The heterogeneous course of OCD - A scoping review on the variety of definitions.

Although effective treatments exist, obsessive-compulsive disorder (OCD) is, according to the views of patients and experts, still associated with chronicity, a term with no clear and consistent definition. To improve patient care and to foster research, a clear distinction between the various concepts of chronicity cited in the literature is crucial. The aim was thus to explicate central concepts related to courses and trajectories in OCD based on an explorative, scoping search of the existing literature. Our review revealed a considerable lack in content validity, as the concepts were operationalized inconsistently. Concepts related to symptom improvement were (complete) recovery, partial/full remission and partial/full response. Terms used in relation with symptom stability or worsening were chronic/continuous, intermittent and episodic course, waxing and waning, relapse, recurrence, deterioration and treatment-refractoriness. All concepts are explained and visualized as a result of the review. Further, based on authors' remarks, we present recommendations on how to enhance care for chronic OCD patients, namely training psychotherapists to apply CBT as intended, managing patient beliefs about disease and treatment, and adapting psychotherapy to OCD subtypes. Finally, we then propose a literature-based definition of treatment-refractory OCD.

Single mild traumatic brain injury results in transiently impaired spatial long-term memory and altered search strategies.

Mild traumatic brain injury (mTBI) can lead to diffuse neurophysical damage as well as cognitive and affective alterations. The nature and extent of behavioral changes after mTBI are still poorly understood and how strong an impact force has to be to cause long-term behavioral changes is not yet known. Here, we examined spatial learning acquisition, retention and reversal in a Morris water maze, and assessed search strategies during task performance after a single, mild, closed-skull traumatic impact referred to as "minimal" TBI. Additionally, we investigated changes in conditioned learning in a contextual fear-conditioning paradigm. Results show transient deficits in spatial memory retention, which, although limited, are indicative of deficits in long-term memory reconsolidation. Interestingly, minimal TBI causes animals to relapse to less effective search strategies, affecting performance after a retention pause. Apart from cognitive deficits, results yielded a sub-acute, transient increase in freezing response after fear conditioning, with no increase in baseline behavior, an indication of a stronger affective reaction to aversive stimuli after minimal TBI or greater susceptibility to stress. Furthermore, western blot analysis showed a short-term increase in hippocampal GFAP expression, most likely indicating astrogliosis, which is typically related to injuries of the central nervous system. Our findings provide evidence that even a very mild impact to the skull can have detectable consequences on the molecular, cognitive and affective-like level. However, these effects seemed to be very transient and reversible.

Effects of Dimeric PSD-95 Inhibition on Excitotoxic Cell Death and Outcome After Controlled Cortical Impact in Rats.

Therapeutic effects of PSD-95 inhibition have been demonstrated in numerous studies of stroke; however only few studies have assessed the effects of PSD-95 inhibitors in traumatic brain injury (TBI). As the pathophysiology of TBI partially overlaps with that of stroke, PSD-95 inhibition may also be an effective therapeutic strategy in TBI. The objectives of the present study were to assess the effects of a dimeric inhibitor of PSD-95, UCCB01-144, on excitotoxic cell death in vitro and outcome after experimental TBI in rats in vivo. In addition, the pharmacokinetic parameters of UCCB01-144 were investigated in order to assess uptake of the drug into the central nervous system of rats. After a controlled cortical impact rats were randomized to receive a single injection of either saline or two different doses of UCCB01-144 (10 or 20 mg/kg IV) immediately after injury. Spatial learning and memory were assessed in a water maze at 2 weeks post-trauma, and at 4 weeks lesion volumes were estimated. Overall, UCCB01-144 did not protect against NMDA-toxicity in neuronal cultures or experimental TBI in rats. Important factors that should be investigated further in future studies assessing the effects of PSD-95 inhibitors in TBI are discussed.

Effects of different delayed exercise regimens on cognitive performance in fimbria­fornix transected rats.

Studies have shown that exercise can positively influence cognitive performance after brain injury. This study investigated the effects of different exercise regimens on allocentric place learning after fimbria­fornix (FF) transection. One hundred and sixteen pre­shaped rats were subjected either to a mechanical transection of the FF or control sham surgery and divided into following groups: i) no exercise (NE), ii) voluntary exercise in a running wheel (RW), iii) forced swimming exercise administered as interval training of short (3x5 min) duration (FS­SI), iv) forced swimming exercise administered as interval training of long (3x15 min) duration (FS­LI), v) forced swimming exercise administered as one session of short (5 min) duration (FS­SS), and vi) forced swimming exercise administered as one session of long (15 min) duration (FS­LS). The exercise was initiated 21 days post­surgery. Subsequently, all animals were administered 28 acquisition sessions in an 8­arm radial maze. Both sham operated and lesioned animals showed a significant learning response, however, the lesion induced a marked and lasting impairment, which was not alleviated neither by voluntary nor forced (spaced or one­session only) exercise regimens. Exercise regimens had no effect on the place learning of control sham animals. We conclude that the lesion location as well as factors related to the exercise­ and cognitive testing protocols can profoundly influence the potential of exercise as a general recovery­promoting method.

Implementation of a Functional Observation Battery for the Assessment of Postoperative Well-being in Rats Subjected to Fimbria-Fornix Transection.

The postoperative well-being of Wistar rats subjected to fimbria-fornix transections was assessed using a functional observational battery (FOB), including observations of relative body weight change, general condition, fur quality, body posture and movement, appetite, and pica behavior. Fimbria-fornix transected animals (FF), sham-operated animals (Sham), and two non-operated control groups with and without administration of buprenorphine (+BUP and -BUP, respectively) were observed twice daily for seven days after surgery. Buprenorphine (0.4 mg/kg) mixed in a nut paste for voluntary ingestion was supplied twice daily for 84 h to all groups except the -BUP control group starting on the day of surgery. Body weight was slightly decreased postoperatively in both surgical groups (FF and Sham) compared to control groups. The +BUP control group lost weight starting at day four after discontinuation of buprenorphine. Furthermore, the FF group exhibited significantly reduced general condition one day after surgery, with significantly affected body posture and movement for two days after surgery. In addition, mild pica behavior was observed in the FF group during the first postsurgical day. In conclusion, the FOB implemented in the present study appears to be a sensitive and accurate protocol for assessing animal well-being in the experimental setup applied. It is apparent that the FF transection is an invasive procedure that causes mildly adverse postoperative effects on the rats' well-being. We therefore recommend that this FOB is applied as a routine welfare monitoring protocol in experiments using mechanical central nervous system injury models, such as FF transection.

Social communication with virtual agents: The effects of body and gaze direction on attention and emotional responding in human observers.

In social communication, the gaze direction of other persons provides important information to perceive and interpret their emotional response. Previous research investigated the influence of gaze by manipulating mutual eye contact. Therefore, gaze and body direction have been changed as a whole, resulting in only congruent gaze and body directions (averted or directed) of another person. Here, we aimed to disentangle these effects by using short animated sequences of virtual agents posing with either direct or averted body or gaze. Attention allocation by means of eye movements, facial muscle response, and emotional experience to agents of different gender and facial expressions were investigated. Eye movement data revealed longer fixation durations, i.e., a stronger allocation of attention, when gaze and body direction were not congruent with each other or when both were directed towards the observer. This suggests that direct interaction as well as incongruous signals increase the demands of attentional resources in the observer. For the facial muscle response, only the reaction of muscle zygomaticus major revealed an effect of body direction, expressed by stronger activity in response to happy expressions for direct compared to averted gaze when the virtual character's body was directed towards the observer. Finally, body direction also influenced the emotional experience ratings towards happy expressions. While earlier findings suggested that mutual eye contact is the main source for increased emotional responding and attentional allocation, the present results indicate that direction of the virtual agent's body and head also plays a minor but significant role.