From nature versus nurture, via nature and nurture, to gene x environment interaction in mental disorders

It is now generally accepted that complex mental disorders are the results of interplay between genetic and environmental factors. This holds out the prospect that by studying G x E interplay we can explain individual variation in vulnerability and resilience to environmental hazards in the development of mental disorders. Furthermore studying G x E findings may give insights in neurobiological mechanisms of psychiatric disorder and so improve individualized treatment and potentially prevention. In this paper, we provide an overview of the state of field with regard to G x E in mental disorders. Strategies for G x E research are introduced. G x E findings from selected mental disorders with onset in childhood or adolescence are reviewed [such as depressive disorders, attention-deficit/hyperactivity disorder (ADHD), obesity, schizophrenia and substance use disorders]. Early seminal studies provided evidence for G x E in the pathogenesis of depression implicating 5-HTTLPR, and conduct problems implicating MAOA. Since then G x E effects have been seen across a wide range of mental disorders (e.g., ADHD, anxiety, schizophrenia, substance abuse disorder) implicating a wide range of measured genes and measured environments (e.g., pre-, peri- and postnatal influences of both a physical and a social nature). To date few of these G x E effects have been sufficiently replicated. Indeed meta-analyses have raised doubts about the robustness of even the most well studied findings. In future we need larger, sufficiently powered studies that include a detailed and sophisticated characterization of both phenotype and the environmental risk.

Factors influencing subjective quality of life in patients with schizophrenia and other mental disorders: a pooled analysis

Subjective quality of life (SQOL) is an important outcome in the treatment of patients with schizophrenia. However, there is only limited evidence on factors influencing SQOL, and little is known about whether the same factors influence SQOL in patients with schizophrenia and other mental disorders. This study aimed to identify the factors associated with SQOL and test whether these factors are equally important in schizophrenia and other disorders. For this we used a pooled data set obtained from 16 studies that had used either the Lancashire Quality of Life Profile or the Manchester Short Assessment of Quality of Life for assessing SQOL. The sample comprised 3936 patients with schizophrenia, mood disorders, and neurotic disorders. After controlling for confounding factors, within-subject clustering, and heterogeneity of findings across studies in linear mixed models, patients with schizophrenia had more favourable SQOL scores than those with mood and neurotic disorders. In all diagnostic groups, older patients, those in employment, and those with lower symptom scores had higher SQOL scores. Whilst the strength of the association between age and SQOL did not differ across diagnostic groups, symptom levels were more strongly associated with SQOL in neurotic than in mood disorders and schizophrenia. The association of employment and SQOL was stronger in mood and neurotic disorders than in schizophrenia. The findings may inform the use and interpretation of SQOL data for patients with schizophrenia.

The missing link between clinical states and biomarkers in mental disorders

Current diagnostic definitions of psychiatric disorders based on collections of symptoms encompass very heterogeneous populations and are thus likely to yield spurious results when exploring biological correlates of mental disturbances. It has been suggested that large studies of biomarkers across diagnostic entities may yield improved clinical information. Such a view is based on the concept of assessment as a collection of symptoms devoid of any clinical judgment and interpretation. Yet, important advances have been made in recent years in clinimetrics, the science of clinical judgment. The current clinical taxonomy in psychiatry, which emphasizes reliability at the cost of clinical validity, does not include effects of comorbid conditions, timing of phenomena, rate of progression of an illness, responses to previous treatments, and other clinical distinctions that demarcate major prognostic and therapeutic differences among patients who otherwise seem to be deceptively similar since they share the same psychiatric diagnosis. Clinimetrics may provide the missing link between clinical states and biomarkers in psychiatry, building pathophysiological bridges from clinical manifestations to their neurobiological counterparts.

Internet-based individually versus group guided self-help treatment for social anxiety disorder: protocol of a randomized controlled trial

BACKGROUND: Social anxiety disorder (SAD) is one of the most common mental disorders and causes subjective suffering and economic burden worldwide. Although effective treatments are available, a lot of cases go untreated. Internet-based self-help is a low-threshold and flexible treatment alternative for SAD. Various studies have already shown that internet-based self-help can be effective to reduce social phobic symptoms significantly. Most of the interventions tested include therapist support, whereas the role of peer support within internet-based self-help has not yet been fully understood. There is evidence suggesting that patients' mutual exchange via integrated discussion forums can increase the efficacy of internet-based treatments. This study aims at investigating the added value of therapist-guided group support on the treatment outcome of internet-based self-help for SAD. METHODS/DESIGN: The study is conducted as a randomized controlled trial. A total of 150 adults with a diagnosis of SAD are randomly assigned to either a waiting-list control group or one of the active conditions. The participants in the two active conditions use the same internet-based self-help program, either with individual support by a psychologist or therapist-guided group support. In the group guided condition, participants can communicate with each other via an integrated, protected discussion forum. Subjects are recruited via topic related websites and links; diagnostic status will be assessed with a telephone interview. The primary outcome variables are symptoms of SAD and diagnostic status after the intervention. Secondary endpoints are general symptomology, depression, quality of life, as well as the primary outcome variables 6 months later. Furthermore, process variables such as group processes, the change in symptoms and working alliance will be studied. DISCUSSION: The results of this study should indicate whether group-guided support could enhance the efficacy of an internet-based self-help treatment for SAD. This novel treatment format, if shown effective, could represent a cost-effective option and could further be modified to treat other conditions, as well.

Effect of preventive interventions in mentally ill parents on the mental health of the offspring: systematic review and meta-analysis

Mental illness in parents affects the mental health of their children. A systematic review and a meta-analysis of the effectiveness of interventions to prevent mental disorders or psychological symptoms in the offspring were performed.

Personality disorders and accentuations in at-risk persons with and without conversion to first-episode psychosis

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Cluster A personality disorders (PDs), particularly schizotypal PD, are considered a part of the schizophrenia spectrum and a risk factor of psychosis. The role of PDs and personality accentuations (PAs) in predicting conversion to psychosis was studied in patients symptomatically considered at risk, assuming a major role of the schizotypal subtype.

Physical long-term health problems and mental comorbidity: evidence from Vietnam

OBJECTIVE: The mental health of children living in low-income countries remains a neglected research area despite the high burden of disease. This study is one of the first that examines the effects of long-term physical health problems on child mental health disorders in a low-income country and investigates whether this association is modified by the socio-economic status of the child's family. METHODS: Community-based cross-sectional survey of 975 eight-year-old children from 20 sites in Vietnam. Long-term physical health problems were measured by a caregiver report and included conditions such as anaemia, congenital malformation, physical disability and skin problems. Child mental disorders were assessed using the strengths and difficulties questionnaire (SDQ). Generalised estimating equations models were fitted to explore the association between long-term physical health problems and child mental disorders. RESULTS: Vietnamese children who suffer from long-term physical health problems have odds 2:1 times greater than children without long-term physical health problems of having a mental disorder (95% CI 1.2 to 3.6, p = 0.006). No significant interaction with socio-economic status was found. CONCLUSIONS: This study showed a high burden of mental disorders among physically ill children, re-enforcing the idea that there is "no health without mental health". While this association needs to be explored longitudinally, children with long-term health problems may be a visible group for targeted mental-health interventions.

Self-Reported Psychotic-Like Experiences Are a Poor Estimate of Clinician-Rated Attenuated and Frank Delusions and Hallucinations

Background: One reason for the decision to delay the introduction of an Attenuated Psychosis Syndrome in the main text of the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders was the concern that attenuated psychotic symptoms (APS) might in fact be common features in adolescents and young adults from the general population of no psychopathological significance in themselves. This concern was based on reports of high prevalence rates of psychotic-like experiences (PLEs) in the general population and the assumption that PLEs are a good estimate of APS. Although the criterion validity of self-reported PLEs had already been studied with respect to clinician-rated psychotic symptoms and found insufficient, it had been argued that PLEs might in fact be more comparable with mild, subclinical expressions of psychotic symptoms and, therefore, with APS. The present paper is the first to specifically study this assumption. Sampling and Methods: The sample consisted of 123 persons seeking help at a service for the early detection of psychosis, of whom 54 had an at-risk mental state or psychosis, 55 had a nonpsychotic mental disorder and 14 had no full-blown mental disorder. PLEs were assessed with the Peters Delusion Inventory and the revised Launay-Slade Hallucination Scale, and psychotic symptoms and APS were assessed with the Structured Interview for Prodromal Syndromes. Results: At a level of agreement between the presence of any PLE (in 98.4% of patients) and any APS (in 40.7%) just exceeding chance (κ = 0.022), the criterion validity of PLEs for APS was insufficient. Even if additional qualifiers (high agreement or distress, preoccupation and conviction) were considered, PLEs (in 52.8%) still tended to significantly overestimate APS, and agreement was only fair (κ = 0.340). Furthermore, the group effect on PLE prevalence was, at most, moderate (Cramer's V ≤ 0.382). Conclusions: The prevalence of APS cannot be deduced from studies of PLEs. Thus, the high population prevalence rate of PLEs does not allow the conclusion that APS are common features of no pathological significance and would lack clinical validity as an Attenuated Psychosis Syndrome in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. Rather, the population prevalence rate of APS has to be assumed to be largely unknown at present but is likely lower than indicated by epidemiological studies of PLEs. Therefore, dedicated studies are warranted, in which APS are assessed in a way that equates to their clinical evaluation.

Adolescence and parental history of alcoholism: insights from the sleep EEG

BACKGROUND Disrupted sleep is a common complaint of individuals with alcohol use disorder and in abstinent alcoholics. Furthermore, among recovering alcoholics, poor sleep predicts relapse to drinking. Whether disrupted sleep in these populations results from prolonged alcohol use or precedes the onset of drinking is not known. The aim of this study was to examine the sleep electroencephalogram (EEG) in alcohol-naïve, parental history positive (PH+), and negative (PH-) boys and girls. METHODS All-night sleep EEG recordings in 2 longitudinal cohorts (child and teen) followed at 1.5 to 3 year intervals were analyzed. The child and teen participants were 9/10 and 15/16 years old at the initial assessment, respectively. Parental history status was classified by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria applied to structured interviews (DIS-IV) resulting in 14 PH- and 10 PH+ children and 14 PH- and 10 PH+ teens. Sleep data were visually scored in 30-second epochs using standard criteria. Power spectra were calculated for EEG derivations C3/A2, C4/A1, O2/A1, O1/A2 for nonrapid eye movement (NREM) and rapid eye movement (REM) sleep. RESULTS We found no difference between PH+ and PH- individuals in either cohort for any visually scored sleep stage variable. Spectral power declined in both cohorts across assessments for NREM and REM sleep in all derivations and across frequencies independent of parental history status. With regard to parental history, NREM sleep EEG power was lower for the delta band in PH+ teens at both assessments for the central derivations. Furthermore, power in the sigma band for the right occipital derivation in both NREM and REM sleep was lower in PH+ children only at the initial assessment. CONCLUSIONS We found no gross signs of sleep disruption as a function of parental history. Modest differences in spectral EEG power between PH+ and PH- children and teens indicate that a marker of parental alcohol history may be detectable in teens at risk for problem drinking.

Associations between mood, anxiety or substance use disorders and inflammatory markers after adjustment for multiple covariates in a population-based study.

Inflammation is one possible mechanism underlying the associations between mental disorders and cardiovascular diseases (CVD). However, studies on mental disorders and inflammation have yielded inconsistent results and the majority did not adjust for potential confounding factors. We examined the associations of several pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and high sensitive C-reactive protein (hsCRP) with lifetime and current mood, anxiety and substance use disorders (SUD), while adjusting for multiple covariates. The sample included 3719 subjects, randomly selected from the general population, who underwent thorough somatic and psychiatric evaluations. Psychiatric diagnoses were made with a semi-structured interview. Major depressive disorder was subtyped into "atypical", "melancholic", "combined atypical-melancholic" and "unspecified". Associations between inflammatory markers and psychiatric diagnoses were assessed using multiple linear and logistic regression models. Lifetime bipolar disorders and atypical depression were associated with increased levels of hsCRP, but not after multivariate adjustment. After multivariate adjustment, SUD remained associated with increased hsCRP levels in men (β = 0.13 (95% CI: 0.03,0.23)) but not in women. After multivariate adjustment, lifetime combined and unspecified depression were associated with decreased levels of IL-6 (β = -0.27 (-0.51,-0.02); β = -0.19 (-0.34,-0.05), respectively) and TNF-α (β = -0.16 (-0.30,-0.01); β = -0.10 (-0.19,-0.02), respectively), whereas current combined and unspecified depression were associated with decreased levels of hsCRP (β = -0.20 (-0.39,-0.02); β = -0.12 (-0.24,-0.01), respectively). Our data suggest that the significant associations between increased hsCRP levels and mood disorders are mainly attributable to the effects of comorbid disorders, medication as well as behavioral and physical CVRFs.