42 research outputs found
Neural processing associated with cognitive empathy in pedophilia and child sexual offending
Behavioral studies found evidence for superior cognitive empathy (CE) in pedophilic men without a history of child sexual offending (P - CSO) compared to pedophilic men with a history of child sexual offending (P + CSO). Functional magnetic resonance imaging (fMRI) studies also point to differences between P - CSO and P + CSO. Neural processing associated with CE has not yet been investigated. Therefore, the present study aimed to explore the neural correlates of CE in subjects with pedophilia with (P + CSO) and without (P - CSO) child sexual offending. 15 P + CSO, 15 P - CSO and 24 teleiophilic male controls (TC) performed a CE task during fMRI. We observed reduced activation in the left precuneus (Pcu) and increased activation in the left anterior cingulate cortex (ACC) in P - CSO compared to P + CSO. P - CSO also showed stronger connectivity between these regions, which might reflect a top-down modulation of the Pcu by the ACC toward an increased self-focused emotional reaction in social situations. There was also evidence for increased right superior temporal gyrus activation in P - CSO that might constitute a potentially compensatory recruitment due to the dampened Pcu activation. These findings provide first evidence for altered neural processing of CE in P - CSO and underline the importance of addressing CE in pedophilia and CSO in order to uncover processes relevant to effective prevention of child sexual abuse
Two Sides of One Coin: A Comparison of Clinical and Neurobiological Characteristics of Convicted and Non-Convicted Pedophilic Child Sexual Offenders
High prevalence of child sexual offending stand in contradiction to low conviction rates (one-tenth at most) of child sexual offenders (CSOs). Little is known about possible differences between convicted and non-convicted pedophilic CSOs and why only some become known to the judicial system. This investigation takes a closer look at the two sides of "child sexual offending" by focusing on clinical and neurobiological characteristics of convicted and non-convicted pedophilic CSOs as presented in the Neural Mechanisms Underlying Pedophilia and sexual offending against children (NeMUP)*-study. Seventy-nine male pedophilic CSOs were examined, 48 of them convicted. All participants received a thorough clinical examination including the structured clinical interview (SCID), intelligence, empathy, impulsivity, and criminal history. Sixty-one participants (38 convicted) underwent an inhibition performance task (Go/No-go paradigm) combined with functional magnetic resonance imaging (fMRI). Convicted and non-convicted pedophilic CSOs revealed similar clinical characteristics, inhibition performances, and neuronal activation. However, convicted subjects' age preference was lower (i.e., higher interest in prepubescent children) and they had committed a significantly higher number of sexual offenses against children compared to non-convicted subjects. In conclusion, sexual age preference may represent one of the major driving forces for elevated rates of sexual offenses against children in this sample, and careful clinical assessment thereof should be incorporated in every preventive approach
Exercise as an add-on treatment in individuals with schizophrenia: results from a large multicenter randomized controlled trial
Current treatment methods do not achieve recovery for most individuals with schizophrenia, and symptoms such as negative symptoms and cognitive deficits often persist. Aerobic endurance training has been suggested as a potential add-on treatment targeting both physical and mental health. We performed a large-scale multicenter, rater-blind, parallel-group randomized controlled clinical trial in individuals with stable schizophrenia. Participants underwent a professionally supervised six-month training comprising either aerobic endurance training (AET) or flexibility, strengthening, and balance training (FSBT, control group), follow-up was another six months. The primary endpoint was all-cause discontinuation (ACD); secondary endpoints included effects on psychopathology, cognition, functioning, and cardiovascular risk.
In total, 180 participants were randomized. AET was not superior to FSBT in ACD and most secondary outcomes, with dropout rates of 59.55% and 57.14% in the six-month active phase, respectively. However, both groups showed significant improvements in positive, general, and total symptoms, levels of functioning and in cognitive performance. A higher training frequency additionally promoted further memory domains. Participants with higher baseline cognitive abilities were more likely to respond to the interventions.
Our results support integrating exercise into schizophrenia treatment, while future studies should aim to develop personalized training recommendations to maximize exercise-induced benefits
Novel genetic loci associated with hippocampal volume
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness
Novel genetic loci underlying human intracranial volume identified through genome-wide association
Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five novel loci for intracranial volume and confirmed two known signals. Four of the loci are also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic=0.748), which indicated a similar genetic background and allowed for the identification of four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, Parkinson’s disease, and enriched near genes involved in growth pathways including PI3K–AKT signaling. These findings identify biological underpinnings of intracranial volume and provide genetic support for theories on brain reserve and brain overgrowth
Genetic architecture of subcortical brain structures in 38,851 individuals
Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease
Genetic architecture of subcortical brain structures in 38,851 individuals
Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease
Theory of Mind - Neurogenetic foundations and clinical relevance
Eine Vielzahl von Studien zeigte übereinstimmend, dass die Theory of Mind
(ToM), die Fähigkeit, mentale Zustände verstehen zu können, bei Patienten mit
Schizophrenie und bipolar affektiver Störung beeinträchtigt ist. Damit
übereinstimmend verweisen bildgebende Studien an diesen Patientengruppen auf
veränderte Hirnaktivierungen in Regionen des ToM-Netzwerks: Dem medialen
präfrontalen Kortex (MPFC), der temporo-parietalen Übergangsregion (TPJ) und
dem Precuneus / posterioren Gyrus cinguli (Pcu/PCC). Da beide Störungen eine
hohe Heritabilität besitzen und auch die Fähigkeit zur ToM eine
Erblichkeitskomponente hat, könnten ToM-Veränderungen und ihre
hirnfunktionellen Korrelate einen intermediären Phänotyp beider Störungen
darstellen. Diese Hypothese wird auch dadurch gestützt, dass entsprechende
Auffälligkeiten zuvor bei nicht erkrankten Verwandten von Patienten gefunden
wurden, State-unabhängig zu sein scheinen und durch genetische Risikovarianten
für Schizophrenie und bipolare Störungen beeinflusst werden. Ziel der
vorliegenden Arbeit war es weitergehend zu untersuchen, ob Veränderungen in
der hirnfunktionellen ToM-Verarbeitung bei beiden Störungen Kriterien für
intermediäre Phänotypen erfüllen. Dabei sollte die vorliegende Datenlage um
Studien zu zwei Kriterien für intermediäre Phänotypen erweitert werden: Die
Assoziation mit den Störungen und das erhöhte Vorkommen bei nicht erkrankten
Verwandten. Anliegen von Studie 1 war die Replikation einer zuvor berichteten
Assoziation einer Risikovariante im Gen ZNF804A für Schizophrenie und bipolare
Störungen mit der Aktivität des ToM-Netzwerks bei psychisch nicht erkrankten
Probanden. In Studie 2 wurden Veränderungen im ToM-Netzwerk bei nicht
erkrankten erstgradigen Verwandten von Patienten mit Schizophrenie untersucht
und in Studie 3 wurden hirnfunktionelle Auffälligkeiten sowohl bei Patienten
mit bipolarer Störung als auch bei nicht erkrankten Verwandten untersucht.
Dabei konnte repliziert werden, dass mit zunehmender Risikoallelzahl in einem
Einzelnukleotidpolymorphismus in ZNF804A Hirnaktivität in Kernregionen des
ToM-Netzwerks abnimmt (Studie 1). Überlappend mit diesen Effekten wiesen
Verwandte von Patienten mit Schizophrenie eine verminderte Aktivierung des
MPFC auf (Studie 2). Darüber hinaus beobachtete Hyperaktivierungen in
posterioren ToM-Regionen waren in dieser Gruppe ferner mit subklinischer
paranoider Symptomatik assoziiert. Bei Patienten mit bipolarer Störung fand
sich verminderte Aktivität der bilateralen TPJ sowie reduzierte funktionelle
Konnektivität zwischen der TPJ und dem MPFC (Studie 3). Zwar wiesen Verwandte
von Patienten dieser Störungsgruppe intermediäre Aktivierungs- und
Konnektivitätsmuster auf, doch waren diese Effekte nicht statistisch
signifikant. Die Gruppe der Verwandten zeigte jedoch eine erhöhte rechts-
temporale Aktivierung im Vergleich zu Patienten sowie eine erhöhte
Konnektivität zwischen dieser Region und dem MPFC. Diese Ergebnisse stützen
die Hypothese, dass Veränderungen in der hirnfunktionellen ToM-Verarbeitung
einen intermediären Phänotyp der Schizophrenie darstellen könnten. In Bezug
auf die bipolare Störung ergaben sich hingegen uneinheitliche Befunde, die
weiterer Erforschung bedürfen.A multitude of studies consistently showed that Theory of Mind (ToM), the
ability to understand mental states, is compromised in patients with
schizophrenia and bipolar disorder. Congruently, functional imaging studies in
these patient populations demonstrated altered activity in core regions of the
ToM network, i.e. the medial prefrontal cortex (MPFC), temporo-parietal
junction (TPJ), and precuneus / posterior cingulate cortex (Pcu/PCC). Since
both disorders are highly heritable and ToM abilities have a heritable
component as well, ToM alterations and its functional brain correlates might
qualify for an intermediate phenotype of both disorders. This hypothesis is
supported by findings that abnormalities were also found in unaffected
relatives of patients. Furthermore, they seem to be state-independent, and
they were shown to be affected by genetic risk variants for schizophrenia and
bipolar disorder. Aim of the present study was to further explore whether
alterations in functional ToM processing would fulfill criteria for
intermediate phenotypes in both disorders. The current state of research was
to be expanded by studies on two criteria for intermediate phenotypes: the
association with the disorders and the higher prevalence in unaffected
relatives. Study 1 was conducted in order to investigate whether a previously
shown association of a risk variant for schizophrenia and bipolar disorders in
the gene ZNF804A with activity of the ToM network could be replicated in
healthy controls. Study 2 focused on ToM network alterations in unaffected
first-degree relatives of patients with schizophrenia and study 3 explored
aberrations in patients with bipolar disorder as well as unaffected relatives.
Decreasing activation of core ToM regions with increasing risk allele dosage
of a single nucleotide polymorphism within ZNF804A was successfully replicated
(study 1). Overlapping with these effects, relatives of patients with
schizophrenia exhibited diminished MPFC recruitment (study 2). In addition,
relatives also showed hyperactivity in posterior ToM regions, which correlated
with subclinical paranoid symptomatology. In patients with bipolar disorder
reduced bilateral TPJ activity as well as diminished functional connectivity
between the TPJ and the MPFC was observable (study 3). Though relatives of
patients with bipolar disorder demonstrated intermediate brain activation and
connectivity patterns, these effects were not statistically significant.
Still, relatives showed increased right middle temporal activation and
enhanced connectivity between this area and the MPFC when compared to
patients. These results support the notion that alterations in functional ToM
processing might represent an intermediate phenotype of schizophrenia.
However, findings for bipolar disorder were equivocal and warrant further
investigation
Neural processing associated with cognitive empathy in pedophilia and child sexual offending
Behavioral studies found evidence for superior cognitive empathy (CE) in pedophilic men without a history of child sexual offending (P - CSO) compared to pedophilic men with a history of child sexual offending (P + CSO). Functional magnetic resonance imaging (fMRI) studies also point to differences between P - CSO and P + CSO. Neural processing associated with CE has not yet been investigated. Therefore, the present study aimed to explore the neural correlates of CE in subjects with pedophilia with (P + CSO) and without (P - CSO) child sexual offending. 15 P + CSO, 15 P - CSO and 24 teleiophilic male controls (TC) performed a CE task during fMRI. We observed reduced activation in the left precuneus (Pcu) and increased activation in the left anterior cingulate cortex (ACC) in P - CSO compared to P + CSO. P - CSO also showed stronger connectivity between these regions, which might reflect a top-down modulation of the Pcu by the ACC toward an increased self-focused emotional reaction in social situations. There was also evidence for increased right superior temporal gyrus activation in P - CSO that might constitute a potentially compensatory recruitment due to the dampened Pcu activation. These findings provide first evidence for altered neural processing of CE in P - CSO and underline the importance of addressing CE in pedophilia and CSO in order to uncover processes relevant to effective prevention of child sexual abuse