Somaia Mohamed

An MRI study of the basal ganglia in autism.

1. High-resolution MRI scans were obtained from 35 relatively high-functioning persons with autism and 36 healthy controls, comparable in age, gender, and IQ. 2. Volumetric measurements were obtained from manual tracing of the bilateral caudate, putamen, and globus pallidus. 3. An increased volume of the caudate nuclei was found in subjects with autism. Caudate enlargement was proportional to increased total brain volume in subjects with autism. 4. Caudate volume was associated with compulsions and rituals, difficulties with minor change, and complex motor mannerisms in autism. 5. Based on evidence of caudate abnormalities, a second MRI study was completed which replicated the finding of caudate enlargement in autism using an independent sample. 6. The caudate may be part of an abnormal distributed neural network in autism and involved in the ritualistic--repetitive behaviors of the disorder.

Cross-sectional and Longitudinal Relationships Between Insight and Attitudes Toward Medication and Clinical Outcomes in Chronic Schizophrenia

BACKGROUND We evaluated the cross-sectional and longitudinal association of measures of both insight and attitudes toward medication to outcomes that included psychopathology and community functioning. METHODS Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) was a large 18-month follow-up study pharmacotherapy of people with schizophrenia. Insight was measured using the Insight and Treatment Attitudes Questionnaire and attitudes toward medication by the Drug Attitude Inventory. Widely known scales were used to assess symptoms of schizophrenia and depression and community functioning. Medication adherence was globally assessed by the treating psychiatrist using several sources of information. Bivariate correlations and mixed model regression analyses were used to test the relationship of insight and medication attitudes to outcomes at baseline and during the follow-up period. Regression models were used to evaluate the relationship between change in insight and medication attitudes and changes outcomes. RESULTS There was a significant relationship at baseline between insight and drug attitudes and symptoms of schizophrenia and depression, as well as with community functioning. Higher levels of insight at baseline were significantly associated with lower levels of schizophrenia symptoms at follow-up while more positive medication attitudes were significantly associated with both lower symptom levels and better community functioning. Change in insight scores over time was associated with declining schizophrenia symptoms but increasing levels of depression. Change toward more positive medication attitudes was associated, independently of changes in insight, with significant decreases in psychopathology, improvement in community functioning, and greater medication compliance. CONCLUSION Greater patient understanding of their illness and more positive attitudes toward medication may improve outcomes. Educational interventions that affect these attitudes may be an important part of psychosocial rehabilitation and/or recovery-oriented services.

Relationship of Cognition and Psychopathology to Functional Impairment in Schizophrenia

OBJECTIVE This study evaluated the association of neurocognition and symptoms with measures of social and occupational functioning in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). METHOD CATIE was an 18-month study of individuals with schizophrenia. Symptoms of 1,386 patients were measured with the positive syndrome scale of the Positive and Negative Syndrome Scale (PANSS) and a PANSS negative symptom scale that eliminated items that most overlap with measures of community functioning or neurocognition. The Heinrichs-Carpenter Quality of Life Scale, which a rater completes on the basis of the patients self-report, and recent employment were used to assess community functioning. Hierarchical regression analyses and mixed models tested the association of neurocognition and symptoms with social/occupational functioning as well as changes in these measures during treatment. RESULTS Both symptoms and neurocognition were associated with quality of life in bivariate correlation analyses. Symptoms contributed more to the incremental explained variance in quality of life than did neurocognitive functioning, but both kinds of measures were significantly related to quality of life. In an analysis including only the positive syndrome scale, the increased explained variance in quality of life was about equal to that associated with neurocognition. Neurocognition and both symptom measures were independently associated with quality of life in the cross-sectional mixed-model analysis. Changes in neurocognition and both symptom measures during treatment were also significantly associated with change in the quality of life. CONCLUSIONS Both psychotic symptoms and neurocognitive deficits appear to contribute independently to decreased quality of life in schizophrenia.

Off-Label Use of Antipsychotic Medications in the Department of Veterans Affairs Health Care System

OBJECTIVE This study aimed to determine the prevalence of prescribing antipsychotics to adults without schizophrenia or bipolar disorder and to identify factors associated with such off-label use. METHODS Patients with at least one prescription for an antipsychotic medication from the Department of Veterans Affairs (VA) during fiscal year (FY) 2007 were identified in national VA administrative databases. Rates of off-label antipsychotic use were determined along with average doses. Multivariate logistic regression models identified sociodemographic and clinical characteristics associated with off-label use. RESULTS Of the 279,778 individuals in FY 2007 who received an antipsychotic medication, 168,442 (60.2%) had no record of a diagnosis for which these drugs are approved. The most common mental illness diagnoses among patients given prescriptions for antipsychotics off label were posttraumatic stress disorder (PTSD, 41.8%), minor depression (39.5%), major depression (23.4%), and anxiety disorder (20.0%). Among VA patients with mental illness other than schizophrenia or bipolar disorder, the proportion who received prescriptions for antipsychotic medications ranged from a low of 9.1% among patients with adjustment reaction; to about 20% for those with depression, dementia, or PTSD; and to a high of 40.7% among patients with other psychoses. Doses were low, with over half of patients who received off-label quetiapine, risperidone, or first-generation antipsychotics receiving doses below those recommended for schizophrenia. In logistic regression models, patients diagnosed as having other psychosis or dementia had the highest odds of receiving an antipsychotic medication off label. CONCLUSIONS Off-label use of antipsychotic medications was common. Given that these drugs are expensive, have potentially severe side effects, and have limited evidence supporting their effectiveness for off-label usage, they should be used with greater caution.

Insight in schizophrenia: Its relationship to measures of executive functions

Lack of awareness of specific symptoms among persons with schizophrenia has not been adequately studied in the context of neuropsychological function. The purpose of this study is to investigate whether poor insight as measured by the Scale to Assess Unawareness of Mental Disorder is empirically related to performance measures having a known association with executive functions in a group of individuals with chronic schizophrenia. The results showed that unawareness and misattribution of negative symptoms are significantly associated with deficits in some aspects of executive functioning even after a test of general intelligence had been partialed from the analyses. We conclude that unawareness of negative symptoms is associated with executive functioning in individuals with chronic schizophrenia. Unawareness of other symptoms (i.e., positive symptoms) may reflect dysfunction in other types of neuropsychological processes, or it may reflect motivation to deceive oneself or others.

Bipolar disorder in middle-aged and elderly adults: is age of onset important?

The literature is mixed about whether age of onset is a useful variable in explaining the heterogeneity of late-life bipolar disorder. The aim of this study was to examine the relationship of age of onset with clinical, family history, and neuropsychological functioning in middle-aged and older patients with bipolar disorder. A total of 87 outpatients with bipolar disorder with a mean age of 59 (range, 42–89) were included in this study. Age of onset was analyzed as a continuous variable and was split at age 40 years into early-onset and late-onset groups. Participants were administered measures of psychopathology, cognitive functioning, and medication usage. Few meaningful differences emerged between early-onset and late-onset groups, except that overall psychopathology was significantly lower in the late-onset group. Age of onset did not relate to differences in family history, depressive symptoms, cognitive functioning, or medication use whether used as a categorical or continuous variable. Thus, the validity of late-onset bipolar disorder as a distinct syndrome was not corroborated by this study. Interpretation of these findings is limited by the sample size, cross-sectional design, and a lack of brain imaging data. Further research on the clinical features and neurobiological aspects of late-life bipolar disorder is needed.

Pharmacologic Treatment of Posttraumatic Stress Disorder Among Privately Insured Americans

OBJECTIVE Although psychological trauma affects millions of Americans, few studies have examined treatment of posttraumatic stress disorder (PTSD) in real-world service environments. This study explored pharmacological treatment of PTSD among privately insured individuals. METHODS Data were from the MarketScan database, which compiles claims from private health insurance plans nationwide. Descriptive statistics and multivariate logistic regression were used to identify predictors of any use of a psychotropic medication and use of three medication classes: antidepressants, anxiolytics or sedative-hypnotics, and antipsychotics. RESULTS Of 860,090 adult mental health care users in 2005, only 10,636 (1.2%) had a diagnosis of PTSD. Sixty percent of PTSD patients received any psychotropic medication: 74.3% of those received antidepressants, 73.7% received anxiolytics or sedative-hypnotics, and 21.3% received antipsychotics. Greater likelihood of any medication use was associated with greater use of mental health services and with several comorbid psychiatric disorders. Having a comorbid diagnosis of an indicated disorder was the most robust predictor of use of each of the three medication classes: major depressive disorder and dysthymia were most strongly associated with antidepressant use, schizophrenia and bipolar disorder were associated with antipsychotic use, and anxiety disorders were associated with use of anxiolytics or sedative-hypnotics. CONCLUSIONS Psychotropic medications were frequently used in the treatment of PTSD among privately insured clients. Although use targeted specifically to PTSD and to comorbid disorders was common, substantial use appeared to be unrelated to diagnosis and may be targeted at specific symptoms rather than diagnosed illnesses. Further research is needed to determine symptom-specific responses to medications across diagnoses.

Insight, quality of life, and functional capacity in middle-aged and older adults with schizophrenia

The quality of life (QOL) for individuals with schizophrenia is determined by a number of factors, not limited to symptomatology. The current study examined lack of insight as one such factor that may influence subjective QOL or functional capacity. It was hypothesized that insight would significantly interact with symptom severity to influence subjective QOL. Insight was not expected to influence the relation between symptom severity and functional capacity.

Impact of second-generation antipsychotics and perphenazine on depressive symptoms in a randomized trial of treatment for chronic schizophrenia.

BACKGROUND According to the American Psychiatric Association Clinical Practice Guidelines for schizophrenia, second-generation antipsychotics may be specifically indicated for the treatment of depression in schizophrenia. We examined the impact of these medications on symptoms of depression using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), conducted between January 2001 and December 2004. METHOD Patients with DSM-IV-defined schizophrenia (N = 1,460) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of 4 second-generation drugs (olanzapine, quetiapine, risperidone, or ziprasidone) and followed for up to 18 months (phase 1). Patients with tardive dyskinesia were excluded from the randomization that included perphenazine. Depression was assessed with the Calgary Depression Scale for Schizophrenia (CDSS). Mixed models were used to evaluate group differences during treatment with the initially assigned drug. An interaction analysis evaluated differences in drug response by whether patients had a baseline score on the CDSS of ≥ 6, indicative of a current major depressive episode (MDE). RESULTS There were no significant differences between treatment groups on phase 1 analysis, although there was a significant improvement in depression across all treatments. A significant interaction was found between treatment and experiencing an MDE at baseline (P = .05), and further paired comparisons suggested that quetiapine was superior to risperidone among patients who were in an MDE at baseline (P = .0056). CONCLUSIONS We found no differences between any second-generation antipsychotic and the first-generation antipsychotic perphenazine and no support for the clinical practice recommendation, but we did detect a signal indicating a small potential difference favoring quetiapine over risperidone only in patients with an MDE at baseline.

The Relationship Between Childhood Trauma, Combat Exposure, and Posttraumatic Stress Disorder in Male Veterans

The current study investigated the effects of combat exposure, childhood trauma, and depression on posttraumatic stress disorder (PTSD) severity. Participants were 299 male veterans from the Korean War, World War II, Vietnam, and the first Gulf War who were being screened for admission to the PTSD unit. Participants were assessed with the Clinician-Administered PTSD Scale (CAPS), Combat Exposure Scale (CES), Hamilton Depression Rating Scale (HAMD), Childhood Trauma Questionnaire (CTQ), and Mississippi Scale for PTSD (MPTSD). Results of multiple regression analyses indicated that, as expected, combat exposure and depression were significant predictors of PTSD severity. When examined with combat exposure, childhood trauma has a complex relationship to PTSD severity. Examination of the interaction between the CES and CTQ suggests that when levels of combat are low and childhood trauma levels are high, the CTQ is related to higher levels of PTSD severity on the CAPS, regardless of depression. Treatment implications are discussed.