Table_6_Structural and Functional Brain Abnormalities Associated With Exposure to Different Childhood Trauma Subtypes: A Systematic Review of Neuroimaging Findings.DOCX

<p>Background: Childhood trauma subtypes sexual abuse, physical abuse, emotional maltreatment, and neglect may have differential effects on the brain that persist into adulthood. A systematic review of neuroimaging findings supporting these differential effects is as yet lacking.</p><p>Objectives: The present systematic review aims to summarize the findings of controlled neuroimaging trials regarding long-term differential effects of trauma subtypes on the human brain.</p><p>Methods: A systematic literature search was performed using the PubMed and PsycINFO databases from January 2017 up to and including January 2018. Additional papers were identified by a manual search in the reference lists of selected papers and of relevant review articles retrieved by the initial database search. Studies were then assessed for eligibility by the first author. Only original human studies directly comparing neuroimaging findings of exposed and unexposed individuals to well-defined emotional, physical or sexual childhood maltreatment while controlling for the effects of other subtypes were included. A visual summary of extracted data was made for neuroimaging modalities for which comparison between trauma subtypes was feasible, taking the studies' numbers and sample sizes into account.</p><p>Results: The systematic literature search yielded 25 publications. Sexual abuse was associated with structural deficits in the reward circuit and genitosensory cortex and amygdalar hyperreactivity during sad autobiographic memory recall. Emotional maltreatment correlated with abnormalities in fronto-limbic socioemotional networks. In neglected individuals, white matter integrity and connectivity were disturbed in several brain networks involved in a variety of functions. Other abnormalities, such as reduced frontal cortical volume, were common to all maltreatment types.</p><p>Conclusions: There is some evidence for long-term differential effects of trauma subtypes on the human brain. The observed alterations may result from both protective adaptation of and damage to the brain following exposure to threatening life events. Though promising, the current evidence is incomplete, with few brain regions and neuroimaging modalities having been investigated in all subtypes. The comparability of the available evidence is further limited by the heterogeneity of study populations regarding gender, age and comorbid psychopathology. Future neuroimaging studies should take this potentially differential role of childhood trauma subtypes into account.</p

Table_8_Structural and Functional Brain Abnormalities Associated With Exposure to Different Childhood Trauma Subtypes: A Systematic Review of Neuroimaging Findings.DOC

<p>Background: Childhood trauma subtypes sexual abuse, physical abuse, emotional maltreatment, and neglect may have differential effects on the brain that persist into adulthood. A systematic review of neuroimaging findings supporting these differential effects is as yet lacking.</p><p>Objectives: The present systematic review aims to summarize the findings of controlled neuroimaging trials regarding long-term differential effects of trauma subtypes on the human brain.</p><p>Methods: A systematic literature search was performed using the PubMed and PsycINFO databases from January 2017 up to and including January 2018. Additional papers were identified by a manual search in the reference lists of selected papers and of relevant review articles retrieved by the initial database search. Studies were then assessed for eligibility by the first author. Only original human studies directly comparing neuroimaging findings of exposed and unexposed individuals to well-defined emotional, physical or sexual childhood maltreatment while controlling for the effects of other subtypes were included. A visual summary of extracted data was made for neuroimaging modalities for which comparison between trauma subtypes was feasible, taking the studies' numbers and sample sizes into account.</p><p>Results: The systematic literature search yielded 25 publications. Sexual abuse was associated with structural deficits in the reward circuit and genitosensory cortex and amygdalar hyperreactivity during sad autobiographic memory recall. Emotional maltreatment correlated with abnormalities in fronto-limbic socioemotional networks. In neglected individuals, white matter integrity and connectivity were disturbed in several brain networks involved in a variety of functions. Other abnormalities, such as reduced frontal cortical volume, were common to all maltreatment types.</p><p>Conclusions: There is some evidence for long-term differential effects of trauma subtypes on the human brain. The observed alterations may result from both protective adaptation of and damage to the brain following exposure to threatening life events. Though promising, the current evidence is incomplete, with few brain regions and neuroimaging modalities having been investigated in all subtypes. The comparability of the available evidence is further limited by the heterogeneity of study populations regarding gender, age and comorbid psychopathology. Future neuroimaging studies should take this potentially differential role of childhood trauma subtypes into account.</p

Table_5_Structural and Functional Brain Abnormalities Associated With Exposure to Different Childhood Trauma Subtypes: A Systematic Review of Neuroimaging Findings.DOCX

<p>Background: Childhood trauma subtypes sexual abuse, physical abuse, emotional maltreatment, and neglect may have differential effects on the brain that persist into adulthood. A systematic review of neuroimaging findings supporting these differential effects is as yet lacking.</p><p>Objectives: The present systematic review aims to summarize the findings of controlled neuroimaging trials regarding long-term differential effects of trauma subtypes on the human brain.</p><p>Methods: A systematic literature search was performed using the PubMed and PsycINFO databases from January 2017 up to and including January 2018. Additional papers were identified by a manual search in the reference lists of selected papers and of relevant review articles retrieved by the initial database search. Studies were then assessed for eligibility by the first author. Only original human studies directly comparing neuroimaging findings of exposed and unexposed individuals to well-defined emotional, physical or sexual childhood maltreatment while controlling for the effects of other subtypes were included. A visual summary of extracted data was made for neuroimaging modalities for which comparison between trauma subtypes was feasible, taking the studies' numbers and sample sizes into account.</p><p>Results: The systematic literature search yielded 25 publications. Sexual abuse was associated with structural deficits in the reward circuit and genitosensory cortex and amygdalar hyperreactivity during sad autobiographic memory recall. Emotional maltreatment correlated with abnormalities in fronto-limbic socioemotional networks. In neglected individuals, white matter integrity and connectivity were disturbed in several brain networks involved in a variety of functions. Other abnormalities, such as reduced frontal cortical volume, were common to all maltreatment types.</p><p>Conclusions: There is some evidence for long-term differential effects of trauma subtypes on the human brain. The observed alterations may result from both protective adaptation of and damage to the brain following exposure to threatening life events. Though promising, the current evidence is incomplete, with few brain regions and neuroimaging modalities having been investigated in all subtypes. The comparability of the available evidence is further limited by the heterogeneity of study populations regarding gender, age and comorbid psychopathology. Future neuroimaging studies should take this potentially differential role of childhood trauma subtypes into account.</p

Table_3_Structural and Functional Brain Abnormalities Associated With Exposure to Different Childhood Trauma Subtypes: A Systematic Review of Neuroimaging Findings.DOCX

<p>Background: Childhood trauma subtypes sexual abuse, physical abuse, emotional maltreatment, and neglect may have differential effects on the brain that persist into adulthood. A systematic review of neuroimaging findings supporting these differential effects is as yet lacking.</p><p>Objectives: The present systematic review aims to summarize the findings of controlled neuroimaging trials regarding long-term differential effects of trauma subtypes on the human brain.</p><p>Methods: A systematic literature search was performed using the PubMed and PsycINFO databases from January 2017 up to and including January 2018. Additional papers were identified by a manual search in the reference lists of selected papers and of relevant review articles retrieved by the initial database search. Studies were then assessed for eligibility by the first author. Only original human studies directly comparing neuroimaging findings of exposed and unexposed individuals to well-defined emotional, physical or sexual childhood maltreatment while controlling for the effects of other subtypes were included. A visual summary of extracted data was made for neuroimaging modalities for which comparison between trauma subtypes was feasible, taking the studies' numbers and sample sizes into account.</p><p>Results: The systematic literature search yielded 25 publications. Sexual abuse was associated with structural deficits in the reward circuit and genitosensory cortex and amygdalar hyperreactivity during sad autobiographic memory recall. Emotional maltreatment correlated with abnormalities in fronto-limbic socioemotional networks. In neglected individuals, white matter integrity and connectivity were disturbed in several brain networks involved in a variety of functions. Other abnormalities, such as reduced frontal cortical volume, were common to all maltreatment types.</p><p>Conclusions: There is some evidence for long-term differential effects of trauma subtypes on the human brain. The observed alterations may result from both protective adaptation of and damage to the brain following exposure to threatening life events. Though promising, the current evidence is incomplete, with few brain regions and neuroimaging modalities having been investigated in all subtypes. The comparability of the available evidence is further limited by the heterogeneity of study populations regarding gender, age and comorbid psychopathology. Future neuroimaging studies should take this potentially differential role of childhood trauma subtypes into account.</p

Correlation between impulsive choice and action after pharmacological manipulations in rats.

<p>In rats (n = 22), there was no correlation between the effects of (A) amphetamine (0.5 mg/kg, r = .22) and (B) atomoxetine (1 mg/kg, r = .21) on the two impulsivity measures: the Δ indifference point ( = drug challenge minus vehicle) of the delayed reward task and the Δ premature responses ( = drug challenge minus vehicle) in the 5-choice serial reaction time task did not correlate.</p

Correlation between impulsive choice and action in humans.

<p>In humans (n = 100), there was no correlation between impulsive choice (log DDT k value) and impulsive action measured as the ratio of commission errors to correct detections in (A) IMT (r = .11) and (B) DMT (r = .16). Within the IMT/DMT (C) there was a correlation between the ratio of commission errors to correct detections in the IMT and DMT (r = .64).</p

Principal component analysis yielding 3 rotated components <i>(N = 100)</i>.

<p>Factor loadings >0.5 as significant.</p>a<p>k values were obtained by a hyperbolic decay function and log transformed.</p>b<p>IMT and DMT scores were calculated as the ratio of commission errors to correct detections.</p><p> <i>DDT: Delay Discounting Task, IMT: Immediate Memory Task, DMT: Delayed Memory Task, SSRT: Stop Signal Reaction Time, BIS-11: Barratt Impulsiveness Scale.</i></p

Correlation between impulsive choice and action in rats.

<p>In rats (n = 22), there was no correlation between impulsive action, based on premature responses in the 5-CSRTT, and impulsive choice, based on (A) the indifference point (r = −.22) or (B) the log k-value (r = .09) in the DRT. Within the 5-CSRTT (C) there was a correlation (r = .77) between impulsive action with a standard inter trial interval (ITI 5 s) and lengthened inter trial interval (ITI 7 s).</p

Pharmacological manipulation of impulsive choice and action in rats.

<p>In rats (n = 22), the preference for the large reward in the DRT decreased with increasing delays (A) and amphetamine (0.5 mg/kg) decreased impulsive choice in rats, whereas atomoxetine (1 mg/kg) increased impulsive choice. In the 5-CSRTT (B), amphetamine increased premature responding, whereas atomoxetine decreased the number of premature responses. *p<0.05, **p<0.001 compared to vehicle.</p

Common genetic variants influence human subcortical brain structures

The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08?×?10-33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction