Evidence for interaction between genetic liability and childhood trauma in the development of psychotic symptoms.

PURPOSE: Whilst childhood trauma (CT) is a known risk factor across the spectrum of psychosis expression, little is known about possible interplay with genetic liability. METHODS: The TwinssCan Study collected data in general population twins, focussing on expression of psychosis at the level of subthreshold psychotic experiences. A multilevel mixed-effects linear regression analysis was performed including 745 subjects to assess the interaction between genetic liability and CT. The Symptom Checklist-90 (SCL-90-R) score of the co-twin was used as an indirect measure of genetic liability to psychopathology, while the Childhood Trauma Questionnaire Short-Form (CTQ-SF) was used to assess CT in the domains of physical, emotional and sexual abuse, as well as physical and emotional neglect. The Community Assessment of Psychic Experience (CAPE) questionnaire was used to phenotypically characterize psychosis expression. RESULTS: In the model using the CAPE total score, the interaction between CT and genetic liability was close to statistical significance (χ2 = 5.6, df = 2, p = 0.06). Analyses of CAPE subscales revealed a significant interaction between CT and genetic liability (χ2 = 8.8, df = 2, p = 0.012) for the CAPE-negative symptoms subscale, but not for the other two subscales (i.e. positive and depressive). CONCLUSION: The results suggest that the impact of CT on subthreshold expression of psychosis, particularly in the negative subdomain, may be larger in the co-presence of significant genetic liability for psychopathology.

[Acceptance of fecal microbiota transfer among patients with chronic inflammatory bowel diseases in a highly specialized outpatient department: a questionnaire-based survey]. / Akzeptanz des therapeutischen fäkalen Mikrobiomtransfers bei Patienten mit chronisch entzündlichen Darmerkrankungen: Ergebnisse einer fragebogenbasierten Erhebung an einer universitären Spezialambulanz.

Recently, research in the treatment of inflammatory bowel diseases has become increasingly focused on fecal microbiota transfer (FMT) due to increasing evidence of its possible benefits. Still, there are doubts about this method, because there is contradicting evidence regarding its effectiveness and the possible side effects are not well known. Furthermore, the majority of patients are not open to this procedure. We performed a questionnaire-based survey amongst 302 patients with an inflammatory bowel disease that received treatment in our specialized outpatient clinic to determine the factors relevant for acceptance or rejection of fecal microbiota transfer as a possible treatment for Crohn's disease or ulcerative colitis. Our data supports the hypothesis that a lack of information about FMT is a key factor for hypothetical acceptance of this method (68 % of pre-informed participants vs. 30 % of not pre-informed participants would accept FMT as treatment, p < 0.001), and, therefore, it highlights patient education as a possible intervention to improve acceptance. The main concern regarding FMT was possible transmission of infections (ranked first by 98 participants). The most accepted method to perform FMT was application via oral capsule (44 % of participants).

High Amounts of Halogenated Natural Products in Sperm Whales (Physeter macrocephalus) from Two Italian Regions in the Mediterranean Sea.

Halogenated natural products (HNPs) are considered to be emerging contaminants whose environmental distribution and fate are only incompletely known. Therefore, several persistent and bioaccumulative HNP groups, together with man-made polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), were quantified in the blubber of nine sperm whales (Physeter macrocephalus) stranded on the coast of the Mediterranean Sea in Italy. The naturally occurring polybrominated hexahydroxanthene derivatives (PBHDs; sum of TetraBHD and TriBHD) were the most prominent substance class with up to 77,000 ng/g blubber. The mean PBHD content (35,800 ng/g blubber) even exceeded the one of PCBs (28,400 ng/g blubber), although the region is known to be highly contaminated with man-made contaminants. Based on mean values, Q1 ∼ PBDEs > MeO-BDEs ∼ 2,2'-diMeO-BB 80 and several other HNPs followed with decreasing amounts. All blubber samples contained an abundant compound whose molecular formula (C16H19Br3O2) was verified using high-resolution mass spectrometry. The only plausible matching isomer was (2S,4'S,9R,9'S)-2,7-dibromo-4'-bromomethyl-1,1-dimethyl-2,3,4,4',9,9'-9,9'-hexahydro-1H-xanthen-9-ol (OH-TriBHD), a hydroxylated secondary metabolite previously detected together with TriBHD and TetraBHD in a sponge known to be a natural producer of PBHDs. The estimated mean amount of the presumed OH-TriBHD was 3000 ng/g blubber, which is unexpectedly high for hydroxylated compounds in the lipids of marine mammals.

Identification of a new fatty acid synthesis-transport machinery at the peroxisomal membrane.

The neurodegenerative disease X-linked adrenoleukodystrophy (X-ALD) is characterized by the abnormal accumulation of very long chain fatty acids. Mutations in the gene encoding the peroxisomal ATP-binding cassette half-transporter, adrenoleukodystrophy protein (ALDP), are the primary cause of X-ALD. To gain a better understanding of ALDP dysfunction, we searched for interaction partners of ALDP and identified binary interactions to proteins with functions in fatty acid synthesis (ACLY, FASN, and ACC) and activation (FATP4), constituting a thus far unknown fatty acid synthesis-transport machinery at the cytoplasmic side of the peroxisomal membrane. This machinery adds to the knowledge of the complex mechanisms of peroxisomal fatty acid metabolism at a molecular level and elucidates potential epigenetic mechanisms as regulatory processes in the pathogenesis and thus the clinical course of X-ALD.

Molecular genetic analysis of 16 XP-C patients from Germany: environmental factors predominately contribute to phenotype variations.

Patients belonging to xeroderma pigmentosum (XP) complementation group C comprise one-third of all XP patients. Only four major reports compiled larger groups of XP-C patients from southern Europe (12 pts), North America (16 pts) and Africa (14 and 56 pts) as well as their genetic background (46 XPC mutations). We identified 16 XP-C patients from Germany. Interestingly, only five patients exhibited severe sun sensitivity. The mean age of XP diagnosis was 9.4 years, and the median age of the first skin cancer was 7 years. Neurological symptoms were absent in all but two patients. Primary fibroblasts from all 16 patients showed reduced post-UV cell survival (mean: 50% vs 93% in normal cells) and reduced reactivation of an UV-treated luciferase reporter gene (mean: 6.4% vs 30.7% in normal cells). XPC mRNA expression was also greatly reduced compared with normal cells (mean: 14.3%; range 8.3-25.7%) except in XP47MA (274.1%). All patients carried homozygous XPC mutations. Four mutations have been described previously: c.1747_1748delTG (found in 4/16), c.567 C>T (4/16), c.1839 C>T (1/16) and a complex insertion/deletion mutation in exon 9 (1/16). The novel frameshift mutations c.446_447delAG (2/16), c.1525insA (1/16) and c.2271delC (1/16) lead to truncated XPC proteins as does the novel nonsense mutation c.843C>T (1/16). XP47MA carries an interesting mutation (c.2538_2540delATC; p.Ile812del) resulting in an in-frame single amino acid deletion. This mutation results in a classical XP phenotype, a non-functional XPC protein, but elevated XPC mRNA expression. Our study indicates that extrinsic factors may contribute to XP-C symptom severity due to nonsense-mediated message decay.

Functional and molecular genetic analyses of nine newly identified XPD-deficient patients reveal a novel mutation resulting in TTD as well as in XP/CS complex phenotypes.

The xeroderma pigmentosum (XP) group D protein is involved in nucleotide excision repair (NER) as well as in basal transcription. Determined by the type of XPD mutation, six different clinical entities have been distinguished: XP, XP with neurological symptoms, trichothiodystrophy (TTD), XP/TTD complex, XP/Cockayne syndrome (CS) complex or the cerebro-oculo-facio-skeletal syndrome (COFS). We identified nine new XPD-deficient patients. Their fibroblasts showed reduced post-UV cell survival, reduced NER capacity, normal XPD mRNA expression and partly reduced XPD protein expression. Six patients exhibited a XP phenotype in accordance with established XP-causing mutations (c.2079G>A, p.R683Q; c.2078G>T, p.R683W; c.1833G>T, p.R601L; c.1878G>C, p.R616P; c.1878G>A, p.R616Q). One TTD patient was homozygous for the known TTD-causing mutation p.R722W (c.2195C>T). Two patients were compound heterozygous for a TTD-causing mutation (c.366G>A, p.R112H) and a novel p.D681H (c.2072G>C) amino acid exchange, but exhibited different TTD and XP/CS complex phenotypes, respectively. Interestingly, the XP/CS patient's cells exhibited a reduced but well detectable XPD protein expression compared with hardly detectable XPD expression of the TTD patient's cells. Same mutations with different clinical outcomes in NER-defective patients demonstrate the complexity of phenotype-genotype correlations, for example relating to additional genetic variations (parental consanguinity), different allelic expression due to SNPs or differences in the methylation status.

Declarative Learning Mechanisms Support Declarative but Not Probabilistic Feedback-Based Learning in Children with Developmental Language Disorder (DLD).

Declarative and probabilistic feedback-based learning was evaluated in 8-12-year-old school-age children with developmental language disorder (DLD; n = 14) and age-matched children with typical development (TD; n = 15). Children performed a visual two-choice word-learning task and a visual probabilistic classification task while their electroencephalogram (EEG) was recorded non-invasively from the scalp. Behavioral measures of accuracy and response to feedback, and electrophysiological responses to feedback were collected and compared between the two groups. While behavioral data indicated poorer performance by children with DLD in both learning paradigms, and similar response patterns to positive and negative feedback, electrophysiological data highlighted processing patterns in the DLD group that differed by task. More specifically, in this group, feedback processing in the context of declarative learning, which is known to be dominated by the medial temporal lobe (MTL), was associated with enhanced N170, an event-related brain potential (ERP) associated with MTL activation. The N170 amplitude was found to be correlated with declarative task performance in the DLD group. During probabilistic learning, known to be governed by the striatal-based learning system, the feedback-related negativity (FRN) ERP, which is the product of the cortico-striatal circuit dominated feedback processing. Within the context of probabilistic learning, enhanced N170 was associated with poor learning in the TD group, suggesting that MTL activation during probabilistic learning disrupts learning. These results are interpreted within the context of a proposed feedback parity hypothesis suggesting that in children with DLD, the system that dominates learning (i.e., MTL during declarative learning and the striatum during probabilistic learning) dominates and supports feedback processing.

Somatostatin-Expressing Neurons in the Ventral Tegmental Area Innervate Specific Forebrain Regions and Are Involved in Stress Response.

Expanding knowledge about the cellular composition of subcortical brain regions demonstrates large heterogeneity and differences from the cortical architecture. Previously we described three subtypes of somatostatin-expressing (Sst) neurons in the mouse ventral tegmental area (VTA) and showed their local inhibitory action on the neighboring dopaminergic neurons (Nagaeva et al., 2020). Here, we report that Sst+ neurons especially from the anterolateral part of the mouse VTA also project far outside the VTA and innervate forebrain regions that are mainly involved in the regulation of emotional behavior, including the ventral pallidum, lateral hypothalamus, the medial part of the central amygdala, anterolateral division of the bed nucleus of stria terminalis, and paraventricular thalamic nucleus. Deletion of these VTASst neurons in mice affected several behaviors, such as home cage activity, sensitization of locomotor activity to morphine, fear conditioning responses, and reactions to the inescapable stress of forced swimming, often in a sex-dependent manner. Together, these data demonstrate that VTASst neurons have selective projection targets distinct from the main targets of VTA dopamine neurons. VTASst neurons are involved in the regulation of behaviors primarily associated with the stress response, making them a relevant addition to the efferent VTA pathways and stress-related neuronal network.

Skin cancer in organ transplant recipients: effects of immunosuppressive medications on DNA repair.

UV-induced skin cancers comprise a major problem in organ transplant recipients (OTRs). Cyclosporin A, a calcineurin inhibitor, is used as a standard immunosuppressant and clearly increases the skin cancer risk. Azathioprine does not appear to result in such an increase in skin cancer risk, and mTOR inhibitors are associated with an even lesser skin cancer risk. The underlying molecular mechanisms of these clinically important differences among immunosuppressants are still unclear and may relate to other than immunological effects. Insights may be gained by the multistep skin cancer theory and xeroderma pigmentosum, where defective nucleotide excision repair (NER) results in a cellular mutator phenotype and cutaneous carcinogenesis. This viewpoint assay summarizes current knowledge about the influence of the most commonly used immunosuppressive drugs in OTRs on DNA repair. Calcineurin inhibition results in a 200-fold increased skin cancer risk compared with the normal population and inhibits NER. The skin cancer risk under azathioprine is threefold less compared with calcineurin inhibitors, which may relate to inhibition of only the last step of NER, i.e. gap filling. mTOR inhibitors do not reduce NER in the global genome and can inhibit the growth of already initiated tumors, which may account for the markedly reduced skin cancer risk compared with calcineurin inhibitors. We conclude that OTRs may benefit from treatment regimens other than calcineurin inhibitors and speculate that a targeted modulation of calcineurin-dependent signalling may prevent UV-induced tumor formation by enhancing NER not only in OTRs but also in the general population, at least in part.

You See What You Smell: Preferential Processing of Chemosensory Satiety Cues and Its Impact on Body Shape Perception.

The current study examines neural responses to satiety- and fasting-related volatiles and their effect on the processing of body shapes. Axillary sweat was sampled with cotton pads from 10 individuals after 12 h of fasting, and after having consumed a standard breakfast. Pure cotton pads served as the control. The chemosensory stimuli were presented to 20 participants (via a constant-flow olfactometer) exclusively, and additionally as context to images of overweight and underweight avatars. EEG was recorded (61 electrodes), and chemosensory (CSERPs; P1, N1, P2, P3) and visual event-related potentials (VERPs; N1, P2, P3a, P3b) were analyzed. The amplitudes of all positive CSERP components differed more strongly from cotton in response to chemosensory satiety cues as compared to fasting cues (P1: p = 0.023, P2: p = 0.083, P3: p = 0.031), paralleled by activity within the middle frontal and temporal gyrus. Overweight compared to underweight body shapes tended to elicit larger VERP P2 amplitudes (p = 0.068), and chemosensory satiety cues amplified the VERP amplitudes in response to any body shape (P2, P3a, P3b; all ps ≤ 0.017) as compared to the cotton control. The results indicate that chemosensory satiety cues transmit complex social information, overriding the processing of analogous visual input.

PGC-1α Signaling Increases GABA(A) Receptor Subunit α2 Expression, GABAergic Neurotransmission and Anxiety-Like Behavior in Mice.

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondria biogenesis and cell stress playing a role in metabolic and degenerative diseases. In the brain PGC-1α expression has been localized mainly to GABAergic interneurons but its overall role is not fully understood. We observed here that the protein levels of γ-aminobutyric acid (GABA) type A receptor-α2 subunit (GABARα2) were increased in hippocampus and brain cortex in transgenic (Tg) mice overexpressing PGC-1α in neurons. Along with this, GABARα2 expression was enhanced in the hippocampus of the PGC-1α Tg mice, as shown by quantitative PCR. Double immunostaining revealed that GABARα2 co-localized with the synaptic protein gephyrin in higher amounts in the striatum radiatum layer of the hippocampal CA1 region in the Tg compared with Wt mice. Electrophysiology revealed that the frequency of spontaneous and miniature inhibitory postsynaptic currents (mIPSCs) was increased in the CA1 region in the Tg mice, indicative of an augmented GABAergic transmission. Behavioral tests revealed an increase for anxiety-like behavior in the PGC-1α Tg mice compared with controls. To study whether drugs acting on PPARγ can affect GABARα2, we employed pioglitazone that elevated GABARα2 expression in primary cultured neurons. Similar results were obtained using the specific PPARγ agonist, N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino) ethyl]-L-tyrosine hydrate (GW1929). These results demonstrate that PGC-1α regulates GABARα2 subunits and GABAergic neurotransmission in the hippocampus with behavioral consequences. This indicates further that drugs like pioglitazone, widely used in the treatment of type 2 diabetes, can influence GABARα2 expression via the PPARγ/PGC-1α system.

Chemogenetic Stimulation and Silencing of the Insula, Amygdala, Nucleus Accumbens, and Their Connections Differentially Modulate Alcohol Drinking in Rats.

The anterior insular cortex is hypothesized to represent interoceptive effects of drug reward in the service of goal-directed behavior. The insula is richly connected, but the insula circuitry in addiction remains poorly characterized. We examined the involvement of the anterior insula, amygdala, and nucleus accumbens, as well as the projections of the anterior insula to the central amygdala, basolateral amygdala (BLA), and nucleus accumbens core in voluntary alcohol drinking. We trained alcohol-preferring Alko Alcohol (AA) rats to drink alcohol during intermittent 2-h sessions. We then expressed excitatory or inhibitory designer receptors [designer receptors exclusively activated by designer drugs (DREADDs)] in the anterior insula, nucleus accumbens, or amygdala by means of adenovirus-mediated gene transfer and activated the DREADDs with clozapine-N-oxide (CNO) prior to the drinking sessions. Next, to examine the role of specific insula projections, we expressed FLEX-DREADDs in the efferent insula → nucleus accumbens core, insula → central amygdala, and insula → BLA projections by means of a retrograde AAV-Cre vector injected into the insula projection areas. In the anterior insula and amygdala, excitatory Gq-DREADDs significantly attenuated alcohol consumption. In contrast, in the nucleus accumbens, the Gq-DREADD stimulation increased alcohol drinking, and the inhibitory Gi-DREADDs suppressed it. The Gq-DREADDs expressed in the insula → nucleus accumbens core and insula → central amygdala projections increased alcohol intake, whereas inhibition of these projections had no effect. These data demonstrate that the anterior insula, along with the amygdala and nucleus accumbens, has a key role in controlling alcohol drinking by providing excitatory input to the central amygdala and nucleus accumbens to enhance alcohol reward.

The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis: A transdiagnostic meta - analysis.

BACKGROUND: Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. OBJECTIVE: A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met). DATA SOURCES: PubMed, Embase, PsychInfo. STUDY ELIGIBILITY CRITERIA: All observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome. STUDY APPRAISAL AND SYNTHESIS METHODS: A meta-analysis was performed using the Meta-analysis of Observational Studies in Epidemiology guidelines and forest plots were generated. Thirteen articles met the selection criteria: 7 clinical studies using a case-only design, 3 clinical studies with a dichotomous outcome, and 3 studies analysing a continuous outcome of psychotic symptoms below the threshold of psychotic disorder. The three study types were analysed separately. Validity of the included studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions". RESULTS: For case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an OR of 1.45 (95% Confidence Interval = 1.05-2.00; Met/Met as the risk genotype). However, there was no evidence for interaction in either the studies including dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16-0.08). LIMITATION: A substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects. CONCLUSION: The interaction term between cannabis use and COMTVal158Met was only statistically significant in the case-only studies, but not in studies using other clinical or non-clinical psychosis outcomes. Future additional high quality studies might change current perspectives, yet currently evidence for the interaction remains unconvincing.

Characterization of three XPG-defective patients identifies three missense mutations that impair repair and transcription.

Only 16 XPG-defective patients with 20 different mutations have been described. The current hypothesis is that missense mutations impair repair (xeroderma pigmentosum (XP) symptoms), whereas truncating mutations impair both repair and transcription (XP and Cockayne syndrome (CS) symptoms). We identified three cell lines of XPG-defective patients (XP40GO, XP72MA, and XP165MA). Patients' fibroblasts showed a reduced post-UVC cell survival. The reduced repair capability, assessed by host cell reactivation, could be complemented by XPG cDNA. XPG mRNA expression of XP165MA, XP72MA, and XP40GO was 83%, 97%, and 82.5%, respectively, compared with normal fibroblasts. XP165MA was homozygous for a p.G805R mutation; XP72MA and XP40GO were both compound heterozygous (p.W814S and p.E727X, and p.L778P and p.Q150X, respectively). Allele-specific complementation analysis of these five mutations revealed that p.L778P and p.W814S retained considerable residual repair activity. In line with the severe XP/CS phenotypes of XP72MA and XP165MA, even the missense mutations failed to interact with the transcription factor IIH subunits XPD and to some extent cdk7 in coimmunoprecipitation assays. Immunofluorescence techniques revealed that the mutations destabilized early recruitment of XP proteins to localized photodamage and delayed their redistribution in vivo. Thus, we identified three XPG missense mutations in the I-region of XPG that impaired repair and transcription and resulted in severe XP/CS.

No association of vitamin D metabolism-related polymorphisms and melanoma risk as well as melanoma prognosis: a case-control study.

Melanoma is one of the most aggressive human cancers. The vitamin D system contributes to the pathogenesis and prognosis of malignancies including cutaneous melanoma. An expression of the vitamin D receptor (VDR) and an anti-proliferative effect of vitamin D in melanocytes and melanoma cells have been shown in vitro. Studies examining associations of polymorphisms in genes coding for vitamin D metabolism-related proteins (1α-hydroxylase [CYP27B1], 1,25(OH)(2)D-24hydroxylase [CYP24A1], vitamin D-binding protein [VDBP]) and cancer risk are scarce, especially with respect to melanoma. Mainly VDR polymorphisms regarding melanoma risk and prognosis were examined although other vitamin D metabolism-related genes may also be crucial. In our hospital-based case-control study including 305 melanoma patients and 370 healthy controls single nucleotide polymorphisms in the genes CYP27B1 (rs4646536), CYP24A1 (rs927650), VDBP (rs1155563, rs7041), and VDR (rs757343, rs731236, rs2107301, rs7975232) were analyzed for their association with melanoma risk and prognosis. Except VDR rs731236 and VDR rs2107301, the other six polymorphisms have not been analyzed regarding melanoma before. To further improve the prevention as well as the treatment of melanoma, it is important to identify further genetic markers for melanoma risk as well as prognosis in addition to the crude phenotypic, demographic, and environmental markers used in the clinic today. A panel of genetic risk markers could help to better identify individuals at risk for melanoma development or worse prognosis. We, however, found that none of the polymorphisms tested was associated with melanoma risk as well as prognosis in logistic and linear regression models in our study population.

Live cell FRET microscopy: homo- and heterodimerization of two human peroxisomal ABC transporters, the adrenoleukodystrophy protein (ALDP, ABCD1) and PMP70 (ABCD3).

The adrenoleukodystrophy protein (ALDP) and the 70-kDa peroxisomal membrane protein (PMP70) are half-ATP-binding cassette (ABC) transporters in the mammalian peroxisome membrane. Mutations in the gene encoding ALDP result in a devastating neurodegenerative disorder, X-linked adrenoleukodystrophy (X-ALD) that is associated with elevated levels of very long chain fatty acids because of impaired peroxisomal beta-oxidation. The interactions of peroxisomal ABC transporters, their role in the peroxisomal membrane, and their functions in disease pathogenesis are poorly understood. Studies on ABC transporters revealed that half-transporters have to dimerize to gain functionality. So far, conflicting observations are described for ALDP. By the use of in vitro methods (yeast two-hybrid and immunoprecipitation assays) on the one hand, it was shown that ALDP can form homodimers as well as heterodimers with PMP70 and ALDR, while on the other hand, it was demonstrated that ALDP and PMP70 exclusively homodimerize. To circumvent the problems of artificial interactions due to biochemical sample preparation in vitro, we investigated protein-protein interaction of ALDP in its physiological environment by FRET microscopy in intact living cells. The statistical relevance of FRET data was determined in two different ways using probability distribution shift analysis and Kolmogorov-Smirnov statistics. We demonstrate in vivo that ALDP and PMP70 form homodimers as well as ALDP/PMP70 heterodimers where ALDP homodimers predominate. Using C-terminal deletion constructs of ALDP, we demonstrate that the last 87 C-terminal amino acids harbor the most important protein domain mediating these interactions, and that the N-terminal transmembrane region of ALDP has an additional stabilization effect on ALDP homodimers. Loss of ALDP homo- or heterodimerization is highly relevant for understanding the disease mechanisms of X-ALD.