| 1 | Am J Psychiatry 2002 Feb 159: 180-90 |
|---|---|
| PMID | 11823257 |
| Title | Amisulpride, an unusual "atypical" antipsychotic: a meta-analysis of randomized controlled trials. |
| Abstract | The "atypical" profile of the new antipsychotics clozapine, olanzapine, quetiapine, and risperidone has been linked to combined antagonism of serotonin 2 (5-HT(2)) and dopamine 2 (D(2)) receptors. Although amisulpride is a highly selective D(3)/D(2) receptor antagonist, it is assumed to have atypical properties as well. The purpose of this article was to compare the atypical profile of amisulpride with that of the 5-HT(2)/D(2) antagonists. Randomized controlled trials that compared amisulpride with conventional antipsychotics or placebo for patients with schizophrenia were identified and included in a meta-analysis. The mean effect sizes found for amisulpride were compared with those of an updated meta-analysis of the 5-HT(2)/D(2) antagonists. Eighteen randomized controlled trials of amisulpride (N=2,214) were found. In 11 studies of acutely ill patients it proved to be consistently more effective than conventional antipsychotics for global schizophrenic symptoms (measured with the Brief Psychiatric Rating Scale) and negative symptoms. Amisulpride is to date the only atypical antipsychotic for which several studies of patients suffering predominantly from negative symptoms have been published. In four such studies amisulpride was significantly more effective than placebo. Three small studies with conventional antipsychotics as comparators showed only a trend in favor of amisulpride in this regard. Amisulpride was associated with clearly lower use of antiparkinsonian medication and with fewer dropouts due to adverse events than conventional antipsychotics. These results CAST some doubt on the notion that combined 5-HT(2)/D(2) antagonism is the reason that the newer antipsychotic medications are effective for negative symptoms and have fewer extrapyramidal side effects. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 2 | Am J Psychiatry 2002 Feb 159: 180-90 |
| PMID | 11823257 |
| Title | Amisulpride, an unusual "atypical" antipsychotic: a meta-analysis of randomized controlled trials. |
| Abstract | The "atypical" profile of the new antipsychotics clozapine, olanzapine, quetiapine, and risperidone has been linked to combined antagonism of serotonin 2 (5-HT(2)) and dopamine 2 (D(2)) receptors. Although amisulpride is a highly selective D(3)/D(2) receptor antagonist, it is assumed to have atypical properties as well. The purpose of this article was to compare the atypical profile of amisulpride with that of the 5-HT(2)/D(2) antagonists. Randomized controlled trials that compared amisulpride with conventional antipsychotics or placebo for patients with schizophrenia were identified and included in a meta-analysis. The mean effect sizes found for amisulpride were compared with those of an updated meta-analysis of the 5-HT(2)/D(2) antagonists. Eighteen randomized controlled trials of amisulpride (N=2,214) were found. In 11 studies of acutely ill patients it proved to be consistently more effective than conventional antipsychotics for global schizophrenic symptoms (measured with the Brief Psychiatric Rating Scale) and negative symptoms. Amisulpride is to date the only atypical antipsychotic for which several studies of patients suffering predominantly from negative symptoms have been published. In four such studies amisulpride was significantly more effective than placebo. Three small studies with conventional antipsychotics as comparators showed only a trend in favor of amisulpride in this regard. Amisulpride was associated with clearly lower use of antiparkinsonian medication and with fewer dropouts due to adverse events than conventional antipsychotics. These results CAST some doubt on the notion that combined 5-HT(2)/D(2) antagonism is the reason that the newer antipsychotic medications are effective for negative symptoms and have fewer extrapyramidal side effects. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 3 | Schizophr. Res. 2003 Apr 60: 157-66 |
| PMID | 12591579 |
| Title | A postmortem study of the mediodorsal nucleus of the thalamus in schizophrenia. |
| Abstract | Four studies have reported that the mediodorsal nucleus of the thalamus (MD) is smaller and contains fewer neurons in schizophrenia. The MD is a key node in a circuit proposed to be dysfunctional in the disorder. However, one study did not find a MD volume loss in schizophrenia, and all the studies to date are relatively small. Given the importance of establishing unequivocally the presence of MD pathology, we have carried out a study of the volume and number of neurons in the left and right MD in 21 patients with schizophrenia and 27 healthy comparison subjects. We also measured the size of MD neurons, and estimated total thalamic volume. We found no difference in the volume of the MD, the number of MD neurons, or the size of MD neurons in either hemisphere in schizophrenia. Neither was total thalamic volume altered. There are no obvious methodological or clinical factors to explain our failure to replicate the finding of MD involvement in schizophrenia. Hence our negative observations, in the largest sample yet investigated, CAST doubt on the robustness and/or the generalisability of MD neuropathology in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 4 | Psychiatry Clin. Neurosci. 2004 Oct 58: 507-15 |
| PMID | 15482582 |
| Title | Can a less pejorative Chinese translation for schizophrenia reduce stigma? A study of adolescents' attitudes toward people with schizophrenia. |
| Abstract | The term jing-shen-fen-lie-zheng (mind-split-disease) has been used to denote schizophrenia in Chinese societies. Many Asian countries, where the Chinese writing system is used, adopt a similar translation. This study examined whether a less pejorative name si-jue-shi-diao (dys-regulation of thought and perception) as a diagnostic label for symptoms of schizophrenia could reduce stigma. Secondary school students (n = 313) were randomly assigned to read a vignette with one of four labels: si-jue-shi-diao, jing-shen-fen-lie-zheng, jing-shen-bin (mental illness), and no label. Students expressed their social distance, stereotypes held, and attributions toward a young adult who met the Diagnostic and Statistical Manual-IV of Mental Health Disorders criteria for schizophrenia. It was found that psychiatric labeling did not have a statistically significant main effect on attitude measures. However, students with religious beliefs were more accepting toward the target individual associated with diagnostic label than one with no labeling. The results CAST doubts that less pejorative labels can reduce the social stigma of schizophrenia. Some potential drawbacks in using politically correct terms to describe schizophrenia are highlighted. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 5 | Mol. Psychiatry 2004 Dec 9: 1091-9 |
| PMID | 15241432 |
| Title | Linkage analysis of psychosis in bipolar pedigrees suggests novel putative loci for bipolar disorder and shared susceptibility with schizophrenia. |
| Abstract | The low-to-moderate resolution of linkage analysis in complex traits has underscored the need to identify disease phenotypes with presumed genetic homogeneity. Bipolar disorder (BP) accompanied by psychosis (psychotic BP) may be one such phenotype. We previously reported a genome-wide screen in a large bipolar pedigree sample. In this follow-up study, we reclassified the disease phenotype based on the presence or absence of psychotic features and subgrouped pedigrees according to familial load of psychosis. Evidence for significant linkage to psychotic BP (genome-wide P<0.05) was obtained on chromosomes 9q31 (lod=3.55) and 8p21 (lod=3.46). Several other sites were supportive of linkage, including 5q33 (lod=1.78), 6q21 (lod=1.81), 8p12 (lod=2.06), 8q24 (lod=2.01), 13q32 (lod=1.96), 15q26 (lod=1.96), 17p12 (lod=2.42), 18q21 (lod=2.4), and 20q13 (lod=1.98). For most loci, the highest lod scores, including those with genome-wide significance (at 9q31 and 8p21), occurred in the subgroup of families with the largest concentration of psychotic individuals (> or =3 in a family). Interestingly, all regions but six--5q33, 6q21, 8p21, 8q24, 13q32 and 18q21--appear to be novel; namely, they did not show notable linkage to BP in other genome scans, which did not employ psychosis for disease classification. Also of interest is possible overlap with schizophrenia, another major psychotic disorder: seven of the regions presumed linked in this study--5q, 6q, 8p, 13q, 15q, 17p, and 18q--are also implicated in schizophrenia, as are 2p13 and 10q26, which showed more modest support for linkage. Our results suggest that BP in conjunction with psychosis is a potentially useful phenotype that may: (1) expedite the detection of susceptibility loci for BP and (2) CAST light on the genetic relationship between BP and schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 6 | Curr Opin Psychiatry 2005 Mar 18: 121-34 |
| PMID | 16639164 |
| Title | Evidence for white matter abnormalities in schizophrenia. |
| Abstract | The purpose of this review is to highlight important recent imaging, histological, and genetic findings relevant to white matter abnormalities in schizophrenia. It is CAST within the context of research findings conducted over the last 5 years, where we analyze their importance in understanding schizophrenia, as well as discuss future directions for research. White matter abnormalities have long been hypothesized in schizophrenia, although only recently has it become possible to investigate them more closely. This has come about as a result of advances in neuroimaging, including new imaging techniques sensitive to white matter structure, as well as advances in computer science, with new analysis techniques making it possible to evaluate several interconnected brain regions at a time. Postmortem studies, with advances such as fluoroscopy and electron microscopy, have also led to quantifying populations of different brain cells, including myelin-forming oligodendrocytes. Moreover, molecular studies enable examination of immunoreactivity of proteins that are responsible for building myelin sheaths. Additionally, microarray genetic studies allow us to investigate myelin-related genes in schizophrenia. Taken together, these technological advances bring us closer to understanding white matter pathology in schizophrenia. Advances in new imaging techniques likely account for the renewed interest in investigating white matter abnormalities in schizophrenia, with over 30 new articles published on this topic in the last 12 months, compared with 11 the year before. We review recent imaging, histological, and genetic findings that suggest white matter abnormalities in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 7 | Schizophr. Res. 2005 Oct 78: 219-24 |
| PMID | 16005190 |
| Title | Quantitative assessment of the frequency of normal associations in the utterances of schizophrenia patients and healthy controls. |
| Abstract | The intrusion of associations into the utterances of schizophrenic individuals typically disrupts the coherence of the patient's utterances. Recent theoretical formulations of these phenomena have emphasized the hyperactivity) of associational networks in such language disturbance (e.g., Maher, B.A. 2003 schizophrenia, aberrant utterance and delusions of control: the disconnection of speech and thought, and the connection of experience and belief. Mind and Language, 18, 1-22). There has been only limited effort to quantify such features in patient populations. We hypothesized that (1) coherent utterances elicited from a sample of schizophrenia patients will present a higher mean frequency of normative associations than in normal controls; and (2) there is a positive association between total associations in utterances and hyperassociative activity (positive facilitation) as assessed by a semantic priming task. Participants included 43 schizophrenic patients and 25 healthy controls. Three measures were employed, a new computer program, Computed Associations in Sequential Text (CAST), to quantify normative associations; a picture description technique for eliciting speech samples; and a semantic priming task to measure associative facilitation. In coherent utterances, schizophrenia patients produced higher mean totals of associations compared to controls. Patients with positive facilitation scores in the controlled processing interval (1250 ms) of the semantic priming procedure, there was a correlation between facilitation scores and total frequency of associations. This effect was absent in controls. These results are consistent with models of language disturbance in schizophrenia that posit hyperactivity of associational networks. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 8 | Schizophr. Res. 2005 Oct 78: 219-24 |
| PMID | 16005190 |
| Title | Quantitative assessment of the frequency of normal associations in the utterances of schizophrenia patients and healthy controls. |
| Abstract | The intrusion of associations into the utterances of schizophrenic individuals typically disrupts the coherence of the patient's utterances. Recent theoretical formulations of these phenomena have emphasized the hyperactivity) of associational networks in such language disturbance (e.g., Maher, B.A. 2003 schizophrenia, aberrant utterance and delusions of control: the disconnection of speech and thought, and the connection of experience and belief. Mind and Language, 18, 1-22). There has been only limited effort to quantify such features in patient populations. We hypothesized that (1) coherent utterances elicited from a sample of schizophrenia patients will present a higher mean frequency of normative associations than in normal controls; and (2) there is a positive association between total associations in utterances and hyperassociative activity (positive facilitation) as assessed by a semantic priming task. Participants included 43 schizophrenic patients and 25 healthy controls. Three measures were employed, a new computer program, Computed Associations in Sequential Text (CAST), to quantify normative associations; a picture description technique for eliciting speech samples; and a semantic priming task to measure associative facilitation. In coherent utterances, schizophrenia patients produced higher mean totals of associations compared to controls. Patients with positive facilitation scores in the controlled processing interval (1250 ms) of the semantic priming procedure, there was a correlation between facilitation scores and total frequency of associations. This effect was absent in controls. These results are consistent with models of language disturbance in schizophrenia that posit hyperactivity of associational networks. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 9 | Schizophr Bull 2005 Jan 31: 55-66 |
| PMID | 15888425 |
| Title | Cognitive strategies versus self-management skills as adjunct to vocational rehabilitation. |
| Abstract | Cognitive dysfunctions and negative symptoms are "rate-limiting factors" for community outcome and response to psychosocial intervention in people with schizophrenia. Therefore, two cognitive-behavioral group therapies were developed-computer-assisted cognitive strategy training (CAST) and training of self-management skills for negative symptoms (TSSN)-to target these barriers to rehabilitation readiness. One hundred thirty-eight DSM-IV schizophrenia inpatients on a rehabilitation ward were randomly assigned to CAST plus vocational rehabilitation, TSSN plus vocational rehabilitation, or vocational rehabilitation alone. CAST included computer-based training in coping strategies focusing on deficits in attention, verbal memory, and planning. TSSN focused on social withdrawal/social anhedonia, lack of drive/volition, and affect flattening using techniques such as time scheduling, mastery, and pleasure techniques. Treatment outcome was assessed at intake and at discharge after 8 weeks. Analyses of covariance controlling for basis-level functioning demonstrated that patients receiving CAST plus vocational rehabilitation showed greater improvement on attention and verbal memory but not on planning ability. Patients receiving TSSN plus vocational rehabilitation failed to demonstrate improvement in negative symptoms. CAST plus vocational rehabilitation was found to be associated with a higher rate of successful job placement at the 12-month followup interval. Hierarchical logistic regression analyses demonstrated that improvement in short- and long-term verbal memory predicted a higher proportion of variance of successful job placement in the followup than pretreatment history of employment alone. Cognitive training as an adjunct to inpatient vocational rehabilitation demonstrated cognitive improvement, which was found to be associated with successful job placement in the followup. TSSN's efficacy was less clear; reasons for this uncertainty are provided. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 10 | Schizophr. Res. 2007 Mar 91: 187-91 |
| PMID | 17317106 |
| Title | Palate and dentition in schizophrenia. |
| Abstract | Although psychotic symptoms are central to the diagnostic criteria for schizophrenia, other neuropsychiatric syndromes as well as widespread anatomical and physiological abnormalities in the periphery are also common in the disorder. We decided to test the hypothesis that developmental abnormalities are present throughout the body by examining the oral cavity and in particular the teeth and dimensions of the palate of patients with schizophrenia. Dental stone models (CASTs) were made from impressions of the teeth and palate in schizophrenia (N=28) and control (N=25) subjects. Blind to group membership, the palate height, palate width, and other features of each subject's CAST were assessed by a dentist. Patients with schizophrenia had significantly wider palates than control subjects; the palatal height did not differ between the two groups. The patients also had a high prevalence of several other anatomical abnormalities, few of which were present in the control subjects. This first blind, quantitative assessment of the palate and teeth of patients with schizophrenia revealed a wide palate and an increased prevalence of developmental abnormalities in the teeth. These findings are consistent with the emerging concept that schizophrenia is not so much a psychotic disorder as a developmental disorder in which psychosis is present, and in which there are a number of other abnormalities in the brain and the periphery. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 11 | Nucl. Med. Biol. 2008 Jan 35: 11-7 |
| PMID | 18158938 |
| Title | Dopamine D2 receptor radiotracers [(11)C](+)-PHNO and [(3)H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo. |
| Abstract | In vitro, the dopamine D2 receptor exists in two states, with high and low affinity for agonists. The high-affinity state is the physiologically active state thought to be involved in dopaminergic illnesses such as schizophrenia. The positron emission tomography radiotracer [(11)C](+)-PHNO ([(11)C](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol), being a D2 agonist, should selectively label the high-affinity state at tracer dose and therefore be more susceptible to competition by agonist as compared to the antagonist [(3)H]raclopride, which binds to both affinity states. We tested this prediction using ex vivo dual-radiotracer experiments in conscious rats. D2 antagonists (haloperidol or clozapine), a partial agonist (aripiprazole), a full agonist [(-)-NPA] or the dopamine-releasing drug amphetamine (AMPH) were administered to rats prior to an intravenous coinjection of [(11)C](+)-PHNO and [(3)H]raclopride. Rats were sacrificed 60 min after radiotracer injection. Striatum, cerebellum and plasma samples were counted for (11)C and (3)H. The specific binding ratio {SBR, i.e., [%ID/g (striatum)-%ID/g (cerebellum)]/(%ID/g (cerebellum)} was used as the outcome measure. In response to D2 antagonists, partial agonist or full agonist, [(11)C](+)-PHNO and [(3)H]raclopride SBRs responded indistinguishably in terms of both ED(50) and Hill slope (e.g., (-)-NPA ED(50) values are 0.027 and 0.023 mg/kg for [(11)C](+)-PHNO and [(3)H]raclopride, respectively). In response to AMPH challenge, [(11)C](+)-PHNO and [(3)H]raclopride SBRs were inhibited to the same degree. We have shown that the SBRs of [(11)C](+)-PHNO- and [(3)H]raclopride do not differ in their response to agonist challenge. These results do not support predictions of the in vivo binding behavior of a D2 agonist radiotracer and CAST some doubt on the in vivo applicability of the D2 two-state model, as described by in vitro binding experiments. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 12 | Schizophr. Res. 2008 Oct 105: 236-44 |
| PMID | 18693084 |
| Title | Prevalence of large cavum septi pellucidi in ultra high-risk individuals and patients with psychotic disorders. |
| Abstract | An increased prevalence of large cavum septum pellucidum (CSP), a marker of midline neurodevelopmental abnormality, has been reported in schizophrenia. However, not all studies have been able to replicate this finding and very few studies have been conducted in large samples. In the current study, magnetic resonance imaging was used to assess the presence of an abnormal CSP in 162 patients with first-episode psychosis (FEP), 89 patients with chronic schizophrenia, 135 ultra high-risk (UHR) individuals, and 87 controls. The prevalence of a large CSP (>5.6 mm) did not differ between the groups (9.3% of the FEP patients, 11.2% of the chronic schizophrenia patients, 11.1% of the UHR individuals, and 11.5% of the controls). The length of the CSP was not associated with sulcal morphology of the anterior cingulate cortex (ACC), suggesting different biological processes responsible for the CSP enlargement versus ACC folding. These findings suggest that the CSP is not a neurodevelopmental marker of psychosis and CAST doubt over the notion that it plays a major role in the neurobiology of psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 13 | Schizophr. Res. 2008 Aug 103: 22-5 |
| PMID | 18248791 |
| Title | No difference in the prevalence of cavum septum pellucidum (CSP) between first-episode schizophrenia patients, offspring of schizophrenia patients and healthy controls. |
| Abstract | The reported prevalence of cavum septum pellucidum (CSP), is extremely variable (from 0.1% to 85%) depending upon the measurement method or imaging resolution. Higher prevalence of CSP has been found in schizophrenia. In this study, we examined the prevalence of CSP in a large number of first-episode schizophrenia patients, young relatives of schizophrenia patients and healthy controls. We manually measured CSP using 1.5 mm T1 MRI scans from ongoing studies at University of Pittsburgh in 89 first-episode patients with schizophrenia (age=23.8+/-7.4, M/F=61/28), 64 genetically at-risk individuals (offspring and siblings of schizophrenia patients, age 15.2+/-3.7, M/F=29/32) and 120 comparison subjects (n=120, age=22.1+/-7.9, M/F62/50). CSP was present in 64% of the first-episode patients (mean length 1.87+/-2.3 mm), 64.6% of the at-risk individuals (1.64+/-1.96 mm) and 64.2% of the normal controls (1.88+/-2.0 mm). There was no difference in the prevalence of CSP exceeding 4 mm. We also did not find any influence of the sex or age in the presence or size of CSP. Our data CAST doubt on the significance of CSP as markers of neurodevelopmental pathology in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 14 | Psychiatry Res 2008 May 159: 207-14 |
| PMID | 18423612 |
| Title | Schizotypal traits impact upon executive working memory and aspects of IQ. |
| Abstract | Previous inconsistent findings concerning a link between working memory dysfunction and negative aspects of non-clinical schizotypy have been interpreted to CAST doubt on the continuity model of 'negative psychosis-proneness'. This study employed the Letter-Number-Sequencing (LNS) task and the Trail-Making Test to assess more demanding, executive working memory. A secondary concern was to rule out possible mediating effects of familial schizophrenia. It was hypothesised that executive working memory impairment would be associated primarily with negative rather than positive schizotypy even in the absence of familial schizophrenia. Matrix reasoning controlled for IQ. In 87 university-student participants with no known family history of schizophrenia, lower LNS scores were associated with higher levels of negative and positive schizotypy traits. Counter to expectations, matrix reasoning scores were also associated with schizotypy, primarily the cognitive/perceptual traits. Results were similar when participants with a known family history of schizophrenia (10) were included (N=97). Findings support the view that impairment of executive working memory (indexed by LNS) is a reliable cognitive marker for negative (and perhaps also positive) schizophrenia vulnerability, independent of familial schizophrenia, and provide the first indication that some facets of IQ (e.g. inductive reasoning) might also be compromised in non-clinical schizotypy. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 15 | Psychiatry Res 2008 May 159: 207-14 |
| PMID | 18423612 |
| Title | Schizotypal traits impact upon executive working memory and aspects of IQ. |
| Abstract | Previous inconsistent findings concerning a link between working memory dysfunction and negative aspects of non-clinical schizotypy have been interpreted to CAST doubt on the continuity model of 'negative psychosis-proneness'. This study employed the Letter-Number-Sequencing (LNS) task and the Trail-Making Test to assess more demanding, executive working memory. A secondary concern was to rule out possible mediating effects of familial schizophrenia. It was hypothesised that executive working memory impairment would be associated primarily with negative rather than positive schizotypy even in the absence of familial schizophrenia. Matrix reasoning controlled for IQ. In 87 university-student participants with no known family history of schizophrenia, lower LNS scores were associated with higher levels of negative and positive schizotypy traits. Counter to expectations, matrix reasoning scores were also associated with schizotypy, primarily the cognitive/perceptual traits. Results were similar when participants with a known family history of schizophrenia (10) were included (N=97). Findings support the view that impairment of executive working memory (indexed by LNS) is a reliable cognitive marker for negative (and perhaps also positive) schizophrenia vulnerability, independent of familial schizophrenia, and provide the first indication that some facets of IQ (e.g. inductive reasoning) might also be compromised in non-clinical schizotypy. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 16 | Psychiatry Res 2008 May 159: 207-14 |
| PMID | 18423612 |
| Title | Schizotypal traits impact upon executive working memory and aspects of IQ. |
| Abstract | Previous inconsistent findings concerning a link between working memory dysfunction and negative aspects of non-clinical schizotypy have been interpreted to CAST doubt on the continuity model of 'negative psychosis-proneness'. This study employed the Letter-Number-Sequencing (LNS) task and the Trail-Making Test to assess more demanding, executive working memory. A secondary concern was to rule out possible mediating effects of familial schizophrenia. It was hypothesised that executive working memory impairment would be associated primarily with negative rather than positive schizotypy even in the absence of familial schizophrenia. Matrix reasoning controlled for IQ. In 87 university-student participants with no known family history of schizophrenia, lower LNS scores were associated with higher levels of negative and positive schizotypy traits. Counter to expectations, matrix reasoning scores were also associated with schizotypy, primarily the cognitive/perceptual traits. Results were similar when participants with a known family history of schizophrenia (10) were included (N=97). Findings support the view that impairment of executive working memory (indexed by LNS) is a reliable cognitive marker for negative (and perhaps also positive) schizophrenia vulnerability, independent of familial schizophrenia, and provide the first indication that some facets of IQ (e.g. inductive reasoning) might also be compromised in non-clinical schizotypy. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 17 | J Int Neuropsychol Soc 2008 Mar 14: 318-26 |
| PMID | 18282329 |
| Title | Social behavior following traumatic brain injury and its association with emotion recognition, understanding of intentions, and cognitive flexibility. |
| Abstract | Although the adverse consequences of changes in social behavior following traumatic brain injury (TBI) are well documented, relatively little is known about possible underlying neuropsychological deficits. Following a model originally developed for social behavior deficits in schizophrenia, we investigated whether impairments in emotion recognition, understanding of other people's intentions ("theory of mind"), and cognitive flexibility soon after first TBI or 1 year later were associated with self and proxy ratings of behavior following TBI. Each of the three functions was assessed with two separate tests, and ratings of behavior were collected on three questionnaires. Patients with TBI (n = 33) were impaired in emotion recognition, "theory of mind," and cognitive flexibility compared with matched orthopedic controls (n = 34). Proxy ratings showed increases in behavioral problems 1 year following injury in the TBI group but not in the control group. However, test performance was not associated with questionnaire data. Severity of the impairments in emotion recognition, understanding intention, and flexibility were unrelated to the severity of behavioral problems following TBI. These findings failed to confirm the used model for social behavior deficits and may CAST doubt on the alleged link between deficits in emotion recognition or theory of mind and social functioning. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 18 | J. Biomed. Mater. Res. Part B Appl. Biomater. 2010 May 93: 562-72 |
| PMID | 20225251 |
| Title | A rapid method for creating drug implants: translating laboratory-based methods into a scalable manufacturing process. |
| Abstract | Low compliance with medication is the major cause of poor outcome in schizophrenia treatment. While surgically implantable solvent-CAST pellets were produced to improve outcome by increased compliance with medication, this process is laborious and time-consuming, inhibiting its broader application (Siegel et al., Eur J Pharm Biopharm 2006;64:287-293). In this study, the previous fabrication process was translated to a continuous and scalable extrusion method. Extrusion processes were modified based on in vitro release studies, drug load consistency examination, and surface morphology analysis using scanning electron microscopy. Afterward, optimized haloperidol implants were implanted into rats for preliminary analysis of biocompatibility. Barrel temperature, screw speed and resulting processing pressure influenced surface morphology and drug release. Data suggest that fewer surface pores shift the mechanism from bulk to surface PLGA degradation and longer lag period. Results demonstrate that extrusion is a viable process for manufacturing antipsychotic implants. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 19 | Curr Opin Psychiatry 2011 Jul 24: 331-5 |
| PMID | 21587077 |
| Title | Sex differences in the disability associated with mental disorders. |
| Abstract | It is well established that women have a higher prevalence of depression and anxiety disorders, but sex differences in the disability associated with depression and anxiety disorders have been less well researched. Earlier studies suggested that women were more disabled by their depression than were men. Studies of schizophrenia, in contrast, have always found that men were more disabled. Recent studies CAST new light on this topic and suggest that sex differences in the disability associated with mental disorders may be more consistent than previously thought. Two general population studies found that men (and boys) with depression or anxiety disorders (or symptoms) reported greater impairment in everyday functioning and social relationships than women with depression and anxiety. These findings are consistent with the research on psychotic disorders and with much of the research on sex differences in long-term sickness absence due to psychiatric disorder. Men experience more functional and social impairment in association with episodes of depression, anxiety, and psychosis than their female counterparts. The greater social isolation among men with mental disorders may be attributable to male reticence about disclosing emotional distress, limiting their access to support. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 20 | Schizophr. Res. 2012 Sep 140: 99-103 |
| PMID | 22819779 |
| Title | Frequency of normative word associations in the speech of individuals at familial high-risk for schizophrenia. |
| Abstract | The intrusion of associations into speech in schizophrenia disrupts coherence and comprehensibility, a feature of formal thought disorder referred to as loosened associations. We have previously proposed that loosened associations may result from hyperactivity in semantic association networks, leading to an increased frequency of associated words appearing in speech. Using Computed Associations in Sequential Text (CAST) software to quantify the frequency of such associations in speech, we have reported more frequent normative associations in language samples from patients with schizophrenia and in individuals with schizotypal characteristics. The present study further examined this deviance in schizophrenia by studying normative associations in those who share genes with an individual with schizophrenia, (i.e. first-degree relatives of probands with schizophrenia; HR) but who do not have an illness. Familial high-risk participants (n=22), and controls (n=24) provided verbal responses to cards from the Thematic Apperception Test. CAST analysis revealed that HR used more associated words in their speech compared to controls. Furthermore, the frequency of normative word associations was positively correlated with dimensional and total scores of schizotypy derived from ratings of the structured interview for schizotypy, which confirms past research showing a relationship between schizotypy and hyperassociations. Our results suggest that some language disturbances in schizophrenia likely arise from an underlying psychopathological mechanism, hyperactivity of semantic associations. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 21 | Schizophr. Res. 2012 Sep 140: 99-103 |
| PMID | 22819779 |
| Title | Frequency of normative word associations in the speech of individuals at familial high-risk for schizophrenia. |
| Abstract | The intrusion of associations into speech in schizophrenia disrupts coherence and comprehensibility, a feature of formal thought disorder referred to as loosened associations. We have previously proposed that loosened associations may result from hyperactivity in semantic association networks, leading to an increased frequency of associated words appearing in speech. Using Computed Associations in Sequential Text (CAST) software to quantify the frequency of such associations in speech, we have reported more frequent normative associations in language samples from patients with schizophrenia and in individuals with schizotypal characteristics. The present study further examined this deviance in schizophrenia by studying normative associations in those who share genes with an individual with schizophrenia, (i.e. first-degree relatives of probands with schizophrenia; HR) but who do not have an illness. Familial high-risk participants (n=22), and controls (n=24) provided verbal responses to cards from the Thematic Apperception Test. CAST analysis revealed that HR used more associated words in their speech compared to controls. Furthermore, the frequency of normative word associations was positively correlated with dimensional and total scores of schizotypy derived from ratings of the structured interview for schizotypy, which confirms past research showing a relationship between schizotypy and hyperassociations. Our results suggest that some language disturbances in schizophrenia likely arise from an underlying psychopathological mechanism, hyperactivity of semantic associations. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 22 | Schizophr. Res. 2012 Sep 140: 99-103 |
| PMID | 22819779 |
| Title | Frequency of normative word associations in the speech of individuals at familial high-risk for schizophrenia. |
| Abstract | The intrusion of associations into speech in schizophrenia disrupts coherence and comprehensibility, a feature of formal thought disorder referred to as loosened associations. We have previously proposed that loosened associations may result from hyperactivity in semantic association networks, leading to an increased frequency of associated words appearing in speech. Using Computed Associations in Sequential Text (CAST) software to quantify the frequency of such associations in speech, we have reported more frequent normative associations in language samples from patients with schizophrenia and in individuals with schizotypal characteristics. The present study further examined this deviance in schizophrenia by studying normative associations in those who share genes with an individual with schizophrenia, (i.e. first-degree relatives of probands with schizophrenia; HR) but who do not have an illness. Familial high-risk participants (n=22), and controls (n=24) provided verbal responses to cards from the Thematic Apperception Test. CAST analysis revealed that HR used more associated words in their speech compared to controls. Furthermore, the frequency of normative word associations was positively correlated with dimensional and total scores of schizotypy derived from ratings of the structured interview for schizotypy, which confirms past research showing a relationship between schizotypy and hyperassociations. Our results suggest that some language disturbances in schizophrenia likely arise from an underlying psychopathological mechanism, hyperactivity of semantic associations. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 23 | CNS Drugs 2012 Aug 26: 663-90 |
| PMID | 22784018 |
| Title | The role of memantine in the treatment of psychiatric disorders other than the dementias: a review of current preclinical and clinical evidence. |
| Abstract | Memantine, a non-competitive NMDA receptor antagonist approved for Alzheimer's disease with a good safety profile, is increasingly being studied in a variety of non-dementia psychiatric disorders. We aimed to critically review relevant literature on the use of the drug in such disorders. We performed a PubMed search of the effects of memantine in animal models of psychiatric disorders and its effects in human studies of specific psychiatric disorders. The bulk of the data relates to the effects of memantine in major depressive disorder and schizophrenia, although more recent studies have provided data on the use of the drug in bipolar disorder as an add-on. Despite interesting preclinical data, results in major depression are not encouraging. Animal studies investigating the possible usefulness of memantine in schizophrenia are controversial; however, interesting findings were obtained in open studies of schizophrenia, but negative placebo-controlled, double-blind studies CAST doubt on their validity. The effects of memantine in anxiety disorders have been poorly investigated, but data indicate that the use of the drug in obsessive-compulsive disorder and post-traumatic stress disorder holds promise, while findings relating to generalized anxiety disorder are rather disappointing. Results in eating disorders, catatonia, impulse control disorders (pathological gambling), substance and alcohol abuse/dependence, and attention-deficit hyperactivity disorder are inconclusive. In most psychiatric non-Alzheimer's disease conditions, the clinical data fail to support the usefulness of memantine as monotherapy or add-on treatment However, recent preclinical and clinical findings suggest that add-on memantine may show antimanic and mood-stabilizing effects in treatment-resistant bipolar disorder. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 24 | Front Hum Neurosci 2012 -1 6: 149 |
| PMID | 22666197 |
| Title | Patients with Schizophrenia Fail to Up-Regulate Task-Positive and Down-Regulate Task-Negative Brain Networks: An fMRI Study Using an ICA Analysis Approach. |
| Abstract | Recent research suggests that the cerebral correlates of cognitive deficits in schizophrenia are nested in the activity of widespread, inter-regional networks rather than being restricted to any specific brain location. One of the networks that have received focus lately is the default mode network. Parts of this network have been reported as hyper-activated in schizophrenia patients (SZ) during rest and during task performance compared to healthy controls (HC), although other parts have been found to be hypo-activated. In contrast to this network, task-positive networks have been reported as hypo-activated compared in SZ during task performance. However, the results are mixed, with, e.g., the dorsolateral prefrontal cortex showing both hyper- and hypo-activation in SZ. In this study we were interested in signal increase and decrease differences between a group of SZ and HC in cortical networks, assuming that the regulatory dynamics of alternating task-positive and task-negative neuronal processes are aberrant in SZ. We compared 31 SZ to age- and gender-matched HC, and used fMRI and independent component analysis (ICA) in order to identify relevant networks. We selected the independent components (ICs) with the largest signal intensity increases (STG, insula, supplementary motor cortex, anterior cingulate cortex, and MTG) and decreases (fusiform gyri, occipital lobe, PFC, cingulate, precuneus, and angular gyrus) in response to a dichotic auditory cognitive task. These ICs were then tested for group differences. Our findings showed deficient up-regulation of the executive network and a corresponding deficit in the down-regulation of the anterior default mode, or effort network during task performance in SZ when compared with HC. These findings may indicate a deficit in the dynamics of alternating task-dependent and task-independent neuronal processes in SZ. The results may CAST new light on the mechanisms underlying cognitive deficits in schizophrenia, and may be of relevance for diagnostics and new treatments. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 25 | Exp Brain Res 2013 Oct 230: 175-85 |
| PMID | 23857169 |
| Title | Differential impairment of interhemispheric transmission in bipolar disease. |
| Abstract | There is abundant evidence that the cerebral white matter and in particular the corpus callosum show several structural abnormalities in both schizophrenia (SCZ) and bipolar disease (BD). However, which cognitive functions are impaired as a result of these anomalies is still unclear. Previous behavioural tests of interhemispheric crosstalk have shown a differential impairment in SCZ with interhemispheric transmission time, as tested with the Poffenberger paradigm, essentially normal but with an abnormally enhanced interhemispheric summation effect, as tested with the redundant signal effect. The present study was inspired by this discrepancy and by the more general question of a possible overlap between the pathophysiology of SCZ and BD. We tested both SCZ and BD patients in the Poffenberger paradigm and redundant signal effect and found a similar dissociation, namely a normal interhemispheric transfer time and an abnormal redundant signal effect. The only difference between the two groups was a selective slowing of speed of response of the dominant right hand in the SCZ group suggesting an impairment of left hemisphere functions. These results CAST further light on the question of common and differential impairments of basic psychological functions in the two diseases. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 26 | Front Psychol 2013 -1 4: 307 |
| PMID | 23755035 |
| Title | The coherent organization of mental life depends on mechanisms for context-sensitive gain-control that are impaired in schizophrenia. |
| Abstract | There is rapidly growing evidence that schizophrenia involves changes in context-sensitive gain-control and probabilistic inference. In addition to the well-known cognitive disorganization to which these changes lead, basic aspects of vision are also impaired, as discussed by other papers on this Frontiers Research Topic. The aim of this paper is to contribute to our understanding of such findings by examining five central hypotheses. First, context-sensitive gain-control is fundamental to brain function and mental life. Second, it occurs in many different regions of the cerebral cortex of many different mammalian species. Third, it has several computational functions, each with wide generality. Fourth, it is implemented by several neural mechanisms at cellular and circuit levels. Fifth, impairments of context-sensitive gain-control produce many of the well-known symptoms of schizophrenia and change basic processes of visual perception. These hypotheses suggest why disorders of vision in schizophrenia may provide insights into the nature and mechanisms of impaired reality testing and thought disorder in psychosis. They may also CAST light on normal mental function and its neural bases. Limitations of these hypotheses, and ways in which they need further testing and development, are outlined. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 27 | Seishin Shinkeigaku Zasshi 2013 -1 115: 180-6 |
| PMID | 23691808 |
| Title | [Early intervention practice in Toyama Prefecture: efforts to improve the clinical service]. |
| Abstract | We report our activity in the Consultation and Support Service in Toyama (CAST), a clinical service provided by the collaboration of Toyama Prefectural Mental Health Center and University Hospital of Toyama(UHT). About 23% of users diagnosed with at-risk mental state (ARMS), during October 2006 until March 2012, transitioned to overt schizophrenia. More than half of the subjects who continued to visit the specialized clinic in UHT were treated with antipsychotic drugs. We encountered a case of schizophrenia in which early treatment with an atypical psychotic drug was effective in normalizing cognitive function and achieving a good social consequence. The ability of mismatch negativity, an event-related potential, to predict progression to psychosis in subjects with ARMS is discussed. Further efforts should be directed towards improving long-term outcomes, such as social function, for users of the CAST. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 28 | Psychol Med 2013 Oct 43: 2077-86 |
| PMID | 23302254 |
| Title | Specificity of childhood psychotic symptoms for predicting schizophrenia by 38 years of age: a birth cohort study. |
| Abstract | Childhood psychotic symptoms have been used as a subclinical phenotype of schizophrenia in etiological research and as a target for preventative interventions. However, recent studies have CAST doubt on the specificity of these symptoms for schizophrenia, suggesting alternative outcomes such as anxiety and depression. Using a prospective longitudinal birth cohort we investigated whether childhood psychotic symptoms predicted a diagnosis of schizophrenia or other psychiatric disorders by 38 years of age. Participants were drawn from a birth cohort of 1037 children from Dunedin, New Zealand, who were followed prospectively to 38 years of age (96% retention rate). Structured clinical interviews were administered at age 11 to assess psychotic symptoms and study members underwent psychiatric assessments at ages 18, 21, 26, 32 and 38 to obtain past-year DSM-III-R/IV diagnoses and self-reports of attempted suicides since adolescence. Psychotic symptoms at age 11 predicted elevated rates of research diagnoses of schizophrenia and posttraumatic stress disorder (PTSD) and also suicide attempts by age 38, even when controlling for gender, social class and childhood psychopathology. No significant associations were found for persistent anxiety, persistent depression, mania or persistent substance dependence. Very few of the children presenting with age-11 psychotic symptoms were free from disorder by age 38. Childhood psychotic symptoms were not specific to a diagnosis of schizophrenia in adulthood and thus future studies of early symptoms should be cautious in extrapolating findings only to this clinical disorder. However, these symptoms may be useful as a marker of adult mental health problems more broadly. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 29 | BMC Psychiatry 2014 -1 14: 56 |
| PMID | 24571621 |
| Title | The rise of assertive community interventions in South Africa: a randomized control trial assessing the impact of a modified assertive intervention on readmission rates; a three year follow-up. |
| Abstract | Many countries have over the last few years incorporated mental health assertive interventions in an attempt to address the repercussions of deinstitutionalization. Recent publications have failed to duplicate the positive outcomes reported initially which has CAST doubt on the future of these interventions. We previously reported on 29 patients from a developing country who completed 12 months in an assertive intervention which was a modified version of the international assertive community treatment model. We demonstrated reduction in readmission rates as well as improvements in social functioning compared to patients from the control group. The obvious question was, however, if these outcomes could be sustained for longer periods of time. This study aims to determine if modified assertive interventions in an under-resourced setting can successfully maintain reductions in hospitalizations. Patients suffering from schizophrenia who met a modified version of Weidens' high frequency criteria were randomized into two groups. One group received a modified assertive intervention based on the international assertive community treatment model. The other group received standard care according to the model of service delivery in this region. Data was collected after 36 months, comparing readmissions and days spent in hospital. The results demonstrated significant differences between the groups. Patients in the intervention group had significantly less readmissions (p = 0.007) and spent less days in hospital compared to the patients in the control group (p = 0.013). Modified assertive interventions may be successful in reducing readmissions and days spent in hospital in developing countries where standard care services are less comprehensive. These interventions can be tailored in such a way to meet service needs and still remain affordable and feasible within the context of an under-resourced setting. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 30 | Psychopharmacology (Berl.) 2014 Jan 231: 243-56 |
| PMID | 23929132 |
| Title | Differential effects of estrogen and testosterone on auditory sensory gating in rats. |
| Abstract | Estrogen has been shown to have beneficial effects in patients with schizophrenia. However, the mechanisms involved in this protective effect are unclear. schizophrenia is associated with deficits in sensory gating, a filtering mechanism which normally prevents sensory overload. In rodent models, acute treatment with drugs such as the dopamine D1/D2 receptor agonist, apomorphine; the dopamine releaser, amphetamine; and the glutamate NMDA receptor antagonists, phencyclidine or MK-801, can induce a phenotype similar to that seen in schizophrenia. Given the putative protective action of estrogen in schizophrenia, here we investigated the effect of ovariectomy (OVX) and estrogen replacement in female rats on drug-induced auditory gating deficits. For comparison, we also assessed the effects of CASTration (CAST) and dihydrotestosterone (DHT) replacement in male rats. Rats were instrumented with cortical surface electrodes. Test sessions comprised of 150 presentations of paired clicks, 500 ms apart (S1 and S2). Administration of all drugs increased the ratio of responses to S2/S1 in sham-operated female and male rats. OVX reduced event-related potential amplitudes but did not alter S2/S1 ratio or drug effects. In OVX rats with 17?-estradiol implants, the effect of apomorphine was abolished, but there was no change in that of amphetamine and phencyclidine. There were no effects of CAST or DHT replacement in male rats. Chronic estrogen replacement in OVX rats protected against sensory gating deficits caused by direct dopamine D1/D2 receptor stimulation. These data could indicate a possible mechanism by which estrogen exerts a protective action in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 31 | Neurosci Biobehav Rev 2015 Jul 54: 57-75 |
| PMID | 25616183 |
| Title | The role of the thalamus in schizophrenia from a neuroimaging perspective. |
| Abstract | The thalamus is a crucial node for brain physiology and part of functional and structural pathways relevant for schizophrenia. Relatively few imaging studies on schizophrenia have focused on this brain region, yet extant evidence supports the association between this brain disorder and thalamic anomalies. Nevertheless, the mechanisms underlying this association remain largely conjectural. Here, we review imaging literature on the relationship between the thalamus and schizophrenia, focusing on critical challenges for future studies, in particular: (i) the anatomical and functional organization of the thalamus in separate nuclei, which are also differently connected with the cortex; (ii) state-dependent variables, which do not allow firm conclusions on the relevance of thalamic correlates as core phenotypes of schizophrenia and (iii) genetic variation, which affects thalamic physiology and may lead to variability of structural and functional patterns. Current evidence from the studies reviewed does not appear conclusive, although the relevance of thalamo-prefrontal interactions clearly emerges. Results from imaging genetics are beginning to CAST insight on possible mechanisms of the involvement of the thalamus in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |