Substance misuse in patients with schizophrenia: epidemiology and management

Substance misuse in individuals with schizophrenia is very common, especially in young men, in communities where use is frequent and in people receiving inpatient treatment. Problematic use occurs at very low intake levels, so that most affected people are not physically dependent (with the exception of nicotine). People with schizophrenia and substance misuse have poorer symptomatic and functional outcomes than those with schizophrenia alone. Unless there is routine screening, substance misuse is often missed in assessments. Service systems tend to be separated, with poor inter-communication, and affected patients are often excluded from services because of their comorbidity. However, effective management of these disorders requires a fully integrated approach because of the close inter-relationship of the disorders. Use of atypical antipsychotics may be especially important in this population because of growing evidence (especially on clozapine and risperidone) that nicotine smoking, alcohol misuse and possibly some other substance misuse is reduced. Several pharmacotherapies for substance misuse can be used safely in people with schizophrenia, but the evidence base is small and guidelines for their use are necessarily derived from experience in the general population.

Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetine

Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat encoding an extended polyglutamine tract in the huntingtin protein. Affected individuals display progressive motor, cognitive and psychiatric symptoms (including depression), leading to terminal decline. Given that transgenic HD mice have decreased hippocampal cell proliferation and that a deficit in neurogenesis has been postulated as an underlying cause of depression, we hypothesized that decreased hippocampal neurogenesis contributes to depressive symptoms and cognitive decline in HD. Fluoxetine, a serotonin-reuptake inhibitor commonly prescribed for the treatment of depression, is known to increase neurogenesis in the dentate gyrus of wild-type mouse hippocampus. Here we show that hippocampal-dependent cognitive and depressive-like behavioural symptoms occur in HD mice, and that the administration of fluoxetine produces a marked improvement in these deficits. Furthermore, fluoxetine was found to rescue deficits of neurogenesis and volume loss in the dentate gyrus of HD mice.

Carbamyl phosphate synthase deficiency: Diagnosed during pregnancy in a 41-year-old

Carbamyl phosphate synthase deficiency (CPS) is a rare urea cycle defect. We present a case of a 41-year-old woman diagnosed with CPS deficiency during pregnancy. She is the oldest CPS-deficient patient, at diagnosis, reported to date and the first to be diagnosed during pregnancy. This case highlights the need for consideration of inborn errors of metabolism in adults presenting with unusual neurological and psychiatric conditions. Crown Copyright (c) 2006 Published by Elsevier Ltd. All rights reserved.

Review of "Comorbidity, disability and the need for treatment for DSM-IV psychiatric disorders in an insured population"

Background: This study presents estimates of 12 month and current prevalences of DSM-IV disorders, and the related comor-bidity, disability and service utilization, derived from a national probability sample in Australia. Methods: The DSM-IV psychiatric disorders among persons aged 18 and over in the Australian population were assessed with data collected by lay interviewers using the Composite International Diagnostic Interview, other screening interviews and measures of disability and service utilization. The response rate was 78.1% and the final sample size was 10,641 adults. Results: Close to 20% reported at least one twelve month disorder and 13% a disorder current within the past 30 days. ICD-10 diagnoses were also derived, DSM-IV was the more conservative classification whether or not the new clinical significance criteria was applied. Major depression, any personality disorder, and alcohol dependence were the three most common twelve month disorders, generalized anxiety disorder replaced alcohol dependence as the third most common current disorder. The sexes has similar rates of any disorder, but women had higher rates of affective and anxiety disorders, men higher rates of substance use disorders. Prevalence of most disorders declined with age and education, and were lower among those employed or married. Respondents whose symptoms met criteria for three or more disorders in the past year had greatly increased rates of disability and of mental health consultations. The affective and somatoform disorders were associated with the highest rates of disability. Only 36% of people with a mental disorder this year had consulted for a mental problem, and most had seen a general practitioner. We identified those with a current disorder who were disabled or multiply comorbid - only half had consulted and of those who had not, more than half said they did not need treatment. Conclusions: The 12 month prevalence was lower than reported in the US National Comorbidity Survey but method factors might account for this. The relationships between prevalence and demographic variables, and between comorbidity, disability and service utilization were similar to those found in the US survey. Australia has a national health insurance scheme with total coverage and access to medical help is available to all, commonly at little or no cost. We identify the high rate of not consulting among those with a current disorder, and additional disability or multiple comorbidity, as an important public health problem. Kessler argued for more research on barriers to professional help seeking. This report reinforces his conclusion and shows that economic barriers are not the dominant issue.

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a cross-sectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.

GABAA receptor β3 subunit gene and psychiatric morbidity in a post-traumatic stress disorder population

GABAergic systems have been implicated in the pathogenesis of anxiety, depression and insomnia. These symptoms are part of the core and comorbid psychiatric disturbances in post-traumatic stress disorder (PTSD) In a sample of Caucasian male PTSD patients, dinucleotide repeat polymorphisms of the GABAA receptor beta3 subunit gene were compared to scores on the General Health Questionnaire-28 (GHQ). As the major allele at this gene locus (GABRB3) was GI, the alleles were divided into GI and non-GI groups. On the total score of the GHQ, which comprises the somatic symptoms, anxiety/insomnia, social dysfunction and depression subscales, patients with the GI non-GI genotype had a significantly higher score when compared to either the G1G1 genotype (alpha = 0.01) or the non-GI non-GI genotype (alpha = 0.05). No significant difference was found between the G1G1 and non-Gl non-G1 genotypes. When the GI non-G1 heterozygotes were compared to the combined G1G1 and non-GI non-GI homozygotes, a significantly higher total GHQ score was found in the heterozygotes (P = 0.002). These observations suggest a heterosis effect. Further analysis of GHQ subscale scores showed that heterozygotes compared to the combined homozygotes had higher scores on the somatic symptoms (P = 0.006), anxiety/insomnia (P = 0.003), social dysfunction (P = 0.054) and depression (P = 0.004) subscales. In conclusion, the present study indicates that in a population of PTSD patients, heterozygosity of the GABRB3 major (GI) allele confers higher levels of somatic symptoms, anxiety/insomnia, social dysfunction and depression than found in homozygosity. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Personality disorders and adult attachment dimensions in a mixed psychiatric sample: A multivariate study

The associations between personality disorders and adult attachment dimensions were assessed in a sample of 487 consecutively admitted psychiatric subjects. Canonical correlation analysis showed that two sets of moderately correlated canonical variates explained the correlations between personality disorders and adult attachment patterns. The first and second attachment variates closely resembled the avoidance and anxiety attachment dimensions, respectively. The first personality disorder variate was mainly characterized by avoidant, depressive, paranoid, and schizotypal personality disorders, whereas dependent, histrionic, and borderline personality disorders loaded on the second canonical variate. However, these linear combinations of personality disorders were different from those obtained from principal component analysis. The results extend previous studies linking personality disorders and attachment patterns and suggest the importance of focusing on specific constellations of symptoms associated with dimensions of insecurity.

Association between apolipoprotein E epsilon 4 and neuropsychiatric symptoms during interferon alpha treatment for chronic hepatitis C

Neuropsychiatric complications are common in patients with chronic hepatitis C undergoing treatment with interferon alpha. These side effects include alterations of mood, cognition, and neuroendocrine function and are unpredictable. In a number of neurological disorders characterized by neuropsychiatric symptoms and cognitive dysfunction, inheritance of an apolipoprotein E (APOE) epsilon4 allele is associated with adverse neuropsychiatric outcomes. The authors present evidence that the APOE genotype may influence a patient's neuropsychiatric response to interferon alpha treatment. The inheritance of APOE genotypes was examined in 110 patients with chronic hepatitis C treated with interferon alpha. A retrospective investigation was conducted by assessing the rates of psychiatric referral and neuropsychiatric symptoms experienced during treatment along with other complaints indicating psychological distress. A highly statistically significant association was seen between APOE genotypes and interferon-induced neuropsychiatric symptoms. Patients with an epsilon4 allele were more likely to be referred to a psychiatrist and had more neuropsychiatric symptoms during antiviral treatment than those without an epsilon4 allele. Additionally, patients with an epsilon4 allele were more likely to experience irritability or anger and anxiety or other mood symptoms. These data demonstrate that an individual's APOE genotype may influence the neuropsychiatric response to antiviral therapy with interferon alpha. Prospective studies evaluating the importance of APOE in susceptibility to interferon alpha-induced neuropsychiatric complications are needed. Moreover, pathways involving APOE should be considered in understanding the pathophysiology of interferon alpha-induced neuropsychiatric complications.

Sex Differences in Symptoms of Depression in Unrelated Individuals and Opposite-Sex Twin and Sibling Pairs

Diagnosis of a major depressive episode by the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association requires 5 out of 9 symptoms to be present. Therefore, individuals may differ in the specific symptoms they experience and reach a diagnosis of depression via different pathways. It has been suggested that depressed women more often report symptoms of sleep disturbance, appetite or weight disturbance, fatigue, feelings of guilt/worthlessness and psychomotor retardation than depressed men. In the current study, we investigate whether depressed men and women differ in the symptoms they report. Two samples were selected from a sample of Dutch and Australian twins and siblings. First, Dutch and Australian unrelated depressed individuals were selected. Second, a matched epidemiological sample was created consisting of opposite-sex twin and sibling pairs in which both members were depressed. No sex differences in prevalence rates for symptoms were found, with the exception of decreased weight in women in the sample of unrelated individuals. In general, the similarities in symptoms seem to far outweigh the differences in symptoms between men and women. This signifies that men and women are alike in their symptom profiles for major depression and genes for depression are probably expressed in the same way in the two sexes.

Review of diagnostic screening instruments for alcohol and other drug use and other psychiatric disorders

In recent years there has been a growing recognition that many people with drug or alcohol problems are also experiencing a range of other psychiatric and psychological problems. The presence of concurrent psychiatric or psychological problems is likely to impact on the success of treatment services. These problems vary greatly, from undetected major psychiatric illnesses that meet internationally accepted diagnostic criteria such as those outlined in the Diagnostic and Statistical Manual (DSM-IV) of the American Psychiatric Association (1994), to less defined feelings of low mood and anxiety that do not meet diagnostic criteria but nevertheless impact on an individual’s sense of wellbeing and affect their quality of life.

Neuroleptic management of schizophrenia: A survey and commentary on Australian psychiatric practice

Objective: We seek to assess Australian psychiatrists' views and practices concerning provision of neuroleptic medication to patients with schizophrenia, and to determine whether such management strategies are likely to have changed over time and the extent to which they correspond to published treatment guidelines. Method: A sample of 139 psychiatrists based in three Australian capital cities was derived, with respondents completing a brief questionnaire by choosing from a limited-option answer set. Co-authors of this paper comment on the extent to which responses are in line with contemporary recommendations driven by experts or empirical studies. Results: Overall, survey findings indicate that there has been considerable change in clinical practice over the last decade and provide some estimate of the extent to which Australian management practices are congruent with contemporary recommendations. We identify a number of issues of concern (more in relation to dose levels of neuroleptic medication rather than treatment duration) revealed by survey data and make recommendations for addressing a number of practical clinical issues. Conclusions: As this report focuses on central issues involved in managing schizophrenia, and integrates a number of treatment guidelines, we suggest that it should be of assistance for practice review by clinicians.

Neuroplasticity and psychiatry

Objective: There is increasing concern that the course of psychiatric disorders may be affected by parameters such as the duration and intensity of symptoms of initial episodes of illness. As this indicates that abnormal function produces long-term changes within the brain, a review of the neuroscience literature regarding neuroplasticity is warranted. Method: This article is a selective review, focusing in particular on results obtained from physiological experiments assessing plasticity within the mammalian neocortex. The possible relevance of results to psychiatry is discussed. Results: While the most dramatic examples of neuroplasticity occur during a critical period of neural development, neuroplasticity can also occur in adult neocortex. Neuroplasticity appears to be activity-dependent: synaptic pathways that are intensively used may become strengthened, and conversely, there may be depression of transmission in infrequently used pathways. Conclusions: Results from neurophysiological experiments fend support to the clinical observation that the intensity and duration of a psychiatric disorder may adversely alter its long-term course. Rapid aggressive treatment may prevent this from occurring. While pharmacotherapy may reduce the duration and severity of symptoms, it may also have an independent, as yet unknown, effect on neuroplasticity.

Sudden death in psychiatric patients

Background The present study investigated histories of prior psychiatric treatment in cases of sudden death reported to the coroner Methods A matching survey linked the register of deaths reported to the coroner with a comprehensive statewide psychiatric case register covering both inpatient and community-based services. Results Sudden death was five times higher in people with histories of psychiatric contact. Suicide accounted for part of this excess mortality but deaths from natural causes and accidents were also elevated. Schizophrenic and affective disorders had similar suicide rates. Comorbid substance misuse doubled the risk of sudden death in affective and schizophrenic disorders. Conclusions The rates of sudden death are sufficiently elevated to raise questions about current priorities in mental health care. There is a need both for greater attention to suicide risk, most notably among young people with schizophrenia, to the early detection of cardiovascular disorders and to the vigorous management of comorbid substance misuse.

Parental reactions to infant death: The effects of resources and coping strategies

The aim of this research was to examine, from a stress and coping perspective, the effects of resources (both personal and environmental) and coping strategies on parental reactions to infant death. One hundred and twenty-seven parents (60 fathers, 67 mothers) participated in the study. The predictors of parental distress (background factors, resources, coping methods) were initially assessed at 4-6 weeks post-loss. Parental distress (assessed using a composite measure of psychiatric disturbance, physical symptoms, and perinatal grief) was further assessed at 6 months post-loss and at 15 months postloss. After control for the stability in adjustment across time, there was consistent evidence that higher levels of education were associated with lower levels of parental distress over time. Among mothers, the number of friends in whom mothers had the confidence to confide emerged as a positive predictor of adjustment to infant death. A reliance on problem-focused coping was associated with greater maternal distress at 6 months post-loss, whereas coping by seeking support was associated with less distress at 15 months post-loss. There is no evidence that background factors and resources influenced parental distress through coping.