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

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

Larger amygdala volume in first-degree relatives of patients with major depression

Objective: Although a heritable contribution to risk for major depressive disorder (MDD) has been established and neural alterations in patients have been identified through neuroimaging, it is unclear which brain abnormalities are related to genetic risk. Studies on brain structure of high-risk subjects – such as individuals carrying a familial liability for the development of MDD – can provide information on the potential usefulness of these measures as intermediate phenotypes of MDD. Methods: 63 healthy first-degree relatives of patients with MDD and 63 healthy controls underwent structural magnetic resonance imaging. Regional gray matter volumes were analyzed via voxel-based morphometry (VBM). Results: Whole-brain analysis revealed significantly larger gray matter volume in the bilateral amygdala in first-degree relatives of patients with MDD. Furthermore, relatives showed significantly larger gray matter volume in anatomical structures found relevant to MDD in previous literature, specifically in the bilateral hippocampus and amygdala as well as the left dorsolateral prefrontal cortex (DLPFC). Bilateral DLPFC volume correlated positively with the experience of negative affect. Conclusions: Larger gray matter volume in healthy relatives of MDD patients point to a possible vulnerability mechanism in MDD etiology and therefore extend knowledge in the field of high-risk approaches in MDD