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Psychopathological aspects of dopaminergic gene polymorphisms in adolescence and young adulthood.

ABSTRACT: Dopamine hypotheses of several psychiatric disorders are based upon the clinical benefits of drugs affecting dopamine transporter or receptors, and have prompted intensive candidate gene research within the dopaminergic system during the last two decades. The aim of this review is to survey the most important findings concerning dopaminergic gene polymorphisms in attention deficit hyperactivity disorder (ADHD), Tourette syndrome (TS), obsessive compulsive disorder, and substance abuse. Also, genetic findings of related phenotypes, such as inattention, impulsivity, aggressive behavior, and novelty seeking personality trait are presented, because recent studies have applied quantitative trait measures using questionnaires, symptom scales, or other objective endophenotypes. Unfortunately, genetic variants with minor effects are problematic to detect in these complex inheritance disorders, often leading to contradictory results. The most consistent association findings relate to ADHD and the dopamine transporter and the dopamine D4 receptor genes. Meta-analyses also support the association between substance abuse and the D2 receptor gene. The dopamine catabolizing enzyme genes, such as monoamine oxidase (MAO) A and catechol-O-methyltransferase (COMT) genes, have been linked to aggressive behaviors.

SUBMITTER: Nemoda Z

PROVIDER: S-EPMC3133854 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Psychopathological aspects of dopaminergic gene polymorphisms in adolescence and young adulthood.

Nemoda Zsofia Z Szekely Anna A Sasvari-Szekely Maria M

Neuroscience and biobehavioral reviews 20110415 8

Dopamine hypotheses of several psychiatric disorders are based upon the clinical benefits of drugs affecting dopamine transporter or receptors, and have prompted intensive candidate gene research within the dopaminergic system during the last two decades. The aim of this review is to survey the most important findings concerning dopaminergic gene polymorphisms in attention deficit hyperactivity disorder (ADHD), Tourette syndrome (TS), obsessive compulsive disorder, and substance abuse. Also, gen ...[more]

PMID: 21527290

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Project description:ImportanceCognitive deficits are core features of mental disorders and are important in predicting long-term prognosis. However, it is still unknown whether individual patterns of cognitive deficits predate specific mental disorders.ObjectiveTo investigate the specificity of the associations of attention, working memory, and inhibition in childhood with borderline personality disorder (BPD), psychosis, depression, and hypomania in adolescence and young adulthood.Design, setting, and participantsThis cohort study obtained data from the Avon Longitudinal Study of Parents and Children in the United Kingdom. All pregnant women resident in Avon, United Kingdom, with an expected date of delivery from April 1, 1991, and December 31, 1992, were eligible. Data analysis was conducted from April 1 to September 30, 2020. The sample initially comprised 13 988 participants who were alive at 1 year of age. For this study, data were available for 6333 individuals reporting on any psychopathological measure at ages 11 to 12 years, 4903 individuals at ages 17 to 18 years, and 2963 individuals at 22 to 23 years.ExposuresSustained attention, selective attention, and attentional control were assessed with the Test of Everyday Attention for Children at age 8 years, and working memory and inhibition were assessed at age 10 years with the Counting Span Task and the stop-signal paradigm, respectively.Main outcomes and measuresSymptoms of BPD were assessed at ages 11 to 12 years, psychotic experiences and depression were examined at ages 17 to 18 years, and hypomania was examined at ages 22 to 23 years.ResultsAmong 5315 individuals included in the statistical analysis, 2551 (48.0%) were male and 2764 (52.0) were female. Higher sustained attention at 8 years was associated with decreased risk of BPD symptoms at ages 11 to 12 years (adjusted odds ratio [aOR], 0.964; 95% CI, 0.933-0.996; P = .03), better performance on inhibition at age 10 years with decreased risk of psychotic experiences at ages 17 to 18 years (aOR, 0.938; 95% CI, 0.890-0.989; P = .02), higher sustained attention at age 8 years with decreased risk of depressive symptoms at ages 17 to 18 years (aOR, 0.969; 95% CI 0.938-0.9997; P = .048), and better performance in working memory at age 10 years with decreased risk of hypomania symptoms at ages 22 to 23 years (aOR, 0.694; 95% CI, 0.529-0.911; P = .008). After controlling for potential psychopathological overlay, all the associations remained, except for working memory and hypomania. Higher sustained attention at age 8 years was associated with decreased risk of BPD symptoms at ages 11 to 12 years (β = -0.05; P < .001) and of depression at ages 17 to 18 years (β = -0.03; P = .04), and better performance in inhibition at age 10 years was associated with decreased risk of psychotic experiences at ages 17 to 18 years (β = -0.03; P = .04).Conclusions and relevanceThese findings suggest that specific cognitive deficits in childhood are distinctively associated with different psychopathological symptoms in young people. Furthermore, these results suggest the potential of early cognitive interventions in childhood as a way of modifying or attenuating risk for subsequent psychopathological symptoms.

Project description:Mixed findings exist in studies comparing brain responses to reward in adolescents and adults. Here we examined the trajectories of brain response, functional connectivity and task-modulated network properties during reward processing with a large-sample longitudinal design. Participants from the IMAGEN study performed a Monetary Incentive Delay task during fMRI at timepoint 1 (T1; n = 1304, mean age=14.44 years old) and timepoint 2 (T2; n = 1241, mean age=19.09 years). The Alcohol Use Disorders Identification Test (AUDIT) was administrated at both T1 and T2 to assess a participant's alcohol use during the past year. Voxel-wise linear mixed effect models were used to compare whole brain response as well as functional connectivity of the ventral striatum (VS) during reward anticipation (large reward vs no-reward cue) between T1 and T2. In addition, task-modulated networks were constructed using generalized psychophysiological interaction analysis and summarized with graph theory metrics. To explore alcohol use in relation to development, participants with no/low alcohol use at T1 but increased alcohol use to hazardous use level at T2 (i.e., participants with AUDIT≤2 at T1 and ≥8 at T2) were compared against those with consistently low scores (i.e., participants with AUDIT≤2 at T1 and ≤7 at T2). Across the whole sample, lower brain response during reward anticipation was observed at T2 compared with T1 in bilateral caudate nucleus, VS, thalamus, midbrain, dorsal anterior cingulate as well as left precentral and postcentral gyrus. Conversely, greater response was observed bilaterally in the inferior and middle frontal gyrus and right precentral and postcentral gyrus at T2 (vs. T1). Increased functional connectivity with VS was found in frontal, temporal, parietal and occipital regions at T2. Graph theory metrics of the task-modulated network showed higher inter-regional connectivity and topological efficiency at T2. Interactive effects between time (T1 vs. T2) and alcohol use group (low vs. high) on the functional connectivity were observed between left middle temporal gyrus and right VS and the characteristic shortest path length of the task-modulated networks. Collectively, these results demonstrate the utility of the MID task as a probe of typical brain response and network properties during development and of differences in these features related to adolescent drinking, a reward-related behaviour associated with heightened risk for future negative health outcomes.

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Psychopathological aspects of dopaminergic gene polymorphisms in adolescence and young adulthood.

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Psychopathological aspects of dopaminergic gene polymorphisms in adolescence and young adulthood.

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