COMT Val158Met-stress interaction in psychosis: role of background psychosis risk

Background: The interplay between the catechol‐O‐methyltransferase (COMT) Val158Met polymorphism and environmental stress may have etiological relevance for psychosis, but differential effects have been reported in healthy control and patient groups, suggesting that COMT Val158Met interactions with stress may be conditional on background genetic risk for psychotic disorder. Methods: Patients with a nonaffective psychotic disorder (n = 86) and control participants (n = 109) were studied with the experience sampling method (a structured diary technique) in order to assess stress, negative affect and momentary psychotic symptoms in the flow of daily life. Results: Multilevel analyses revealed significant three‐way interactions between group status (patient or control), COMT genotype and stress in the model of negative affect (χ²(2) = 13.26, P < 0.01) as well as in the model of momentary psychotic symptoms (χ²(2) = 6.92, P < 0.05). Exploration of the three‐way interaction revealed that in patients, COMT genotype moderated the association between stress and negative affect (χ²(4) = 11.50, P < 0.005), as well as the association between stress and momentary psychosis (χ²(4) = 12.79, P < 0.005). Met/Met genotype patients showed significantly increased psychotic and affective reactivity to stress in comparison to the Val/Met and Val/Val genotypes. In contrast, healthy controls did not display large or significant COMT Val158Met X stress interactions. Conclusions: Important differences exist in the effect of COMT Val158Met on stress reactivity, which may depend on background risk for psychotic disorder. Differential sensitivity to environmental stress occasioned by COMT Val158Met may be contingent on higher order interactions with genetic variation underlying psychotic disorder.     

Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress

Peerbooms O, Rutten BPF, Collip D, Lardinois M, Lataster T, Thewissen V, Mafi Rad S, Drukker M, Kenis G, van Os J, Myin‐Germeys I, van Winkel R. Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress. Objective: A functional interaction between Catechol‐O‐Methyltransferase (COMT) Val158Met and methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to differentially affect cognition in patients with schizophrenia and healthy controls; the effect of COMT Val158Met × MTHFR interaction on resilience to stress in patients and controls remains to be examined. Method: A total of 98 patients with non‐affective psychotic disorder and 118 controls were genotyped for MTHFR C677T, MTHFR A1298C, and COMTVal158Met. Daily life reactivity to stress, modelled as the effect of daily life stress on psychotic experiences, was measured using the experience sampling method (ESM). Results: The MTHFR C677T genotype moderated the interaction between COMT Val158Met genotype and stress in patients (P < 0.0001), but not in controls (P = 0.68). Further examination of this interaction revealed that in patients with the MTHFR 677 T‐allele, COMT Met/Met individuals displayed the largest increases in psychotic symptoms in reaction to ESM stress [χ²(2) = 29.51; P < 0.0001], whereas in patients with the MTHFR 677 C/C genotype no significant COMT Val158Met × ESM stress interaction was apparent [χ²(2) = 3.65; P = 0.16]. No moderating effect of MTHFR A1298C was found. Conclusion: Stress reactivity associated with COMT Val158Met in patients with psychosis may crucially depend on MTHFR C677T genotype.     

Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism

Estrada G, Fatjó‐Vilas M, Muñoz MJ, Pulido G, Miñano MJ, Toledo E, Illa JM, Martín M, Miralles ML, Miret S, Campanera S, Bernabeu C, Navarro ME, Fañanás L. Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism. Objective: To examine, in a sample of young psychiatric patients, (n = 157, mean age 17.01 years (SD = 3.6)) whether i) age at first cannabis use and age at emergence of psychiatric disorders are related and ii) such a relationship is modulated by the Val158Met polymorphism in the COMT gene. Method: Cannabis use profiles and COMT Val158Met genotypes were obtained from 80 inpatients with schizophrenia‐spectrum disorders and 77 inpatients with other non‐psychotic disorders. Results: First, age at first cannabis use correlates with age at onset in both schizophrenia‐spectrum and other psychiatric disorder groups: those who started using cannabis earlier had an earlier age at onset of psychiatric disorders. Second, the distribution of the Val158Met genotypes was not different either between diagnosis groups or between cannabis users and non‐users. Third, an interaction between Val158Met genotypes and cannabis use was observed specifically on age at emergence of psychotic disorders, with Val/Val genotype carriers showing an earlier age at onset than Met carriers. Conclusion: Our results suggest the importance of brain maturation timing in which exposure to cannabis occurs. The COMT Val158Met genotype seems to modulate the association between cannabis and age at onset of psychotic disorders. These results are consistent with previous studies.     

The catechol o‐methyltransferase (COMT) val158met polymorphism modulates the association of serious life events (SLE) and impulsive aggression in female patients with borderline personality disorder (BPD)

Wagner S, Baskaya Ö, Anicker NJ, Dahmen N, Lieb K, Tadi? A. The catechol o‐methyltransferase (COMT) val¹⁵⁸met polymorphism modulates the association of serious life events (SLE) and impulsive aggression in female patients with borderline personality disorder (BPD). Objective: We analyzed i) the effects of serious life events (SLE) on impulsive aggression, and ii) modulating effects of the COMT Val¹⁵⁸Met polymorphism on the association between SLEs and impulsive aggression in borderline personality disorder (BPD). Method: One hundred and twelve female BPD patients from Germany were included in this study. Impulsive aggression was assessed by the Buss‐Durkee‐Hostility Inventory (BDHI). Results: Childhood sexual abuse was associated with lower BDHI sum score (P = 0.003). In COMT Val¹⁵⁸Val carriers, but not in Val/Met and Met/Met carriers, childhood sexual abuse and the cumulative number of SLEs were associated with lower BDHI sum scores (P < 0.05). Conclusion: This study analyzing a specific gene × environment interaction in female BPD patients suggests an association between SLEs and impulsive aggression, as well as a modulating effect of the COMT Val¹⁵⁸Val genotype on the relation between SLEs and impulsive aggression.     

Impact of COMT Val158Met‐polymorphism on appetitive conditioning and amygdala/prefrontal effective connectivity

Appetitive conditioning is an important mechanism for the development, maintenance, and treatment of psychiatric disorders like substance abuse. Therefore, it is important to identify genetic variations, which impact appetitive conditioning. It has been suggested that the Val¹⁵⁸Met‐polymorphism in the Catechol‐O‐Methyl‐Transferase (COMT) is associated with the alteration of neural processes of appetitive conditioning due to the central role of the dopaminergic system in reward processing. However, no study has so far investigated the relationship between variations in the COMT Val¹⁵⁸Met‐polymorphism and appetitive conditioning. In this fMRI study, an appetitive conditioning paradigm was applied, in which one neutral stimulus (CS+) predicted appetitive stimuli (UCS) while a second neutral stimulus (CS?) was never paired with the UCS. As a main result, we observed a significant association between the COMT Val¹⁵⁸Met‐genotype and appetitive conditioning: skin conductance responses (SCRs) revealed a significant difference between CS+ and CS? in Val/Val‐allele carriers but not in the other genotype groups. Val/Val‐allele carriers showed increased hemodynamic responses in the amygdala compared with the Met/Met‐allele group in the contrast CS+ > CS?. In addition, psychophysiological‐interaction analysis revealed increased effective amygdala/ventromedial prefrontal cortex connectivity in Met/Met‐allele carriers. The increased amygdala activity points to facilitated appetitive conditioning in Val/Val‐allele carriers while the amygdala/prefrontal connectivity results could be regarded as a marker for altered emotion regulation during conditioning, which potentially impacts appetitive learning sensitivity. The SCRs finding indicates a stronger conditioned response in the Val/Val‐allele group and dovetails with the neural differences between the groups. These findings contribute to the current research on COMT in emotional processing. Hum Brain Mapp 36:1093–1101, 2015. © 2014 Wiley Periodicals, Inc.     

The flexible mind is associated with the catechol-O-methyltransferase (COMT) ValMet polymorphism: Evidence for a role of dopamine in the control of task-switching

Genetic variability related to the catechol-O-methyltransferase (COMT) gene (Val¹⁵⁸Met polymorphism) has received increasing attention as a possible modulator of cognitive control functions. Recent evidence suggests that the Val¹⁵⁸Met genotype may differentially affect cognitive stability and flexibility, in such a way that Val/Val homozygous individuals (who possess low prefrontal dopamine levels) may show more pronounced cognitive flexibility than Met/-carriers (who possess high prefrontal dopamine levels). To test this, healthy humans (n = 87), genotyped for the Val¹⁵⁸Met polymorphism at the COMT gene, performed a task-switching paradigm, which provides a relatively diagnostic index of cognitive flexibility. As predicted, Met/-carriers showed larger switching costs (i.e., less cognitive flexibility), F(1,85) = 4.28, p < 0.05, than Val/Val homozygous individuals. Our findings support the idea that low prefrontal dopamine levels promote cognitive flexibility.     

Executive attention in schizophrenic males and the impact of COMT Val108/158Met genotype on performance on the attention network test

Background: Executive control of attention in schizophrenia has recently been assessed by means of the Attention Network Test (ANT). In the past, for tasks assessing executive attention, findings in schizophrenia have been contradictory, among others suggesting a lack of increased stimulus interference effects. Attention and executive functioning are substantially influenced by candidate genes of schizophrenia, including the functional single-nucleotide polymorphism catechol-o-methyltransferase (COMT) Val^108/158Met, with task-dependent, specific effects of Met allele load on cognitive function. Therefore, we aimed at investigating executive attention in schizophrenic patients (SZP) as compared with healthy controls (HC), and to assess the specific impact of COMT Val^108/158Met on executive attention, using ANT. Methods: We applied ANT to 63 SZP and 40 HC. We calculated a general linear model to investigate the influence of affection status and the COMT Val^108/158Met genotype on executive attention as assessed by the ANT. Results: Multivariate analysis of variance revealed a significant effect of group on executive attention. SZP exhibited smaller conflict effects in the ANT. Met allele load significantly modulated executive attention efficiency, with homozygous Met individuals showing low overall reaction time but increased effects conflicting stimulus information in executive attention. Conclusions: Our data suggest a disease-related dissociation of executive attention with reduced conflict effects in SZP. Furthermore, they support the hypothesis of differential tonic-phasic dopamine activation and specific dopamine level effects in different cognitive tasks, which helps interpreting contradictory findings of Met allele load on cognitive performance. Disease status seems to modulate the impact of COMT Val^108/158Met on cognitive performance.     

Association between Novelty Seeking of opiate-dependent patients and the catechol-O-methyltransferase ValMet polymorphism

Background

Candidate genes of the dopaminergic system have been reported as key elements in shaping human temperament. Catechol-O-methyltransferase (COMT) plays a vital role in dopamine inactivation, and the Val¹⁵⁸Met single nucleotide polymorphism (rs4680) in its gene has been recently associated with the Novelty Seeking (NS) temperament scale of the Temperament and Character Inventory in studies of healthy adults, as well as methamphetamine abusers.

Method

Our goal was to examine the association between temperament dimensions of the Temperament and Character Inventory and the COMT Val¹⁵⁸Met variation in a Hungarian sample of 117 heroin-dependent patients and 124 nondependent controls.

Results

Case-control analysis did not show any significant difference in allele or genotype distributions. However, dimensional approach revealed an association between the COMT Val¹⁵⁸Met and NS (P = .01): both controls and opiate users with Met/Met genotypes showed higher NS scores compared to those with the Val allele. The NS scores are also significantly higher among opiate users; however, no interaction was found between group status and COMT genotype.

Conclusion

Association of the COMT polymorphism and NS temperament scale has been shown for heroin-dependent patients and controls regardless of group status.     

Association analysis between gene variants of the tyrosine hydroxylase and the serotonin transporter in borderline personality disorder

Abstract

objectives. For patients with borderline personality disorder (BPD), we previously reported an independent effect of the catechol-o-methyl-transferase (COMT) low-activity (Met¹⁵⁸) allele and an interaction with the low-expression allele of the deletion/insertion (short/long or S/L, resp.) polymorphism in the serotonin transporter-linked promoter region (5-HTTLPR). The purpose of the present study was to extend these findings to the tyrosine hydroxylase (TH) Val⁸¹Met single nucleotide polymorphism (SNP), the 5-HTTLPR S/L polymorphism incorporating the recently described functional A/G SNP within the long allele of the 5-HTTLPR (rs25531) as well as the variable number of tandem repeat (VNTR) polymorphism within intron 2 of the serotonin transporter gene (STin2). Methods. In 156 Caucasian BPD patients and 152 healthy controls, we tested for association between BPD and the TH Val⁸¹Met SNP, the 5-HTTLPR/rs25531 polymorphism, the STin2, the interaction of the TH Val⁸¹Met SNP with the tri-allelic 5-HTTLPR/rs25531, the interaction of the TH Val⁸¹Met SNP with STin2. Results. Between BPD patients and controls, we observed a slight over-representation of the TH Met⁸¹Met genotype in BPD patients compared to controls, but no statistically significant differences in genotype distribution of the individual markers after adjusting for multiple testing. Logistic regression analysis showed a lack of interaction between the TH Val⁸¹Met and the 5-HTTLPR/rs25531 as well as between the TH Val⁸¹Met and the STin2 polymorphism. Conclusions. These data do not suggest independent or interactive effects of the TH Val⁸¹Met, the 5-HTTLPR/rs25531, or the STin2 polymorphisms in BPD.     

COMT Val158Met polymorphism is related with interpersonal problem solving in schizophrenia

ObjectiveThe aim of this study was to investigate associations between COMT Val¹⁵⁸Met polymorphism, and interpersonal problem solving capacity and cognitive functions in schizophrenia.MethodsCOMT Val¹⁵⁸Met polymorphism was studied with ARMS-PCR method in 99 outpatients with schizophrenia. Brief Psychiatric Rating Scale was used to assess symptom severity. The Assessment of Interpersonal Problem Solving Skills (AIPSS) was used to evaluate problem solving capacity. Continuous Performance Test (CPT) and Wisconsin Card Sorting Test (WCST), were used to measure cognition.ResultsPatients with Met/Met genotype had higher AIPSS subscores for detecting the problem, than those with Val/Val at baseline (p = 0.02). Met allele was also found to be related with higher AIPSS-receiving skills (p = 0.04). Val allele was found to be related with more commission errors in CPT (p = 0.03). There was no relation between Val¹⁵⁸Met polymorphism and WCST and clinical measurements.ConclusionOur findings suggest that Val allele might be related to poor performance on detecting the interpersonal problems, and attention in schizophrenia.     

Catechol-O-methyltransferase Val158Met polymorphism and negative symptoms after acute antipsychotic treatment in first-episode non-affective psychosis

Genetic factors play an important role in the understanding of clinical response to antipsychotic treatments. We aimed to assess the effect of the catechol-O-methyltransferase (COMT) genotype in the short-term (6 weeks) clinical response of 161 first-episode psychosis patients. COMT genotype was not related to clinical response at 6 weeks. Val homozygote patients showed higher negative symptoms than Met homozygote patients. The COMT Val158 genotype seems to be related to the severity of negative symptoms rather than to clinical response.     

Effect of COMT Val108/158Met Genotype on Risk for Polydipsia in Chronic Patients with Schizophrenia

Polydipsia is a serious condition often seen among patients with schizophrenia (SCZ). The cause of polydipsia is unknown; hence, it is hard to treat or manage. Animal studies showed that the drinking behavior is regulated by central dopaminergic neurotransmission at the hypothalamus. Meanwhile, the existence of a genetic predisposition to polydipsia in patients with SCZ has been suggested. The purpose of this study was to assess whether a functional polymorphism, Val^108/158Met in the gene for catechol-O-methyltransferase (COMT), is associated with susceptibility to polydipsia using a Japanese sample of SCZ. Our sample includes 330 chronic patients with SCZ (83 polydipsic patients and 247 non-polydipsic controls). The common COMT Val^108/158Met polymorphism was genotyped, and the differences in genotype distribution and allele frequency between cases and controls were evaluated using the χ ² test. A significant association between the COMT Val^108/158Met polymorphism and polydipsia was found (genotype distribution: χ ² = 13.0, df = 2, p = 0.001; allele frequency: χ ² = 7.50, df = 1, p = 0.006). The high-COMT activity group (Val/Val) was more frequent among patients with polydipsia compared with the low-COMT activity group (Val/Met + Met/Met) [odds ratio (OR) = 2.46]. The association survived after controlling for other possible confounding factors, including gender, age, age of onset, current antipsychotic dose, and smoking status. Our results suggest that the COMT Val^108/158Met genotype may confer susceptibility to polydipsia in SCZ. To our knowledge, this is the first association study between the COMT gene and polydipsia in SCZ. Further studies with larger sample sizes are warranted to confirm present findings.     

The dynamics of symptomatic and non-symptomatic coping with psychotic symptoms in the flow of daily life

Objective: Previous research has suggested that going along with psychotic symptoms (symptomatic coping) is less effective than other coping strategies with psychotic symptoms. This pilot study aims to validate such findings using a momentary assessment strategy of coping with stress in daily life. Method: Patients with psychosis (n = 35) were studied with the Experience Sampling Method (ESM; a structured diary technique) to assess coping with stress in daily life. This was analysed in relation to coping with psychotic symptoms using a previously validated interview (Maastricht Assessment of Coping Strategies). Results: Symptomatic and non‐symptomatic coping were negatively associated with each other. Symptomatic coping was negatively associated with the level of coping in daily life, whereas a positive association was apparent for non‐symptomatic coping. Non‐symptomatic coping, but not symptomatic coping, predicted appraisals of distress associated with psychotic symptoms. Conclusion: Effective coping may be associated with the tendency to develop conscious appraisals of distress associated with psychotic symptoms.     

Influence of cannabis use on incidence of psychosis in people at clinical high risk

Aims

Evidence for case–control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of psychosis. Secondary aims were to assess associations between cannabis use and the persistence of psychotic symptoms, and with functional outcome.

Methods

Current and previous cannabis use were assessed in individuals at clinical high risk of psychosis (n = 334) and healthy controls (n = 67), using a modified version of the Cannabis Experience Questionnaire. Participants were assessed at baseline and followed up for 2 years. Transition to psychosis and persistence of psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States criteria. Level of functioning at follow up was assessed using the Global Assessment of Functioning disability scale.

Results

During follow up, 16.2% of the clinical high-risk sample developed psychosis. Of those who did not become psychotic, 51.4% had persistent symptoms and 48.6% were in remission. There was no significant association between any measure of cannabis use at baseline and either transition to psychosis, the persistence of symptoms, or functional outcome.

Conclusions

These findings contrast with epidemiological data that suggest that cannabis use increases the risk of psychotic disorder.     

Associations between COMTVal158Met polymorphism and cognition: direct or indirect effects?

BACKGROUND: Previous work suggests that reaction time variability (RTV) in attentional tasks, as a measure of cognitive stability, is associated with degree of Val loading in COMT Val(158)Met genotype, and that this association may be relevant for the aetiology of schizophrenia. This study examined (i) to what degree RTV pertaining to tasks of varying cognitive complexity would be associated with increased risk for schizophrenia and (ii) to what degree this would be mediated by Val loading. METHODS: COMT genotyping was investigated in a sample of 23 patients with schizophrenia, 33 first-degree relatives, and 21 controls. All participants performed the Flanker continuous performance test. RESULTS: Schizophrenia liability was associated with number of correct trials of the Flanker test, but not with RTV, and this association was not mediated by COMT Val(158)Met genotype. Similarly, Met loading was associated with number of correct trials and with RTV, but this was not mediated by schizophrenia liability. CONCLUSIONS: Associations between COMT Val(158)Met genotype and RTV do not appear to reflect transmission of schizophrenia liability in families. Differential associations with Val and Met alleles across studies suggest indirect effects through gene-gene interactions or the influence of a functional polymorphism near COMT Val(158)Met.     

COMT,neuropsychological function and brain structure in schizophrenia: a systematic review and neurobiological interpretation

Background

Endophenotypes in genetic psychiatry may increase our understanding of the molecular mechanisms underlying disease risk and its manifestations. We sought to investigate the link between neuropsychological impairments and brain structural abnormalities associated with the COMT Val¹⁵⁸Met polymorphism in patients with schizophrenia to improve understanding of the pathophysiology of this disorder.

Methods

We performed a systematic review using studies identified in PubMed and MEDLINE (from the date of the first available article to July 2012). Our review examined evidence of an association between the COMT Val¹⁵⁸Met polymorphism and both neuropsychological performance and brain structure in patients with psychosis, in their relatives and in healthy individuals (step 1). The review also explored whether the neuropsychological tasks and brain structures identified in step 1 met the criteria for an endophenotype (step 2). Then we evaluated evidence that the neuropsychological endophenotypes identified in step 2 are associated with the brain structure endophenotypes identified in that step (step 3). Finally, we propose a neurobiological interpretation for this evidence.

Results

A poorer performance on the n-back task and the Continuous Performance Test (CPT) and smaller temporal and frontal brain areas were associated with the COMT Val allele in patients with schizophrenia and their relatives and met most of the criteria for an endophenotype. It is possible that the COMT Val¹⁵⁸Met polymorphism therefore contributes to the development of these neuropsychological and brain structural endophenotypes of schizophrenia, in which the prefrontal cortex may represent the neural substrate underlying both n-back and CPT performances.

Limitations

The association between a single genetic variant and an endophenotype does not necessarily imply a causal relationship between them.

Conclusion

This evidence and the proposed interpretation contribute to explain, at least in part, the biological substrate of 4 important endophenotypes that characterize schizophrenia.     

Lack of influence of COMT Val158Met genotype on cognition in first-episode non-affective psychosis

COMT gene is a logical candidate gene for schizophrenia. Moreover, variations in the COMT Val158Met functional polymorphism have been associated with prefrontal cognitive abnormalities among patients with schizophrenia, healthy relatives and controls. In this study, using an epidemiologically-based sample of 130 patients experiencing a first-episode of a non-affective psychosis, we examined whether COMT Val158Met genotype influenced cognitive performance on the phenotypic expression of psychosis. We found no significant differences in any cognitive measure according to COMT genotype. These findings, together with previously published research, put the relationship between COMT genotype and cognitive performance in doubt.     

精神分裂症儿茶酚氧位甲基转移酶功能基因多态性研究

目的 :分析儿茶酚氧位甲基转移酶 (COMT)功能基因多态性与精神分裂症患者精神症状严重程度和抗精神病药急性期治疗疗效的相关性。　方法 :采用多聚酶链反应 限制性内切酶片断长度多态性技术 (PCR RFLP)方法分析 138例首次治疗的精神分裂症患者COMT基因缬氨酸 (Val) 15 8蛋氨酸(Met)功能多态性 ;采用阳性症状和阴性症状量表 (PANSS)评定患者治疗前后精神症状 ,并分析等位基因和基因型与临床指标、治疗前PANSS分值及治疗 10周后PANSS减分率的相关性。　结果 :COMTVal15 8Met基因型在患者组和男女亚组的分布频率均符合Hardy Weinberg定律 ;等位基因和基因型在治疗显效组和未显著进步组分布频率差异均无显著性 ;各基因型亚组及是否携带Met等位基因亚组的临床指标差异均无显著性 ;基因型与治疗前PANSS总分和阴性症状分显著相关 ,而与PANSS总减分率和各分值减分率无显著相关。　结论 :COMTVal/Val基因型主要与首次治疗精神分裂症患者阴性症状相关 ,支持COMTVal等位基因是精神分裂症脑前额皮质多巴胺功能低下的遗传影响因子的研究发现。     

Prefrontal dopamine and the dynamic control of human long-term memory

Dopaminergic projections to the prefrontal cortex support higher-order cognitive functions, and are critically involved in many psychiatric disorders that involve memory deficits, including schizophrenia. The role of prefrontal dopamine in long-term memory, however, is still unclear. We used an imaging genetics approach to examine the hypothesis that dopamine availability in the prefrontal cortex selectively affects the ability to suppress interfering memories. Human participants were scanned via functional magnetic resonance imaging while practicing retrieval of previously studied target information in the face of interference from previously studied non-target information. This retrieval practice (RP) rendered the non-target information less retrievable on a later final test—a phenomenon known as retrieval-induced forgetting (RIF). In total, 54 participants were genotyped for the catechol-O-methyltransferase (COMT) Val^108/158Met polymorphism. The COMT Val^108/158Met genotype showed a selective and linear gene-dose effect on RIF, with the Met allele, which leads to higher prefrontal dopamine availability, being associated with greater RIF. Mirroring the behavioral pattern, the functional magnetic resonance imaging data revealed that Met allele carriers, compared with Val allele carriers, showed a greater response reduction in inhibitory control areas of the right inferior frontal cortex during RP, suggesting that they more efficiently reduced interference. These data support the hypothesis that the cortical dopaminergic system is centrally involved in the dynamic control of human long-term memory, supporting efficient remembering via the adaptive suppression of interfering memories.     

Young people at risk for psychosis: case finding and sample characteristics of the Oulu Brain and Mind Study

Aim: Set within the general population‐based Northern Finland Birth Cohort 1986, the Oulu Brain and Mind Study aims to explore the causes and pathogenesis of psychotic illness by following young people at risk for psychosis due to having a first‐degree relative with psychotic illness or due to having experienced psychotic‐like symptoms themselves. We report the study methods and explore the relationship between these definitions of high risk for psychosis and operational criteria for a prodromal psychosis syndrome based on interview. Methods: Prospectively collected data from earlier follow‐ups of this cohort were combined with health register data to categorize subjects as those with familial risk (n = 272), symptomatic risk (n = 117), psychosis (n = 78), attention deficit hyperactivity disorder (ADHD) (n = 103) and a sample of controls (n = 193) drawn randomly from the remaining cohort. The Structured Interview for Prodromal Syndromes (SIPS) was applied to all, 295 participants together with questionnaires measuring psychosis vulnerability and schizotypal traits. Results: There were 29 (10%) current prodromal cases. Criteria for the current prodromal syndrome were fulfilled by 12% of the familial risk group and 19% of the symptomatic risk group, compared with 5% of the ADHD group and 4% of controls. Conclusion: We successfully detected young people with a prodromal psychosis syndrome although relatively few subjects deemed to be at high risk met the full operational criteria according to the SIPS interview. Combining methods from familial, clinical and psychometric high‐risk approaches provides a tractable method for studying risk of psychosis in the general population.