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Objective: Neurocognitive impairments in schizophrenia are well replicated and widely regarded as candidate endophenotypes that may facilitate understanding of schizophrenia genetics and pathophysiology, The Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) aims to identify genes underlying liability to schizophrenia. The unprecedented size of its study group (N=1,872), made possible through use of a computerized neurocognitive battery, can help further investigation of the genetics of neurocognition. The current analysis evaluated two characteristics not fully addressed in prior research: 1) heritability of neurocognition in African American families and 2) relationship between neurocognition and psychopathology in families of African American probands with schizophrenia or schizoaffective disorder. Method: Across eight data collection sites, patients with schizophrenia or schizoaffective disorder (N=610), their biological relatives (N=928), and community comparison subjects (N=334) completed a standardized diagnostic evaluation and the computerized neurocognitive battery. Performance accuracy and response time (speed) were measured separately for 10 neurocognitive domains. Results: The patients with schizophrenia or schizoaffective disorder exhibited less accuracy and speed in most neurocognitive domains than their relatives both with and without other psychiatric disorders, who in turn were more impaired than comparison subjects in most domains. Estimated trait heritability after inclusion of the mean effect of diagnostic status, age, and sex revealed significant heritabilities for most neurocognitive domains, with the highest for accuracy of abstraction/ flexibility, verbal memory, face memory, spatial processing, and emotion processing and for speed of attention. Conclusions: Neurocognitive functions in African American families are heritable and associated with schizophrenia. They show potential for gene-mapping studies. (Am J Psychiatry 2010; 167:459-472) doi: 10.1176/appi.ajp.2009.08091351

Objective: The present study investigated a new set of families of Latin American ancestry in order to detect the location of genes predisposing to schizophrenia and related psychotic disorders. Method: A genome-wide scan was performed for 175 newly recruited families with at least two siblings suffering from a psychotic disorder. Best-estimate consensus procedures were used to arrive at diagnoses, and nonparametric allele-sharing statistics were calculated to detect linkage. Results: Genome-wide significant evidence for linkage for the phenotype of DSM-IV schizophrenia or schizoaffective disorder was found in a region on chromosome 17q21 (lod score, 3.33). A region on chromosome 15q22-23 showed suggestive evidence of linkage with this same phenotype (lod score, 2.11). Analyses using a broader model (any psychosis) yielded evidence of suggestive linkage for the 17q21 region only, and no region achieved genome-wide significance of linkage. Conclusions: The new set of 175 families of Mexican and Central American ancestry delineates two new loci likely to harbor predisposition genes for schizophrenia and schizoaffective disorder. The region with the strongest support for linkage in this sample, 17q21, has been implicated in meta-analyses of schizophrenia genome screens, but the authors found no previous reports of it as a locus for schizophrenia in specific population-or family-based studies, and it may represent the location of a schizophrenia predisposition gene (or genes) of special relevance in Mexican and Central American populations.

Objective: The authors previously demonstrated significant association between markers within NOS1AP and schizophrenia in a set of Canadian families of European descent, as well as significantly increased expression in schizophrenia of NOS1AP in unrelated postmortem samples from the dorsolateral prefrontal cortex. In this study the authors sought to apply novel statistical methods and conduct additional biological experiments to isolate at least one risk allele within NOS1AP. Method: Using the posterior probability of linkage disequilibrium (PPLD) to measure the probability that a single nucleotide polymorphism (SNP) is in linkage disequilibrium with schizophrenia, the authors evaluated 60 SNPs from NOS1AP in 24 Canadian families demonstrating linkage and association to this region. SNPs exhibiting strong evidence of linkage disequilibrium were tested for regulatory function by luciferase reporter assay. Two human neural cell lines (SK-N-MC and PFSK-1) were transfected with a vector containing each allelic variant of the SNP, the NOS1AP promoter, and a luciferase gene. Alleles altering expression were further assessed for binding of nuclear proteins by electrophoretic mobility shift assay. Results: Three SNPs produced PPLDs >40%. One of them, rs12742393, demonstrated significant allelic expression differences in both cell lines tested. The allelic variation at this SNP altered the affinity of nuclear protein binding to this region of DNA. Conclusions: The A allele of rs12742393 appears to be a risk allele associated with schizophrenia that acts by enhancing transcription factor binding and increasing gene expression.

Objective: Aripiprazole is a dopamine partial agonist approved for use in adults for short- and long-term treatment of schizophrenia and bipolar disorder. This study was designed to examine the acute efficacy, safety, and tolerability of aripiprazole for adolescents with schizophrenia. Method: This was a 6-week multicenter, double-blind, randomized, placebo-controlled trial. Subjects 13 to 17 years old with a DSM-IV diagnosis of schizophrenia and a Positive and Negative Syndrome Scale (PANSS) total score of 70 or more were randomly assigned (1:1:1 ratio) to placebo or 10 or 30 mg/day of aripiprazole. The primary endpoint was mean change from baseline to endpoint (last observation carried forward) in PANSS total score. Assessments of safety and tolerability included spontaneously reported adverse events, extrapyramidal symptom scores, serum prolactin concentration, body weight, and metabolic measures. Results: Of 302 patients, 85% completed the 6-week study. The mean baseline PANSS score was 94.1. At the end of the study, both aripiprazole doses showed statistically significant differences from placebo in reduction in PANSS total score. Adverse events occurring in more than 5% of either aripiprazole group and with a combined incidence at least twice the rate for placebo were extrapyramidal disorder, somnolence, and tremor. Mean changes in prolactin were -8.45, -11.93, and -15.14 ng/ml for placebo and 10 mg and 30 mg of aripirazole, respectively. Mean body weight changes were -0.8, 0.0, and 0.2 kg for placebo and 10 mg and 30 mg of aripiprazole, respectively. Conclusion: Both 10- and 30-mg/day doses of aripiprazole were superior to placebo in the acute treatment of adolescents with schizophrenia. Aripiprazole was generally well tolerated.

Objective: Studies of emotion recognition abilities in schizophrenia show greater impairment for non-Caucasians with schizophrenia compared with Caucasians. These studies, however, included only Caucasian faces as stimuli. There is evidence from healthy individuals for a performance disadvantage on face memory and emotion recognition when processing faces from a different ethnicity. The authors sought to measure the 'other-race effect' in schizophrenia, which could account for previous findings and provide information about sensitivity to such social cues in patients. Method: The study included 540 participants from four groups: African Americans with schizophrenia (N=135), Caucasians with schizophrenia (N=135), African American community comparison subjects (N=135), and Caucasian community comparison subjects (N=135). All participants completed face recognition and facial emotion identification tasks that included both Caucasian and African American faces as stimuli. Results: Although comparison participants performed better than individuals with schizophrenia across all tasks, both comparison participants and participants with schizophrenia exhibited a strong and significant other-race effect for face memory and emotion recognition. The magnitude of the other-race effect did not differ between these two groups. Conclusions: These findings reveal an intact other-race effect in patients with schizophrenia and highlight a methodological concern in the measurement of face processing abilities in schizophrenia, namely, that findings of greater impairment in African American patients are spurious when Caucasian faces are used as stimuli. Despite overall impairments in face memory and emotion recognition, the presence of a normative other-race effect in schizophrenia may reflect typical experiences with faces during development.

Objective: Although schizophrenia is generally regarded as an illness with onset in late adolescence or early adult life, a sizeable minority of patients first become ill in middle or old age. Inconsistencies in diagnostic systems and nomenclature, coupled with a tendency among most schizophrenia researchers to ascribe late-onset psychoses to organic factors, have led to such cases occupying an ambiguous position in relation to schizophrenia. Through systematic review of the literature and publication of a consensus statement from an international group of experts in the field, this article aims to clarify the positions of late-onset schizophrenia and very-late-onset schizophrenia-like psychosis. Method: The authors conducted a MEDLINE literature review and developed a consensus statement summarizing the findings from 2 days of debate and discussion by members of the International Late-Onset Schizophrenia Group. Results: The group achieved consensus on diagnosis, nomenclature, treatment guidelines, and future research directions. Conclusions: In terms of epidemiology, symptom profile, and identified pathophysiologies, the diagnoses of late-onset schizophrenia (illness onset after 40 years of age) and very-late-onset schizophrenia-like psychosis (onset after 60 years) have face validity and clinical utility. General adoption of these categories will foster systematic investigation of such patients.

Objective: The authors investigated whether striatal dopamine [D.sub.2] receptor binding characteristics in vivo are similar in men and women and whether there are sex-related differences in the decline in [D.sub.2] receptor density due to aging. Method: Striatal [D.sub.2] receptor density ([B.sub.max]), affinity ([K.sub.d]), and binding potential ([B.sub.max]/[K.sub.d]) were measured with positron emission tomography and [11C]raclopride in 54 healthy subjects (33 men and 21 women). Results: Women had generally lower [D.sub.2] receptor affinity than men, and this difference was statistically significant in the left striatum. [B.sub.max] and [B.sub.max]/[K.sub.d] tended to decline with age twice as fast in men as in women, but the difference did not reach statistical significance. Conclusions: These results confirm the age-related reduction of [D.sub.2] receptor density and binding potential in both sexes in vivo. The lower [D.sub.2] receptor affinity suggests an increased endogenous striatal dopamine concentration in women. This may have implications for the differential vulnerability of men and women to psychiatric disorders like schizophrenia and alcohol and substance dependence.

Objective: The view of schizophrenic men as having poorer premorbid development, earlier age at onset, and worse outcome than schizophrenic women predicts greater neuropsychological impairment in the former than the latter. The authors examined in detail neuropsychological functioning in a large group of schizophrenic patients and a healthy comparison group. Method: Neuropsychological functioning in 132 male and 63 female patients with schizophrenia or schizoaffective disorder was extensively studied and compared with that of 99 (40 male, 59 female) healthy individuals. Results: As expected, the schizophrenic patients as a group were pervasively and significantly more impaired than the comparison group. Within schizophrenia, in contrast to the prediction, women performed significantly more poorly than men in verbal memory, spatial memory, and visual processing. Female schizophrenic patients also had significantly poorer right than left hemisphere performance, whereas male schizophrenic patients had identical scores for right and left hemisphere impairment. Conclusions: The findings are consistent with the hypothesis that schizophrenia among women may be partially understood as a right hemisphere dysfunction. Sampling, diagnostic, and epidemiologic factors may have affected the results.

Objective: This study was undertaken to determine whether the incidence of schizophrenia is equivalent for males and females. Method: An attempt was made to identify every first-episode case of psychosis in a large Canadian city over a period of 2 1/2 years. A comprehensive referral network was established that included hospital and community settings where psychotic persons might appear. More than 300 potential subjects were identified, 175 of whom underwent a structured psychiatric interview and were assigned diagnoses according to five different diagnostic systems. Results: The incidence of schizophrenia was two to three times higher among males than among females. Even though the use of different diagnostic systems yielded slightly different risk rates, the elevated risk for males remained consistent. There were no differences between the sexes in the incidence of affective psychosis. In comparison with schizophrenia, the incidence rates for mood disorders with psychotic features were sometimes lower and sometimes higher, depending on the diagnostic system used. Conclusions: The findings, coupled with reports in the past 10 years from other investigators, challenge the conventional belief that the incidence of schizophrenia is the same for the two sexes. (Am J Psychiatry 1992; 149:1070-1074)

Although schizophrenia is a mental illness that affects both men and women, it has long been known that there are gender-related differences in this disease. Previous studies have provided evidence that women schizophrenics respond better to psychotropic drugs and have a better prognosis than schizophrenic men. Also, onset of disease is typically earlier in men than in women. Other studies indicate that the range and extent of schizophrenic symptoms also differ by gender. Morphological abnormalities of the brain have been associated with schizophrenia, and gender differences in this area have been suggested also. Specifically, lateral ventricle size has been reported to be larger than normal in schizophrenic patients. Most studies of brain differences have not considered sex factors. This study reported on the results of brain imaging studies of lateral ventricle size in schizophrenic patients using computerized tomography and magnetic resonance imaging, which were used to determine a ventricle-brain ratio. Two previously reported studies were examined, along with the results of two additional studies that evaluated male and female schizophrenics and control subjects (individuals undergoing imaging examinations for other than psychiatric reasons, and who had prior scan results that were normal). The total number of subjects in all studies considered was about 200 patients and 200 controls. No differences in ventricle size were found between female schizophrenics and female control subjects. Although no differences were noted among any of the female subjects, in three of the four studies reported, male schizophrenics had larger ventricles than the male control subjects. Implications of the data are discussed. These results may be useful in categorizing subtypes of schizophrenia; correlations with enlarged ventricles and other mental disorders may also be possible. (Consumer Summary produced by Reliance Medical Information, Inc.)

Clinical symptoms of adult-onset schizophrenia are believed to begin between the ages of 20 and 25 years. But because research reveals that genetic factors and brain abnormalities are involved in schizophrenia, it makes sense that the pathology is at work at a much earlier age. Since data collected retrospectively have been shown to be inconsistent and unreliable, it is difficult to identify early developmental predictors of schizophrenia. Follow-back studies using school records and teachers' comments show that the first behavioral distinguishing point is adolescence, when pre-schizophrenic subjects have a greater incidence of behavioral problems. Schizophrenic subjects also showed significant deficits in test scores as far back as first grade. Using home movies to look for distinguishing factors between pre-schizophrenic children and their healthy siblings provides a unique opportunity. Home movies of five schizophrenic patients and their healthy siblings from birth to eight years of age were viewed by 13 graduate psychology students and six experienced clinicians. The viewers did not know the psychiatric status of any of the children, but were told that one child in each family later became schizophrenic. They were asked to identify which child they thought this was by using their own criteria, and to comment on which characteristics entered into their decisions. The viewers were also asked to rate their confidence in their judgment on a 4-point scale of no confidence to very confident. There was no significant relationship between accuracy and this confidence rating, or the experience of the viewer. In a preliminary study using the films of one of the schizophrenics and his siblings, five out of seven graduate psychology students correctly selected the patient, even though the parents had said that they had detected no signs of impending disorder until the patient was 22 years of age, and out of all their children he was the one they would have least expected to develop a problem. All the viewers had commented that they perceived this child to manifest abnormal emotional expressions and movements. All pre-schizophrenic children were identified at above-chance levels, and the viewers noted less responsiveness, eye contact, and positive expression, and poorer fine and gross motor coordination as identifying characteristics. It is suggested that these observable manifestations which helped make the correct selection may not be specific for schizophrenia, but may be signs of vulnerability that increase the risk for a variety of disorders. (Consumer Summary produced by Reliance Medical Information, Inc.)

Autism, a developmental disorder, and schizophrenia are not generally thought to be related, but there is some evidence to suggest that those with autism are at higher risk of developing schizophrenia later in life. The conditions may therefore be related, calling into question the differentiation maintained by the Diagnostic and Statistical Manual of Mental Disorder, third Edition, revised (DSM-III-R), which is a major diagnostic aid for clinicians and researchers. To evaluate the likelihood of a relationship between autism and schizophrenia, case records of 163 adolescents and adults, all with a history of autism, were reviewed for history of schizophrenia. Only one patient (0.6 percent) had a definitive history of schizophrenia, which is similar to the frequency at which this condition is seen in the general population. The authors discuss limitations, such as the size, and the potential biases of the study. However, based on the data, no evidence of a relationship between autism and schizophrenia was found. It is concluded that current diagnostic conventions are not in need of re-evaluation. (Consumer Summary produced by Reliance Medical Information, Inc.)

When speaking of the symptomatology of mental illness, a distinction is made between what are termed positive symptoms, such as delusions and hallucinations, and negative symptoms, such as emotional deficits and thought disorders. In studying social dysfunction among schizophrenics, opinions differ as to whether its roots lie in negative, positive, or a mixture of both types of symptoms. To further clarify this issue, 151 schizophrenic subjects and their twins were analyzed for the presence of negative and positive symptoms. Significant differences between positive and negative symptoms were not found between male and female schizophrenic subjects. Schizophrenic men had significantly more social problems both before and after onset of their illness than schizophrenic women. Because this was not associated with more negative symptoms, it suggests that disordered social relationships result from separate functional processes in the development of schizophrenia. Based on these findings, the authors suggest that social functioning in schizophrenics should be examined separately from negative symptoms, and not simply included as one component of negative symptomatology. (Consumer Summary produced by Reliance Medical Information, Inc.)

Symptoms of schizophrenia include delusions, hallucinations, and thought disorders. In late-onset schizophrenia, initial symptoms occur any time after the age of 45. Most early-onset schizophrenia starts between age 20 and 40. Risk factors for this disorder include genetic predisposition (family history), sensory impairment, and social isolation. The medical records were reviewed of three groups of psychiatric inpatients in an East Baltimore clinic, namely young early-onset schizophrenics, elderly early-onset schizophrenics and late-onset schizophrenics. Approximately 80 percent of the subjects were women, possibly suggesting that male patients were less likely to seek treatment. Fifty percent of the late-onset patients were living alone at onset of illness, compared to none in the other elderly group. Thought disorder and loss of affect, or feeling, were less prevalent in the late-onset group. Occurrence of these symptoms decreased with increasing age of onset. The two older groups more frequently experienced hallucinations than the younger group. The late-onset group experienced more types of hallucinations than the early-onset groups. Both older groups had more delusions, but the late-onset group again had more. Visual and hearing impairments were more common in the late-onset elderly group than the other elderly group. A diagnosis of schizoid premorbid personality was assigned to 63 percent of the late-onset group, 50 percent of the elderly early-onset group, and almost 28 percent of the younger group. Almost half of the late-onset group responded with complete remission to antipsychotic drug therapy, and approximately 25 percent responded either partially or not at all. Thought disorder and schizoid premorbid personality criteria were noted to predict poor response to treatment with antipsychotic drugs, and family and gender had no effect on treatment outcome. These results confirm a relationship between social isolation and late-onset schizophrenia, but whether it is a symptom or cause is not clear. There is a trend in the United States to ignore the same symptoms in an older patient which would be sufficient for a diagnosis of schizophrenia in a young person. These results show more similarities in onset groups and accent optimistic expectations for therapy.

An earlier study by the authors indicated that olfactory (sense of smell) function in schizophrenic patients was reduced. The ability to identify specific smells was found to be lacking in the study group. However, female subjects did not seem to have this impairment. This observation led to the current study which consisted of 41 schizophrenic patients (15 women and 26 men) being treated with antipsychotic drugs and 43 normal control subjects (20 women and 23 men). These four groups were given the Pennsylvania Smell Identification Test to measure their ability to distinguish different odors. Both acuity of smell, or sensitivity, as well as ability to differentiate were measured. Olfactory acuity was found to be normal in all 84 subjects and, therefore, it was concluded that the inability to distinguish smells was not a function of diminished acuity. Medication-induced olfactory impairment was also ruled out and test performance was not related to the severity of the patients' schizophrenia. The men and women in the normal control group scored comparably. The score for the female schizophrenic group was comparable to the scores of the control groups. The male schizophrenics were the exception with a lower mean score. The results suggest that the reduced ability to identify odors affects male but not female schizophrenics. Other distinctions between male and female schizophrenics have been noted, such as differing responses to neuroleptic therapy and neurological signs, different long-term social adjustment, as well as overall social skills prior to illness. Male patients often exhibit more severe symptoms of the disease. This implies that sex may very well be a critical variable in the processes involved in schizophrenia.