleasure, has recently been recognized as a non-motor symptom of Parkinson's disease.

Objective

To identify the frequency of anhedonia and the factors influencing hedonic tone in Japanese patients with Parkinson's disease.

Patients and methods

We recruited 86 consecutive outpatients with a clinical diagnosis of PD attending two Japanese hospitals (one university hospital and one community hospital) in February 2010. We used the self-rating Snaith–Hamilton Pleasure Scale (SHAPS) translated into Japanese language from the original English version to assess and quantify hedonic tone as a subjectively experienced phenomenon. We studied the association of anhedonia with the variables age, age at onset, gender, disease duration, disease severity and antiparkinsonian drugs.

Results

Thirty-nine patients (45%) were male and 47 (55%) were female. Mean age was 72.01 ± 9.07 (49–89) years, with mean age at onset of 64.93 ± 11.42 (31–88) years. Mean disease duration was 7.20 ± 5.54 (1–23) years. The mean Hoehn and Yahr scale was 2.76 ± 0.78. The mean SHAPS score of the total sample was 1.19 ± 1.86. The SHAPS score of 14 patients (16.3%) was 3 or more, indicating anhedonia. The mean SHAPS score was lower in patients taking pramipexole (0.58 ± 0.97) than in patients not taking pramipexole (1.57 ± 2.16). Multiple linear regression analysis identified pramipexole as a significant negative influencing factor on the SHAPS score, while disease severity and entacapone treatment were identified as positive influencing factors. The age, onset age, gender, disease duration, and use of pergolide, amantadine, zonisamide, selegiline, anticholinergic agents and droxidopa did not significantly affect the SHAPS score.

Conclusion

Anhedonia is not rare non-motor symptom in Japanese patients with Parkinson's disease. This study suggests an anti-anhedonic property of pramipexole.     

Correlates of cruelty to animals in the United States: Results from the National Epidemiologic Survey on Alcohol and Related Conditions

Objective

To examine the sociodemographic, behavioral, and psychiatric correlates of cruelty to animals in the US.

Materials and methods

Data were derived from a nationally representative sample of adults residing in the US Structured psychiatric interviews (N = 43,093) were completed by trained lay interviewers between 2001 and 2002. Personality, substance use, mood, and anxiety disorders and cruelty to animals were assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule (DSM-IV) version.

Results

The lifetime prevalence of animal cruelty in US adults was 1.8%. Men, African-Americans, Native-Americans/Asians, native-born Americans, persons with lower levels of income and education and adults living the western region of the US reported comparatively high levels of cruelty to animals, whereas Hispanics reported comparatively low levels of such behavior. Cruelty to animals was significantly associated with all assessed antisocial behaviors. Adjusted analyses revealed strong associations between lifetime alcohol use disorders, conduct disorder, antisocial, obsessive-compulsive, and histrionic personality disorders, pathological gambling, family history of antisocial behavior, and cruelty to animals.

Conclusions

Cruelty to animals is associated with elevated rates observed in young, poor, men with family histories of antisocial behavior and personal histories of conduct disorder in childhood, and antisocial, obsessive-compulsive and histrionic personality disorders, and pathological gambling in adulthood. Given these associations, and the widespread ownership of pets and animals, effective screening of children, adolescents and adults for animal cruelty and appropriate mental health interventions should be deployed.     

Thalamic morphology in schizophrenia and schizoaffective disorder

Background

Biomarkers are needed that can distinguish between schizophrenia and schizoaffective disorder to inform the ongoing debate over the diagnostic boundary between these two disorders. Neuromorphometric abnormalities of the thalamus have been reported in individuals with schizophrenia and linked to core features of the disorder, but have not been similarly investigated in individuals with schizoaffective disorder. In this study, we examine whether individuals with schizoaffective disorder have a pattern of thalamic deformation that is similar or different to the pattern found in individuals with schizophrenia.

Method

T1-weighted magnetic resonance images were collected from individuals with schizophrenia (n = 47), individuals with schizoaffective disorder (n = 15), and controls (n = 42). Large-deformation, high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. Multiple analyses of variance were used to test for group differences in volume and measures of surface shape.

Results

Individuals with schizophrenia or schizoaffective disorder have similar thalamic volumes. Thalamic surface shape deformation associated with schizophrenia suggests selective involvement of the anterior and posterior thalamus, while deformations in mediodorsal and ventrolateral regions were observed in both groups. Schizoaffective disorder had distinct deformations in medial and lateral thalamic regions.

Conclusions

Abnormalities distinct to schizoaffective disorder suggest involvement of the central and ventroposterior medial thalamus which may be involved in mood circuitry, dorsolateral nucleus which is involved in recall processing, and the lateral geniculate nucleus which is involved in visual processing.     

Reduced interhemispheric coherence in dyslexic adults

Introduction

Developmental dyslexia has been associated with reduced interhemispheric neural connectivity in children. The present study investigated functional interhemispheric connectivity in male dyslexic adults.

Methods

A group of 19 dyslexic men were compared to a group of 15 controls on interhemispheric coherence of the dominant frequency in the power spectrum during a visuo-spatial attention task. The coherence between a left hemisphere central-parietal electrode and the respective right hemisphere electrode and surrounding sites was analysed.

Results

Compared to controls, the dyslexic group demonstrated reduced, and more diffuse, interhemispheric coherence of alpha activity in the central-parietal cortex. No group differences in interhemispheric coherence were found on frontal, temporal or central sites.

Conclusions

The deviant pattern of functional connectivity in dyslexics is suggestive of an altered development of neural circuitry that may lead to deficits in magnocellular processing.     

Prenatal exposure to tobacco and risk for schizophrenia: a retrospective epidemiological study

Introduction

In animal studies, long-term prenatal nicotinic exposure alters the development of dopaminergic neurons. To determine whether prenatal smoking exposure was associated with schizophrenia, using a retrospective design study, we compared the prevalence of tobacco use during pregnancy in mothers of subjects with and without schizophrenia.

Methods

One hundred patients with schizophrenia, 100 nonschizophrenic-matched subjects, and their respective mothers were interviewed. The prevalence of smoking was measured in these individuals as well as in their respective mothers during the pregnancy.

Results

Patients with schizophrenia smoked more often compared with controls (73% vs 57%). In contrast, the prevalence of smoking during pregnancy did not differ between the groups of mothers. Indeed, the amount of tobacco used was significantly lower in mothers of patients with schizophrenia vs mothers of nonpsychotic subjects.

Conclusion

This study did not show any association between prenatal tobacco exposure and further development of schizophrenia.     

Reduced prepulse inhibition as an early vulnerability marker of the psychosis prodrome in adolescence

Background

The onset of psychosis is thought to be preceded by neurodevelopmental changes in the brain. However, the timing and nature of these changes have not been established. The aim of the present study was to determine whether three “classic” neurophysiological markers of schizophrenia are also characteristic of young adolescents (12-18 years) at ultra-high risk for psychosis (UHR).

Methods

63 young UHR individuals and 68 typically developing, age-, sex- and IQ-matched controls were recruited for neurophysiological assessment. Data for P50 suppression, prepulse inhibition (PPI) and smooth pursuit eye movements (SPEM) were gathered and compared.

Results

UHR individuals showed reduced PPI compared to controls, which became more pronounced when controls were directly compared to medication-naive UHR individuals (N = 39). There were no group differences in P50 or SPEM measures.

Conclusions

These results suggest that PPI is a relatively early vulnerability marker, while changes in other neurophysiological measures may only be detected or affected later during the illness course. Antipsychotic and antidepressant medication may aid in elevating PPI levels and potentially have a neuroprotective effect.     

Inefficiently increased anterior cingulate modulation of cortical systems during working memory in young offspring of schizophrenia patients

Background

Children and adolescent offspring of schizophrenia patients are at increased risk for schizophrenia and are also characterized by impairments in brain structure and function. To date, few studies have investigated whether functional interactions between brain regions are intact or altered. Using an established verbal working memory paradigm with variable levels of memory load, we investigated the modulatory effect of activity in cognitive control regions of the brain (specifically the dorsal anterior cingulate cortex) on activity in core working memory regions, in particular the dorsal prefrontal cortex and the parietal lobe.

Methods

Forty four subjects participated. An n-back task with two levels of working memory load (1- and 2-back) was employed during fMRI (4 T Bruker MedSpec system). Data were processed with SPM5 and the modulatory effects of the anterior cingulate were investigated using psycho-physiological interaction (PPI).

Results

In spite of only subtle activation differences, and no significant differences in performance accuracy, a significant group x memory load interaction in the parietal lobe, indicated aberrantly increased modulatory inputs to this region under conditions of high working memory load in schizophrenia offspring.

Discussion

Increased modulatory inputs from a central control region like the anterior cingulate presumably reflect relative inefficiency in intra-cortical interactions in the vulnerable brain. This inefficiency may reflect a developmentally mediated impairment in functional brain interactions in this important vulnerable population. It is highly plausible that the resultant effect of these altered interactions is an increased vulnerability to impaired brain development, and therefore to psychiatric disorders including schizophrenia.     

Prefrontal-posterior parietal networks in schizophrenia: primary dysfunctions and secondary compensations

Background

Working memory (WM) deficits are well known in schizophrenia and have been associated with abnormal activation patterns of the prefrontal cortex (PFC) during cognitive performance. The magnitude and particularly the direction of the PFC activation— i.e., increased (hyperfrontality) or decreased (hypofrontality)— in schizophrenia, as well as its pathophysiological implications, remain controversial. Working memory is supported by a distributed neural network, whose main components are the PFC and the posterior parietal (PPC) cortices. Monkey studies indicate that, during WM performance, PFC functional lesions may be compensated by the PPC if task demands center mainly on anticipating responses, but not if they center on remembering cues. We hypothesized that a primarily dysfunctional PFC in schizophrenia might show hypofrontality or hyperfrontality as a result, respectively, of efficient or inefficient PPC compensation, as dictated by task demands. To test our proposition, we biased the demands of WM tasks toward anticipating responses or remembering cues and measured its impact on the PFC-PPC functional balance in a group of schizophrenic patients and one of normal control subjects.

Methods

We used functional magnetic resonance imaging to measure correlates of neuronal activity in the PFC and PPC of schizophrenic patients and control subjects performing WM tasks that either demanded information retention or allowed for response anticipation.

Results

When compared to control subjects, schizophrenic patients exhibited decreased PFC activation and increased PPC activation during anticipatory WM performance, and increased PFC activation during mnemonic WM performance.

Conclusions

In schizophrenia, a PFC dysfunction results in hypo- or hyperfrontality as a function of whether other alternate areas of a PFC-PPC network for WM are available and efficacious in supporting specific task demands.