Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk.

Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings.

Finding Relevant Psychoeducation Content for Adolescents Experiencing Symptoms of Depression: Content Analysis of User-Generated Online Texts.

BACKGROUND: Symptoms of depression are frequent in youth and may develop into more severe mood disorders, suggesting interventions should take place during adolescence. However, young people tend not to share mental problems with friends, family, caregivers, or professionals. Many receive misleading information when searching the internet. Among several attempts to create mental health services for adolescents, technological information platforms based on psychoeducation show promising results. Such development rests on established theories and therapeutic models. To fulfill the therapeutic potential of psychoeducation in health technologies, we lack data-driven research on young peoples' demand for information about depression. OBJECTIVE: Our objective is to gain knowledge about what information is relevant to adolescents with symptoms of depression. From this knowledge, we can develop a population-specific psychoeducation for use in different technology platforms. METHODS: We conducted a qualitative, constructivist-oriented content analysis of questions submitted by adolescents aged 16-20 years to an online public information service. A sample of 100 posts containing questions on depression were randomly selected from a total of 870. For analysis, we developed an a priori codebook from the main information topics of existing psychoeducational programs on youth depression. The distribution of topic prevalence in the total volume of posts containing questions on depression was calculated. RESULTS: With a 95% confidence level and a ±9.2% margin of error, the distribution analysis revealed the following categories to be the most prevalent among adolescents seeking advice about depression: self-management (33%, 61/180), etiology (20%, 36/180), and therapy (20%, 36/180). Self-management concerned subcategories on coping in general and how to open to friends, family, and caregivers. The therapy topic concerned therapy options, prognosis, where to seek help, and how to open up to a professional. We also found young people dichotomizing therapy and self-management as opposite entities. The etiology topic concerned stressors and risk factors. The diagnosis category was less frequently referred to (9%, 17/180). CONCLUSIONS: Self-management, etiology, and therapy are the most prevalent categories among adolescents seeking advice about depression. Young people also dichotomize therapy and self-management as opposite entities. Future research should focus on measures to promote self-management, measures to stimulate expectations of self-efficacy, information about etiology, and information about diagnosis to improve self-monitoring skills, enhancing relapse prevention.

Genetic loci shared between major depression and intelligence with mixed directions of effect.

Genome-wide association studies (GWAS) have identified several common genetic variants influencing major depression and general cognitive abilities, but little is known about whether the two share any of their genetic aetiology. Here we investigate shared genomic architectures between major depression (MD) and general intelligence (INT) with the MiXeR statistical tool and their overlapping susceptibility loci with conjunctional false discovery rate (conjFDR), which evaluate the level of overlap in genetic variants and improve the power for gene discovery between two phenotypes. We analysed GWAS data on MD (n = 480,359) and INT (n = 269,867) to characterize polygenic architecture and identify genetic loci shared between these phenotypes. Despite non-significant genetic correlation (rg = -0.0148, P = 0.50), we observed large polygenic overlap and identified 92 loci shared between MD and INT at conjFDR < 0.05. Among the shared loci, 69 and 64 are new for MD and INT, respectively. Our study demonstrates polygenic overlap between these phenotypes with a balanced mixture of effect.

Genome-wide association study identifies common variants associated with pharmacokinetics of psychotropic drugs.

Individual variation in pharmacokinetics of psychotropic drugs, particularly metabolism, is an important factor to consider in pharmacological treatment in psychiatry. A large proportion of this variance is still not accounted for, but evidence so far suggests the involvement of genetic factors. We performed a genome-wide association study (GWAS) with concentration dose ratio (CDR) as sub-phenotype to assess metabolism rate of psychotropic drugs in a homogenous Norwegian sample of 1334 individuals diagnosed with a severe mental disorder. The GWAS revealed one genome-wide significant marker (rs16935279, p-value=3.95×10(-10), pperm=7.5×10(-4)) located in an intronic region of the lncRNA LOC100505718. Carriers of the minor allele have a lower metabolism rate of antiepileptic drugs compared to major allele carriers. In addition, several nominally significant associations between single nucleotide polymorphisms (SNPs) and CDR for antipsychotic, antidepressant and antiepileptic drugs were disclosed. We consider standardised CDR to be a useful measure of the metabolism rate of a drug. The present findings indicate that common gene variants could affect the metabolism of psychotropic drugs. This warrants further investigations into the functional mechanisms involved as it may lead to identification of predictive markers as well as novel drug targets.

Ten year neurocognitive trajectories in first-episode psychosis.

OBJECTIVE: Neurocognitive impairment is commonly reported at onset of psychotic disorders. However, the long-term neurocognitive course remains largely uninvestigated in first episode psychosis (FEP) and the relationship to clinically significant subgroups even more so. We report 10 year longitudinal neurocognitive development in a sample of FEP patients, and explore whether the trajectories of cognitive course are related to presence of relapse to psychosis, especially within the first year, with a focus on the course of verbal memory. METHOD: Forty-three FEP subjects (51% male, 28 ± 9 years) were followed-up neurocognitively over five assessments spanning 10 years. The test battery was divided into four neurocognitive indices; Executive Function, Verbal Learning, Motor Speed, and Verbal Fluency. The sample was grouped into those relapsing or not within the first, second and fifth year. RESULTS: The four neurocognitive indices showed overall stability over the 10 year period. Significant relapse by index interactions were found for all indices except Executive Function. Follow-up analyses identified a larger significant decrease over time for the encoding measure within Verbal Memory for patients with psychotic relapse in the first year [F (4, 38) = 5.8, p = 0.001, η(2) = 0.40]. CONCLUSIONS: Main findings are long-term stability in neurocognitive functioning in FEP patients, with the exception of verbal memory in patients with psychotic relapse or non-remission early in the course of illness. We conclude that worsening of specific parts of cognitive function may be expected for patients with on-going psychosis, but that the majority of patients do not show significant change in cognitive performance during the first 10 years after being diagnosed.

High prevalence of childhood trauma in patients with schizophrenia spectrum and affective disorder.

OBJECTIVE: Childhood trauma (CT) is a major risk factor for various psychiatric disorders. We wanted to determine the prevalence of CT in a catchment area-based sample of schizophrenia spectrum and affective disorder (including bipolar disorder and depressive episodes with psychotic features) and to explore potential differences in types of CT between the diagnostic groups. METHOD: Three hundred five patients were recruited consecutively from psychiatric units at 3 major hospitals in Oslo, Norway, diagnosed with Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Traumatic childhood events were assessed with Childhood Trauma Questionnaire. RESULTS: Eighty-two percent of the patients had experienced one or more CT events, the most frequent subtype of trauma being emotional neglect. The schizophrenia spectrum group reported significantly more physical abuse and physical neglect than the affective group. CONCLUSION: A high prevalence of CT in patients with severe mental disorder was detected. This reminds us of the importance of exploring this issue when we treat such patients. The mechanisms behind these differences are unclear. Further research is needed to study potential associations between CT and the clinical picture of the disorder.

Previous hospital admissions and disease severity predict the use of antipsychotic combination treatment in patients with schizophrenia.

BACKGROUND: Although not recommended in treatment guidelines, previous studies have shown a frequent use of more than one antipsychotic agent among patients with schizophrenia. The main aims of the present study were to explore the antipsychotic treatment regimen among patients with schizophrenia in a catchment area-based sample and to investigate clinical characteristics associated with antipsychotic combination treatment. METHODS: The study included 329 patients diagnosed with schizophrenia using antipsychotic medication. Patients were recruited from all psychiatric hospitals in Oslo. Diagnoses were obtained by use of the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Additionally, Global Assessment of Functioning (GAF), Positive and Negative Syndrome Scale (PANSS) and number of hospitalisations and pharmacological treatment were assessed. RESULTS: Multiple hospital admissions, low GAF scores and high PANSS scores, were significantly associated with the prescription of combination treatment with two or more antipsychotics. The use of combination treatment increased significantly from the second hospital admission. Combination therapy was not significantly associated with age or gender. Regression models confirmed that an increasing number of hospital admission was the strongest predictor of the use of two or more antipsychotics. CONCLUSIONS: Previous hospital admissions and disease severity measured by high PANSS scores and low GAF scores, predict the use of antipsychotic combination treatment in patients with schizophrenia. Future studies should further explore the use of antipsychotic drug treatment in clinical practice and partly based on such data establish more robust treatment guidelines for patients with persistently high symptom load.

Specific personality traits evoke different countertransference reactions: an empirical study.

The main aim of this study was to examine the relationship between patients' self-reported personality characteristics, treatment outcome and therapists' countertransference reactions. Eleven therapists filled in the Feeling Word Checklist 58 (FWC-58) for each patient admitted to a day treatment program. The patients completed the Circumplex of Interpersonal Problems (CIP) at admission and discharge. Outcome measures were assessed at the end of treatment. At the start of treatment, therapists reported fewer feelings of rejection and being on guard in response to patients who reported high avoidant, exploitable, overly nurturing and intrusive CIP subscale traits. At the end of the treatment, the CIP subscales of being domineering, vindictive and cold correlated with fewer positive and more negative countertransference feelings. The study revealed a strong relationship between improvement and countertransference feelings. This study confirms clinical narratives on relationships between the therapists' countertransference reactions and patients' reported interpersonal problems and outcome.

Staff members' emotional reactions to aggressive and suicidal behavior of inpatients.

OBJECTIVE: This study examined the relationship between the characteristics of inpatients and staff members' emotional reactions to the patients, particularly the extent to which the reactions were related to patients' aggressive or suicidal behavior. METHODS: The Feeling Word Checklist-58 was used to measure staff members' feelings. Two positive and five negative feeling dimensions were examined: important, confident, rejected, on guard, bored, overwhelmed, and inadequate. A total of 253 staff members from a wide variety of psychiatric wards at a university-affiliated hospital in Oslo, Norway, completed a total of 2473 checklists about their emotional reactions to 207 patients. For each patient, a member of the research team used information from ward staff who knew the patient to complete a Social Dysfunction and Aggression Scale measuring whether the patient had been aggressive (outward aggression) or suicidal (inward aggression). RESULTS: Staff reported positive feelings about patients much more frequently than negative feelings. Multiple regression analysis revealed that patient characteristics explained much more of the variance in negative feelings than in positive feelings. Outward aggression explained an average of 22 percent of the variance in scores on the five negative dimensions. Inward aggression explained an average of 12 percent more of the variance in scores on the five negative dimensions. Gender, age, amount of medication, and diagnosis (psychotic or not psychotic) explained only a small proportion of the variance in feeling scores. CONCLUSIONS: Even though the level of negative feelings toward patients was low, patients' aggressive and suicidal behavior explained a large proportion of the variance in negative feelings.

Psychiatric staff members' emotional reactions toward patients. A psychometric evaluation of an extended version of the Feeling Word Checklist (FWC-58).

The study evaluated the psychometric properties of an extended version of the Feeling Word Checklist (FWC-58), which measure the therapists' emotional reactions toward patients. Doctors, psychologists, nurses and aides from 23 wards in seven widely different psychiatric departments completed a total of 3012 forms. The original Feeling Word Checklist (Whyte CR, Constantopoulos C, Bevans HG. Br J Med Psychol 1982;55:187-201) was expanded with 28 feeling words covering more feelings of being invaded, idealized, devalued and of being secure. The rating scale was changed from a two-point (yes/no) scale to a five-point scale ranging from not at all (=0) to very much (=4). The factor analysis revealed ten factors with an eigenvalue equal or greater than 1.0. The two first factors were clearly the strongest but a two-factor solution did not satisfactorily reflect the data. The scree test indicated four to seven factors. We chose a seven-factor solution, as this seemed clinically most meaningful. Based on the factors we developed seven indices which were named: Important, Rejected, Confident, Bored, On guard, Overwhelmed and Inadequate. The subscales had satisfactory internal consistency and described meaningful emotional profiles of the different psychiatric wards and the individual patients. The seven subscales seem well worth to use in further research and in a clinical context.