First-degree Relatives Of Schizophrenic Patients Research Articles

SOCIAL COGNITION AND OXIDATIVE STRESS IN SCHIZOPHRENIA PATIENTS AND FIRST-DEGREE RELATIVES OF PATIENTS.

Misattribution of motivational salience to non-salient (neutral) stimuli could be viewed as a hallmark of psychosis in schizophrenia. Studies have recently revealed increased subjective experience of emotional arousal (EA) to neutral social stimuli in paranoid schizophrenia psychosis, suggesting a misattribution of emotional salience to them. We examined this phenomenon directly by quantifying the level of EA subjectively attributed to low-arousal, neutral-valenced faces. Patients with remitted schizophrenia (PG) (n=26), first-degree relatives of schizophrenic patients (RG) (n=25), and healthy controls (HCG) (n=36) were compared in terms of oxidative stress parameters -serum Superoxide Dismutase, Catalase, Glutathione Peroxidase (GPx), Nitrite, Nitrate, Malondialdehyde, and Total Glutathione levels-, social cognition measured by the Reading the Mind in the Eyes Test and working memory measured by the N-back Task. Groups were compared, assuming that HCG had a genetically lower risk of schizophrenia compared to PG and RG. HCG performed significantly better than PG and RG, who were genetically at high risk, in terms of social cognition (respectively p=0.000, p=0.014), working memory (respectively p=0.001, p=0.003), and had statistically lower Glutathione Peroxidase (GPX) level than the PG and RG (both p:0.000). After controlling for the effect of the general intellectual abilities measured by the Raven Standard Progressive Matrices Test and working memory the differences between groups on the Eyes Test disappeared (p=0.057). However, this value tended to be significant. It was concluded that social cognition and working memory and GPx level may be used as endophenotypes and social cognition, working memory, and general intellectual skills are different but strongly related constructs. Endophenotypes guide treatment targets even after the disease has developed. The results of our study showed that in addition to psychopharmacological treatments, interventions to reduce oxidative stress and approaches to improve cognitive skills will have a positive impact on the disease's progression.

The Cardiorespiratory Network in Healthy First-Degree Relatives of Schizophrenic Patients.

Impaired heart rate- and respiratory regulatory processes as a sign of an autonomic dysfunction seems to be obviously present in patients suffering from schizophrenia. Since the linear and non-linear couplings within the cardiorespiratory system with respiration as an important homeostatic control mechanism are only partially investigated so far for those subjects, we aimed to characterize instantaneous cardiorespiratory couplings by quantifying the casual interaction between heart rate (HR) and respiration (RESP). Therefore, we investigated causal linear and non-linear cardiorespiratory couplings of 23 patients suffering from schizophrenia (SZO), 20 healthy first-degree relatives (REL) and 23 healthy subjects, who were age-gender matched (CON). From all participants’ heart rate (HR) and respirations (respiratory frequency, RESP) were investigated for 30 min under resting conditions. The results revealed highly significant increased HR, reduced HR variability, increased respiration rates and impaired cardiorespiratory couplings in SZO in comparison to CON. SZO were revealed bidirectional couplings, with respiration as the driver (RESP → HR), and with weaker linear and non-linear coupling strengths when RESP influencing HR (RESP → HR) and with stronger linear and non-linear coupling strengths when HR influencing RESP (HR → RESP). For REL we found only significant increased HR and only slightly reduced cardiorespiratory couplings compared to CON. These findings clearly pointing to an underlying disease-inherent genetic component of the cardiac system for SZO and REL, and those respiratory alterations are only clearly present in SZO seem to be connected to their mental emotional states.

Resting-state Functional Connectivity between Dorsolateral Prefrontal Cortex and Left Temporal Language-related Region in Unaffected First-degree Relatives of Schizophrenia Patients

According to the large body of literature data, patients with schizophrenia demonstrate altered (decreased) functional connectivity (FC) between the brain regions involved in executive functions and language (in particular, dorsolateral prefrontal cortex (DLPFC) and left temporal regions). However, the analysis of similar FC in the genetic risk group has not been done, although such data are significant for studying the neurobiological markers of schizophrenia, linked to the genetic architecture of the disorder (its traits or so-called endophenotypes). The aim of this study was to investigate whether FC between the DLPFC and left temporal language-related region was altered in unaffected first-degree relatives of patients with schizophrenia. First-degree unaffected relatives of patients with schizophrenia (12 subjects) and healthy individuals without family history of mental disorders (13 subjects) underwent resting-state functional magnetic resonance imaging at 3T Philips scanner. The FC between the regions of interest (left/right DLPFC, on the one hand, and left temporal region, on the other hand) was compared between groups as well as indexes of Verbal fluency and the Scale of Prodromal Symptoms (SOPS). As compared to controls, the relatives of patients with schizophrenia were characterized by increased FC between the left DLPFC and left temporal language-related region, although they did not differ in the other indexes, and there were no correlations between the indexes and FC. The findings might reflect some compensatory functional processes in unaffected first-degree relatives of schizophrenic patients.

Altered Neural Activity during Irony Comprehension in Unaffected First-Degree Relatives of Schizophrenia Patients-An fMRI Study.

Irony is a type of figurative language in which the literal meaning of the expression is the opposite of what the speaker intends to communicate. Even though schizophrenic patients are known as typically impaired in irony comprehension and in the underlying neural functions, to date no one has explored the neural correlates of figurative language comprehension in first-degree relatives of schizophrenic patients. In the present study, we examined the neural correlates of irony understanding in schizophrenic patients and in unaffected first-degree relatives of patients compared to healthy adults with functional MRI. Our aim was to investigate if possible alterations of the neural circuits supporting irony comprehension in first-degree relatives of patients with schizophrenia would fulfill the familiality criterion of an endophenotype. We examined 12 schizophrenic patients, 12 first-degree relatives of schizophrenia patients and 12 healthy controls with functional MRI while they were performing irony and control tasks. Different phases of irony processing were examined, such as context processing and ironic statement comprehension. Patients had significantly more difficulty understanding irony than controls or relatives. Patients also showed markedly different neural activation pattern compared to controls in both stages of irony processing. Although no significant differences were found in the performance of the irony tasks between the control group and the relative group, during the fMRI analysis, the relatives showed stronger brain activity in the left dorsolateral prefrontal cortex during the context processing phase of irony tasks than the control group. However, the controls demonstrated higher activations in the left dorsomedial prefrontal cortex and in the right inferior frontal gyrus during the ironic statement phase of the irony tasks than the relative group. Our results show that despite good task performance, first-degree relatives of schizophrenia patients had alterations in the neural circuits during irony processing. Thus, we suggest that neural alteration of irony comprehension could be a potential endophenotypic marker of schizophrenia.

Striatal Response to Reward Anticipation

Attenuated ventral striatal response during reward anticipation is a core feature of schizophrenia that is seen in prodromal, drug-naive, and chronic schizophrenic patients. Schizophrenia is highly heritable, raising the possibility that this phenotype is related to the genetic risk for the disorder. To examine a large sample of healthy first-degree relatives of schizophrenic patients and compare their neural responses to reward anticipation with those of carefully matched controls without a family psychiatric history. To further support the utility of this phenotype, we studied its test-retest reliability, its potential brain structural contributions, and the effects of a protective missense variant in neuregulin 1 (NRG1) linked to schizophrenia by meta-analysis (ie, rs10503929). Examination of a well-established monetary reward anticipation paradigm during functional magnetic resonance imaging at a university hospital; voxel-based morphometry; test-retest reliability analysis of striatal activations in an independent sample of 25 healthy participants scanned twice with the same task; and imaging genetics analysis of the control group. A total of 54 healthy first-degree relatives of schizophrenic patients and 80 controls matched for demographic, psychological, clinical, and task performance characteristics were studied. Blood oxygen level-dependent response during reward anticipation, analysis of intraclass correlations of functional contrasts, and associations between striatal gray matter volume and NRG1 genotype. Compared with controls, healthy first-degree relatives showed a highly significant decrease in ventral striatal activation during reward anticipation (familywise error-corrected P < .03 for multiple comparisons across the whole brain). Supplemental analyses confirmed that the identified systems-level functional phenotype is reliable (with intraclass correlation coefficients of 0.59-0.73), independent of local gray matter volume (with no corresponding group differences and no correlation to function, and with all uncorrected P values >.05), and affected by the NRG1 genotype (higher striatal responses in controls with the protective rs10503929 C allele; familywise error-corrected P < .03 for ventral striatal response). Healthy first-degree relatives of schizophrenic patients show altered striatal activation during reward anticipation in a directionality and localization consistent with prior patient findings. This provides evidence for a functional neural system mechanism related to familial risk. The phenotype can be assessed reliably, is independent of alterations in striatal structure, and is influenced by a schizophrenia candidate gene variant in NRG1. These data encourage us to further investigate the genetic and molecular contributions to this phenotype.

A resting-state functional magnetic resonance imaging study on the first-degree relatives of persons with schizophrenia

In this study, resting state fMRI images and BOLD signals were recorded from 13 first-degree relatives of schizophrenic patients and 13 healthy controls. The data were analyzed with the ReHo approach after realignment, registration, and normalization in statistical parametric mapping 2 (SPM2). A two-sample t-test was used to analyze the ReHo differences between first-degree relatives and healthy controls in a voxel by voxel manner. A combined threshold of p < 0.005 and number of voxels >5 was designated as statistically significant. To evaluate cognitive deficits in first-degree relatives, attention/vigilance and verbal/visual memory were measured. Significant impairments in attention were observed in first-degree relatives compared to healthy controls. Significant abnormalities in ReHo were observed in resting brain in first-degree relatives. Decreased ReHo was found to be distributed over the bilateral middle frontal, middle temporal, cingulate gyrus and cerebellar tonsil; the left inferior frontal gyrus, inferior parietal lobule and dorsolateral prefrontal cortex; the right superior frontal gyrus and dorsolateral prefrontal cortex. Increased ReHo was found to be distributed in the right precuneus and superior temporal gyrus. These changes in ReHo suggest abnormality in the resting state brain function of first-degree relatives of schizophrenic patients and may be early signs for the development of schizophrenia.

PW01-146 - Neuronal correlates of working memory deficits in patients with schizophrenia and their relatives

Studies of schizophrenia with functional MRI showed hyper- and hypoactivations in various brain regions including the prefrontal cortex. Functional abnormalities have also been reported in first-degree relatives of schizophrenic patients. The aim of this study was to examine working memory related brain functions in healthy subjects, schizophrenic patients and unaffected relatives and to determine the influence of psychopathology on these processes.A parametric n-back working memory task and functional MRI were used to examine 61 schizophrenic patients on antipsychotic medication, 11 nonpsychotic relatives of schizophrenic patients and a comparison group of 61 healthy subjects. The task difficulty was incrementally increased using a parametric task (0-back, 1-back, 2-back, and 3-back) to examine the relationship between working memory load, performance, and brain activity.The results indicated that during the attention task (0-back) behavioral responses of patients and healthy subjects hardly differed but BOLD responses were considerably enhanced in schizophrenic patients. With increasing task difficulty differences between groups in BOLD responses diminished whereas behavioral deficits of patients increased. The examination of attention-independent working memory-functions (2- vs. 0-back) produced hypoactivations in patients, especially in frontal, temporal and subcortical brain regions. Behavioral performance and neural responses of unaffected relatives of schizophrenic patients were intermediate between schizophrenic patients and controls indicating slight brain dysfunctions. In addition, compensatory strategies were demonstrated.These findings suggest that the genetic risk for schizophrenia is accompanied by neural inefficiency which is associated with cognitive deficits, especially in difficult tasks.

Inefficient neural activity in patients with schizophrenia and nonpsychotic relatives of schizophrenic patients: Evidence from a working memory task

Studies of schizophrenia with functional MRI have shown hyper- and hypoactivations in various brain regions including the prefrontal cortex. Functional anomalies have also been reported in first-degree relatives of schizophrenic patients. The aim of this study was to examine working memory related brain functions in healthy subjects, schizophrenic patients and unaffected relatives and to determine the influence of psychopathology on these processes. A parametric n-back working memory task and functional MRI were used to examine 61 patients with schizophrenia, 11 nonpsychotic relatives of schizophrenic patients and a comparison group of 61 healthy subjects. The results indicated increased as well as decreased brain functions in schizophrenic patients compared to the control group depending on the task difficulty and the performance: during the attention task (0-back), which served as control condition, behavioral responses of patients and healthy subjects hardly differed but BOLD responses were considerably enhanced in schizophrenic patients. With increasing task difficulty differences between groups in BOLD responses diminished whereas behavioral deficits of patients increased. The examination of attention-independent working memory-functions (2- vs. 0-back) produced hypoactivations in patients, especially in frontal, temporal and subcortical brain regions. Furthermore, positive symptoms were associated with parietal dysfunctions. Behavioral performance and neural responses of unaffected relatives of schizophrenic patients were intermediate between schizophrenic patients and controls indicating slight brain dysfunctions. In addition, compensatory strategies were demonstrated. These findings suggest that the genetic risk for schizophrenia is accompanied by neural inefficiency which is associated with cognitive deficits, especially in difficult tasks.

P03-125 Backward masking performance in schizophrenic patients and their healthy relatives

Over the past years, studies of unaffected first-degree relatives of schizophrenic patients have reported cognitive deficits in the domains of executive functions, memory, and attention. However, these deficits may rely on lower level information processing deficits. Here, we investigated visual information processing with a visual backward masking task. A vernier target was followed by a grating mask. Observers had to indicate the offset direction of the vernier. We determined the SOA between the vernier and the grating onset for schizophrenic patients, their healthy first order relatives, and a healthy control group. Schizophrenic patients needed SOAs about three times longer than healthy controls to reach a predefined criterion level. Backward masking performance of unaffected relatives was significantly better than the one of patients but significantly worse than performance of controls. This result adds further evidence that low level deficits as determined by visual backward masking are endophenotypes of schizophrenia.

Paraoxonase-1 55/192 genotypes in schizophrenic patients and their relatives in Turkish population

Oxidative stress and free radical-induced toxicity have been implicated in the pathophysiology of schizophrenia. In this study, we examined paraoxonase (PON1)-55/192 polymorphisms and PON1 activity in patients with schizophrenia, first-degree relatives of schizophrenic patients, and healthy controls. This study consisted of 292 healthy participants, 267 unrelated patients with schizophrenia and 311 first-degree relatives of schizophrenic patients. PON1 55 (rs 854560) and PON1 192 (rs 662) polymorphisms were performed by restriction fragment length polymorphism. The frequencies of the QQ and LL genotypes were significantly overpresented in controls compared with those of schizophrenic patients and their relatives. In contrast, the RR genotype was more prevalent in patients than their relatives and healthy controls. The frequencies of the LM and QR genotypes in relatives were higher than controls. Serum PON1 activities of controls were significantly higher when compared with both schizophrenic patients and their relatives. The RR and LL genotypes were associated with a significantly increased PON1 activity as compared with QR or QQ and MM or LM genotypes, respectively, in all groups. This is the first study that shows the association between PON1-55/192 polymorphisms and schizophrenia. Our data suggest that the subjects carrying R allele or RR genotype might be susceptible to schizophrenia and subjects with QQ or LL might be protected against schizophrenia. First-degree relatives of schizophrenic patients have higher heterozygote genotypes, suggesting that this group can shift either to patient or control group depending on their allele types and environmental factors. PON1 genetic variations are also associated with PON1 activities. Reduced PON1 activity in patients and their relatives might result from the combined effects of more than one polymorphic variant in PON1 or other genes and/or increased oxidative stress, supporting the hypothesis that reactive oxygen species-mediated cellular damage might contribute to the neuropathology of schizophrenia.

Cognitive performance and basic symptoms in first-degree relatives of schizophrenic patients

The aim of the present study was to examine cognitive performance and basic symptoms (BS) in the relatives of schizophrenic patients. The experimental sample comprised 24 first-degree relatives of patients. Each relative was matched to one control. Cognitive tests were: Continuous Performance Test (CPT), N-Back Working Memory Test (N-BACK), Negative Priming Test (NPT), and Span of Apprehension Test (SPAN). The Basic Symptoms Questionnaire (FBF) was used to measure subjective disturbances. The relatives showed only slightly worse cognitive performance than the controls, especially in the tasks with greater cognitive processing load. The relatives also revealed more BS than the controls in the domain of thought, attention, memory, language, and visual representation. Only CPT performance was hardly associated with BS. The negative correlation between FBF and CPT was strongly evident in the relatives with poorer processing capacity. This finding suggests that the BS are associated with sustained attention performance. Future research is needed to clarify whether BS are related to other cognitive domains.

Autonomic dysfunction in first-degree relatives of schizophrenic patients

Background: It has been described that patients suffering from schizophrenia have a decreased vagal activity that might be associated with an increased cardiac mortality. So reduced parameters of heart rate variability (HRV) and baroreflex sensitivity (BRS) as well as increased QT- variability measures have been shown. The aim of this study was to examine whether first-degree relatives of schizophrenic patients show similar changes in autonomic parameters as patients.

Social judgement in clinically stable patients with schizophrenia and healthy relatives: behavioural evidence of social brain dysfunction

Patients with schizophrenia have been found to display abnormalities in social cognition. The aim of the study was to test whether patients with schizophrenia and unaffected first-degree relatives of schizophrenic patients display behavioural signs of social brain dysfunction when making social judgements. Eighteen patients with schizophrenia, 24 first-degree unaffected relatives and 28 healthy comparison subjects completed a task which involves trustworthiness judgements of faces. A second task was completed to measure the general ability to recognize faces. Patients with schizophrenia rated faces as more trustworthy, especially those that were judged to be untrustworthy by healthy comparison subjects. Siblings of schizophrenia patients display the same bias, albeit to a lesser degree. The pattern of more positive trustworthiness judgements parallels the results from studies of patients with abnormalities in brain areas involved in social cognition. Because patients and siblings did not differ significantly from controls in their general ability to recognize faces, these findings cannot be dismissed as abnormalities in face perception by itself.

More severe sustained attention deficits in nonpsychotic siblings of multiplex schizophrenia families than in those of simplex ones

Sustained attention deficits measured by the Continuous Performance Test (CPT) have been proposed as an endophenotype of schizophrenia. However, little is known about whether sustained attention deficits in first-degree relatives of schizophrenic patients are associated with familial loading for schizophrenia. We examined 107 parents and 84 siblings of simplex schizophrenia families as well as 72 parents and 56 siblings of multiplex schizophrenia families, all nonpsychotic, using the Diagnostic Interview for Genetic Studies and two sessions of the CPT (undegraded and degraded). The effect of perceptual load was assessed using the residual of the regression of the degraded score on the undegraded one. Statistical models that can adjust for familial correlations were used to compare the CPT performance of relatives between the two types of families. Siblings from multiplex families exhibited worse performance on the degraded CPT and less proficiency in processing the perceptual load than those from simplex families. No such difference was observed for the parents on either CPT version. We concluded that sustained attention along with perceptual load processing is more impaired in the siblings of schizophrenic patients with high familial loading and that this finding might be useful for future genetic dissection of schizophrenia.

Impaired working speed and executive functions as frontal lobe dysfunctions in young first-degree relatives of schizophrenic patients

The aim of the investigation was to detect neuropsychological markers, such as sustained and selective attention and executive functions, which contribute to the vulnerability to schizophrenia especially in young persons. Performance was assessed in 32 siblings and children of schizophrenic patients and 32 matched controls using Wisconsin Card Sorting Test, Colour-Word-Interference-Test, Trail Making Test, and d2-Concentration-Test. The first-degree relatives showed certain impairments on all four tests, in particular, slower times on all time-limited tests. These results suggest the need for more time when completing neuropsychological tasks involving selected and focused attention, as well as cognitive flexibility, as a possible indicator of genetic vulnerability to schizophrenia.

Substance abuse and related diagnoses in early psychosis

Substance abuse seems to be common among those with early signs of evolving psychosis. This article seeks to determine the prevalence of substance abuse and substance use disorders (SUDs) and the association of abuse and SUD with vulnerability psychosis among a sample of first-degree relatives of schizophrenic patients (n = 70), help-seekers (n = 29), and control subjects (n = 34). The Structured Interview for Prodromal Symptoms (SIPS) 1.0 was used to define the vulnerability status and the Structured Clinical Interview for DSM-IV Axis I to diagnose the subjects. Data on various other measures, including premorbid adjustment, personality disorder symptoms, psychological distress, and abuse of substances, were collected. Those who were identified as vulnerable to psychosis reported significantly more lifetime alcohol abuse and had more commonly an SUD than controls. Substance use disorder, as well as alcohol and drug abuse, correlated significantly with personality disorder symptoms and current positive SIPS score and both types of abuse also with disorganization SIPS score. The odds ratio for having an SUD among those vulnerable to psychosis was 6.33 (95% confidence interval, 1.77-22.73). Early psychosis and substance abuse frequently occur together.

Cortical inhibition in first-degree relatives of schizophrenic patients assessed with transcranial magnetic stimulation

Although cortical inhibition deficit has been shown in schizophrenia patients by transcranial magnetic stimulation (TMS), some controversies remain, possibly due to confounding factors such as medication use and clinical state at the time of assessment. First-degree relatives of schizophrenia patients, who share various degrees of genetic vulnerability with the patients, but are free from confounds related to medication and/or florid psychosis, have not been studied to date. We compared 12 relatives with 14 controls on several paradigms with TMS. Three of the 12 healthy relatives lacked transcallosal inhibition (TI) in one or more of the stimulation levels. There were no significant differences in other parameters. The lack of TI in 25% of the relatives is an important finding that needs to be replicated in larger samples that are heterogeneous in terms of psychosis-proneness.

Tests of executive functions in first-degree relatives of schizophrenic patients: a meta-analysis

Executive dysfunctions in relatives of schizophrenic patients may be trait markers of genetic liability and thus help us to elucidate the aetiology of schizophrenia. As a large amount of data has been published, a synthesis through a meta-analysis was needed to demonstrate the existence of executive impairments in relatives of schizophrenic patients and to assess their magnitude. We conducted a meta-analysis of articles that compared performances of controls and relatives of schizophrenic patients on the four tests most frequently used to assess executive functions: the Wisconsin Card Sorting Test (WCST), the Trail Making Test (TMT), the Stroop Test and the Verbal Fluency (VF) Test. When needed and possible, published data were supplemented with information from the authors. After assessing the homogeneity of the data, effect sizes were estimated and publication bias was tested by use of funnel plots. Relatives of schizophrenic patients performed less well than controls on all executive tests analysed. Effect estimates were in the small to moderate range (from 0.26 to 0.49) for Stroop, WCST and TMT, but were greater for the fluency tests (0.65 for phonological and 0.87 for semantic VF). Relatives of schizophrenic patients appear to have wide, although not severe, executive dysfunctions. As the sensitivity of the different tests for impairments in relatives is not the same, the choice of test and method used should be carefully assessed.

A study of hippocampal shape anomaly in schizophrenia and in families multiply affected by schizophrenia or bipolar disorder.

Hippocampal shape anomaly (HSA), characterised by a rounded hippocampus, has been documented in congenital malformations and epileptic patients. Subtle structural hippocampal abnormalities have been demonstrated in patients with schizophrenia. We tested the hypothesis that HSA is more frequent in schizophrenia, particularly in patients from families multiply affected by schizophrenia, and that HSA is transmitted within these families. We also aimed to define the anatomical features of the hippocampus and other cerebral structures in the HSA spectrum and to determine the prevalence of HSA in a control group. We reviewed the magnetic resonance imaging of a large number of subjects with schizophrenia and bipolar disorder, many of who came from multiply affected families, relatives of the affected probands, and controls. Quantitative measures of hippocampal shape and position and other qualitative anatomical measures were performed (including depth of dominant sulcus cortical cap, angle of dominant sulcus and hippocampal fissure, bulk of collateral white matter, prominence of temporal horn lateral recess and blurring of internal hippocampal architecture) on subjects with HSA. A spectrum of mild, moderate and severe HSA was defined. The prevalence of HSA was, 7.8% for the controls (n=218), 9.3% for all schizophrenic subjects (n=151) and 12.3% for familial schizophrenic subjects (n=57). There was a greater prevalence of moderate or severe forms of HSA in familial schizophrenics than controls. However, there was no increase in the prevalence of HSA in the unaffected first-degree relatives of schizophrenic patients or in patients with familial bipolar disorder. HSA was rarely transmitted in families. HSA was frequently associated with a deep, vertical collateral/occipito-temporal sulcus and a steep hippocampal fissure. Our data raise the possibility that HSA is linked to disturbances of certain neurodevelopmental genes associated with schizophrenia. However, the lack of any increase in prevalence in the unaffected relatives of patients and the lack of clustering within individual pedigrees argues against this developmental anomaly being commonly associated with genetic predisposition to the illness.

The impact of pharmacotherapy on the spectra in magnetic resonance spectroscopy

Magnetic resonance spectroscopy (MRS) is a very powerful tool to determine different biological components of brain tissue in the living human brain. There is currently a growing literature suggesting reduced NAA/Cho ratios in the frontal lobe of schizophrenics which would be compatible as a sign for reduced neural integrity in this region. This finding correlates very well with neuropsychological deficits especially concerning working memory domains. Data on first-degree relatives of schizophrenic patients seem to suggest that part of these changes are mainly due to the vulnerability to the disorder and not related to medication or other treatment options. On the other hand, there are several studies suggesting a quite clear-cut influence of pharmacotherapy on MRS-spectra in schizophrenia. The goal of this talk is to bring these two lines of data together.