At issue: a default analysis for schizophrenia research

The concept that there are at least three clinical syndromes within schizophrenia has been influential, and the significance of these syndromes is supported by a growing number of studies. However, the meaning of these syndromes is not clear. The yield of research studies could be increased by the application of a "default" data analysis, in which the differential association--if any--of the three syndromes with the dependent variable(s) of a study is determined.     

At issue: The future of cognitive rehabilitation of schizophrenia

Cognitive rehabilitation is becoming an increasingly popular intervention in treatment programs for people with schizophrenia. Despite this increased acceptance, however, the evidence base on its effectiveness is not impressive. Moreover, given the evidence of cognitive recovery in treated patients who do not receive cognitive rehabilitation--from newer medications and from other evidence-based psychosocial interventions--it is not clear whether cognitive rehabilitation is worth its expense in time and resources. We believe that the slow progress in the field of cognitive rehabilitation of schizophrenia is related to failure to address several critical issues: (1) the importance of manipulating stimulus and context structure in rehabilitative interventions; (2) the need to base a cognitive rehabilitation of schizophrenia on cognitive neuroscience as opposed to neuropsychology; (3) the importance of systematically addressing motivation, self-esteem, and affective factors when designing cognition-enhancing interventions; (4) the need to move beyond one-size-fits-all interventions and develop individualized treatments; and (5) the need to address abnormalities in the experience of the self when designing interventions to optimize cognitive and behavioral performance. Suggestions for addressing these issues are discussed.     

At issue: schizophrenia and rheumatoid arthritis: the negative association revisited

A strong negative association between schizophrenia and rheumatoid arthritis (RA), implying low comorbidity, has been found in 12 of 14 previous studies, which we review. To this literature we add two recently acquired data sets encompassing 28,953 schizophrenia patients, only 31 of whom had comorbid RA. Integrating our new data into those of the previous nine studies, which stratified their populations according to psychiatric diagnosis, we obtain a median frequency of RA in schizophrenia populations of 0.09 percent and a mean frequency of 0.66 percent, well below the expected range of 1 percent. These data robustly support prior studies. We also present a meta-analysis evaluating the association between the two diseases by integrating information derived from nine data sets, each furnishing an estimate of the relative risk of RA in schizophrenia patients versus that in other psychiatric patients. We find that the estimated rate of RA among schizophrenia patients is only 29 percent of the corresponding rate in other psychiatric patients. Further, the relative risk of RA in schizophrenia patients versus that in the general population is even less than 29 percent and could be as low as one-third of this value. We present a new hypothesis involving the platelet activating factor system in an effort to account for this negative association and review the suggestions of other investigators toward this end. Finally, we consider the glutamatergic system dysfunction hypothesis of schizophrenia and suggest a possible common pharmacological approach that may ameliorate some of the symptomatology of both schizophrenia and RA.     

Sex, gender, and neuropsychological functioning in schizophrenia

Sex and gender represent substantially different concepts. While there are consistent sex differences reported on selected neuropsychological tasks, there is no systematic literature on comparable gender differences. We examined sex and gender effects on seven domains of neuropsychological functioning among 197 schizophrenia/schizoaffective patients and 94 healthy individuals. We found main effects of sex on two neuropsychological domains, main effects of gender on five neuropsychological domains, and no interaction effects on any of the domains. Healthy individuals performed better than individuals with schizophrenia/schizoaffective disorder. Executive functioning was unaffected by sex or gender, supporting its role as a behavioral marker of schizophrenia.     

At issue: assessment of schizophrenia: getting closer to the cause

Traditionally, the diagnosis of schizophrenia has depended on the presence of specific behavioral phenomena assessed by way of behavioral observation and patient symptomatic report. Even though the introduction of explicit diagnostic criteria and structured interviews has improved the reliability of schizophrenia diagnosis, it is still unclear how best to define schizophrenia in order to further etiologic research. This situation persists despite ample evidence that schizophrenia is a heritable brain disorder and the existence of laboratory measures that tap into this neurobiological genetic diathesis. We contend that such laboratory measures can be used to supplement traditional clinical assessment in order to improve the definition of schizophrenia, thereby enhancing research into schizophrenia's origins. Ultimately, this increased understanding of the disorder's etiology should facilitate the development of targeted therapeutic interventions.     

At issue: management of medication noncompliance in schizophrenia by families in India

Noncompliance with medication during a symptomatic phase is a common problem in the treatment of schizophrenia patients. In India, a majority of patients live with their families and those families supervise patients' medication intake. In a study of patients attending an urban outpatient care center in India, it was noted that when the patients were acutely ill and refused to take medication, the families administered medication to them without patients' knowledge, under the supervision of the psychiatrist. This method had been practiced by families in half the cases of patient noncompliance. Many families felt that there was no other viable alternative under the circumstances. Only a minority of patients was aware of having received medication through this method, and many of them reacted negatively to it. However, the patients were subsequently taking treatment voluntarily following the reduction in the severity of the behavioral disorder with the involuntary treatment. The issues involved in this form of treatment are discussed with regard to the social and health care environment in the country.     

Sex/gender differences in the brain and cognition in schizophrenia

The early conceptualizations of schizophrenia have noted some sex/gender differences in epidemiology and clinical expression of the disorder. Over the past few decades, the interest in differences between male and female patients has expanded to encompass brain morphology and neurocognitive function. Despite some variability and methodological shortcomings, a few patterns emerge from the available literature. Most studies of gross neuroanatomy show more enlarged ventricles and smaller frontal lobes in men than in women with schizophrenia; finding reflecting normal sexual dimorphism. In comparison, studies of brain asymmetry and specific corticolimbic structures, suggest a disturbance in normal sexual dimorphism. The neurocognitive findings are somewhat consistent with this picture. Studies of cognitive functions mediated by the lateral frontal network tend to show sex differences in patients which are in the same direction as those observed in the general population, whereas studies of processes mediated by the corticolimbic system more frequently reveal reversal of normal sexual dimorphisms. These trends are faint and future research would need to delineate neurocognitive differences between men and women with various subtypes of schizophrenia (e.g., early versus late onset), while taking into consideration hormonal status and gender of tested participants.     

At issue: siblings of patients with schizophrenia: sibling bond, coping patterns, and fear of possible schizophrenia heredity

Siblings of schizophrenia patients are from the patient's perspective important support providers, but most studies on family burden have focused on the parental role. This study aims to develop a detailed analysis of the psychological aspects of having a sibling with schizophrenia. We did a qualitative study with audiotaped semistructured interviews of 16 siblings. The reliability of the inductive categorization of data was high. A unifying theme appeared to be an emotional sibling bond characterized by feelings of love, sorrow, anger, envy, guilt, and shame. The major categories linked to coping with the situation were avoidance, isolation, normalization, caregiving, and grieving. A third major theme consisted of a fear of possible schizophrenia heredity. The siblings described concerns about the impact of a family history of psychiatric illness, a fear of becoming mentally ill, and reflections about "bad genes." Our findings support earlier findings of coping patterns but complement them by providing a model that includes awareness of genetic vulnerability as an important part of siblings' subjective burden.     

Age-at-onset and schizophrenia: reversed gender effect

OBJECTIVE: This study seeks an explanation for reversed gender effect on age-at-onset (AAO) in schizophrenia. The hypothesis is older AAO in males would be detected in a sample where higher infant mortality (IMR) prevailed. METHOD: Case records of International Classification of Diseases-10 (ICD-10) schizophrenia patients from two states (n=70 each) with an IMR of 13 and 67 per thousand were reviewed and AAO was obtained by using the recorded age and duration of illness. RESULTS: In the sample from the state with lower IMR, AAO did not differ between the two sexes. However, men had older AAO than women in the state with fivefold higher IMR. CONCLUSION: Gender differences in AAO may be a function of perinatal complications. In places where infants with perinatal complications are less likely to survive, hence high IMR, a small group of potentially youngest AAO schizophrenic males may be eliminated thus changing the gender effect on AAO.     

Sex differences in schizophrenia

Evidence suggests sex differences in schizophrenia reflect differences in both neurodevelopmental processes and social effects on disease risk and course. Male:female incidence approximates 1.4:1 but at older onset women predominate. Prevalence differences appear smaller. Men have poorer premorbid adjustment and present with worse negative and less depressive symptoms than women, which may explain their worse medium term outcome according to a range of measures. Substance abuse is a predominantly male activity in this group, as elsewhere. Findings of sex differences in brain morphology are inconsistent but occur in areas that normally show sexual dimorphism, implying that the same factors are important drivers of sex differences in both normal neurodevelopmental processes and those associated with schizophrenia. There are sex differences in antipsychotic responses but sex-specific endocrine effects on illness and response to antipsychotics are potentially complex. Oestrogen's role as an adjunctive medication is not yet clear due to methodological differences between the few randomized controlled trials. Services that are sensitive to differences in gender can better meet their patients’ specific needs and potentially improve outcome.     

Sex differences in schizophrenia

Evidence suggests sex differences in schizophrenia reflect differences in both neurodevelopmental processes and social effects on disease risk and course. Male:female incidence approximates 1.4:1 but at older onset women predominate. Prevalence differences appear smaller. Men have poorer premorbid adjustment and present with worse negative and less depressive symptoms than women, which may explain their worse medium term outcome according to a range of measures. Substance abuse is a predominantly male activity in this group, as elsewhere. Findings of sex differences in brain morphology are inconsistent but occur in areas that normally show sexual dimorphism, implying that the same factors are important drivers of sex differences in both normal neurodevelopmental processes and those associated with schizophrenia. There are sex differences in antipsychotic responses but sex-specific endocrine effects on illness and response to antipsychotics are potentially complex. Oestrogen's role as an adjunctive medication is not yet clear due to methodological differences between the few randomized controlled trials. Services that are sensitive to differences in gender can better meet their patients' specific needs and potentially improve outcome.     

Sex differences in schizophrenia

Demographic and clinical characteristics of 275 schizophrenics consecutively admitted to seven hospitals were examined. Males were younger than females when first hospitalized, diagnosed and treated. Psychiatrists rated on two rating scales by using a structured interview to compare the symptomatology. Female schizophrenics were more agitated, inappropriate, silly, irrelevant, over-talkative, and exhibiting more flight of ideas, while male schizophrenics were more slowed, hypoactive, grandiose, withdrawn, and showing more blocking, auditory hallucinations and poor communications. Katz Adjustment Scales were rated by the patients and their relatives. Female schizophrenics were perceived by relatives to be more helpless and withdrawn-depressed than male schizophrenics.     

Sex differences in schizophrenia: A review

During the past decade schizophrenia research has emphasized the importance of sex differences. Most studies have found that lifetime risk of schizophrenia has been equally common in both sexes. Men develop schizophrenia 3-4 years earlier than women, regardless of culture, but late-onset schizophrenia has been found to be commoner in women. Women more often have a favorable course of schizophrenia than men: they experience fewer and shorter hospitalizations, survive longer in the community, and also have better social functioning. Men more often have chronic and more severe forms of schizophrenia, they have negative symptoms more often, and their doses of neuroleptic medication are higher. Men with schizophrenia tend to have more central nervous system abnormalities than women. In the future it is important to study factors that have been observed in sex differences, heredity, and brain physiology as they relate to schizophrenia. Sex differences as they relate to treatment programs are important both from a scientific perspective and from a practical point of view.     

Living with schizophrenia in India: gender perspectives

This study explores gender issues from a sociocultural perspective related to stigma among people suffering from schizophrenia in India. Stigma experiences were assessed by conducting semistructured interviews with 200 patients attending urban or rural psychiatry clinics. The resulting narratives were examined by thematic content analysis. Men with schizophrenia reported being unmarried, hid their illness in job applications and from others, and experienced ridicule and shame. They reported that their experience of stigma was most acute at their places of employment. Women reported experiences of stigma in relation to marriage, pregnancy, and childbirth. Both men and women revealed specific cultural myths about their illnesses and described how these had negatively affected their lives. Information gathered from this study can be useful to understand the needs of individuals who suffer from schizophrenia to improve the quality of their treatment, and plan culturally appropriate interventions to counter stigma and discrimination.     

Insular volumes in first-episode schizophrenia: gender effect

Insula is a multimodal sensory integration region that acts as a gateway between somatosensory areas and limbic structures such as amygdala. Only a handful of region of interest (ROI) studies have suggested insular volume reduction in patients with schizophrenia but none have documented a gender effect on the volume of this structure. The authors used magnetic resonance images to measure insular volumes in previously untreated patients with first-episode schizophrenia (N=30) relative to those of healthy comparison subjects (N=30). Correlations with symptom severity were carried out. Intracranial volume was used as a covariate in the analysis. Female patients (N=15) had significantly reduced right insular volume relative to healthy female comparison subjects (p<0.05). On preliminary analysis, the right and left insular volumes in female patients had significant negative correlations with the positive symptoms scores (p<0.05), but not on correcting for multiple comparisons. Insula is developmentally and phylogenetically a watershed region where the more primitive allocortex transitions into the more developed isocortex. Thus its role as a substrate of neurodevelopmental hypothesis in schizophrenia and the interplay with gender deserves more attention.