Severe Affective Disorders Research Articles

1044 – A prospective comparison between formerly and never violent patients living in psychiatric residential facilities

Persons with severe mental disorders and a history of violent offending are usually seen as a difficult-tomanage population: most have schizophrenia or severe affective disorders, while some suffer from severe personality disorders. To investigate the sociodemographic, clinical, and treatment-related characteristics of a sample of patients living in RFs with a history of antisocial behaviour (‘violent’ group); to compare the characteristics of the ‘violent’ group with residents never violent; and to compare the rate of violent behaviour in the two groups over two years and to assess the likelihood of discharge in the two groups. This is prospective observational cohort study involved 23 RFs of the St John of God Order in Northern Italy. The sample was divided into two groups: non-violent patients and ‘violent’ patients. The last included patients at last one time admitted in FMH or arrested for violent crimes or acted violent behaviors against people. For each inpatient was filled out a “Patient Schedule”: socio-demographic and clinical data were collected, including a specific session to assess aggressive behavior lifetime and in the last year. The study involved 403 patients: 89 ‘violents’ and 314 non-violent. ‘Violent’ group was mainly male, younger, with a prevalence of personality disorders. Coherently, in the group of ‘violent’ there were more people lifetime arrested and admitted to a FMH. There are some differences in the monitoring of violent behavior in the two years of assessment. We observed more threatening, slap, punch, inappropriate sexual harassment, etc. in the ‘violents’ group.

Electroconvulsive Therapy in an Adolescent With Autism and Bipolar I Disorder

We report a positive response to electroconvulsive therapy in a severely functionally impaired adolescent with autistic disorder and classic bipolar I disorder, including an episodic pattern of decreased need for sleep, hypersexuality, expansive and agitated affect, aggression, self-injury, and property destruction. After ineffective trials of mood stabilizers and antipsychotics as well as inability to sustain a positive response to lithium due to medication noncompliance, a course of acute and maintenance electroconvulsive therapy was attempted. A marked and sustained improvement across all symptom categories, as measured by directly observed frequency counts of target behaviors in an inpatient setting, was obtained. Electroconvulsive therapy should be considered a potentially useful intervention in cases of children with autistic disorder and a severe comorbid affective disorder.

Distinguishing young people with emerging bipolar disorders from those with unipolar depression

To facilitate early intervention, there is a need to distinguish unipolar versus bipolar illness trajectories in adolescents and young adults with adult-type mood disorders. Detailed clinical and neuropsychological evaluation of 308 young persons (aged 12 to 30 years) with moderately severe unipolar and bipolar affective disorders. Almost 30% (90/308) of young people (mean age=19.4±4.4yr) presenting for care with affective disorders met criteria for a bipolar-type syndrome (26% with bipolar I). Subjects with bipolar- and unipolar-type syndromes were of similar age (19.8 vs. 19.2yr) and reported comparable ages of onset (14.5 vs. 14.3yr). Clinically, those subjects with unipolar and bipolar-type disorders reported similar levels of psychological distress, depressive symptoms, current role impairment, neuropsychological dysfunction and alcohol or other substance misuse. Subjects with unipolar disorders reported more social anxiety (p<0.01). Subjects with bipolar disorders were more likely to report a family history of bipolar (21% vs. 11%; [χ(2)=4.0, p<.05]) or psychotic (19% vs. 9%; [χ(2)=5.5, p<.05]), or substance misuse (35% vs. 23%; [χ(2)=3.9, p<.05]), but not depressive (48% vs. 53%; χ(2)=0.3, p=.582]) disorders. Young subjects with bipolar disorders were best discriminated by a family history of bipolar, psychotic or substance use disorders. Early in the course of illness, clinical features of depression, or neuropsychological function, do not readily differentiate the two illness trajectories.

P-1376 - Speed of response in bitemporal and bifrontal ECT: a case series

There is robust evidence recommending electroconvulsive therapy (ECT) in treating severe acute affective disorders. The clinical use of bitemporal electrode placement is still favoured to unilateral placement with just a relative disadvantage in cognitive side effects. Recently, bifrontal placement has gained popularity but there is still limited evidence on its relative benefits. Compare bitemporal and bifrontal ECT efficacy in patients with pharmacologically resistant affective disorders, based on the number of acute phase treatments required to reach symptomatic remission. Review of all patients' charts submitted to acute phase ECT, between June 2006 and June 2011. A total of 70 ECT treatment courses performed in a group of 67 patients met inclusion criteria. Thirty-eight of the total 70 courses received bitemporal ECT, and 32 received bifrontal ECT. A statistical analysis was performed. An attempt to use t-test was foiled due to breach of population variance homogeneity (p = 0,021). The non-parametric Mann-Whitney test was the alternative choice (M-W = 534;p = 0,377). Bitemporal and bifrontal groups matched for age and sex. Bitemporal patients received on average five ECT treatments, while the average of bifrontal treatments to remission was six, but this difference was not statistically significant (p > 0.05). Our results showed that bitemporal and bifrontal placements are equally effective. According to the largest randomised controlled trial conducted on ECT in depressive illness (Kellner et al,2010), bitemporal placement led to a faster rate of improvement. Additional studies and larger samples are required to understand if bifrontal placement's efficacy and cognitive advantages justify its popularity.

The Labeling Paradox

Although research supports the stigma and labeling perspective, empirical evidence also indicates that a social safety net remains intact for those with mental illness, recalling the classic "sick role" concept. Here, insights from social networks theory are offered as explanation for these discrepant findings. Using data from individuals experiencing their first contact with the mental health treatment system, the effects of diagnosis and symptoms on social networks and stigma experiences are examined. The findings suggest that relative to those with less severe affective disorders, individuals with severe diagnoses and more visible symptoms of mental illness have larger, more broadly functional networks, as well as more supporters who are aware of and sympathetic toward the illness situation. However, those with more severe diagnoses are also vulnerable to rejection and discrimination by acquaintances and strangers. These findings suggest that being formally labeled with a mental illness may present a paradox, simultaneously initiating beneficial social processes within core networks and detrimental ones among peripheral ties.

The effects of centralised and specialised combined pharmacological and psychological intervention compared with decentralised and non-specialised treatment in the early course of severe unipolar and bipolar affective disorders - design of two randomised clinical trials

BackgroundIn unipolar, and bipolar affective disorders, there is a high risk of relapse that increases as the number of episodes increases. Naturalistic follow-up studies suggest that the progressive development of the diseases is not prevented with the present treatment modalities. It is not known whether centralised and specialised secondary care intervention initiated early after the onset of the diseases can prevent the progression and thereby improve the prognosis.MethodsTwo randomised clinical multi-centre trials comparing a centralised and specialised outpatient intervention program consisting of combined pharmacological and psychological intervention with standard decentralised psychiatric treatment. Patients discharged from their first, second, or third hospitalisation due to a manic episode or bipolar disorder (trial 1) or to a single depressive episode or recurrent depressive disorder (trial 2) were randomised. Central randomisations for both trials were stratified for the number of hospitalisations and treatment centre. The primary outcome measure for the two trials is time to re-hospitalisation with an affective episode.DiscussionThese trials are the first to evaluate the effect of a centralised and specialised intervention in patients with early severe affective disorders. The trials used a pragmatic design comparing a specialised mood disorder clinic intervention with decentralised, non-specialised standard psychiatric treatment.Trial RegistrationClinicalTrials.gov: NCT00253071

Prospective evaluation of specialist inpatient treatment for refractory affective disorders

BackgroundLittle data exist to inform the treatment of severe and resistant affective disorders. We report here the effectiveness of specialist multimodal inpatient treatment for refractory affective disorders. MethodsProspective evaluation of 225 consecutive patients admitted to the National Affective Disorders Unit between 2001 and 2008. ResultsPatients were highly treatment-resistant: most had already received ECT, lithium augmentation and over 10 prior treatment trials. Even so, sequential assessment with the Hamilton Depression Rating Scale found that 69% showed a clinical response (≥50% reduction in Hamilton score) to intensive therapy during admission; 50% continued to sustain a full response and 71% at least a partial response on discharge. Patients' self-ratings (57% very much or much improved, 24% slightly improved) and relative and referrer reports (75% and 68% respectively rated patients as improved) gave similar levels of improvement. LimitationsThis was an observational study, without any untreated control group. The generalisability of the findings is limited by the highly specialised nature of the unit. ConclusionsMost patients with depression highly resistant to prior treatment respond to specialist and intensive multimodal inpatient therapy.

CBT and Recovery From Psychosis in the ISREP Trial: Mediating Effects of Hope and Positive Beliefs on Activity

CBT and Recovery From Psychosis in the ISREP Trial: Mediating Effects of Hope and Positive Beliefs on Activity

The long-term effectiveness of clozapine and lamotrigine in a patient with treatment-resistant rapid-cycling bipolar disorder

The challenges in the management of treatment-resistant rapid-cycling bipolar disorder are multifaceted and represent a significant burden to the patient. There is a need for more exploration into the potential utility of various combination therapies in the setting of severe affective states. A 52-year-old woman with a history of severe treatment-resistant rapid-cycling bipolar affective disorder (BPAD) was hospitalized for the treatment of a severe mixed episode. The introduction of lamotrigine and clozapine in combination proved remarkably effective and well tolerated in both the acute management and in subsequent maintenance. The patient has remained asymptomatic during the 5-year follow-up without any further mood disturbance. Lamotrigine and clozapine are among the less-prescribed agents for BPAD and there is as yet little research into their use in combination. It is possible that these agents have complementary modes of action on various facets of the affective pathology, resulting in superior mood stabilization in this patient.

PW01-42 - Escitalopram in treatment of disability in major depressive patients

Major depressive disorder (MDD) is a common, and often severe affective disorder which causes significant psychological distress, reduces quality of life and incised suicidal risk and mortality. Neurobiological basis of MDD involves at first serotoninergic and noradrenergic neuronal systems. Escitalopram is highly potent and highly selective serotonin re-uptake inhibitor.Purpose of this study was toEstimate efficacy of the escitalopram in treatment of disability and impairment in social, professional and family life in patients with MDD.MethodsThis prospective clinical study included 110 patients with MDD diagnosed by ICD-10 criteria for MDD, who are randomly divided into control (40 patients) and experimental group (70 patients). Antidepressants were tested, for 6 months in hospital and outpatients conditions, according to specially designed protocol, which included Hamilton Depression Rating Scale (HAMD) and Sheehan Disability Scale (SDS). Control group was treated with mianserine (30-90 mg/24h) and experimental group was treated with escitalopram (10-20 mg/24h).ResultsEscitalopram therapy influenced on HAMD score with high statistical significance vs. Mianserine, p=0.000. Escitalopram therapy improves all SDS scores after 6 months in comparison to Mianserine therapy with high statistical significance in Social life p=0.000, Family life/home responsibilities p=0.000, Days lost p=0.036 and Days unproductive p=0.003. Percentage of adverse effects is significantly lower in Escitalopram (10.76%) than in Mianserine (26.67%) group.ConclusionEscitalopram has significantly better efficacy in treatment of MDD and disability and impairment in MDD patients comparing to Mianserine, with significantly lower adverse effects rate.

Escitalopram in Treatment of Sleep Disturbances in Major Depressive Disorder

Major depressive disorder (MDD) is common and severe affective disorder with sleep disturbances and non-bizarre delusions which are organized in permanent and unshakeable delusional system. Neurobiological basis of MDD is still completely unknown, but significant role has serotoninergic and noradrenergic neuronal systems. Escitalopram is highly potent and highly selective serotonin re-uptake inhibitor.Purpose of this study was to estimate efficacy of the escitalopram in treatment of sleep disturbances in MDD.Methods:This prospective clinical study included 95 patients diagnosed by ICD-10 criteria for MDD, who are randomly divided into control (30 patients) and experimental group (65 patients). Patients were observed for 6 months in hospital and outpatients conditions, according to specially designed protocol, which included Hamilton Depression Rating Scale (HAMD) and Leeds Sleeping Evaluation Questionnaire (LSEQ). Control group was treated with maprotiline (75-150 mg/24h) and experimental group with escitalopram (10-20 mg/24h).Results:Escitalopram therapy influenced on HAMD score with high statistical significance vs. maprotiline, p=0.000. Escitalopram therapy improves LSEQ score after 6 months in comparison to maprotiline therapy with high statistical significance p=0.000. Percentage of adverse effects is significantly lower in escitalopram (10.76%) than in maprotiline (26.67%) group.Conclusion:Escitalopram has significantly better efficacy and lower adverse effects rate in treatment of depressive symptoms and sleep disturbances in MDD patients comparing to maprotiline.

COGNITIVE FUNCTIONING IN SEVERE PSYCHIATRIC DISORDERS IN A POPULATION BASED SAMPLE

Introduction: It is well established from clinical study samples that patients with severe psychiatric disorders have cognitive impairments. Less is known whether this also applies to samples derived from the general population. We set out to study cognitive functioning in a representative population-based sample comprising individuals with schizophrenia, other non-affective psychoses, bipolar disorders, major depressive disorder, and a control group derived from the same population. Methods: In the Psychosis in Finland (PIF)–study, a large general population sample was screened for psychotic and severe affective disorders, and screen positives and a random sample of screen negatives were invited to a SCID-I interview and neuropsychological testing. The current analysis is based on 148 persons with severe mental disorders, and 66 controls. Results: Compared with controls, subjects with diagnosis of schizophrenia had a generalized cognitive impairment (effect sizes 0.431.07), while those with other non-affective psychoses were impaired in verbal memory functions and processing speed (effect sizes 0.430.59). Subjects with the bipolar disorder spectrum diagnoses were unimpaired, while those with unipolar major depressive disorder had slowed processing speed (effect size -0.64). Conclusions: Our results on cognitive impairments in subjects with schizophrenia and other non-affective psychoses derived from the general population support previous findings of a generalized cognitive dysfunction in these subjects. However, subjects with bipolar disorders from non-clinical populations may have no significant cognitive impairments. Our results also emphasize the importance of representative control samples in evaluating cognitive functioning of subjects with severe mental disorders. Acknowledgements: The Academy of Finland is acknowledged for grants for the present study References

Sociodemographic, Functional and Clinical Correlates in Outpatients with Schizophrenia: Comparison with Affective Disorders

To describe the demographic, social and functional characteristics and service utilization of people with schizophrenia attending four public psychiatric services in New Zealand and to compare this with (i) people with severe affective disorders attending the same four services and (ii) the New Zealand general population; and to examine conformity with evidence-based pharmacological treatment of schizophrenia. Clinical files for all adult outpatients attending the four specialist services were reviewed in October 2004 (n =6164). Patient characteristics, social and functional indicators, diagnosis, duration of illness, and admission information were recorded and analysed for schizophrenia, bipolar disorder and depression (n =5032). Antipsychotic treatment was recorded for those with schizophrenia. Outpatients with schizophrenia made up 47% of the outpatient population; 66% were male, the mean age 39 years and the mean illness duration was 14 years. Sixty-seven percent of schizophrenia outpatients had never been married, 69% had no regular occupational activity, 49% had no formal qualifications, 24% were living in group homes and 26% were treated compulsorily. These characteristics were consistently different compared to outpatients with severe affective disorders and the general population; schizophrenia patients were the most impaired, depression the least and the bipolar group in between. The majority of schizophrenia patients received evidence-based antipsychotic treatment; 84% received monotherapy; 81% prescribed an atypical; 33% prescribed clozapine. The study shows significant impairment for schizophrenia patients in areas of intimate relationships, occupational activity, living situation, qualifications and specialist mental health service use despite evidence-based pharmacological treatment. To improve outcome optimal care must incorporate existing evidence-based, cost-effective interventions that focus on both symptoms and function. More effective treatments also need to be developed.

Research Issues for Improving Treatment of U.S. Hispanics With Persistent Mental Disorders

Research Issues for Improving Treatment of U.S. Hispanics With Persistent Mental Disorders

Troubles anxieux et dépressifs chez 4 425 patients consommateurs de benzodiazépines au long cours en médecine générale

Consumption rates of anxiolytic drugs, and especially of benzodiazepines, remain very high in France compared to other Western countries, whereas clinical guidelines limit their indications to short term treatments and only for some precise anxiety disorders. Recent epidemiologic surveys in the community indicated that more than 15% of people used once or more an anxiolytic drug in the past year. The issue of chronic treatments is particularly crucial because of their poor benefit/risk ratio in most anxiety disorders (limited efficacy, cognitive side effects, withdrawal and dependence problems). To address this important public health issue, and knowing that, in France, benzodiazepines are prescribed mainly by general physicians, our aims were to explore psychiatric diagnoses in GP's patients with chronic use of anxiolytic benzodiazepines. We included 4 425 patients consuming such drugs regularly for six months or more, and assessed their anxiety and depression symptoms through various clinical scales (Hospital Anxiety and Depressive scale - HAD, Clinical Global Impression scale - CGI, Sheehan Disability Scale - SDS, Cognitive Dependence to Benzodiazepines scale - CDB) and with the Mini International Neuropsychiatric Interview for DSM IV criteria. Only 2.2% of the subjects had neither anxious nor depressive symptoms as indicated by low scores on both subscores (less than 8) of the HAD scale, used as a screener. Nearly three quarters of the 4,257 subjects (73.2%), had CGI scores of at least 5 (markedly ill to extremely ill). Social and familial disability was also high in more than 40% of the sample (marked to extreme disruption according to SDS scores). About half of the sample had CDB scores suggesting a benzodiazepine dependence. According to the MINI, 85.1% of the patients had at least one current DSM IV diagnosis of affective disorder. The most frequent diagnoses were major depressive episode (60%), generalized anxiety disorder (61.2%), and panic disorder (22.5%). An anxiety and depressive comorbidity wad found in 41.9% of the subjects. Some methodological limitations must be taken into account in the discussion of our results, and especially the fact that the included patients were not supposed to be totally representative of all patients consuming anxiolytic benzodiazepines in general practice. However, the size of our sample is sufficiently large to limit possible biases in patient selection. The main result of this study is that a great majority of the patients had significant symptomatology, in particular major depressive episodes and generalized anxiety disorder, often with marked severity and disability. These data are in line with the knowledge of a lack of efficacy of benzodiazepines in depressive and most anxiety disorders, despite long term treatment. They also confirm the current guidelines which recommend prescribing serotoninergic antidepressants, and not benzodiazepines, when long term treatments are needed for severe and chronic affective disorders. This epidemiologic study leads to the conclusion that a specific and attentive diagnostic assessment should be done in all patients receiving benzodiazepines for more than three months, in order to purpose in many cases other long term therapeutic strategies.

Chromosomal abnormalities and psychosis

The search for susceptibility genes for schizophrenia and severe affective disorder has been enhanced by the study of cytogenetic abnormalities that disrupt genes directly. One such gene is DISCI and there is increasing evidence that it may be an important modulator of risk of psychosis.

The risk of affective disorders in patients with adrenocortical insufficiency

To investigate the risk of affective disorders among patients hospitalised with adrenocortical insufficiency in the study period: 1977-1999. Using data from Danish registers, two study cohorts were identified by their ICD diagnoses at discharge from hospital: one comprising all patients with a first hospital admission with an index diagnosis of adrenocortical insufficiency; the other a control cohort comprising all patients with a first hospital admission with an index diagnosis of osteoarthritis. Subsequent admissions to psychiatric hospital wards with discharge ICD diagnoses of affective disorders were used as events of interest. Rates of readmission were estimated using Poisson regression models in survival analyses. Age, sex, duration of time after index discharge, and calendar time were included as co-variables. The primary analysis included all patients with adrenocortical insufficiency. Thereafter, the subgroup of patients with primary adrenocortical insufficiency (Addison's disease) was investigated separately in a secondary analysis. A study sample of 989 patients with adrenocortical insufficiency and 124,854 patients with osteoarthritis was identified. Eight hundred and fifty-two patients were subsequently readmitted with a diagnosis of affective disorder. Patients with adrenocortical insufficiency had a 2.68 (95% CI: 1.62-4.42) times greater rate of affective disorders and a 2.12 (95% CI: 1.16-3.86) times greater rate of depressive disorder when compared with the rate for patients with osteoarthritis. Patients with Addison's disease had a 2.14 (95% CI: 1.14-4.03) times greater rate of affective disorders, and a 1.71 (95% CI: 0.81-3.63) times greater rate of depressive disorder compared with the rate of patients with osteoarthritis. Patients with adrenocortical insufficiency may be at increased risk of developing severe affective disorders. Conventional replacement therapy with hydrocortisone may not be sufficient to ensure the psychiatric well-being of these patients.

Service innovations: developing a specialised (tertiary) service for the treatment of affective disorders

Although the majority of people with mental health problems have their treatment needs met within local services, the Department of Health's Specialised Service National Definition Set (Department of Health, 2002) outlines areas that are thought to require specialised services. Complex and/or treatment-resistant disorders (including severe and/or complex affective disorders) are one of ten mental health areas identified.

Klinefelter's syndrome (XXY) as a genetic model for psychotic disorders

Males with an extra-X chromosome (Klinefelter's syndrome) frequently, although not always, have an increased prevalence of psychiatric disturbances that range from attention deficit disorder in childhood to schizophrenia or severe affective disorders during adulthood. In addition, they frequently have characteristic verbal deficits. Thus, examining brain magnetic resonance imaging (MRI) scans of these individuals may yield clues to the influence of X chromosome genes on brain structural variation corresponding to psychiatric and cognitive disorders. Eleven adult XXY and 11 age matched XY male controls were examined with a structured psychiatric interview, battery of cognitive tests, and an MRI scan. Ten of eleven of the XXY men had some form of psychiatric disturbance, four of whom had auditory hallucinations compared with none of the XY controls. Significantly smaller frontal lobe, temporal lobe, and superior temporal gyrus (STG) cortical volumes were observed bilaterally in the XXY men. In addition, diffusion tensor imaging (DTI) of white matter integrity resulted in four regions of reduced fractional anisotropy (FA) in XXY men compared with controls, three in the left hemisphere, and one on the right. These correspond to the left posterior limb of the internal capsule, bilateral anterior cingulate, and left arcuate bundle. Specific cognitive deficits in executive functioning attributable to frontal lobe integrity and verbal comprehension were noted. Thus, excess expression of one or more X chromosome genes influences both gray and white matter development in frontal and temporal lobes, as well as white matter tracts leading to them, and may in this way contribute to the executive and language deficits observed in these adults. Future prospective studies are needed to determine which gene or genes are involved and whether their expression could be modified with appropriate treatments early in life. Brain expressed genes that are known to escape inactivation on extra-X chromosomes would be prime candidates.

Anxiety disorder comobidity in Bipolar I Disorder: Relationship to depression severity and treatment outcome

The present study investigated the greater symptom severity and poorer treatment response found in patients with bipolar illness and anxiety comorbidity, and examined depression as a potential mediator of this relationship. The sample consisted of 92 patients in an acute episode of Bipolar I Disorder with a current or past history of an anxiety disorder. Diagnoses were based on structured clinical interview, and participants were assessed at pre-treatment and then randomly assigned to pharmacotherapy alone or pharmacotherapy plus family intervention. Patients were assessed on a monthly basis by blind assessors over 28 months. Compared to patients without anxiety comorbidity, individuals with bipolar disorder and an anxiety disorder possessed greater current symptom severity, even after controlling for depression severity. Logistic regression analysis identified that being female and having higher current depression but not manic severity predicted comorbid anxiety. Comorbid anxiety was associated with poorer treatment response in the sample regardless of treatment type, particularly in subsequent depressive symptoms. Multiple regression analyses indicated that current depression but not manic severity partially mediated the relationship between comorbid anxiety and treatment outcome. Results from the current study investigating comorbid anxiety disorders are consistent with past research limited to anxiety symptoms. Depression only partially accounted for the link between comorbid anxiety and greater symptom severity and poorer treatment response, and examination of other factors is warranted. Because of the clinical relevance of comorbid anxiety in severe affective disorders, treatments designed to specifically address both concerns are needed.