Background. Despite the availability of efficacious medications and psychotherapies, care of bipolar disorder in everyday practice is often deficient. This trial evaluated the effectiveness of a multi-component care management program in a population-based sample of people with bipolar disorder.

Method. Four hundred and forty-one patients treated for bipolar disorder during the prior year were randomly assigned to continued usual care or usual care plus a systematic care management program including: initial assessment and care planning, monthly telephone monitoring including brief symptom assessment and medication monitoring, feedback to and coordination with the mental health treatment team, and a structured group psychoeducational program – all provided by a nurse care manager. Blinded quarterly assessments generated week-by-week ratings of severity of depression and mania symptoms using the Longitudinal Interval Follow-Up Evaluation.

Results. Participants assigned to the intervention group had significantly lower mean mania ratings averaged across the 12-month follow-up period (Z=2·44, p=0·015) and approximately one-third less time in hypomanic or manic episode (2·59 weeks v. 1·69 weeks). Mean depression ratings across the entire follow-up period did not differ significantly between the two groups, but the intervention group showed a greater decline in depression ratings over time (Z statistic for group-by-time interaction=1·98, p=0·048).

Conclusions. A systematic care program for bipolar disorder significantly reduces risk of mania over 12 months. Preliminary results suggest a growing effect on depression over time, but longer follow-up will be needed.

Background. This study examined the relationship of childhood abuse, both physical and sexual, with subsequent lifetime depressive and anxiety disorders – depression or dysthymia, post-traumatic stress disorder (PTSD), and panic or generalized anxiety disorder (GAD) – among American Indians (AIs).

Method. Three thousand and eighty-four AIs from two tribes – Southwest and Northern Plains – participated in a large-scale, community-based study. Participants were asked about traumatic events and family history, and were administered standard diagnostic measures of depressive/anxiety disorders.

Results. Prevalence of childhood physical abuse was approximately 7% for both tribes. The Southwest tribe had higher prevalence of depressive and anxiety disorders, with rates of PTSD being the highest. Childhood physical abuse was significant in bivariate models of depressive/anxiety disorders, and remained so in the multivariate models.

Conclusions. Childhood physical abuse was a significant predictor of all disorder groups for males in both tribes except for panic/GAD for the Northern Plains tribe in multivariate models; females showed a more varied pattern. Childhood sexual abuse did not significantly differ for males and females, and was an independent predictor of PTSD for both tribes, controlling for childhood physical abuse and other factors, and was significant for the other disorder groups only in the Southwest. Additional covariates that increased the odds of depressive/anxiety disorders were adult physical or sexual victimization, chronic illness, lifetime alcohol or drug disorder, and parental problems with depression, alcohol, or violence. Results provided empirical evidence of childhood and later life risk factors and expanded the population at risk to include males.

Background. The latent structure of depression was examined using taxometric analysis, a family of statistical procedures designed specifically to test whether a given construct is best conceptualized as a distinct category or a continuous dimension.

Method. Data were derived from the Australian National Survey of Mental Health and Well-Being, a large epidemiological survey that measured the prevalence of the major DSM-IV and ICD-10 mental disorders. Two taxometric procedures, maximum covariance (MAXCOV) and mean above minus below a cut (MAMBAC), were carried out on a sample of 1933 community volunteers. Simulated categorical and dimensional datasets aided in the interpretation of the research data.

Results. The results of the taxometric analyses in the subsample who endorsed at least one symptom of depression were consistent with a dimensional latent structure of depression.

Conclusions. The findings of the current study suggest that depression, as measured in this subsample, is best conceptualized, measured and classified as a continuously distributed syndrome rather than as a discrete diagnostic entity. Incorporation of dimensional measurement into psychiatric classification systems remains a challenge for the future.

Background. Mental health status may be closely related to an instability of intentions toward a premature death, but little is known about such instability following an explicit request for euthanasia or physician-assisted suicide (EAS) and patient characteristics associated with a change of mind.

Method. A questionnaire was sent to 6596 general practitioners in The Netherlands (response rate 60%). Of these, 1681 provided descriptions of the most recent explicit request for EAS they had received in the preceding 18 months.

Results. Symptoms of depression and anxiety were related to a change of mind, but no relationship was found with the total score of the NOSGER Mood Dimension. Multinomial regression analysis revealed that patients who changed their mind had more mental health problems and less mental clarity than those who died by EAS. They also had fewer general health problems, had less unbearable and pointless suffering (according to the physician), were less concerned about loss of dignity and alternative treatment options were more frequently available. A further analysis revealed that mental health problems were more prevalent among patients whose requests were refused than among those who changed their mind. The physicians' evaluations of the reasons why a patient requested EAS were similar to a more objective measure of the patient characteristics.

Conclusions. These findings suggest that mental health status must be carefully assessed, and possible instability of desire must be taken into account in the course of a request for EAS. These results require replication, and future studies should adopt a prospective method.

Background. Autism is a neurodevelopmental disorder with an estimated genetic origin of 90%. Previous studies have reported an increase in brain volume of approximately 5% in autistic subjects, especially in children. If this increase in brain volume is genetically determined, biological parents of autistic probands might be expected to show brain enlargement, or at least intracranial enlargement, as well. Identifying structural brain abnormalities under genetic control is of particular importance as these could represent endophenotypes of autism.

Method. Using quantitative anatomic brain magnetic resonance imaging, volumes of intracranial, total brain, frontal, parietal, temporal and occipital lobe, cerebral and cortical gray and white matter, cerebellum, lateral ventricle, and third ventricle were measured in biological, non-affected parents of autistic probands (19 couples) and in healthy, closely matched control subjects (20 couples).

Results. No significant differences were found between the parents of the autistic probands and healthy control couples in any of the brain volumes. Adding gender as a factor in a second analysis did not reveal a significant interaction effect of gender by group.

Conclusions. The present sample of biological, non-affected parents of autistic probands did not show brain enlargements. As the intracranium is not enlarged, it is unlikely that the brain volumes of the parents of autistic probands have originally been enlarged and have been normalized. Thus, increased brain volume in autism might be caused by the interaction of paternal and maternal genes, possibly with an additional effect of environmental factors, or increased brain volumes might reflect phenotypes of autism.

Background. Little research has examined genetic and environmental contributions to psychopathic personality traits. Additionally, no studies have examined etiological connections between psychopathic traits and the broad psychopathological domains of internalizing (mood and anxiety) and externalizing (antisocial behavior, substance abuse). The current study was designed to fill these gaps in the literature.

Method. Participants were 626 pairs of 17-year-old male and female twins from the community. Psychopathic traits were indexed using scores on the Multidimensional Personality Questionnaire (MPQ). Symptoms of internalizing and externalizing psychopathology were obtained via structured clinical interviews. Structural equation modeling was used to estimate genetic and environmental influences on psychopathic personality traits as well as the degree of genetic overlap between these traits and composites of internalizing and externalizing.

Results. Twin analyses revealed significant genetic influence on distinct psychopathic traits (Fearless Dominance and Impulsive Antisociality). Moreover, Fearless Dominance was associated with reduced genetic risk for internalizing psychopathology, and Impulsive Antisociality was associated with increased genetic risk for externalizing psychopathology.

Conclusions. These results indicate that different psychopathic traits as measured by the MPQ show distinct genetically based relations with broad dimensions of DSM psychopathology.

Background. A limited number of studies have examined neuropsychological functioning in the family members of ADHD youth, and none have focused exclusively on relatives of females.

Method. Structured diagnostic interviews and neuropsychological batteries were administered to parents and siblings enrolled in a family study of girls with and without ADHD. Relatives were stratified into three groups: relatives of DSM-IV ADHD probands with ADHD (n=106), relatives of ADHD probands without ADHD (n=189) and relatives of controls without ADHD (n=243). Analyses were also conducted on a subgroup of families in which more than one member had ADHD.

Results. The neuropsychological battery as a whole distinguished affected and unaffected ADHD relatives from controls. The Wechsler Oral Arithmetic subtest, the Stroop Word, Color and Color-Word subscales were impaired in affected ADHD relatives, as were the WRAT-R Arithmetic and Reading subtests. Only the Stroop Color-Word and Interference subtests and the WRAT-R Arithmetic subtest showed significant impairments in unaffected relatives. In multiplex families, additional impairments were found in unaffected relatives on the Stroop Color subtest and the Wechsler Oral Arithmetic subtest. Analyses based on DSM-III-R diagnoses produced nearly identical results. Minor differences emerged across relatives of probands with different DSM-IV subtypes.

Conclusions. Data were consistent with our previous study of relatives of boys with ADHD. Neuropsychological impairments in relatives of female ADHD probands were primarily associated with the diagnosis of ADHD, but subtle cognitive impairments that index familial vulnerability to the disorder may exist.

Background. The frequency and clinical, neuropsychological and neuroimaging correlates of apathy in patients who have had a stroke are inadequately defined.

Method. A total of 167 consecutive patients admitted to the stroke units of two university hospitals after an ischaemic stroke and 109 controls received extensive medical, psychiatric and neuropsychological assessments; a subset received a magnetic resonance imaging (MRI) scan. The groups were matched for sex and age. Patients were assessed 3–6 months after their stroke. The sample for this study comprised 135 patients and 92 controls who completed the Apathy Evaluation Scale (AES).

Results. Apathy was present in 26·7% of stroke patients compared to 5·4% of controls. Apathetic stroke patients were older, more functionally dependent and had lower Mini-Mental State Examination (MMSE) scores than those without apathy. Apathy was not associated with risk factors for cerebrovascular disease or stroke severity. There was a weak but significant correlation between apathy and self-reported depression but not with clinician-rated depression. Neuropsychologically, after correction for age, premorbid intelligence (IQ) and depression, apathy was associated with reduced attention and speed of information processing. On neuroimaging there were trends for associations of apathy with the extent of hyperintensities in the right hemisphere and right fronto-subcortical circuit, but not with total stroke volume or number of strokes.

Conclusions. Apathy is common following a cerebrovascular event. Presence of apathy may be related to older age and right fronto-subcortical pathway pathology, rather than stroke severity. It is associated with functional impairment and cognitive deficits.

Background. This study examined the relationship between internal source monitoring and disordered speech in patients with schizophrenia or schizoaffective disorder. It was predicted that internal source monitoring would relate specifically to one type of communication disturbance, the missing information reference.

Method. Immediate, working, and internal source memory were assessed in 47 out-patients diagnosed with schizophrenia or schizoaffective disorder. Speech samples were also collected from this sample and coded for six types of communication disturbance.

Results. Of the six types of communication disturbance coded in this study, internal source monitoring indices were uniquely related to the frequency of the missing information reference. Furthermore, internal source monitoring was the only type of short-term memory process assessed in this study that was related to the missing information reference. Neither immediate nor working-memory capacity was related significantly to the frequency of this type of communication disturbance.

Conclusions. This study adds to our knowledge of the neurocognitive processes that underlie communication disturbance in the speech of patients with schizophrenia.

Background. The opportunity to study district-wide educational interventions on suicide rates is rarely available. In 1997, the authors carried out a district-wide training programme for primary care, accident and emergency, and mental health workers (47% of eligible staff trained), and demonstrated improvements in skills, attitude and confidence among the recipients of the training.

Method. Suicide rates (including definite suicides and undetermined deaths) and population statistics were collected for a district and region of England from official sources from 1993–2001. A before-and-after (1994–1996 and 1998–2000) training intervention analysis was conducted on suicide rates.

Results. The suicide rate in 1994–1996 was 8·8 per 100000 before our educational intervention and unchanged at 8·6 per 100000 in 1998–2000 after it (p=0·783).

Conclusion. Brief educational interventions to improve the assessment and management of suicide for front-line health professionals in contact with suicidal patients may not be sufficient to reduce the population suicide rate.

Background. Few epidemiological studies have examined the temporal relationship between chronic pain and depression using longitudinal data. In the present study, we examined major depression as both an antecedent risk factor and consequence of chronic back pain (CBP) in the general population.

Method. Data on 9909 pain-free individuals 15 years and older with no history of back problems were drawn from cycle 1 of the National Population Health Survey and followed up 24 months later. Major depression was assessed using a structured diagnostic interview.

Results. At cycle 2, the rate of new cases of CBP in persons who were depressed at cycle 1 was 3·6% compared to 1·1% in non-depressed persons. Compared to pain-free individuals, new cases of CBP were more likely to perceive their health status as poor or fair at cycle 1, were less likely to be working, reported more chronic health problems, and sustained a back or neck injury in the preceding 12 months. After controlling for other factors, pain-free individuals diagnosed as major depressed at cycle 1 were almost three times more likely (OR 2·9, 95% CI 1·2–7·0) to develop CBP at cycle 2.

Conclusions. Consistent with other longitudinal studies major depression increases the risk of developing future chronic pain. The causal mechanism linking these conditions is unknown however depression may represent a modifiable risk factor in the development of CBP.

Background. Classification of psychosis lacks a biological basis and current diagnostic categories may obscure underlying continuities. Data reduction methods of symptom profiles within a population-based cohort of people with a wide range of affective and non-affective psychoses may permit an empirical classification of psychosis.

Method. OPCRIT (operational criteria) analysis was performed on 387 adults aged 18–65 years in an attempted ascertainment of all patients with psychosis from a geographical area with a stable population. The data were analysed firstly using principal components analysis with varimax rotation to identify factors, and secondly to establish latent classes. Information relating to key variables known to be of relevance in schizophrenia was coded blind to the establishment of the classes and dimensions.

Results. Striking correspondence was obtained between the two methods. The four dimensions emerging were labelled ‘depression’, ‘reality distortion’, ‘mania’ and ‘disorganization’. Latent classes identified were ‘depression’, ‘bipolar’, ‘reality distortion/depression’ and ‘disorganization’. The latent classes corresponded well with DSM-III-R diagnoses, but also revealed groupings usually obscured by diagnostic boundaries. The latent classes differed on gender ratio, fertility, age of onset and self-harming behaviour, but not on substance misuse or season of birth.

Conclusions. Both dimensional and categorical approaches are useful in tapping the latent constructs underlying psychosis. Broad agreement with other similar studies suggests such findings could represent discrete pathological conditions. The four classes described appear meaningful, and suggest that the term non-affective psychosis should be reserved for the disorganization class, which represents only a subgroup of those with schizophrenia.

Background. In many biomedical disorders, early age at onset (AAO) is an index of high liability to illness which is manifest by an increased risk of illness in relatives. Most but not all prior studies report such a pattern for major depression (MD).

Method. Lifetime MD and AAO were assessed at personal interview using modified DSM-III-R criteria in 13864 twin pairs, including 4229 onsets of MD, from the Swedish National Twin Registry. Analyses were conducted using Cox proportional hazards models.

Results. Controlling for year of birth, gender, zygosity, co-twin history of MD and the interaction of zygosity and co-twin history, the best-fit model showed a significant main effect and a quadratic effect of AAO of MD in the co-twin on the log hazard ratio for MD in the index twin. When examined together, these effects predicted that from the ages of 15 to ~35 years, AAO of MD is moderately negatively related to risk of illness in relatives. However, past age 35, the function flattens out, with little change of risk in relatives with further increases of AAO. Even when the co-twin had a late AAO, the risk in the index twin substantially exceeded that seen when the co-twin had no history of MD.

Conclusion. In this large sample, AAO is a meaningful, albeit modest, index of familial liability to MD. The relationship is nonlinear and results largely from an increased liability in individuals with an early AAO. These results should be interpreted in the context of the limitations of long-term recall.

Background. Many patients with major depression are non-adherent to antidepressant medication and do not receive care according to current guidelines. There is increasing evidence that treatment of depression in primary care can be improved. Comparison between effective interventions may help to establish the active ingredients of such interventions.

Method. In a randomized trial two interventions to improve treatment of major depression in primary care were compared (1) a depression care programme, targeting general practitioners (GPs), patients, and systematic follow-up, and (2) a systematic follow-up programme. Thirty GPs were randomized and 211 primary-care patients with current major depression were included. All patients were prescribed a selective serotonin reuptake inhibitor. Outcome measures included adherence to antidepressant medication, and depression outcome.

Results. No significant differences in adherence rates and treatment outcome measures were demonstrated between interventions at week 10 or week 26. Adherence rates were high and treatment outcome was favourable.

Conclusions. The depression care programme was not superior to the systematic follow-up programme. Systematic follow-up in depression treatment in primary care seems to be an intervention per se, having the potential to improve adherence and treatment outcome.

Background. A lack of inhibitory control has been suggested to be the core deficit in children with attention deficit hyperactivity disorder (ADHD). This means that a primary deficit in behavioral inhibition mediates a cascade of secondary deficits in other executive functions, such as arousal regulation. Clinical observations have revealed that with increasing age symptoms of hyperactivity and impulsivity decline at a higher rate than those of inattention. This might imply that a deficit in attention rather than a lack of inhibitory control is the major feature in adult ADHD.

Method. To study whether an attentional or inhibitory deficit predominates, the stop-signal task and the stop-change task were presented to 24 adults with ADHD combined subtype and 24 controls.

Results. Relative to controls, the stop-signal reaction time (SSRT) was significantly more prolonged than the go-stimulus reaction time (RT) in patients with ADHD. This disproportionate elongation of the SSRT was comparable across tasks, even though the stop-change task exerted more complex (or at least different) demands on the inhibitory system than the stop-signal task. ADHD patients had a higher proportion of choice errors, possibly reflecting more premature responses. Specifically in the stop-change task, patients had more variable choice responses and made more inappropriate change responses, which may also reflect enhanced impulsivity.

Conclusions. The results support a core deficit in behavioral inhibition in adults with ADHD. We further suggest that there is more evidence for a critical role of deficient inhibitory control in adults than in children with ADHD.

Background. Research has documented high levels of co-morbidity among childhood externalizing disorders, but its etiology remains in dispute. Specifically, although all behavior genetic studies of the etiology of the co-occurrence of attention deficit-hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) agree that genetic factors are important, differences exist across studies in the relative weight assigned to genetic, shared environmental factors (i.e. factors that increase similarity among family members), and non-shared environmental factors (i.e. factors that decrease similarity among family members). Because heritability estimates can vary across informants, we used a biometric informant-effects model to determine whether these discrepancies were a function of systematic differences in maternal and child informant reports of ADHD, CD, and ODD.

Method. We studied 1782 11-year-old twins from the Minnesota Twin Family Study. Symptom counts for each disorder were obtained from interviews administered to twins and their mothers. We fit a model that allowed us to examine, both across and within informants, the genetic and environmental contributions to the co-occurrence among ADHD, CD, and ODD.

Results. The results revealed that the co-occurrence among the disorders common to maternal and child informant reports was influenced largely by shared environmental forces. Genetic factors also contributed, though their impact was only marginally significant. In contrast, the co-occurrence unique to each informant was influenced exclusively by either genetic or non-shared environmental factors.

Conclusions. Such findings offer additional evidence that shared environmental factors are important to the co-morbidity among ADHD, CD, and ODD, and highlight the necessity of considering informant effects when drawing conclusions about the origins of co-morbidity from analyses of genetically informative data.

Objective. Although studies have indicated that the human basal ganglia have a specific role in different memory systems, the functional significance of the striatal dopamine activities for the basal ganglia remains less clear. This study assessed the relationship between measures of striatal dopamine activities and indices of different memory systems in healthy individuals.

Method. Single photon emission computed tomography and [123I]IBZM (iodobenzamide) were used to assess the striatal dopamine D2/D3 receptor density in 62 healthy volunteers aged between 19 and 61 years. All subjects underwent a Wechsler Memory Scale – Revised test.

Results. Dopamine D2/D3 receptor densities in the striatum decline with age. Stepwise regression analysis showed that verbal delayed recall and working memory account for most of the variance in dopamine D2/D3 measurements. These relationships remain significantly after controlling for age effects.

Conclusions. Brain striatal dopamine activities are also significantly associated with various memory systems, in addition to motor functions. This may explain why patients with neuropsychiatric disorders may have both memory and motor impairments.

Background. Magnetic resonance imaging (MRI) studies have especially reported smaller hippocampal volume in patients with post-traumatic stress disorder (PTSD), most of them war or sexual abuse victims. The present study compares the hippocampal volumes of out-patients with PTSD who had low co-morbidity rates to those of trauma-exposed control subjects without PTSD, and measures hippocampal volume changes in these patients after brief eclectic psychotherapy. We hypothesized that smaller hippocampal volumes are specific to PTSD and that hippocampal volume changes after effective psychotherapy would be measurable.

Method. Eighteen patients with PTSD and 14 traumatized control subjects were examined with MRI. In a randomized clinical trial, the PTSD patients were assigned to treatment (n=9) or waiting-list group (n=9). After the former received psychotherapy for 4 months, the MRI was repeated on both PTSD groups. Three temporal lobe structures were manually segmented: hippocampus, amygdala, and parahippocampal gyrus. Volumetric analysis was used to measure grey matter, white matter, and cerebrospinal fluid.

Results. PTSD patients had significantly smaller hippocampal volumes at baseline (total 13·8%, right 13·5%, left 14·1%) compared to the control subjects. After effective psychotherapy, however, no volume changes were found in the smaller hippocampi.

Conclusions. We confirmed previous findings of smaller hippocampal volume in PTSD in a new population made up of out-patients who experienced different types of traumas, reducing co-morbidity to a minimum. Smaller hippocampal volumes did not change after effective psychotherapy, even while symptoms resolved.

Background. In resource-poor countries, there remains an alarming treatment gap for people with schizophrenia, particularly those living in rural areas. Decentralization of mental health services, including community-based outreach programmes, represents one obvious strategy for bringing appropriate care to these communities. This study set out to assess the costs and effects of such a programme in rural Karnataka in India.

Method. Eight rural communities were visited by an outreach team, who identified cases of drug-naive or currently untreated schizophrenia. Recruited cases were provided with appropriate psychotropic medication and psychosocial support, and after obtaining informed consent were assessed every 3 months over one and a half years on symptomatology, disability, family burden, resource use and costs. A repeated-measures analysis was carried out to test for significant change in these outcome measures over this period.

Results. A total of 100 cases of untreated schizophrenia were recruited, of whom 28% had never received antipsychotic medication and the remaining 72% had not been on medication for the past 6 months. Summary scores for psychotic symptoms, disability and family burden were all reduced significantly, with particular improvement observed at the first follow-up assessment. Increases in treatment and community outreach costs over the follow-up period were accompanied by reductions in the costs of informal-care sector visits and family care-giving time.

Conclusions. Efforts to organize community-based care such as outreach services for people with schizophrenia living in more remote areas of resource-constrained countries can bring substantial benefits to patients and families alike.

Background. There is empirical evidence suggesting that individuals with bulimia nervosa vary considerably in terms of psychiatric co-morbidity and personality functioning. In this study, latent profile analysis was used to attempt to identify clusters of bulimic subjects based on psychiatric co-morbidity and personality.

Method. A total of 178 women with bulimia nervosa or a subclinical variant of bulimia nervosa completed a series of self-report inventories of co-morbid psychopathology and personality, and also provided a buccal smear sample for genetic analyses.

Results. Three clusters of bulimic women were identified: an affective-perfectionistic cluster, an impulsive cluster, and a low co-morbid psychopathology cluster. The clusters showed expected differences on external validation tests with both personality and eating-disorder measures. The impulsive cluster showed the highest elevations on dissocial behavior and the lowest scores on compulsivity, while the affective-perfectionistic cluster showed the highest levels of eating-disorder symptoms. The clusters did not differ on genetic variations of the serotonin transporter gene.

Conclusions. This study corroborates previous findings suggesting that the bulimia nervosa diagnostic category is comprised of three classes of individuals based on co-morbid psychopathology and personality. These differences may have significant etiological and treatment implications.