| 1 | Pac Health Dialog 2005 Mar 12: 43-6 |
|---|---|
| PMID | 18181462 |
| Title | Preventive intervention for early psychosis in adolescents--the Palau Youth at Risk Project. |
| Abstract | We have studied a total of 393 adolescents 14 to 19 years from Palau, where the lifetime morbid risk for broadly defined schizophrenia is 2.67% and cases cluster in large extended families. These Palauan adolescents included 52 offspring of a schizophrenic parent designated as "Genetically Highest Risk" or GHR+ and 61 nieces/nephews of affected sib-pairs/trios, designated "Genetically High Risk" or GHR. The remaining 280 subjects were recruited based on the results of a survey of Palauan high school students that was designed to screen for clinically HR and normal control adolescents with no close affected relatives. Among the selected high school students were 60 adolescents with one affected second or third degree relative who were designated as "Genetically Moderate Risk" (GMR). The remaining 220 subjects with no close affected relatives were designated as "Genetically Low Risk" (GLR). Based on a comprehensive clinical assessment using the K-SADS, we identified a total of 230 Palauan adolescents with early psychosis, 48 or 21% of whom had already transitioned to a DSM-IV psychotic disorder, predominantly schizophrenia. Together, the two highest genetic risk groups contributed 35% of the adolescent-onset DSM-IV psychosis cases and 26% of the prodromals. More than half of the early psychosis cases (55%) had no close affected relatives, indicating that genetic liability provides only a partial explanation of elevated risk. Our results support the value of screening for early psychosis in the high schools, conducting a full-scale clinical assessment to identify adolescents with early "prodromal" symptoms, and initiating a family-based intervention program designed to delay or even prevent the onset of florid psychosis. This intervention program comprises regular symptom reassessments so that referrals for treatment can be made as needed plus family psycho-education designed to engage the family in a program of care and support for the early psychosis patient. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Pac Health Dialog 2005 Mar 12: 43-6 |
| PMID | 18181462 |
| Title | Preventive intervention for early psychosis in adolescents--the Palau Youth at Risk Project. |
| Abstract | We have studied a total of 393 adolescents 14 to 19 years from Palau, where the lifetime morbid risk for broadly defined schizophrenia is 2.67% and cases cluster in large extended families. These Palauan adolescents included 52 offspring of a schizophrenic parent designated as "Genetically Highest Risk" or GHR+ and 61 nieces/nephews of affected sib-pairs/trios, designated "Genetically High Risk" or GHR. The remaining 280 subjects were recruited based on the results of a survey of Palauan high school students that was designed to screen for clinically HR and normal control adolescents with no close affected relatives. Among the selected high school students were 60 adolescents with one affected second or third degree relative who were designated as "Genetically Moderate Risk" (GMR). The remaining 220 subjects with no close affected relatives were designated as "Genetically Low Risk" (GLR). Based on a comprehensive clinical assessment using the K-SADS, we identified a total of 230 Palauan adolescents with early psychosis, 48 or 21% of whom had already transitioned to a DSM-IV psychotic disorder, predominantly schizophrenia. Together, the two highest genetic risk groups contributed 35% of the adolescent-onset DSM-IV psychosis cases and 26% of the prodromals. More than half of the early psychosis cases (55%) had no close affected relatives, indicating that genetic liability provides only a partial explanation of elevated risk. Our results support the value of screening for early psychosis in the high schools, conducting a full-scale clinical assessment to identify adolescents with early "prodromal" symptoms, and initiating a family-based intervention program designed to delay or even prevent the onset of florid psychosis. This intervention program comprises regular symptom reassessments so that referrals for treatment can be made as needed plus family psycho-education designed to engage the family in a program of care and support for the early psychosis patient. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2007 Jan 144B: 5-9 |
| PMID | 17034019 |
| Title | The Palau Early Psychosis Study: distribution of cases by level of genetic risk. |
| Abstract | The Palau Early Psychosis Study (PEPS) was designed to examine the pathogenesis of early psychosis in a high-risk population isolate. This paper describes the characteristics of our community-based, non-help seeking sample of 404 Palauan adolescents and quantifies the presence of early psychosis by level of genetic risk. The sample included 53 offspring of a schizophrenic parent designated as "Genetically Highest Risk" (GHR+) and 68 nieces/nephews of sib-pairs/trios, designated as "Genetically High Risk" (GHR). The remaining subjects were recruited through a high school survey that identified 62 "Genetically Moderate Risk" (GMR) adolescents with an affected second or third degree relative and 221 "Genetically Low Risk" (GLR) subjects with no close affected relatives. The GLR adolescents included 117 symptomatic or "Clinically High Risk" (CHR) adolescents and 104 asymptomatic normal controls. Based on a modified K-SADS-PL assessment, we identified 221 adolescents with early psychosis, 62 or 28% of whom had already transitioned to a psychotic disorder. Together, the two highest risk groups contributed 31% of the adolescent-onset psychosis cases and 27% of the prodromals. More than half of the early psychosis cases (53%) were GLR adolescents. The mean age of onset for DSM-IV psychosis was 12.9 years, and males transitioned at an earlier age than females. Our results indicate that Palauan adolescents, even GLR adolescents with no close affected relatives, have elevated rates of early psychosis. These young subjects can contribute valuable information about the familial transmission of schizophrenia, the developmental course of the illness, and rates of transition to frank psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2007 Jan 144B: 5-9 |
| PMID | 17034019 |
| Title | The Palau Early Psychosis Study: distribution of cases by level of genetic risk. |
| Abstract | The Palau Early Psychosis Study (PEPS) was designed to examine the pathogenesis of early psychosis in a high-risk population isolate. This paper describes the characteristics of our community-based, non-help seeking sample of 404 Palauan adolescents and quantifies the presence of early psychosis by level of genetic risk. The sample included 53 offspring of a schizophrenic parent designated as "Genetically Highest Risk" (GHR+) and 68 nieces/nephews of sib-pairs/trios, designated as "Genetically High Risk" (GHR). The remaining subjects were recruited through a high school survey that identified 62 "Genetically Moderate Risk" (GMR) adolescents with an affected second or third degree relative and 221 "Genetically Low Risk" (GLR) subjects with no close affected relatives. The GLR adolescents included 117 symptomatic or "Clinically High Risk" (CHR) adolescents and 104 asymptomatic normal controls. Based on a modified K-SADS-PL assessment, we identified 221 adolescents with early psychosis, 62 or 28% of whom had already transitioned to a psychotic disorder. Together, the two highest risk groups contributed 31% of the adolescent-onset psychosis cases and 27% of the prodromals. More than half of the early psychosis cases (53%) were GLR adolescents. The mean age of onset for DSM-IV psychosis was 12.9 years, and males transitioned at an earlier age than females. Our results indicate that Palauan adolescents, even GLR adolescents with no close affected relatives, have elevated rates of early psychosis. These young subjects can contribute valuable information about the familial transmission of schizophrenia, the developmental course of the illness, and rates of transition to frank psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Schizophr. Res. 2007 Jan 89: 299-307 |
| PMID | 17005375 |
| Title | The Palau Early Psychosis Study: neurocognitive functioning in high-risk adolescents. |
| Abstract | The purpose of the present study was to evaluate both the independent and joint effects of genetic risk and clinical status on neurocognitive functioning in adolescents from a population isolate with an elevated risk for schizophrenia and strong familial aggregation of cases. The subjects were 310 non-help seeking, drug-naïve adolescents 14-19 years of age from the Republic of Palau. The sample comprised 98 Genetically High Risk (GHR) adolescents, 54 of whom were symptomatic, and 212 Genetically Low Risk (GLR) adolescents, including 113 Clinically High Risk (CHR) subjects who were symptomatic and 99 normal controls who were non-symptomatic. Neurocognitive testing was conducted after the clinical assessment and included Wechsler Memory Scale tests of logical, visual and working memory, the perceptual organization and processing speed subtests of the WISC-III, CPT-IP measures of sustained attention, and tests of fine and gross neuromotor function. GHR adolescents showed impairments in immediate logical memory, verbal working memory, CPT-IP performance, and fine motor skills. The only two cognitive components influenced by the presence of early psychosis symptoms were WISC-III perceptual organization and spatial working memory. Neurocognitive deficits did not increase with increasing levels of psychopathology. We found no significant interactive effects of genetic risk and clinical status on neurocognitive functioning. Genetic risk and clinical status exert independent effects on neurocognitive function in HR adolescents, and genetic risk has a broader impact than clinical status. Our results suggest that many of the neurocognitive impairments associated with early psychosis are genetically mediated and can occur in genetically vulnerable individuals regardless of their clinical status. However, visuospatial processing appears to be uniquely disrupted by emerging symptomatology. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Psychopathology 2008 -1 41: 236-44 |
| PMID | 18408419 |
| Title | Potential vulnerability markers within the affective domain in subjects at genetic and clinical high risk for schizophrenia. |
| Abstract | Relative to ample high-risk studies on neurocognitive function, only a few high-risk studies have examined affective functioning components as possible vulnerability markers. In this study, we comprehensively assessed baseline affective functioning in subjects at clinical high risk (CHR) and genetic high risk (GHR) for schizophrenia, and healthy controls (HC), and compared the results to elucidate possible vulnerability markers in the affective domain. We studied 3 groups of subjects: those with CHR (n = 28) or GHR (n = 28) and a HC group (n = 24). Affective-process- and affective-content-related functioning were assessed using 5 emotion-related scales. In affective process, CHR subjects showed impairments in emotional awareness and mood repair, with some trend of impaired emotional expressivity as well as aggression control relative to either HC or GHR subjects, whereas GHR subjects showed only a trend of impairment in mood repair. In affective content, CHR subjects had less positive and more negative affect scores than the other 2 groups. These results correspond to previous findings of prodrome studies of schizophrenia and chronic schizophrenia and suggest that impaired mood repair and emotional awareness, as well as less positive and more negative affect may be potential candidates of vulnerability markers. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Aust N Z J Psychiatry 2008 Aug 42: 678-85 |
| PMID | 18622775 |
| Title | Social functioning deficits in young people at risk for schizophrenia. |
| Abstract | Impairment in social functioning is a central feature of schizophrenia and is known to be evident before the onset of psychosis, acting as a potential vulnerability marker. The aim of the present study was to test the hypothesis that social impairment is simultaneously a state and trait marker of risk for schizophrenia and schizophrenia-related disorder. Social functioning was examined in three groups: ultra-high-risk subjects (UHR, n =32), genetic high-risk subjects (GHR, n =32), and age- and IQ-matched healthy controls (HC, n =30). Social functioning was assessed using the Social Functioning Scale (SFS), and prodromal symptoms were assessed in high-risk subjects using the Comprehensive Assessment of At-Risk Mental States (CAARMS). Both the UHR and GHR groups exhibited significantly impaired social functioning compared with the HC group, and the UHR group was more impaired than the GHR group. In the UHR group, duration of prodromal symptoms was related to impaired 'interpersonal behaviour'. Positive and negative symptoms were not significantly associated with social functioning, whereas disorganized and general symptoms were significantly correlated with poor 'independence-competence' in UHR individuals. The findings support the hypothesis that impairment in social functioning is both a trait and state marker of risk for schizophrenia and other psychotic disorders, implying that social impairment constitutes a mediating vulnerability indicator of psychotic disorders including schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2008 Jul 32: 1326-30 |
| PMID | 18513845 |
| Title | Cavum septum pellucidum in subjects at ultra-high risk for psychosis: compared with first-degree relatives of patients with schizophrenia and healthy volunteers. |
| Abstract | The cavum septum pellucidum (CSP) is a space between the two leaflets of the septum pellucidum, and is a putative marker of disturbance in early brain development. We examined whether CSP was present more frequently in subjects at ultra-high risk (UHR) for psychosis compared to first-degree relatives of patients with schizophrenia (genetic high risk, GHR) and healthy controls (HC). We evaluated CSP in 87 subjects (30 UHR, 23 GHR, and 34 HC) according to a published grading system using high-resolution magnetic resonance imaging (MRI) with 0.45-mm slice thickness. We also assessed two other criteria: presence of CSP on at least one MRI slice, and abnormally large CSP (i.e., > or =6 mm in length). Correlational analysis between CSP measures and clinical symptoms was also examined. Based on the grading scale, the UHR group exhibited a significantly higher incidence of abnormal CSP (grades 2, 3, and 4) compared to the HC group, but there were no significant differences in the incidence of abnormal CSP between the UHR and GHR or the GHR and HC groups. There were no significant differences among the groups in the presence of CSP on at least one MRI slice or abnormally large CSP based on the length of CSP. In addition, no significant correlations between CSP measures and clinical symptoms were found. These findings suggest that abnormal CSP might be associated with susceptibility to psychosis, although the CSP itself might be a normal anatomical variant. Further studies using a larger sample are needed to clarify issues on neurodevelopmental perspective in subjects at high risk for psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Schizophr. Res. 2010 Sep 122: 179-84 |
| PMID | 20570111 |
| Title | Social skill and social cognition in adolescents at genetic risk for psychosis. |
| Abstract | Adolescents at genetic high risk (GHR) for schizophrenia have shown social skill impairments and there is some evidence to suggest they have Theory of Mind (ToM) deficits; however no research has used a standardized, performance-based behavioral measure to assess social functioning in this population nor evaluated ToM with a well-validated measure. We evaluated the psychometric properties of a new, theoretically-derived assessment of social functioning in GHR adolescents: the "High-Risk Social Challenge" task (HiSoC). The second aim was to explore whether GHR adolescents would show social skill and ToM deficits as compared to a non-psychiatric control (NPC) group. The present study evaluated social functioning with the HiSoC and ToM with the Eyes Test in 23 GHR adolescents and 31 NPCs. The HiSoC demonstrated high levels of reliability and validity. The GHR adolescents showed social skill impairments, but not ToM deficits. The results suggest that the HiSoC is a potentially useful new measure of social functioning in GHR adolescents. Furthermore, the findings add to the current body of literature that indicates that social skill impairments are related to schizophrenia vulnerability. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | Early Interv Psychiatry 2010 May 4: 153-61 |
| PMID | 20536971 |
| Title | Early signs and symptoms of psychosis among Palauan adolescents. |
| Abstract | This study was designed to identify early symptoms associated with the occurrence of psychosis during adolescence. Participants were recruited in the Republic of Palau, an isolated island nation in Micronesia with a prevalence rate for schizophrenia of 1.99%. Diagnostic interviews were used to obtain reports of early and current symptoms from 112 genetically high-risk (GHR) and 208 genetically low-risk (GLR) adolescents (ages 16-23). Based on current psychotic symptoms, participants were sorted into three groups: non-clinical, at-risk/symptomatic risk and clinically symptomatic. Multivariate analysis of variance revealed several between-group differences on rates of early symptoms. Most notably, youth who were in the GHR-clinically symptomatic group reported significantly higher rates of early marijuana use than GLR-clinically symptomatic youth, who were significantly more likely to report early symptoms of depression and behaviour disorders. In addition, several gender based differences in the link between early symptoms and adolescent onset psychosis were noted. Findings are generally consistent with previous research on early indicators, though several unexpected findings suggest that results from this study may not be fully generalizable beyond this relatively isolated and culturally distinct Micronesian nation. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | Schizophr. Res. 2011 Apr 127: 58-65 |
| PMID | 21277171 |
| Title | Reduced prefrontal functional connectivity in the default mode network is related to greater psychopathology in subjects with high genetic loading for schizophrenia. |
| Abstract | Neuroimaging studies in subjects at genetic high risk (GHR) of schizophrenia can provide clues to the causes for the development of schizophrenia. Little is known about genetic influence on functional connectivity status, although studies on schizophrenia have reported an abnormal default mode network (DMN). We sought to identify putative genetic vulnerability markers by examining whether aberrant DMN connectivity was present in GHR subjects with high genetic loading. Sixteen GHR subjects who had at least two relatives with schizophrenia and 16 age- and sex-matched controls were included and scanned using resting-state functional magnetic resonance imaging. A posterior cingulate cortex (PCC) seed region connectivity analysis was used to identify the DMN. Correlations between severity of psychopathology, level of genetic loading and DMN connectivity were calculated. The DMN network in GHR subjects showed reduced functional connectivity in the prefrontal areas, PCC, and precuneus. In addition, this reduced connectivity in the prefrontal cortices correlated with total and general scores on the Positive and Negative Syndrome Scale. GHR subjects having two first-degree relatives with schizophrenia showed a trend toward greater reduction in DMN connectivity in the precuneus and anterior cingulate cortex. This study suggests significant abnormalities in the DMN of subjects at GHR of schizophrenia. Alterations of DMN connectivity in the prefrontal cortex may reflect psychopathologies such as an inability to allocate resources properly between internal thoughts and external stimuli. Dysfunction of the anterior cingulate cortex and precuneus might be related to genetic risk for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 12 | Curr. Pharm. Des. 2012 -1 18: 5070-80 |
| PMID | 22716152 |
| Title | Effects of cannabis use on human brain structure in psychosis: a systematic review combining in vivo structural neuroimaging and post mortem studies. |
| Abstract | It is unclear yet whether cannabis use is a moderating or causal factor contributing to grey matter alterations in schizophrenia and the development of psychotic symptoms. We therefore systematically reviewed structural brain imaging and post mortem studies addressing the effects of cannabis use on brain structure in psychosis. Studies with schizophrenia (SCZ) and first episode psychosis (FEP) patients as well as individuals at genetic (GHR) or clinical high risk for psychosis (ARMS) were included. We identified 15 structural magnetic resonance imaging (MRI) (12 cross sectional / 3 longitudinal) and 4 post mortem studies. The total number of subjects encompassed 601 schizophrenia or first episode psychosis patients, 255 individuals at clinical or genetic high risk for psychosis and 397 healthy controls. We found evidence for consistent brain structural abnormalities in cannabinoid 1 (CB1) receptor enhanced brain areas as the cingulate and prefrontal cortices and the cerebellum. As these effects have not consistently been reported in studies examining nonpsychotic and healthy samples, psychosis patients and subjects at risk for psychosis might be particularly vulnerable to brain volume loss due to cannabis exposure. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 13 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2012 Apr 37: 50-5 |
| PMID | 22155177 |
| Title | Increased white matter integrity in the corpus callosum in subjects with high genetic loading for schizophrenia. |
| Abstract | White matter abnormalities in the corpus callosum (CC) of schizophrenia have been reported to predate the illness onset. This study aimed to investigate the effect of genetic predisposition on the white matter integrity of the CC, in subjects at genetically high risk for schizophrenia (GHR) and schizophrenia patients. Fractional anisotropy (FA) of the mid-sagittal CC in 22 young GHR, 15 schizophrenia, and 26 control subjects were examined. GHR subjects were defined as non-prodromal individuals who had more than two relatives with schizophrenia within third-degree relatives, one of whom must be a first-degree relative. ANCOVA with age and gender as covariates revealed overall difference of FA in the genu and splenium among the three groups. Post-hoc analysis found significantly increased FA in the genu of GHR subjects compared to controls (corrected p<0.01), whereas schizophrenia patients showed significantly decreased FA in the splenium. The white matter change of the CC in young GHR subjects was the opposite of that in schizophrenia. To consider previous reports on FA decrease in the CC in schizophrenia and the impaired frontal functioning in GHR group, the increased FA may be an indicator of compensatory alteration in white matter integrity in young GHR people. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 14 | Schizophr. Res. 2012 Nov 141: 197-203 |
| PMID | 22998933 |
| Title | Regional cortical thinning in subjects with high genetic loading for schizophrenia. |
| Abstract | Although recent studies have revealed regional cortical thinning in patients with schizophrenia, it is not clear whether cortical thinning reflects a genetic liability for schizophrenia. The present study investigated the change of cortical thickness in subjects at genetic high risk (GHR) for schizophrenia with a relatively high genetic loading compared with healthy controls (HC) and patients with schizophrenia. The effect of genetic loading on cortical thinning was also measured by comparing GHR subgroups according to the levels of genetic loading. Cortical thickness was measured by the Constrained Laplacian-based Automated Segmentation with Proximities algorithm using 1.5-T structural MRI scans. The cortical thickness of the subjects at GHR (n=31) was compared with that of HC (n=29) and patients with schizophrenia (n=31). We then compared the cortical thickness of the GHR subgroups according to the number of first-degree relatives with schizophrenia to measure the effect of genetic loading. Relative to HC, GHR subjects showed significant cortical thinning in the right anterior cingulate cortex (ACC), left paracingulate and posterior cingulate regions; bilateral frontal regions including frontal pole and ventromedial prefrontal cortex; bilateral temporal regions including the left parahippocampal gyrus; and bilateral inferior parietal and occipital regions; however, patients with schizophrenia showed more widespread cortical thinning in the fronto-temporo-parietal region. GHR subjects who had two or more first-degree relatives with schizophrenia showed a greater reduction in cortical thickness in the right ACC and in the left paracingulate cortex than did those who had only one first-degree relative with schizophrenia. Our findings suggest that the level of genetic loading may have a dose-dependent effect on cortical thinning in the right ACC and in the left paracingulate cortex and that cortical thinning in GHR subjects may represent neurodevelopmental alterations that result from genetic liability for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 15 | Schizophr Bull 2012 Nov 38: 1189-99 |
| PMID | 21518920 |
| Title | Phase-specific brain change of spatial working memory processing in genetic and ultra-high risk groups of schizophrenia. |
| Abstract | Spatial working memory (WM) processing has 3 distinct phases: encoding, maintenance, and retrieval and its dysfunction is a core feature in schizophrenia. We examined phase-specific brain activations associated with spatial WM in first-degree relatives of schizophrenia (genetic high risk, GHR), ultra-high risk (UHR) subjects, patients with schizophrenia, and healthy controls. We used an event-related functional magnetic resonance imaging in 17 GHR subjects, 21 UHR subjects, 15 clinically stable patients with schizophrenia and 16 healthy controls, while subjects were performing a spatial delayed-response task. During the encoding phase, the GHR group showed increased activation in the fronto-parietal regions, whereas the UHR and schizophrenia groups showed significantly less activation in these regions than did the healthy control group. Especially, frontal activation was strongest in GHR subjects, followed by healthy controls, and occurred to a lesser degree in the UHR group, with the least activation occurring in the schizophrenia group. During the maintenance phase, the thalamus showed a differential activation, similar to frontal activation pattern during the encoding phase. During the retrieval phase, no prominent differential activations were found. Increased activations were observed in the superior temporal gyrus during the encoding and maintenance phases in the GHR, UHR, and schizophrenia groups relative to healthy controls. Our findings suggest that functional deficits associated with spatial WM processing emerge in the UHR before the onset of schizophrenia and compensatory neural processes exist in the GHR with genetic liability to schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 16 | Neuroscience 2013 Sep 249: 172-91 |
| PMID | 23298853 |
| Title | Stress and neurodevelopmental processes in the emergence of psychosis. |
| Abstract | The notion that stress plays a role in the etiology of psychotic disorders, especially schizophrenia, is longstanding. However, it is only in recent years that the potential neural mechanisms mediating this effect have come into sharper focus. The introduction of more sophisticated models of the interplay between psychosocial factors and brain function has expanded our opportunities for conceptualizing more detailed psychobiological models of stress in psychosis. Further, scientific advances in our understanding of adolescent brain development have shed light on a pivotal question that has challenged researchers; namely, why the first episode of psychosis typically occurs in late adolescence/young adulthood. In this paper, we begin by reviewing the evidence supporting associations between psychosocial stress and psychosis in diagnosed patients as well as individuals at clinical high risk for psychosis. We then discuss biological stress systems and examine changes that precede and follow psychosis onset. Next, research findings on structural and functional brain characteristics associated with psychosis are presented; these findings suggest that normal adolescent neuromaturational processes may go awry, thereby setting the stage for the emergence of psychotic syndromes. Finally, a model of neural mechanisms underlying the pathogenesis of psychosis is presented and directions for future research strategies are explored. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 17 | Schizophr. Res. 2013 Nov 150: 512-8 |
| PMID | 24035404 |
| Title | Altered asymmetry of the anterior cingulate cortex in subjects at genetic high risk for psychosis. |
| Abstract | Many studies have reported that patients with schizophrenia often have structural abnormalities of the anterior cingulate cortex (ACC) and that some of these seem to be of genetic origin, therefore predating the onset of illness. The present study aimed to investigate whether these alterations in the ACC are genetic in origin by comparing the morphological patterns of three groups: normal controls, subjects at genetic high risk (GHR) for psychosis, and patients with schizophrenia. The relationships between morphological variations and executive function were also investigated. This study examined the magnetic resonance images of cingulate sulcus/paracingulate sulcus (CS/PCS) folding patterns in 222 subjects (103 normal subjects, 30 individuals at GHR, and 89 patients with schizophrenia) and evaluated differences in the morphological and asymmetrical patterns of the ACC among groups. Neurocognitive tests were then performed and differences in cognitive performance were analyzed according to morphological variation. Differences in PCS folding were detected; the control group was significantly more likely than were other groups to show a well-developed left PCS (p=0.009) and leftward asymmetry of the PCS (p<0.001). However, neither GHR subjects (p=0.346) nor patients (p=0.784) showed this leftward asymmetry. No statistically significant differences in CS continuity were observed. A more prominent left PCS (p=0.031) and leftward PCS asymmetry (p=0.030) were both associated with higher scores on the working memory task. The results suggest that GHR subjects have distinct neurodevelopmental anomalies that resemble those of patients with schizophrenia even though they do not display any psychotic symptoms. Certain developmental alterations in the ACC, such as the loss of leftward sulcal asymmetry in patients with schizophrenia, might be related to genetic factors. Additionally, this morphological alteration might partly account for the impaired executive function in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |