The effects of FreeSurfer version, workstation type, and Macintosh operating system version on anatomical volume and cortical thickness measurements.

FreeSurfer is a popular software package to measure cortical thickness and volume of neuroanatomical structures. However, little if any is known about measurement reliability across various data processing conditions. Using a set of 30 anatomical T1-weighted 3T MRI scans, we investigated the effects of data processing variables such as FreeSurfer version (v4.3.1, v4.5.0, and v5.0.0), workstation (Macintosh and Hewlett-Packard), and Macintosh operating system version (OSX 10.5 and OSX 10.6). Significant differences were revealed between FreeSurfer version v5.0.0 and the two earlier versions. These differences were on average 8.8 ± 6.6% (range 1.3-64.0%) (volume) and 2.8 ± 1.3% (1.1-7.7%) (cortical thickness). About a factor two smaller differences were detected between Macintosh and Hewlett-Packard workstations and between OSX 10.5 and OSX 10.6. The observed differences are similar in magnitude as effect sizes reported in accuracy evaluations and neurodegenerative studies.The main conclusion is that in the context of an ongoing study, users are discouraged to update to a new major release of either FreeSurfer or operating system or to switch to a different type of workstation without repeating the analysis; results thus give a quantitative support to successive recommendations stated by FreeSurfer developers over the years. Moreover, in view of the large and significant cross-version differences, it is concluded that formal assessment of the accuracy of FreeSurfer is desirable.

Prediction of transition from common adolescent bipolar experiences to bipolar disorder: 10-year study.

BACKGROUND: Although (hypo)manic symptoms are common in adolescence, transition to adult bipolar disorder is infrequent. AIMS: To examine whether the risk of transition to bipolar disorder is conditional on the extent of persistence of subthreshold affective phenotypes. METHOD: In a 10-year prospective community cohort study of 3021 adolescents and young adults, the association between persistence of affective symptoms over 3 years and the 10-year clinical outcomes of incident DSM-IV (hypo)manic episodes and incident use of mental healthcare was assessed. RESULTS: Transition to clinical outcome was associated with persistence of symptoms in a dose-dependent manner. Around 30-40% of clinical outcomes could be traced to prior persistence of affective symptoms. CONCLUSIONS: In a substantial proportion of individuals, onset of clinical bipolar disorder may be seen as the poor outcome of a developmentally common and usually transitory non-clinical bipolar phenotype.

A community study of psychosocial functioning and weight in young children and adolescents.

BACKGROUND: Children with either underweight or overweight may be at risk for mental health problems and require mental health service use. The present study investigated the relationship between weight status and psychosocial dysfunctioning in children of two different age groups (5-6 and 13-14 years). METHODS: Using height and weight measurements collected during routine medical examinations of all children in a circumscribed geographical region, measures of underweight and overweight were calculated in young children (aged 5-6 years; n=797) and in adolescents (13-14 years; n=614). In addition, parent-reported questionnaires (young children) and adolescent-reported questionnaires (adolescents), including the Strengths and Difficulties Questionnaire (SDQ), provided information on psychopathology subscales including emotional symptoms, conduct problems, hyperactivity-inattention, peer problems and prosocial behaviour. RESULTS: Few associations were apparent after controlling for confounding variables. Young children who were underweight (but not severely underweight) less frequently displayed conduct problems, while adolescents who were overweight or obese reported more peer problems and less prosocial behaviour than did children of normal weight. Children who were underweight and children who were overweight did not score higher on any of the other psychopathology scales than did children of normal weight in either age group. CONCLUSION: Our findings suggest that the domains of weight problems and psychopathology do not display strong associations. However, there are indications that some areas of psychopathology may be differentially associated with weight problems. Further longitudinal research is warranted.

The psychology of psychiatric genetics: evidence that positive emotions in females moderate genetic sensitivity to social stress associated with the BDNF Val-sup-6-sup-6Met polymorphism.

Previous work indicated protective effects of positive emotions on genetically influenced stress sensitivity. Given the fact that expression of brain-derived-neurotrophic-factor (BDNF) is associated with stress-induced behavioral changes, it was hypothesized that the BDNF Val-sup-6-sup-6Met genotype may mediate genetic effects on stress sensitivity, conditional on the level of concurrent positive emotions. Subjects (n=446) participated in a momentary assessment study, collecting appraisals of stress and affect in the flow of daily life. Multilevel regression analyses examined moderation of daily life stress-induced negative affect (NA) by BDNF genotype, and to what degree this was conditional on concurrent positive emotions. Results showed that heterozygous BDNF "Met" carriers exhibited an increased NA response to social stress compared with "Val/Val" subjects. Positive emotions at the time of the stressor decreased BDNF genetic moderation of the NA response to social stress in a dose-response fashion. This effect was most pronounced in BDNF Met carriers. Thus, the impact of BDNF genotype on stress sensitivity is conditional on the experience of positive emotions. Interdisciplinary research in psychology and psychiatric genetics may lead to the improvement of treatment choices in stress-related disorders.

Susceptibility to depression expressed as alterations in cortisol day curve: a cross-twin, cross-trait study.

OBJECTIVE: To examine, using a cross-twin cross-trait design, the hypotheses 1) that the genetic and environmental susceptibility to depression is expressed, in part, as alterations in cortisol day curves and 2) that cortisol abnormalities are not merely the consequence of depressive states or the stressors associated with its onset. Alteration of diurnal secretion of cortisol is a possible endophenotype of depression, as depressed patients show alterations in cortisol dynamics over the day. METHODS: Salivary cortisol measurements were obtained in a sample of 279 twin pairs at 10 random times a day for 5 days. A structured clinical interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) axis I mood disorder (SCID) was administered. Using multilevel regression analysis, the moderating influence of a lifetime diagnosis of depression in the co-twin on the association between time of day and cortisol concentrations in the proband twin was examined. RESULTS: Diurnal variation in cortisol in the proband twin differed as a function of lifetime diagnosis of depression in the co-twin. In addition, this moderating effect was significantly stronger for dizygotic than for monozygotic twins. CONCLUSIONS: Probands of co-twins with lifetime depression have a different diurnal cortisol profile than those without, suggesting that altered hypothalamic-pituitary-adrenal axis functioning is an indicator of depression susceptibility.

Evidence that the COMTVal158Met polymorphism moderates subclinical psychotic and affective symptoms in unaffected first-degree relatives of patients with schizophrenia.

OBJECTIVES: Psychotic patients with COMT(Val158Met) Met alleles were recently found to display more intense psychotic and affective responses to daily life stressors. We aimed to test the hypothesis that the Met allele is implicated in the development of affective and psychotic symptomatology in subjects genetically at risk for schizophrenia, by testing if unaffected first-degree relatives of patients with schizophrenia who share a Met allele have greater concordance of symptomatology than relatives not sharing a Met allele. METHODS: Unaffected relatives (n=38) were arranged in as many genetically related pairs as possible (n=26), and Met-sharing between Index Unaffected Subject (IUS) and Related Unaffected Subject (RUS) was assessed. Symptomatology was assessed with the Brief Psychiatric Rating Scale (BPRS) total score. RESULTS: Multilevel regression revealed an interaction between RUS BPRS score and Met-sharing in the model of IUS BPRS score (interaction chi(2)=3.78, p=0.05). Stratified analyses revealed that IUS-RUS total BPRS scores were significantly associated in the case of Met-sharing (B=0.57, 95% CI: 0.22-0.93, p=0.002), but were not when there was no Met-sharing. CONCLUSION: These findings support the hypothesis that the Met allele may be involved in the causation of psychopathology, at least in populations with a genetic predisposition to psychosis.

The use of the Camberwell Assessment of Need in treatment: what unmet needs can be met?

BACKGROUND: A useful way of operationalising treatment effects in routine outcome assessment data may be to assess the rate at which unmet needs at time point t change to met needs at time point t + 1. METHODS: Data were obtained from the local Cumulative Needs for Care Register (CNCR), a cumulative data set of needs (Camberwell Assessment of Need), psychopathology, well being and functioning of psychiatric patients living both inside and outside the hospital, in a circumscribed geographical area. RESULTS: In the group of relatively new patients, the number of met needs (sum score) increased over time. Higher unmet needs sum score predicted higher met needs at time point t + 1. Unmet needs in the areas of accommodation, household skills, self-care, safety to others (in new patients only), alcohol, drugs, money and benefits were associated with met needs on these items at time point t + 1, but there was no such association for occupation/daytime activities, psychotic symptoms, psychological distress and self-harm. CONCLUSION: Treatment outcomes in psychiatric practice can be usefully tracked and quantified using the rate of change from unmet to met needs. Needs in the area of the ability to live independently may represent outcomes that are more sensitive to treatment effects than needs in the realm of psychopathology and daytime activities.

Evidence for a relationship between mentalising deficits and paranoia over the psychosis continuum.

OBJECTIVE: Failing of mentalising has been suggested to underlie certain symptoms of psychosis. An as yet unresolved issue is whether mentalising deficits reflect a characteristic which can also be detected in people at risk for psychosis or people with evidence of subclinical expression of psychosis. This study wanted to assess an aspect of mentalising in four groups with different levels of psychosis vulnerability, and to examine associations between mentalising and symptoms of psychosis. METHOD: The study included i) 40 patients with psychosis, ii) 49 non-psychotic first-degree relatives (familial risk), iii) 41 subjects from the general population with a high level of positive psychotic experiences (psychometric risk) and iv) 54 healthy controls. All subjects performed the 'Hinting Task'. RESULTS: There was a significant association between psychosis risk and impairment on the Hinting Task (beta linear trend=0.37, p<0.001). Using the control group as the reference, the association with impairment on the Hinting Task was highest for the patient group (beta=0.46, p<0.001), whereas the familial risk group (beta=0.16, p=0.06) displayed an intermediate probability of failure. The psychometric risk group did not significantly differ from the control group (beta=0.04, p=0.653). In the patient group, impairment on the Hinting Task was associated with current hallucinations and paranoid symptoms. In the familial risk group, there was an association between the Hinting Task and paranoid symptoms. DISCUSSION: These results suggest that vulnerability to psychosis is expressed as an impairment in mentalising, which may have a mediating role in the formation of certain positive symptoms of psychosis.

The BDNF Val(66)Met x 5-HTTLPR x child adversity interaction and depressive symptoms: An attempt at replication.

Kaufman et al. [2006] reported a higher order interaction effect between specific genetic and environmental factors in a model of depressive symptoms, requiring independent replication. BDNF Val(66)Met and 5-HTTLPR genotypes were determined in female participants pertaining to a large ongoing twin study. Participants also filled in questionnaires on childhood adversity and depressive symptoms. Two- and three-way interactions between genetic polymorphisms and early adversity were examined in models of depressive symptoms. BDNF Met allele(s) moderated the effect of early adversity on depressive symptoms (two-way interaction), and this BDNF Met x childhood adversity interaction in turn was moderated by 5-HTTLPR genotype (three-way interaction). However, a main effect of BDNF Met on childhood adversity was also observed, possibly indicating confounding by gene-environment correlation. Higher order interaction effects involving BDNF Val(66)Met, 5-HTTLPR and childhood adversity may contribute to the etiology of depressive illness.

The catechol-O-methyl transferase Val158Met polymorphism and experience of reward in the flow of daily life.

Genetic moderation of experience of reward in response to environmental stimuli is relevant for the study of many psychiatric disorders. Experience of reward, however, is difficult to capture, as it involves small fluctuations in affect in response to small events in the flow of daily life. This study examined a momentary assessment reward phenotype in relation to the catechol-O-methyl transferase (COMT) Val(158)Met polymorphism. A total of 351 participants from a twin study participated in an Experience Sampling Method procedure to collect daily life experiences concerning events, event appraisals, and affect. Reward experience was operationalized, as the effect of event appraisal on positive affect (PA). Associations between COMT Val(158)Met genotype and event appraisal on the one hand and PA on the other were examined using multilevel random regression analysis. Ability to experience reward increased with the number of 'Met' alleles of the subject, and this differential effect of genotype was greater for events that were experienced as more pleasant. The effect size of genotypic moderation was quite large: subjects with the Val/Val genotype generated almost similar amounts of PA from a 'very pleasant event' as Met/Met subjects did from a 'bit pleasant event'. Genetic variation with functional impact on cortical dopamine tone has a strong influence on reward experience in the flow of daily life. Genetic moderation of ecological measures of reward experience is hypothesized to be of major relevance to the development of various behavioral disorders, including depression and addiction.

The relationship between cognitive dysfunction and stress sensitivity in schizophrenia: a replication study.

The aim of the current study was to replicate the finding that cognitive impairments are not or inversely associated with sensitivity to stress in a sample of 25 patients diagnosed with psychotic disorder. The results indicated that impairments in performance on the Trailmaking Test and the Stroop Color Word Test were inversely associated with sensitivity to stress in daily life, whereas impairment in a subtest of the Behavioral Assessment of Dysexecutive Syndrome (BADS) was not associated with stress-sensitivity. The data thus show that in some instances cognitive functioning is not, and in other instances is inversely associated with momentary sensitivity to stress. Cognitive impairment and affective reactivity thus appear to be independent or mutually exclusive mechanisms in psychosis, suggesting competing causal pathways.

Impairment of self-monitoring: part of the endophenotypic risk for psychosis.

BACKGROUND: A disorder of self-monitoring may underlie the positive symptoms of psychosis. The cognitive mechanisms associated with these symptoms may also be detectable in individuals at risk of psychosis. AIMS: To investigate (a) whether patients with psychosis show impaired self-monitoring, (b) to what degree this is associated with positive symptoms, and (c) whether this is associated with liability to psychotic symptoms. METHOD: The sample included: individuals with a lifetime history of non-affective psychosis (n=37), a genetically defined risk group (n=41), a psychometrically defined risk group (n=40), and control group (n=49). All participants carried out an action-recognition task. RESULTS: Number of action-recognition errors was associated with psychosis risk (OR linear trend over 3 levels:1.12, 95% CI1.04-1.20) and differential error rate was associated with the degree of delusional ideation in a dose-response fashion (OR linear trend over 3 levels:1.13, 95% CI1.00-1.26). CONCLUSIONS: Alterations in self-monitoring are associated with psychosis with evidence of specificity for delusional ideation. In the risk state, this is expressed more as failure to recognise self-generated actions, whereas in illness failure to recognise alien sources come to the fore.