The Bergen 4-day treatment for panic disorder: adapting to COVID-19 restrictions with a hybrid approach of face-to-face and videoconference modalities.

BACKGROUND: The Bergen 4-day treatment (B4DT) is a concentrated exposure-based therapy that has been shown to be effective in the treatment of anxiety disorders. The current study sought to examine the effectiveness of B4DT for panic disorder (PD), when delivered with a combination of face-to-face sessions and videoconferencing. METHODS: Treatment was delivered to 50 patients from April 2020 to May 2021. Because of regulations during the pandemic, a significant portion of the treatment was conducted via videoconference. The primary outcome measure was the clinician-rated Panic Disorder Severity Scale (PDSS), and secondary measures included patient-rated symptoms of panic disorder, agoraphobia, generalized anxiety, depression, and treatment satisfaction. Changes in symptom levels over time were estimated using multilevel models. RESULTS: Patients showed a significant reduction in clinician-rated symptoms of panic disorder (Measured by PDSS) from before treatment to post treatment (d = 2.18) and 3-month follow-up (d = 2.01). At three months follow-up 62% of patients were classified as in remission, while 70% reported a clinically significant response. We also found a reduction in symptoms of depression and generalized anxiety, and the patients reported high satisfaction with the treatment. CONCLUSION: The current study suggests that B4DT delivered in a combination of videoconference and face-to-face meetings may be a useful treatment approach. As the study is uncontrolled, future studies should also include more strictly designed investigations.

Spawning time in adult polar cod (Boreogadus saida) altered by crude oil exposure, independent of food availability.

Fish early life stages are well known for their sensitivity to crude oil exposure. However, the effect of crude oil exposure on adults and their gametes during their spawning period is not well studied. Polar cod, a key arctic fish, may be at risk for crude oil exposure during this potentially sensitive life stage. Additionally, this species experiences lower food availability during their spawning season, with unknown combined consequences. In the present study, wild-caught polar cod were exposed to decreasing levels of a water-soluble fraction (WSF) of crude oil or control conditions and fed either at a low or high feed ration to assess the combined effect of both stressors. Samples were taken during late gonadal development, during active spawning (spawning window), and in the post-spawning period. Histology analysis of gonads from fish sampled during the spawning window showed that oil-exposed polar cod were more likely to have spawned compared to controls. Oil-exposed females had 947 differentially regulated hepatic genes, and their eggs had a higher polycyclic aromatic hydrocarbon body burden compared to controls. Feed ration did not consistently affect polar cod's response to oil exposure for the endpoints measured, however, did alone result in decreases in some sperm motility parameters. These results suggest that polar cod's spawning period is a sensitive life event to crude oil exposure, while feed limitation may play a minor role for this supposedly capital breeder. The effects of adult exposure to crude oil on gamete quality and the next generation warrant further investigation.

Crude oil exposure of early life stages of Atlantic haddock suggests threshold levels for developmental toxicity as low as 0.1 µg total polyaromatic hydrocarbon (TPAH)/L.

Atlantic haddock (Melanogrammus aeglefinus) embryos bind dispersed crude oil droplets to the eggshell and are consequently highly susceptible to toxicity from spilled oil. We established thresholds for developmental toxicity and identified any potential long-term or latent adverse effects that could impair the growth and survival of individuals. Embryos were exposed to oil for eight days (10, 80 and 300 µg oil/L, equivalent to 0.1, 0.8 and 3.0 µg TPAH/L). Acute and delayed mortality were observed at embryonic, larval, and juvenile stages with IC50 = 2.2, 0.39, and 0.27 µg TPAH/L, respectively. Exposure to 0.1 µg TPAH/L had no negative effect on growth or survival. However, yolk sac larvae showed significant reduction in the outgrowth (ballooning) of the cardiac ventricle in the absence of other extracardiac morphological defects. Due to this propensity for latent sublethal developmental toxicity, we recommend an effect threshold of 0.1 µg TPAH/L for risk assessment models.

Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive-Behavioral Therapy in Children With Obsessive-Compulsive Disorder.

OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

An fMRI study of cognitive planning before and after symptom provocation in pediatric obsessive-compulsive disorder.

BACKGROUND: Pediatric obsessive-compulsive disorder (OCD) has been associated with poorer planning in laboratory, school and home settings. It is unclear whether this impairment is a standalone cognitive issue or the result of OCD symptoms. No study has examined the influence of provoked distress on planning performance and neural correlates in pediatric OCD. METHODS: Before and after a symptom provocation task, youth with OCD (n = 23; 9 boys; mean age ± standard deviation 15.1 ± 2.6 years) and matched healthy controls (n = 23) completed the Tower of London task during functional MRI scanning. RESULTS: During planning, participants with OCD recruited the left superior frontal gyrus to a greater extent than healthy controls after symptom provocation (group × time point interaction; t 44 = 5.22, p < 0.001). In a seeded, region of interest-constrained, functional connectivity analysis, we identified greater connectivity between the left superior frontal gyrus and the right middle frontal gyrus, left precuneus and left inferior parietal lobule in participants with OCD than healthy controls. We also identified greater connectivity between the right amygdala and right medial frontal gyrus in patients with OCD than healthy controls, but only before symptom provocation. LIMITATIONS: The fixed-order design of the study and the number of participants taking medication (n = 20) should be noted. CONCLUSION: Participants with OCD demonstrated greater amygdalar-cortical connectivity before symptom provocation, while sustaining greater recruitment and connectivity of task-related planning areas throughout the task. These results suggest that brain activity and connectivity is altered after symptom provocation, in the absence of impaired planning performance.

Longitudinal changes in neurometabolite concentrations in the dorsal anterior cingulate cortex after concentrated exposure therapy for obsessive-compulsive disorder.

BACKGROUND: The dorsal anterior cingulate cortex (dACC) plays an important role in the pathophysiology of obsessive-compulsive disorder (OCD) due to its role in error processing, cognitive control and emotion regulation. OCD patients have shown altered concentrations in neurometabolites in the dACC, particularly Glx (glutamate+glutamine) and tNAA (N-acetylaspartate+N-acetyl-aspartyl-glutamate). We investigated the immediate and prolonged effects of exposure and response prevention (ERP) on these neurometabolites. METHODS: Glx and tNAA concentrations were measured using magnetic resonance spectroscopy (1H-MRS) in 24 OCD patients and 23 healthy controls at baseline. Patients received concentrated ERP over four days. A subset was re-scanned after one week and three months. RESULTS: No Glx and tNAA abnormalities were observed in OCD patients compared to healthy controls before treatment or over time. Patients with childhood or adult onset differed in the change over time in tNAA (F(2,40) = 7.24, É³2p= 0.27, p = 0.004): concentrations increased between one week after treatment and follow-up in the childhood onset group (t(39) = -2.43, d = -0.86, p = 0.020), whereas tNAA concentrations decreased between baseline and follow-up in patients with an adult onset (t(42) = 2.78, d = 1.07, p = 0.008). In OCD patients with versus without comorbid mood disorders, lower Glx concentrations were detected at baseline (t(38) = -2.28, d = -1.00, p = 0.028). Glx increased after one week of treatment within OCD patients with comorbid mood disorders (t(30) = -3.09, d = -1.21, p = 0.004). LIMITATIONS: Our OCD sample size allowed the detection of moderate to large effect sizes only. CONCLUSION: ERP induced changes in neurometabolites in OCD seem to be dependent on mood disorder comorbidity and disease stage rather than OCD itself.

First thorough assessment of de novo oocyte recruitment in a teleost serial spawner, the Northeast Atlantic mackerel (Scomber scombrus) case.

The understanding of teleost fecundity type (determinate or indeterminate) is essential when deciding which egg production method should be applied to ultimately estimate spawning stock biomass. The fecundity type is, however, unknown or controversial for several commercial stocks, including the Northeast Atlantic mackerel (Scomber scombrus). Aiming at solving this problem, we applied state-of-the-art laboratory methods to document the mackerel fecundity type, including any de novo oocyte recruitment during spawning. Initially, active mackerel spawning females were precisely classified according to their spawning status. The number and size of all phasei-specific oocytes (12 phases), with a special attention to previtellogenic oocytes phases (PVO [PVO2 to PVO4a-c]), were also thoroughly investigated. Examinations of relative fecundity (RFi) clarified that the latest phase of PVOs (PVO4c) are de novo recruited to the cortical alveoli-vitellogenic pool during the spawning period, resulting in a dome-shaped seasonal pattern in RFi. Hence, we unequivocally classify mackerel as a true indeterminate spawner. As PVO4c oocytes were currently identified around 230 µm, mackerel fecundity counts should rather use this diameter as the lower threshold instead of historically 185 µm. Any use of a too low threshold value in this context will inevitably lead to an overestimation of RFi and thereby underestimated spawning stock biomass.

Diffusion Tensor Imaging Before and 3 Months After Concentrated Exposure Response Prevention in Obsessive-Compulsive Disorder.

Background: Subtle differences in white matter microstructure have been found in obsessive-compulsive disorder (OCD) compared to controls using diffusion tensor imaging (DTI), but it is unclear if and how this change after treatment. The primary aim of this pre-registered study was to investigate white matter integrity between OCD patients and controls and changes after concentrated exposure and response prevention (ERP). Methods: Fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) and mean diffusivity (MD) were estimated using FMRIB Software Library (FSL). The images were registered to a study-specific template using a longitudinal pipeline based on full tensor information in DTI-TK. Voxel-based analysis was performed using tract-based spatial statistics (TBSS). Using SPSS, we compared the integrity in three bilateral regions of interest (ROI), the sagittal stratum, posterior thalamic radiation and cingulum, in 32 OCD patients and 30 matched healthy controls at baseline. Patients received a four-day concentrated ERP format. We investigated longitudinal changes in 26 OCD patients and 22 healthy controls at 3months follow-up using repeated-measures ANOVA. Exploratory t-tests were conducted for AD and MD. Secondary hypothesis used linear regression to investigate if baseline FA predict treatment outcome 3 months later, and if patients with illness onset before 18 years of age would show lower FA in sagittal stratum. Finally, we performed sensitivity analysis on medication and comorbidity influences on FA. Results: Three months after treatment, 77% of the patients were in remission. Contrary to our hypotheses, we did not find any significant differences in FA, RD, AD or MD between the groups before treatment, nor significant group by time effects in any of the ROI. None of the baseline FA measures significantly predicted treatment outcome. Illness onset before 18 years of age did not significantly predict FA in the sagittal stratum. Adjusting for medication or comorbid anxiety or mood disorder did not influence the results. Conclusions: Although concentrated ERP in OCD lead to high remission, we did not find significant long-term changes by DTI. Future studies will benefit from using larger sample sizes and multi-shell diffusion-weighted imaging when investigating white matter microstructure in OCD and underlying neurobiological mechanisms of treatment.

Disentangling Within- and Between-Person Effects During Response Inhibition in Obsessive-Compulsive Disorder.

Background: Obsessive-compulsive disorder (OCD) has been related to worse performance, abnormal brain activity, and functional connectivity during response inhibition. Whether these findings are indications of stable traits that contribute to the development of the disorder, or whether they are a result of the state severity of obsessions and anxiety, remains unclear since previous research mainly has employed cross-sectional designs. The present study aimed to assess longitudinal between- and within-person relationships between symptoms, task performance, right inferior frontal gyrus brain activation, and connectivity between the right amygdala and the right pre-supplementary motor area in 29 OCD patients before and after concentrated exposure and response prevention treatment. Method: Patients received exposure and response prevention delivered during 4 consecutive days, following the Bergen 4-day Treatment format. Patients performed a Stop Signal Task during 3T functional Magnetic Resonance Imaging the day before treatment, as well as 1 week and 3 months after treatment completion. Multilevel models were used to analyze disaggregated within- and between-person effects over time. Independent variables were scores on the symptom severity scales for OCD, anxiety, depression, and state distress during scanning. Dependent variables were reaction time for go trials, stop signal response time, task-related brain activation and connectivity. Results: A positive between-person effect was found for obsessive-compulsive, anxiety, and depressive symptom severity on go trial reaction time, indicating that patients with higher symptom scores on average respond slower during accurate go trials. We also found no significant between- or within-person relations between symptom severity and task-related activation or fronto-limbic connectivity. Conclusions: The between-person findings may point toward a general association between slower processing speed and symptom severity in OCD. Longitudinal studies should disaggregate between- and within-person effects to better understand variation over time.

Untangling mechanisms of crude oil toxicity: Linking gene expression, morphology and PAHs at two developmental stages in a cold-water fish.

Early life stages of fish are highly sensitive to crude oil exposure and thus, short term exposures during critical developmental periods could have detrimental consequences for juvenile survival. Here we administered crude oil to Atlantic haddock (Melanogrammus aeglefinus) in short term (3-day) exposures at two developmental time periods: before first heartbeat, from gastrulation to cardiac cone stage (early), and from first heartbeat to one day before hatching (late). A frequent sampling regime enabled us to determine immediate PAH uptake, metabolite formation and gene expression changes. In general, the embryotoxic consequences of an oil exposure were more severe in the early exposure animals. Oil droplets on the eggshell resulted in severe cardiac and craniofacial abnormalities in the highest treatments. Gene expression changes of Cytochrome 1 a, b, c and d (cyp1a, b, c, d), Bone morphogenetic protein 10 (bmp10), ABC transporter b1 (abcb1) and Rh-associated G-protein (rhag) were linked to PAH uptake, occurrence of metabolites of phenanthrene and developmental and functional abnormalities. We detected circulation-independent, oil-induced gene expression changes and separated phenotypes linked to proliferation, growth and disruption of formation events at early and late developmental stages. Changes in bmp10 expression suggest a direct oil-induced effect on calcium homeostasis. Localized expression of rhag propose an impact on osmoregulation. Severe eye abnormalities were linked to possible inappropriate overexpression of cyp1b in the eyes. This study gives an increased knowledge about developmentally dependent effects of crude oil toxicity. Thus, our findings provide more knowledge and detail to new and several existing adverse outcome pathways of crude oil toxicity.

Effects of Bergen 4-Day Treatment on Resting-State Graph Features in Obsessive-Compulsive Disorder.

BACKGROUND: Exposure and response prevention is an effective treatment for obsessive-compulsive disorder (OCD), but it is unclear how symptom reduction is related to changes in the brain. We aimed to determine the effects of a 4-day concentrated exposure and response prevention program (Bergen 4-day treatment) on the static and dynamic functional connectome in patients with OCD. METHODS: Thirty-four patients with OCD (25 unmedicated) underwent resting-state functional magnetic resonance imaging the day before the Bergen 4-day treatment, and 28 (21 unmedicated) were rescanned after 1 week. Twenty-eight healthy control subjects were also scanned for baseline comparisons and 19 of them were rescanned after 1 week. Static and dynamic graph measures were quantified to determine network topology at the global, subnetwork, and regional levels (including efficiency, clustering, between-subnetwork connectivity, and node flexibility in module allegiance). The Yale-Brown Obsessive Compulsive Scale was used to measure symptom severity. RESULTS: Twenty-four patients (86%) responded to treatment. We found significant group × time effects in frontoparietal-limbic connectivity (ηp2 = 0.19, p = .03) and flexibility of the right subgenual anterior cingulate cortex (ηp2 = 0.18, p = .03), where, in both cases, unmedicated patients showed significant decreases while healthy control subjects showed no significant changes. Healthy control subjects showed increases in global and subnetwork efficiency and clustering coefficient, particularly in the somatomotor subnetwork. CONCLUSIONS: Concentrated exposure and response prevention in unmedicated patients with OCD leads to decreased connectivity between the frontoparietal and limbic subnetworks and less flexibility of the connectivity of the subgenual anterior cingulate cortex, suggesting a more independent and stable network topology. This may represent less limbic interference on cognitive control subnetworks after treatment.

Production and verification of the first Atlantic salmon (Salmo salar L.) clonal lines.

BACKGROUND: In several fish species homozygous and heterozygous clonal lines have been produced using gynogenetic and androgenetic techniques. These lines are standardized and can be reproduced over generations. In rainbow trout such lines have existed for decades and has become important research tools in genome studies as well as in studies of commercially important traits. The Atlantic salmon is one of the best studied fish species globally, but all experiments are done on fish of wild or domesticated origin and access to standardized immortal fish lines would be of great benefit. Here, we describe the protocols developed to produce mitotic gynogenes, and from these the first clonal lines in Atlantic salmon. RESULTS: Atlantic salmon eggs fertilized with UV irradiated sperm combined with a pressure shock applied at 4700-4800 minC at 8 °C gave all homozygous (doubled haploid) gynogenetic progeny with high survival. From the six first maturing females, five all homozygous clonal lines were produced by meiotic gynogenesis and were verified as clonal and identical to their mother with microsatellite markers. CONCLUSIONS: We have now produced the first documented cloned Atlantic salmon lines. This work demonstrates the potential for production of further Atlantic salmon clonal lines, potentially with distinct characteristics. Such lines will provide an important resource for further elucidation of phenotypic and genetic traits in this globally important species.

Development of a new 'ultrametric' method for assessing spawning progression in female teleost serial spawners.

The collection and presentation of accurate reproductive data from wild fish has historically been somewhat problematic, especially for serially spawning species. Therefore, the aim of the current study was to develop a novel method of assessing female spawning status that is robust to variation in oocyte dynamics between specimens. Atlantic cod (Barents Sea stock) were used to develop the new 'ultrametric' method, that is based on the progressive depletion of the vitellogenic oocyte pool relative to the rather constant previtellogenic oocyte (PVO) pool. Fish were subsequently partitioned into one of four categories that accurately reflected changes in their oocyte size frequency distribution characteristics and gonadosomatic index throughout spawning. The ultrametric method overcomes difficulties associated with presence of bimodal oocyte distributions, oocyte tails, lack of clear hiatus region, and presence of free ova, and can be implemented at a single sampling point. Much of the workflow is fully automated, and the technique may circumvent the need for histological analysis depending on the desired outcome. The ultrametric method differs from the traditional autodiametric method in that PVOs can be separated by ultrasonication and then enumerated, and ovarian homogeneity is not a mandatory requirement per se. The method is designed for determinate spawners but might be extended to include indeterminate spawners.

Triploid Atlantic salmon Salmo salar have a higher dietary phosphorus requirement for bone mineralization during early development.

The effect of a dietary phosphorus regime in freshwater on vertebra bone mineralization was assessed in diploid and triploid Atlantic salmon, Salmo salar. Fish were fed either a low phosphorus (LP) diet containing 10.5 g kg-1 total phosphorus or a normal phosphorus (NP) diet containing 17.4 g kg-1 total phosphorus from ∼3 to ∼65 g (day 126) in body weight. Two further groups were fed the NP diet from ∼3 g in body weight, but were then switched to the LP diet after 38 (∼10 g in body weight) or 77 (∼30 g in body weight) days. Growth, vertebral ash content (% ash) and radiologically detectable vertebra pathologies were assessed. Triploids were initially smaller than diploids, and again on day 77, but there was no ploidy effect on days 38 or 126. Vertebral ash content increased with increasing body size and those fish fed the NP diet had higher vertebral ash content than those groups fed the LP diet during the intervening time period, but this diet effect became less apparent as fish grew, with all groups having relatively equal vertebral ash content at termination. In general, triploids had lower vertebral ash content than diploids on day 38 and this was most evident in the group fed the LP diet. On day 77, those triploids fed the LP diet during the intervening time period had lower vertebral ash content than diploids. At termination on day 126, the triploids had the same vertebral ash content as diploids, irrespective of diet. There was a ploidy × diet interaction on vertebral deformities, with triploids having higher prevalences of fish with ≥1 deformed vertebra in all dietary groups except continuous NP. In conclusion, between days 0 and 77 (3-30 g body size), triploids required more dietary phosphorus than diploids in order to maintain similar vertebral ash content. A possible link between phosphorus feeding history and phosphorus demand is also discussed.

Stable inhibition-related inferior frontal hypoactivation and fronto-limbic hyperconnectivity in obsessive-compulsive disorder after concentrated exposure therapy.

Response inhibition has previously been suggested as an endophenotype for obsessive-compulsive disorder (OCD), evidenced by studies showing worse task performance, and altered task-related activation and connectivity. However, it's unclear if these measures change following treatment. In this study, 31 OCD patients and 28 healthy controls performed a stop signal task during 3 T functional magnetic resonance imaging before treatment, while 24 OCD patients and 17 healthy controls were rescanned one week and three months after concentrated exposure and response prevention over four consecutive days using Bergen 4-Day Format. To study changes over time we performed a longitudinal analysis on stop signal reaction time and task-related activation and amygdala connectivity during successful and failed inhibition. Results showed that there was no group difference in task performance. Before treatment, OCD patients compared to controls showed less inhibition-related activation in the right inferior frontal gyrus, and increased functional connectivity between the right amygdala and the right inferior frontal gyrus and pre-supplementary motor area. During error-processing, OCD patients versus controls showed less activation in the pre-SMA before treatment. These group differences did not change after treatment. Pre-treatment task performance, brain activation, and connectivity were unrelated to the degree of symptom improvement after treatment. In conclusion, inferior frontal gyrus hypoactivation and increased fronto-limbic connectivity are likely trait markers of OCD that remain after effective exposure therapy.

New insights in oocyte dynamics shed light on the complexities associated with fish reproductive strategies.

Information on temporal variations in stock reproductive potential (SRP) is essential in fisheries management. Despite this relevance, fundamental understanding of egg production variability remains largely unclear due to difficulties in tracking the underlying complex fluctuations in early oocyte recruitment that determines fecundity. We applied advanced oocyte packing density theory to get in-depth, quantitative insights across oocyte stages and seasons, selecting the commercially valuable European hake (Merluccius merluccius) as a case study. Our work evidenced sophisticated seasonal oocyte recruitment dynamics and patterns, mostly driven by a low-cost predefinition of fecundity as a function of fish body size, likely influenced also by environmental cues. Fecundity seems to be defined at a much earlier stage of oocyte development than previously thought, implying a quasi-determinate - rather than indeterminate - fecundity type in hake. These results imply a major change in the conceptual approach to reproductive strategies in teleosts. These findings not only question the current binary classification of fecundity as either determinate or indeterminate, but also suggest that current practices regarding potential fecundity estimation in fishes should be complemented with studies on primary oocyte dynamics. Accordingly, the methodology and approach adopted in this study may be profitably applied for unravelling some of the complexities associated with oocyte recruitment and thereby SRP variability.

Emotion Regulation in Obsessive-Compulsive Disorder, Unaffected Siblings, and Unrelated Healthy Control Participants.

BACKGROUND: Functional neuroimaging endophenotypes of obsessive-compulsive disorder (OCD) have been suggested during executive tasks. The purpose of this study was to investigate whether behavioral and neural responses during emotion processing and regulation also represent an endophenotype of OCD. METHODS: Forty-three unmedicated adult OCD patients, 19 of their unaffected siblings, and 38 healthy control participants underwent 3T functional magnetic resonance imaging during an emotion regulation task including neutral, fear-inducing, and OCD-related visual stimuli. Stimuli were processed during natural appraisal and during cognitive reappraisal, and distress ratings were collected after each picture. We performed between-group comparisons on task behavior and brain activation in regions of interest during emotion provocation and regulation. RESULTS: Siblings reported similar distress as healthy control participants during provocation, and significantly less than patients. There was no significant three-group difference in activation during fear provocation or regulation. Three-group comparisons showed that patients had higher amygdala and dorsomedial prefrontal cortex activation during OCD-related emotion provocation and regulation, respectively, while siblings were intermediate between patients and control participants but not significantly different from either. Siblings showed higher left temporo-occipital activation (compared with both healthy control participants and patients) and higher frontolimbic connectivity (compared with patients) during OCD-related regulation. CONCLUSIONS: Unaffected siblings do not show the same distress and amygdala activation during emotional provocation as OCD patients. Siblings show distinct activation in a temporo-occipital region, possibly related to compensatory cognitive control. This suggests that emotion regulation is not a strong endophenotype for OCD. When replicated, this contributes to our understanding of familial risk and resilience for OCD.

Symptom dimensions in obsessive-compulsive disorder as predictors of neurobiology and treatment response.

PURPOSE OF REVIEW: Specific symptom dimensions of obsessive-compulsive disorder (OCD) have been suggested as an approach to reduce the heterogeneity of obsessive-compulsive disorder, predict treatment outcome, and relate to brain structure and function. Here, we review studies addressing these issues. RECENT FINDINGS: The contamination and symmetry/ordering dimensions have not been reliably associated with treatment outcome. Some studies found that greater severity of sexual/aggressive/religious symptoms predicted a worse outcome after cognitive behavioral therapy (CBT) and a better outcome after serotonin reuptake inhibitors (SRIs). Contamination symptoms have been related to increased amygdala and insula activation in a few studies, while sexual/aggressive/religious symptoms have also been related to more pronounced alterations in the function and structure of the amygdala. Increased pre-treatment limbic responsiveness has been related to better outcomes of CBT, but most imaging studies show important limitations and replication in large-scale studies is needed. We review possible reasons for the strong limbic involvement of the amygdala in patients with more sexual/aggressive/religious symptoms, in relation to their sensitivity to CBT. SUMMARY: Symptom dimensions may predict treatment outcome, and patients with sexual/religious/aggressive symptoms are at a greater risk of not starting or delaying treatment. This is likely partly due to more shame and perceived immorality which is also related to stronger amygdala response. Competently delivered CBT is likely to help these patients improve to the same degree as patients with other symptoms.

Judging a salmon by its spots: environmental variation is the primary determinant of spot patterns in Salmo salar.

BACKGROUND: In fish, morphological colour changes occur from variations in pigment concentrations and in the morphology, density, and distribution of chromatophores in the skin. However, the underlying mechanisms remain unresolved in most species. Here, we describe the first investigation into the genetic and environmental basis of spot pattern development in one of the world's most studied fishes, the Atlantic salmon. We reared 920 salmon from 64 families of domesticated, F1-hybrid and wild origin in two contrasting environments (Hatchery; tanks for the freshwater stage and sea cages for the marine stage, and River; a natural river for the freshwater stage and tanks for the marine stage). Fish were measured, photographed and spot patterns evaluated. RESULTS: In the Hatchery experiment, significant but modest differences in spot density were observed among domesticated, F1-hybrid (1.4-fold spottier than domesticated) and wild salmon (1.7-fold spottier than domesticated). A heritability of 6% was calculated for spot density, and a significant QTL on linkage group SSA014 was detected. In the River experiment, significant but modest differences in spot density were also observed among domesticated, F1-hybrid (1.2-fold spottier than domesticated) and wild salmon (1.8-fold spottier than domesticated). Domesticated salmon were sevenfold spottier in the Hatchery vs. River experiment. While different wild populations were used for the two experiments, on average, these were 6.2-fold spottier in the Hatchery vs. River experiment. Fish in the Hatchery experiment displayed scattered to random spot patterns while fish in the River experiment displayed clustered spot patterns. CONCLUSIONS: These data demonstrate that while genetics plays an underlying role, environmental variation represents the primary determinant of spot pattern development in Atlantic salmon.

Emotional Processing in Obsessive-Compulsive Disorder: A Systematic Review and Meta-analysis of 25 Functional Neuroimaging Studies.

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) experience aversive emotions in response to obsessions, motivating avoidance and compulsive behaviors. However, there is considerable ambiguity regarding the brain circuitry involved in emotional processing in OCD, especially whether activation is altered in the amygdala. METHODS: We conducted a systematic literature review and performed a meta-analysis-seed-based d mapping-of 25 whole-brain neuroimaging studies (including 571 patients and 564 healthy control subjects) using functional magnetic resonance imaging or positron emission tomography, comparing brain activation of patients with OCD and healthy control subjects during presentation of emotionally valenced versus neutral stimuli. Meta-regressions were employed to investigate possible moderators. RESULTS: Patients with OCD, compared with healthy control subjects, showed increased activation in the bilateral amygdala, right putamen, orbitofrontal cortex extending into the anterior cingulate and ventromedial prefrontal cortex, and middle temporal and left inferior occipital cortices during emotional processing. Right amygdala hyperactivation was most pronounced in unmedicated patients. Symptom severity was related to increased activation in the orbitofrontal and anterior cingulate cortices and precuneus. Greater comorbidity with mood and anxiety disorders was associated with higher activation in the right amygdala, putamen, and insula as well as with lower activation in the left amygdala and right ventromedial prefrontal cortex. CONCLUSIONS: Patients with OCD show increased emotional processing-related activation in limbic, frontal, and temporal regions. Previous mixed evidence regarding the role of the amygdala in OCD has likely been influenced by patient characteristics (such as medication status) and low statistical power.