Sustained specialized and family treatment in first-episode schizophrenia or related disorders: a 5-year randomized controlled trial.

BACKGROUND: The long-term outcome of first-episode schizophrenia needs improvement. Here, we evaluate the effectiveness of 5 years sustained specialist treatment (ST), ST including Parent groups (ST + P) or treatment as usual (TAU) on psychotic relapse and social functioning. METHODS: A three condition randomized, parallel assigned, single-blind efficacy trial, in which 198 first-episode psychosis (FEP) patients aged 15-28 years were included. The effect on time to first relapse, first relapse rates, mean number of relapses per patient, and time to the improvement of social functioning were analyzed using Cox regression or ANOVA. RESULTS: We found no significant differences between treatment conditions in the ITT analysis concerning time to first relapse, nor first relapse rate. Mean number of relapses per patient differed at a trend level between ST, ST + P or TAU conditions, respectively: 0.72; 0.62 or 1.02 (p = 0.069). No evidence was found for differential effect of treatment conditions on social functioning. CONCLUSION: Five years sustained ST of FEP nor addition of parent groups increased time to first relapse or reduced first relapse rate, compared to sustained TAU. Indications for favorable effects of parent groups were found on relapses per patient.

Groin Pain Characteristics and Recurrence Rates: Three-year Results of a Randomized Controlled Trial Comparing Self-gripping Progrip Mesh and Sutured Polypropylene Mesh for Open Inguinal Hernia Repair.

OBJECTIVE: The aim of this study was to investigate long-term groin pain and inguinal hernia recurrence rates of 2 types of mesh and to describe the evolution of postoperative groin sensory disturbances. SUMMARY OF BACKGROUND DATA: Some patients with an inguinal hernia develop chronic pain following open mesh insertion. Previous trials comparing a semi-resorbable, self-gripping Progrip mesh with a standard sutured polypropylene mesh found conflicting results regarding recurrence rates and residual groin pain. METHODS: Patients aged >18 years scheduled for open primary hernia repair were randomized to a self-gripping mesh (Progrip) or a polypropylene mesh (standard). Removal of the inguinal nerves was left to the discretion of the surgeon. Pain was measured using Visual Analogue Scale (VAS) over a 3-year period. Pain characteristics and hernia recurrences were determined using physical examination. RESULTS: Data of 274 patients were complete (75% three-year follow-up rate). Pain steadily decreased over time in both groups in a similar fashion (moderate pain 3.7% in each group). Hyperesthesia was experienced by 2.2% and 3.7% and hypoesthesia in 12% and 19% in Progrip and standard group, respectively. One of seven Progrip patients reported a foreign body feeling versus 1 of 5 standard patients (P = 0.06). Altered skin sensations were not related to a neurectomy. Hernia recurrence rate was 11.5% in the Progrip and 5% in the standard group (P = 0.05). CONCLUSIONS: Three years after insertion of a self-gripping Progrip mesh or a sutured polypropylene mesh for an open primary inguinal hernia repair, groin pain is minimal, although altered groin skin sensations and foreign body feeling are quite common. A Progrip hernia repair is associated with a high recurrence rate.

Factor structure of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) in a large sample of patients with schizophrenia or related disorders and comorbid obsessive-compulsive symptoms.

In the past decade there has been an increasing interest in the levels of obsessive-compulsive symptoms (OCS) found in patients with schizophrenia or related disorders. The widely acknowledged gold standard measure of the severity of OCS is the content-free version of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) (Goodman et al., 1989a,b). However, factor analytic research in patients with obsessive-compulsive disorder (OCD) provided varied results. So far no study has been conducted on the factor structure of the Y-BOCS in patients with schizophrenia. The present study addresses this issue. We administered the Y-BOCS in a sample of 217 patients with schizophrenia or related disorders and comorbid OCS who participated in a multicentre cohort study. We used principal component analysis (PCA) to explore the underlying factor structure. A two-factor solution consistent with the originally proposed scoring structure of the Y-BOCS provided the optimal fit. We also found some support for a three-factor solution consistent with earlier findings by Kim et al. and Moritz et al. (Kim et al., 1994; Moritz et al., 2002). The produced factors showed good reliability and strong correlations with the Y-BOCS Total score. However, the resistance to compulsion item failed to demonstrate adequate correlation to the Total score, a finding consistent with earlier findings in several studies with patients with OCD.

Prediction of recurrence in recurrent depression and the influence of consecutive episodes on vulnerability for depression: a 2-year prospective study.

OBJECTIVE: Depression is a recurring disease. Identifying risk factors for recurrence is essential. The purpose of this study was to identify factors predictive of recurrence and to examine whether previous depressive episodes influence vulnerability for subsequent depression in a sample of remitted recurrently depressed patients. METHOD: Recurrence was examined prospectively using the Structured Clinical Interview for DSM-IV Axis I Disorders in 172 euthymic patients with recurrent depression (DSM-IV) recruited from February 2000 through September 2000. Illness-related characteristics, coping, and stress (life events and daily hassles) were examined as predictors. RESULTS: Risk factors for recurrence were a high number of previous episodes, more residual depressive symptomatology and psychopathology, and more daily hassles. Factors with both an increasing and decreasing pathogenic effect with increasing episode number were detected. CONCLUSION: We found some support for dynamic vulnerability models that posit a change of vulnerability with consecutive episodes. Preventive interventions should be considered in patients with multiple recurrences, focusing on residual symptomatology and specific coping styles.

Preventing relapse/recurrence in recurrent depression with cognitive therapy: a randomized controlled trial.

This article reports on the outcome of a randomized controlled trial of cognitive group therapy (CT) to prevent relapse/recurrence in a group of high-risk patients diagnosed with recurrent depression. Recurrently depressed patients (N = 187) currently in remission following various types of treatment were randomized to treatment as usual, including continuation of pharmacotherapy, or to treatment as usual augmented with brief CT. Relapse/recurrence to major depression was assessed over 2 years. Augmenting treatment as usual with CT resulted in a significant protective effect, which intensified with the number of previous depressive episodes experienced. For patients with 5 or more previous episodes (41% of the sample), CT reduced relapse/recurrence from 72% to 46%. Our findings extend the accumulating evidence that cognitive interventions following remission can be useful in preventing relapse/recurrence in patients with recurrent depression.

Hyperresponsiveness of hypothalamic-pituitary-adrenal axis to combined dexamethasone/corticotropin-releasing hormone challenge in female borderline personality disorder subjects with a history of sustained childhood abuse.

BACKGROUND: High coincidence of childhood abuse, major depressive disorder (MDD), and posttraumatic stress disorder (PTSD) has been reported in patients with borderline personality disorder (BPD). Animals exposed to early trauma show increased stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity due to an enhanced corticotropin-releasing hormone (CRH) drive and glucocorticoid feedback resistance. In humans, PTSD and MDD are associated with decreased and increased resistance to glucocorticoid feedback, respectively, which might reflect persistent changes in neuroendocrine sequelae following childhood abuse. METHODS: We investigated the relationship between childhood abuse and HPA axis function using a combined dexamethasone/CRH (DEX/CRH) test in 39 BPD patients with (n = 24) and without (n = 15) sustained childhood abuse and comorbid PTSD (n = 12) or MDD (n = 11) and 11 healthy control subjects. RESULTS: Chronically abused BPD patients had a significantly enhanced corticotropin (ACTH) and cortisol response to the DEX/CRH challenge compared with nonabused subjects. Comorbid PTSD significantly attenuated the ACTH response. CONCLUSIONS: Hyperresponsiveness of the HPA axis in chronically abused BPD subjects might be due to the enhanced central drive to pituitary ACTH release. Sustained childhood abuse rather than BPD, MDD, or PTSD pathology accounts for this effect. Possibly due to an enhanced efficacy of HPA suppression by dexamethasone, PTSD attenuates the ACTH response to DEX/CRH.

SSRI treatment of borderline personality disorder: a randomized, placebo-controlled clinical trial for female patients with borderline personality disorder.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are recommended for treatment of affect lability, impulsivity, and aggression in patients with borderline personality disorder. This recommendation is based on positive findings in at least 10 open studies and one small double-blind study of SSRIs for patients with borderline personality disorder and one study of impulsive aggressive patients with different personality disorders. A randomized, placebo-controlled SSRI study with borderline personality disorder patients, however, provided inconclusive results because of a large response to placebo. It was, therefore, decided to conduct a new randomized trial with a larger study group. METHOD: A double-blind, placebo-controlled, randomized trial using the SSRI fluvoxamine for 6 weeks followed by a blind half-crossover for 6 weeks and an open follow-up for another 12 weeks was conducted with 38 nonschizophrenic, nonbipolar female patients with borderline personality disorder. The outcome measures were the rapid mood shift, impulsivity, and aggression subscales from the Borderline Personality Disorder Severity Index. RESULTS: Fluvoxamine but not placebo produced a robust and long-lasting reduction in the scores on the subscale for rapid mood shifts. In contrast, no difference between the fluvoxamine and placebo groups was observed in the effect on the impulsivity and aggression scores. CONCLUSIONS: In this study, fluvoxamine significantly improved rapid mood shifts in female borderline patients, but not impulsivity and aggression. This latter finding may be due to gender-specific differences in impulsivity and aggression.

Fluvoxamine reduces responsiveness of HPA axis in adult female BPD patients with a history of sustained childhood abuse.

The aim of the study is to test whether fluvoxamine affects the function of the hypothalamic pituitary adrenal (HPA) axis in female borderline (borderline personality disorder, BPD) patients with and without a history of sustained childhood abuse. Special attention is given to the presence of comorbid major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The HPA axis of 30 female BPD patients with (n = 17) and without (n = 13) a history of sustained childhood abuse was challenged with a combined dexamethasone and corticotropin releasing hormone test (DEX/CRH test) before and after 6 (n = 14) and 12 (n = 16) weeks of fluvoxamine treatment (150 mg/day). Both 6- and 12-week fluvoxamine treatments were associated with a significant and robust reduction of the adrenocorticotrophic hormone (ACTH) and cortisol response to the DEX/CRH test. The magnitude of the reduction was dependent on the presence of sustained childhood abuse, but not on the presence of comorbid MDD or PTSD: patients with a history of sustained childhood abuse showed the strongest reduction in ACTH and cortisol. In conclusion, Fluvoxamine treatment reduces the hyperresponsiveness of the HPA axis in BPD patients with a history of sustained childhood abuse. This effect is likely to be obtained in the first 6 weeks of treatment.

Psychiatric disorders in a representative sample of incarcerated boys in the Netherlands.

OBJECTIVE: To determine the prevalence of psychiatric disorders among incarcerated male adolescents and to investigate the influence of psychopathology on allocation to either plain detention or detention with compulsory treatment. METHOD: A cross-sectional study of a representative sample (N = 204) of incarcerated boys aged 12 to 18, using the Diagnostic Interview Schedule for Children (DISC). Data were collected from December 1998 to December 1999. RESULTS: Of the eligible subjects, 79% agreed to participate. Ninety percent reported at least one psychiatric disorder: disruptive behavior disorder 75% (95% confidence interval [CI]: 68-81%), substance use disorder 55% (95% CI: 48-63%), psychotic symptoms 34% (95% CI: 27-41%), ADHD 8% (95% CI: 5-13%), anxiety disorder 9% (95% CI: 6-15%), and affective disorder 6% (95% CI: 3-10%). After controlling for a broad range of sociodemographic characteristics and former treatment parameters, the presence of a psychiatric disorder was not associated with allocation to compulsory treatment. CONCLUSIONS: Compared with North American studies, relatively low rates of anxiety and affective disorders were found, probably due to the better availability of mental health services to disadvantaged youths with internalizing problems in the Netherlands. It should be examined whether standardized psychiatric assessments can improve the efficiency of allocation to detention programs with or without psychiatric treatment options.

Attitudes of patients toward the first psychotic episode and the start of treatment.

Consecutively admitted patients with recent-onset schizophrenia disorders (n = 56) were interviewed about their awareness of mental disorder at first occurrence of psychotic symptoms, their views about the necessity of psychiatric treatment, their perception of the role of others in initiating psychiatric treatment, and suggestions they might have about getting treatment started at an earlier point in time. About 57 percent of the patients had at least some awareness of having a mental disorder at onset of psychotic symptoms, and 61 percent of the sample believed psychiatric help was unnecessary prior to the start of psychiatric treatment. A majority of the patients (91%) perceived others to be essential in initiating treatment. Most patients (82%) thought that no change is needed on the part of professional caregivers in order to facilitate early treatment. Some awareness of mental disorder at onset was related to a shorter duration of untreated psychosis (DUP). Delaying treatment until patients themselves become aware of the need for treatment may enlarge DUP.

Psychotic symptoms among male adolescent detainees in The Netherlands.

This study investigated the prevalence of psychotic symptoms among incarcerated boys as well as the relationship between these symptoms and violent offending and criminal recidivism. The presence of psychotic symptoms was assessed in a representative sample of 204 incarcerated boys aged 12-18 using the Diagnostic Interview Schedule for Children (DISC-2.3). Seventy-two percent of the study participants had committed a violent index offense and 30 percent were criminal recidivists. Thirty-four percent (95% confidence interval [CI]: 27-41%) were DISC-2.3 psychosis screen positive: 25% (95% CI: 19-31%) reported at least one pathognomonic of schizophrenia symptom and 9% (95% CI: 6-14%) reported at least three non-pathognomonic psychotic symptoms. In addition, 33 percent (95% CI: 26-40%) reported one or two isolated, atypical psychotic symptoms. The presence of psychotic symptoms was not associated with violent offending or criminal recidivism. The high prevalence rate of psychotic symptoms among incarcerated boys calls for increased attention to diagnosis and treatment of psychosis. To obtain conclusive answers regarding the relationship between psychosis and violent offending, additional studies are needed in general population samples.

The 5-year course of obsessive-compulsive symptoms and obsessive-compulsive disorder in first-episode schizophrenia and related disorders.

OBJECTIVE: To determine the course of obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD) in first-episode schizophrenia and related disorders and their relationship with clinical characteristics. METHODS: Consecutively, admitted patients with a first-episode of schizophrenia, schizophreniform disorder, or schizoaffective disorder were screened for OCS, and these were measured with the Yale-Brown Obsessive-Compulsive Scale. Positive and Negative Syndrome Scale and Montgomery Åsberg Depression Rating Scale were used to assess severity of other symptoms. The course of 3- and 5-year symptoms, psychotic relapse, substance use, remission, full recovery, suicide, and social functioning were assessed. RESULTS: One hundred and eighty-six consecutively admitted and consenting patients were included. Five years after admission, OCS could be assessed in 172 patients. Ninety-one patients (48.9%) reported no OCS symptoms on any of the assessments. OCS restricted to the first assessments occured in 15.1%, 13.4% had persistent OCS, 7.0% had no OCS at first assessment but developed OCS subsequently, and 15.6% had intermittent OCS. The proportion of patients with comorbid OCD varied between 7.3% and 11.8% during follow-up. OCD was associated with more severe depressive symptoms and poorer premorbid functioning and social functioning at follow-up. CONCLUSIONS: The 5-year course of OCS/OCD in patients with first-episode schizophrenia or related disorders is variable. OCS/OCD comorbidity was not associated with a more severe course of psychotic symptoms and relapse. Comorbid OCD was associated with more severe depressive symptoms, social dysfunction and worse premorbid functioning. Specific treatment options for schizophrenia patients with comorbid OCD are needed.

Sustained medically unexplained physical symptoms in euthymic patients with recurrent depression: predictive value for recurrence and associations with omega 3- and 6 fatty acids and 5-HTTLPR?

BACKGROUND: Identification of potentially modifiable risk factors for recurrence in recurrent depression could provide opportunities to improve preventive interventions. In this study we aimed to examine the predictive value of medically unexplained physical symptoms (MUPS) on time to recurrence in recurrent depression. Additionally, to elucidate pathophysiological mechanisms that could explain the relations between MUPS and depression, we investigate the association between a sustained high level of MUPS, and (I) omega (ω)-3 and -6 fatty acid (FA)-status and (II) functional polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR). METHODS: Based on three Physical Symptom Checklist (PCS) scores over 12 months, we defined two groups of remitted recurrently depressed patients: 41 patients with a sustained high number of MUPS and 34 patients with a sustained low number or no MUPS. Patients were followed-up for 3.5 years while recurrence of their depression was monitored. In addition, we analyzed patients' erythrocyte's FA-profiles and triallelically genotyped their 5-HTTLPR. RESULTS: A sustained high level of MUPS predicted consecutive depression recurrence over 3.5 years (adjusted relative risk 2.8). FA-status and distribution of 5-HTTLPR variant frequencies did not differ between patients with sustained high compared to low/absent MUPS-levels. LIMITATIONS: Our sample was relatively small. CONCLUSION: Remitted recurrently depressed patients with sustained MUPS have a considerably increased risk of recurrence. Having sustained MUPS is not associated with either erythrocyte ω-3 or -6 FA-levels or 5-HTTLPR polymorphism. Recognition and reducing MUPS in an early state could prevent a (depressive) relapse.

Sexual dysfunction and hormonal changes in first episode psychosis patients on olanzapine or risperidone.

Atypical antipsychotics interfere with central and peripheral neurotransmitter systems and with hormonal production. In this study we compared the effect of olanzapine and risperidone on hormonal state and sexual function (by using the Questionnaire for Sexual Dysfunction, QSD) in 40 patients with a first episode psychosis. Results were compared to those of 34 healthy controls. Patients using risperidone had significant higher prolactin levels than patients using olanzapine. Patients using olanzapine had significantly higher 17beta-estradiol levels than patients using risperidone. Overall satisfaction with sexuality was less in patients compared to controls, but not different between patients using olanzapine and those using risperidone. Problems with sexual arousal were significantly higher in patients using olanzapine compared to patients using risperidone. A significantly higher frequency of problems with ejaculation and problems with insensibility of genitals were found in patients compared to healthy controls. We found no relation between medication, prolactin and 17beta-estradiol levels, frequency of sexual activity, overall satisfaction with sexuality and any of the 18 sexual dysfunctions we investigated. Our results suggests that sexual dysfunction in patients with first episode psychosis might occur despite normal prolactin levels. Also, sexual dysfunction is highly prevalent in healthy controls. Awareness should be raised of potential sexual problems in young adults.

Long-term effects of preventive cognitive therapy in recurrent depression: a 5.5-year follow-up study.

OBJECTIVE: Major depressive disorder (MDD) was projected to rank second on a list of 15 major diseases in terms of burden in 2030. A crucial part of the treatment of depression is the prevention of relapse/recurrence in high-risk groups, ie, recurrently depressed patients. The long-term preventive effects of group cognitive therapy (CT) in preventing relapse/recurrence in recurrent depression are not known. This article reports on the long-term (5.5-year) outcome of a randomized controlled trial to prevent relapse/recurrence in patients with recurrent depression. We specifically evaluated the long-term effects of CT in relation to the number of previous episodes experienced. METHOD: From February through September 2000, patients with recurrent depression (DSM-IV-diagnosed) who were in remission (N = 172) were recruited from primary and specialty care facilities. They were randomly assigned to treatment as usual (TAU) versus TAU augmented with brief group CT. The primary outcome measure was time to relapse/recurrence, which was assessed over 5.5 years. RESULTS: Over 5.5 years, augmenting TAU with CT resulted in a significant protective effect (P = .003), which intensified with the number of previous depressive episodes experienced. For patients with 4 or more previous episodes (52% of the sample), CT significantly reduced cumulative relapse/recurrence from 95% to 75% (medium effect size). CONCLUSIONS: Our findings indicate that brief CT, started after remission from a depressive episode on diverse types of treatment in patients with multiple prior episodes, has long-term preventive effects for at least 5.5 years. Implementation of brief relapse prevention CT should be considered in the continued care of patients with recurrent depression. TRIAL REGISTRATION: ccmo-online.nl Identifier: NTR454.

Differential predictors of response to preventive cognitive therapy in recurrent depression: a 2-year prospective study.

BACKGROUND: Major depressive disorder is a recurrent disease. Brief cognitive therapy (CT), added to either regular care or medication, is helpful in preventing relapse/recurrence. Little is known which type of persons benefit from preventive CT, the so called 'aptitude treatment interaction' effect. METHOD: The present cohort included exclusively patients with at least two previous episodes remitted on various types of treatments (n = 172). They were assessed within a clinical trial comparing treatment as usual (TAU) with preventive CT added to TAU. Differential demographic, illness-related, psychological and biological risk factors in postponing recurrence by preventive CT were examined. RESULTS: Significant aptitude-treatment-interaction effects were found for the number of previous episodes, daily hassles and life events, avoidant coping, gender, and morning cortisol levels. Preventive CT seemed ineffective in patients with life events (as more frequently reported by women in our study) and in patients with high episode number characterized by higher levels of avoidant coping. Generic predictors indicate that in CT, as in TAU, patients with more residual depressive symptomatology and higher levels of dysfunctional attitudes profit less from preventive CT. CONCLUSION: The finding that preventive CT protects against the influence of a consistently found risk factor of relapse/recurrence, i.e. the number of depressive episodes, underlines the potential of psychological preventive interventions. Preventive CT seemed to be especially effective in reducing presumably internally provoked, relapse/recurrence but may be quite ineffective in reducing externally provoked relapse/recurrence. CT possibly prevents either stress generation or disrupts kindling effects. Kindling effects probably cannot be disrupted in patients with higher levels of avoidant coping who experienced a high number of episodes, and patients who experienced life events.

Reliability and validity of the Yale-Brown Obsessive-Compulsive Scale in schizophrenia patients.

Although a sizeable minority of people with schizophrenia manifest obsessive and compulsive symptoms, to our knowledge there are no studies of the psychometric performance of measures such as the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). The present study examined psychometric properties of the Y-BOCS in patients with recent-onset schizophrenia and comorbid obsessive-compulsive symptoms (OCS). To 37 patients with recent-onset schizophrenia and related disorders and comorbid OCS taken from 135 consecutively admitted patients we administered the Y-BOCS at admission and 6 weeks later. The Y-BOCS showed good internal consistency and interrater reliability in this population; however, findings concerning the divergent validity against depressive and negative symptoms are inconsistent.

Substance use, substance use disorders, and comorbidity patterns in a representative sample of incarcerated male Dutch adolescents.

The aim of this study was to investigate the prevalence of substance use and substance use disorders (SUDs) among incarcerated boys, and comorbidity patterns and the relationship between SUDs and violent offending and criminal recidivism. The presence of SUDs and other psychiatric disorders was assessed in a representative sample of 204 incarcerated boys aged 12 to 18 years using the Diagnostic Interview Schedule for Children (DISC). Ninety-two percent had used alcohol, 86% had used cannabis, and 33% had used other substances. The 6-month prevalence of SUDs was 55%, and 22% reported polysubstance abuse or dependence. SUDs were positively associated with comorbid externalizing and psychotic disorders. Substance dependence was negatively associated with violent offending but not with criminal recidivism. These high prevalence rates call for more attention to diagnosis and management of SUDs among incarcerated male adolescents. The negative association between substance dependence and the violent nature of the index offense needs further investigation.