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PURPOSE: The Severity Indices of Personality Problems 118 (SIPP-118) is a self-report questionnaire that aims to measure core components of (mal)adaptive personality functioning that can change over time. In this study, we aimed to assess the facet strength of the 16 facets across three large clinical samples. METHODS: Data from Norwegian and Dutch psychiatric patients were analyzed in this international multi-center study (N1 = 2814, N2 = 4751, N3 = 2217). Bi-factor modeling was used to assess to what degree the SIPP items tap into an overall general factor. The incremental value (distinctiveness) of the facets was studied using proportional reduction in mean squared error (PRMSE) based statistics. RESULTS: The estimated model showed adequate fit. The explained common variance (ECV) attributable to the general factor equaled 50% for all three samples. All but two facets (stable self-image and frustration tolerance) showed sufficient levels of distinctiveness. The findings were observed to be comparable across the three samples. CONCLUSION: Our findings showed that the general factor was relatively weak, and the facets had a clear incremental value.

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PURPOSE: There is a need to assess the quality of treatment for Substance Use Disorder (SUD), and document SUD patients' health-related quality of life (HRQoL). The study aims to describe Norwegian SUD patients' HRQoL as measured by EQ-5D, compared to a general population sample, and discuss the potential usefulness of the EQ-5D to monitor HRQoL for SUD patients. METHODS: One hundred seventy eight SUD patients (66.3% male) were administered the EQ-5D-3L at treatment start. Patients and general population samples were compared in terms of reported EQ-5D-3L health states, problems by dimension, UK index values, and EQ VAS scores. We investigated specific drug dependence, mental health disorders, sex, age, and education as predictors of EQ-5D-3L values and EQ VAS scores. Anxiety/depression dimension scores were compared to Hopkins symptom Checklist (HSCL-25) scores. RESULTS: 91.6% of the patient sample reported problems on the EQ-5D-3L, with 29.8% reporting extreme problem, compared to 39.8% and 3.0% in the general population sample. Mean index (EQ VAS) score among SUD patients was .59 (59.9) compared to .90 (84.1) in the general population. Regression analyses identified phobic anxiety and cocaine dependence as statistically significant predictors of higher EQ-5D-3L index scores. CONCLUSION: SUD patients report substantially reduced HRQoL, as measured using the EQ-5D-3L. The most frequently reported problems were for the anxiety/depression, pain/discomfort, and usual activities dimensions. The EQ-5D may be a useful and practical instrument for monitoring HRQoL in SUD patients.

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BACKGROUND: Treatment completion is the greatest challenge for the treatment of substance use disorders (SUDs). A previous investigation showed that complementary horse-assisted therapy (cHAT) was associated with higher retention in treatment and completion than standard treatment alone. This randomized controlled trial further explored the benefits of cHAT for patients with SUDs. METHODS: Fifty patients in residential SUD treatment at the Department of Addiction Treatment, Oslo University Hospital, were randomly allocated to either cHAT (cHAT group) or treatment as usual alone (TAU-only group). The primary end-point was treatment completion. Secondary end-points were dropout, transfer to another treatment, and time in treatment. RESULTS: The multinomial logistic regression analysis found no statistically significant association between intervention (cHAT) and treatment outcome (completion, dropout, transferred) among the 37 participants who were ultimately recruited to the study. Some unforeseen challenges were encountered in the study: a high number of subjects transferred to another treatment, variable attendance at cHAT sessions, and long temporary exits. Nevertheless, 44% of participants in the cHAT group completed their treatment, compared with 32% in the TAU-only group; this observation encourages further investigation in a larger sample. CONCLUSIONS: Though no association was identified between cHAT and treatment retention or completion, our study may have been underpowered. Further work in a larger clinical population is needed; observational studies with repeated measures may also be useful for investigating whether cHAT increases retention in treatment or rates of completion, two important factors for successful SUD treatment. Trial registration The trial was registered and approved on 14 October 2011 by the Regional Committee for Medical and Health Research Ethics with registration number 2011/1642 and registered at ClinicalTrials.gov on 21 February 2013 with registration number NCT01795755.

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Objective: Co-occurrence of substance use disorder and personality disorder (PD) is associated with greater functional impairment and mutual deterioration of the prognosis. More information is needed about the extent of personality problems in substance use disorder patients and when these problems can be assessed in a reliable way. The aim of this study was to compare the levels and scale reliability of (mal)adaptive personality functioning in four different samples and to discuss the possible clinical implications. Methods: Personality problems were assessed using the self-report Severity Indices of Personality Problems (SIPP) questionnaire in four samples: (a) 136 patients in the detoxification phase, (b) 187 patients with substance use disorder in long-term inpatient treatment, (c) 1,399 patients with PD in day and outpatient treatment, and (d) a community population of 935 respondents. Scale reliability of the SIPP facets was computed for each sample and levels of personality problems were compared among samples. Results: The scale reliability was acceptable for most of the SIPP facets in both substance use disorder samples. The substance use disorder samples had scores on SIPP that reflected greater personality dysfunction compared with the general community population and at a level similar to the PD population. Conclusions: SIPP appears to be a promising instrument for assessing personality pathology in substance use disorder treatment. The finding of high levels of maladaptive personality functioning in substance use disorder populations challenges the clinical management of the substance use disorder patient group and supports the development of integrated treatment approaches.

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BACKGROUND: Combination of drugs is the main cause of fatal overdose, and polydrug use is associated with greater treatment needs. This study investigates the prevalence and registration of multiple substance dependence. MATERIAL AND METHOD: Substance dependence diagnoses for 147 inpatients at the Department of Addiction Treatment, Oslo University Hospital were registered and reassessed with a focus on the ICD-10 diagnosis F19 (chaotic intake of multiple substances). The resulting diagnoses were also assessed according to ICD-11. RESULTS: Altogether 116 (79 %) out of 147 patients were addicted to two or more drugs. Only 22 (15 %) out of 147 were diagnosed with F19, but this figure increased to 52 (35 %) after reassessment. Using ICD-11 we found a prevalence of the diagnosis 6C4F (multiple substance dependence) of 79 %. INTERPRETATION: We found an underreporting of the ICD-10 diagnosis F19. It is important to use the F19 diagnosis, because polydrug use is underreported, even though it predicts overdose, prognosis and treatment needs.

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INTRODUCTION: Dropout from inpatient treatment for substance use disorder (SUD) is an ongoing challenge. The aim of this study was to identify demographic, substance use, and psychological factors that predict dropout from postdetoxification inpatient SUD treatment. MATERIALS AND METHODS: A total of 454 patients from 5 inpatient SUD centers in Central Norway were consecutively included in this naturalistic, prospective cohort study. RESULTS: A total of 132 patients (28%) did not complete the planned treatment stay (dropped out). Cox regression analysis showed that higher levels of intrinsic motivation for changing personal substance use reduced the dropout risk (adjusted hazard ratio [adjHR]: 0.62, 95% confidence interval [CI]: 0.48-0.79). Higher levels of mental distress were associated with an increased risk for dropout (adjHR: 1.48, 95% CI: 1.11-1.97). CONCLUSIONS: The role of mental health and motivation in reducing dropout risk from inpatient SUD treatment should be targeted in future prospective intervention studies.

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Dropout from substance use disorder treatment is usually investigated and understood from a perspective of quantitative patient-related factors. Patients' own perspectives (user perspective) are rarely reported. This study, therefore, aimed to explore patients' own understanding of their dropout from residential substance use disorder treatment. The participants were 15 males and females, aged 19-29 years, who had dropped out of residential substance use disorder treatment at the Department of Addiction Treatment, Oslo University Hospital, Norway. Qualitative methodology with semistructured interviews was used to explore how the participants described their dropout and their reasons for doing so. Thematic analysis was used as the framework for analyzing the data derived from the interviews. Dropout had different meanings for different participants. It was understood as a break from treatment, as an end to treatment, or as a means of reduced treatment intensity. Against that background, four main themes for dropout were found: drug craving, negative emotions, personal contact, and activity. Patient and treatment factors seem to interact when participants explore reasons for their dropout. A complex pattern of variables is involved. As remedies, participants suggested that substance use disorder treatment should provide more focus on drug craving and training to understand and tolerate emotional discomfort. They also wanted closer contact with the staff during treatment, more activities, and rigorous posttreatment follow-up. These findings from the user perspective have important implications for substance use disorder treatment, clinical and social work practice, management, and research.

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INTRODUCTION: Polysubstance use disorder is prevalent in treatment-seeking patients with substance use disorder (SUD), with a higher risk of developing comorbid psychiatric symptoms, more pervasive deficits in cognitive functions, and inferior treatment results. The present study investigates if individuals with polysubstance use disorder who achieve at least one year of abstinence show greater improvements in satisfaction with life, executive functions, and psychological distress, compared to relapsers and controls. The prospective recovery from polysubstance use disorder assessed with broad output indicators remains understudied. A better understanding of the pattern of recovery of the chosen output indicators could shed light on the recovery process for this group of patients. MATERIAL AND METHODS: We investigated changes in satisfaction with life, executive functions and psychological distress over a period of 12months in patients who remained abstinent and in those who relapsed. Subjects with polysubstance use disorder (N=115) were recruited from outpatient and residential treatment facilities; healthy controls (N=34) were recruited by posters exhibited at social welfare and GP offices. Executive functions were assessed by the Behaviour Rating Inventory of Executive Function-Adult self-report version (BRIEF-A), psychological distress by the Symptom Checklist-90-R (SCL-90-R), and satisfaction with life by the Satisfaction With Life Scale (SWLS). Substance use was assessed by self-reports on the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders Identification Test (DUDIT). Participants were categorized as "relapsers" if they had AUDIT score ≥8, or DUDIT score ≥2 for women and ≥6 for men. RESULTS: Results indicated that the abstinent group had the greatest improvement on all the indicators compared with relapsers and controls. Participants who successfully quit substance use for one year showed improved satisfaction with life, executive functions, and psychological distress compared to participants who relapsed and controls. CONCLUSIONS: Our study provides support for the view that there is a clinically and statistically significant recovery of satisfaction with life, executive functions, and psychological distress for SUD patients following one-year of abstinence. This knowledge highlights the importance of time and continued abstinence. Our findings suggest that a gradual and careful step-up of learning requirement should be adopted, and SUD treatment should initially focus on stabilizing the patient and achieving abstinence, while interventions for co-morbid problems and more cognitively demanding treatment components are more likely to succeed later in the treatment sequence.

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INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is a common comorbid disorder in patients suffering from substance use disorder (SUD). Individuals with co-occurring SUD and ADHD are more likely than SUD patients without ADHD to have developed SUD at a younger age, be polysubstance users, and need inpatient treatment more often. The present study investigates whether individuals with polysubstance use disorder who remain abstinent for a year after entering treatment have a more substantial reduction in ADHD symptoms than those who relapsed and controls. MATERIAL AND METHODS: Subjects were SUD patients (N = 115) and healthy controls (N = 34). ADHD symptoms were assessed using the adult ADHD Self-Report Scale (ASRS). Substance use was assessed by self-reports on the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders Identification Test (DUDIT). Participants were defined as having relapsed if they had an AUDIT score ≥ 8 or a DUDIT score ≥ 2 for women and ≥ 6 for men. RESULTS: Patients who remained abstinent for one year reported a substantial reduction of ADHD symptoms compared to patients who relapsed and controls. CONCLUSIONS: Abstinence alleviates ADHD symptoms among patients with polysubstance use disorder. We suggest that confirmation of an ADHD diagnosis should follow a period of abstinence to avoid identification of false-positive cases.

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INTRODUCTION: Chronic polysubstance abuse (SUD) is associated with neurophysiological and neuroanatomical changes. Neurocognitive impairment tends to affect quality of life, occupational functioning, and the ability to benefit from therapy. Neurocognitive assessment is thus of importance, but costly and not widely available. Therefore, in a busy clinical setting, procedures that include readily available measures targeting core cognitive deficits would be beneficial. This paper investigates the utility of psychometric tests and a questionnaire-based inventory to assess "hot" and "cold" neurocognitive measures of executive functions (EF) in adults with a substance use disorder. Hot decision-making processes are associated with emotional, affective, and visceral responses, while cold executive functions are associated with rational decision-making. MATERIAL AND METHODS: Subjects with polysubstance abuse (n=126) and healthy controls (n=32) were compared on hot (Iowa Gambling Task) and cold (Stroop and the Trail Making Test) measures of EF, in addition to a questionnaire assessing everyday EF related problems (BRIEF-A; Behavior Rating Inventory of Executive Function - Adult, self-report version). Information about the substance abuse and social adjustment were assessed by self-report. Logistic regression analyses were applied to assess independent correlates of SUD status and social adjustment. A multiple linear regression was performed to predict the number of previous treatment attempts. RESULTS: The psychometric test of hot EF (the Iowa Gambling Task) did not differentiate the patients with polysubstance abuse from controls, and was not associated with social adjustment. The psychometric tests of cold EF distinguished somewhat between the groups and were associated with one indicator of social adjustment. The BRIEF-A differentiated between groups on all the clinical scales and was associated with three out of five social adjustment indicators ("criminal lifestyle," "conflict with caregiver," and "stable housing."). CONCLUSIONS: The BRIEF-A inventory was the most sensitive measure of executive function in patients with substance use disorder, followed by measures of cold executive function. BRIEF-A should therefore be considered as an integral part of the clinical routine when assessing patients with SUD.

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BACKGROUND: Keeping substance use disorder patients actively engaged in treatment is a challenge. Horse-assisted therapy (HAT) is increasingly used as a complementary therapy, with claimed motivational and other benefits to physical and psychological health. This naturalistic study aimed to assess HAT's impact on the duration and completion of treatment for young substance users at Oslo University Hospital. METHODS: Discharge and other data were derived from the Youth Addiction Treatment Evaluation Project (YATEP) database for patients (n = 108) admitted during an 18-month period. An intention-to-treat design, and univariate and multivariate analyses were used to compare those receiving treatment as usual (n = 43) with those who received treatment as usual plus HAT (n = 65). RESULTS: Despite a lack of randomization, the baseline characteristics of the two groups were similar. However, more HAT participants completed treatment (56.9 vs 14 %, p < 0.001), remained in treatment for longer (mean 141 vs 70 days, p < 0.001) and had a significantly higher chance of completing their treatment than those not given the HAT program. Excluding time in treatment, and after controlling for the potentially confounding influence of age, sex, education, number and severity of substances used, psychological distress and number of temporary exits, the adjusted odds ratio for treatment completion was 8.4 in the HAT group compared with those not participating in HAT (95 % CI 2.7-26.4, p < 0.001). CONCLUSION: The study found a statistically significant association between HAT participation and time in treatment, and between HAT participation and completion of treatment. This association does not infer causality. However, it adds supporting evidence for the development of an innovative therapy, and warrants investment in further research in relation to its inclusion in substance use disorder treatment.

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Abstract Objectives. Although serotonergic mechanisms have been implicated in pathological gambling (PG), no ligand-based imaging studies have assessed serotonin receptors in individuals with PG. Given its role in substance addictions and its abundance in brain regions implicated in PG, we evaluated serotonin 1B receptors (5-HT1BRs) in PG. Methods. Ten medication-free subjects with PG (mean ± SD age = 36.3 ± 9.4 years, nine men) and ten control comparison (CC) subjects (mean ± SD age = 35.8 ± 9.9 years, nine men) underwent [(11)C]P943 positron emission scanning on a high resolution research tomograph. Results. 5-HT1BR BPND values were similar in PG and CC subjects (P > 0.1). Among PG subjects, scores on the South Oaks Gambling Screen (SOGS) correlated positively with 5-HT1BR BPND values in the ventral striatum (r = 0.66; P = 0.04), putamen (r = 0.67; P = 0.03) and anterior cingulate cortex (r = 0.73; P = 0.02). Conclusions. These findings provide the first evidence that PG severity in humans is linked to increased levels of 5-HT1BRs in regions previously implicated in functional neuroimaging studies of PG. These findings indicate a potential role for serotonergic function in the ventral striatum and anterior cingulate cortex contributing to problem gambling severity and warrant further studies to investigate whether numbers of available 5-HT1BRs might represent a vulnerability factor for PG or develop in relationship to problem gambling.

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UNLABELLED: Previous imaging studies have suggested that there is an age-related decline in brain serotonin (5-hydroxytryptamine) measures in healthy subjects. This paper addresses whether the availability of 5-hydroxytryptamine receptor 1B (5-HT(1B)) is seen to decrease with aging via PET imaging. METHODS: Forty-eight healthy control subjects (mean age ± SD, 30 ± 10 y; age range, 18-61 y; 33 men, 15 women) underwent (11)C-P943 scanning on a high-resolution PET tomograph. Regions were examined with and without gray matter masking, the latter in an attempt to control for age-related gray matter atrophy on nondisplaceable binding potential (BP(ND)) as determined by a validated multilinear reference tissue model. RESULTS: 5-HT(1B) BP(ND) decreased in the cortex at an average rate of 8% per decade without and 9% with gray matter masking. A negative association with age was also observed in all individual cortical regions. Differences in the putamen and pallidum (positive association) were significant after adjustment for multiple comparisons. No sex- or race-related effects on 5-HT(1B) BP(ND) were found in any regions. CONCLUSION: These findings indicate that age is a relevant factor for 5-HT(1B) in the cortex of healthy adults.

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This pilot study tested whether posttraumatic stress disorder (PTSD) patients with impaired conditioned fear acquisition were refractory to open-label duloxetine treatment. Patients with a differential conditioned fear response at pre-treatment subsequently demonstrated significant reductions in PTSD symptoms. These data provide initial evidence of a putative biomarker of selective treatment response in PTSD.

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Bipolar disorder (BPD) is a major medical and social burden, but little is known about the specific pathophysiology of BPD. The key biogenic amines in the aminergic system include serotonin (5-HT), norepinephrine (NE), dopamine (DA), and acetylcholine (ACh). By analyzing these neurotransmitters, this chapter highlights three hypotheses in the pathophysiology of BPD: the biogenic amine hypothesis, the cholinergic-aminergic balance hypothesis, and the permissive hypothesis. Evidence from select studies of cerebrospinal fluid, postmortem subjects, neuroimaging, genetic factors, and pharmacological agents will be used to reconcile these hypotheses. Possible explanations for discrepancies in these hypotheses are given, and directions for future studies are suggested.

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Reduced serotonergic neurotransmission is implicated in impulsive behavior. We studied the triallelic system of the serotonin transporter gene linked polymorphic region (5-HTTLPR) and acute manipulation of serotonin together to further delineate the mechanisms by which serotonergic neurotransmission affects impulsivity. Fifty-two healthy participants (38 men and 14 women) underwent acute tryptophan depletion (ATD) or placebo in a randomized, double-blind, parallel group experiment. Impulsive response style was measured on two versions of the Continuous Performance Task (CPT), and calculated using signal detection theory. We observed a dose-dependent effect for the short (S') allele of the 5-HTTLPR on impulsive response style. Individuals who had the S'/S' genotype were more impulsive than individuals with the L/S' genotype. Participants with the L/S' genotype were more impulsive than those with the L/L genotype. ATD increased impulsivity in men, and decreased impulsivity in women. These data demonstrate for the first time that reduced serotonergic tone as a result of either 5-HTTLPR genotype, or experimental ATD, are both independently and additively, associated with elevated impulsive response style in Caucasian men.

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Rare apoptosis-promoting functional variants in the apoptosis protease activating factor 1 (APAF1) gene were recently reported to co-segregate with major depression in male members of families from Utah. In order to estimate the impact of these variants on risk for major depressive disorder (MDD) in the general population, we surveyed the frequency of the APAF1 putative MDD risk alleles using re-sequencing in a large sample of northern European and European-American subjects, including a large number of males with MDD. The E777K and N782T APAF1 variants previously described by Harlan et al. [Harlan et al. (2006) Mol Psychiatry 11(1):76-85] were found at low frequencies in affected individuals and population controls. The C450W and Q465R variants were not detected in any of the 632 subjects sequenced. These results show that the APAF1 variants associated with risk for MDD in the Utah pedigrees are very rare in Northern European and European-American populations. In addition, the E777K and N782T variants were found at low frequencies both in patients and population controls, suggesting that these variants have limited impact on risk for MDD.

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Rapid tryptophan depletion studies investigate serotonin using amino acid precursor depletion, which transiently reduces the brain level of serotonin. This study compares the effects of serotonin reduction given on the first test day (when the situation is novel) with the effects of serotonin reduction given on the second test day (when the environment and test battery are familiar). A total of 24 healthy young males were given either active tryptophan depletion or placebo in this randomized cross-over design, while impulsivity was measured by a continuous performance test. The participants showed more impulsive responses and reduced attention during tryptophan depletion, but only when this was given on the first test day when the task was novel. This could be caused by a synergic effect between novel situations and reduced neurotransmission of serotonin.

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BACKGROUND: Serotonin (5-HT) plays a central role in mood regulation and impulsivity. We studied whether healthy men and women react differently on mood and impulsivity measures during acute tryptophan depletion (ATD). We also studied the relative contribution of a functional length triallelic polymorphism in the promoter region of the serotonin transporter, designated 5-HTTLPR, to the behavioral responses to ATD. METHODS: Thirty-nine men and 44 women participated in a randomized, double-blind, parallel group ATD study. Behavioral measures of impulsivity and mood were obtained. RESULTS: During ATD, women reported mood reduction and showed a cautious response style, which is commonly associated with depression. Men showed an impulsive response style and did not report mood reduction. The 5-HTTLPR influenced the mood response to ATD in women. CONCLUSIONS: Healthy men became more impulsive, whereas healthy women showed mood reduction in response to ATD. This suggests that 5-HT could be one mechanism contributing to the sex differences in the prevalence of mood and impulsivity disorders. The influence of 5-HTTLPR on mood responses in women further substantiates the relevance of this variant in the pathophysiology of at least a subgroup of patients with major depressive disorder.

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